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Bringing Stem Cells to War: Meet the Blood Pharmers
New research from DARPA could open the door to on-demand blood-cell manufacturing on battlefields and in hospitals. All
medics need is a machine that uses a nanofiber that mimics bone marrow to turn a handful of stem cells into gallons of
blood. Who needs blood donations when you have blood pharming?
By Michael Milstein
Published on: December 16, 2008
Fresher blood is better than stale: It carries more oxygen and, when transfused into patients, speeds recovery.
Military medics are all too familiar with this problem in the field, where donated blood may take two or more weeks to
reach soldiers who need it immediately. But medical researchers—also known as blood pharmers—are working on
manufacturing the red stuff on the spot.
With a machine the size of a few refrigerators, the Defense Department's advanced research arm, the Defense Advanced
Research Projects Agency (DARPA) envisions liter upon liter of fresh blood churning out, destined for the veins of injured soldiers. It
doesn't get any fresher than that. And if it works for the military, it should also work for domestic hospitals that are paying
increasingly pricey bills for blood that's in short supply, says DARPA project scientist Jon Mogford, who was awarded nearly $2
million to Cleveland-based Arteriocyte for blood-pharming research.
The company's key ingredient is umbilical-cord stem cells, the Houdini of human cells, that can transform into whatever other cells
the body might need to repair or replace injured ones. Arteriocyte researchers were trying to grow big batches of stem cells when
they realized that the growing conditions they used—such as temperature and levels of oxygen and carbon dioxide —caused the
stem cells to turn into an early stage of red blood cell. At first they were frustrated because they wanted stem cells. Then they
realized that they may have unintentionally found a clever way to produce new blood.
Blood is in extremely short supply, and not only on the battlefield. Americans today do not donate blood as often as they used to and
many are ineligible to donate because of the risk of hepatitis and other diseases tied to ubiquitous tattoos and piercings. The
shortage has driven the cost of blood up and hospitals are having a hard time getting the kind that they need when they need it.
Even when they do, it may be several days old. On battlefields, the blood may be even older: "It often takes seven to 14 days to get
from my arm to a staging center," said Arteriocyte CEO Donald Brown.
The trick isn't producing red blood cells—the company has that figured out—it is producing them in enough volume to do patients
some good. The cells can be finicky: they need just the right environment to grow. For that, Arteriocyte is relying on a technique
developed at Johns Hopkins University that uses nanofibers to mimic the three-dimensional structure of bone marrow, which
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manufactures blood in the body. Parent stem cells readily multiply in the matrix. "You're trying to replicate what goes on in human
bone marrow," Brown says.
The DARPA award gives Arteriocyte three years to scale up to a self-contained system that could turn out 100 units of universal
blood (which could be transfused into people with any blood type) a week for eight weeks. The system can measure no more than
47 cu ft and must stand up to the rigors of frontline military deployment. DARPA then wants to submit the system to the FDA for
approval. In the end, if the system works, soldiers and civilian patients could have all the blood they need available on tap.
Thursday, December 18, 2008
Wednesday, December 17, 2008
ZYVOX INDICATIONS
http://www.zyvox.com/index.asp?hcp=true
ZYVOX INDICATIONS
ZYVOX® (linezolid) is indicated in the treatment of the following infections caused by susceptible strains of the designated microorganisms:
Nosocomial pneumonia caused by Staphylococcus aureus(methicillin-susceptible and -resistant strains) or Streptococcus pneumoniae(including multidrug-resistant strains [MDRSP]). MDRSP refers to isolates resistant to 2 or more of the following antibiotics: penicillin, second-generation cephalosporins, macrolides, tetracycline, and trimethoprim/sulfamethoxazole.
Complicated skin and skin structure infections, including diabetic foot infections, without concomitant osteomyelitis, caused by Staphylococcus aureus (methicillin-susceptible and -resistant strains), Streptococcus pyogenes, or Streptococcus agalactiae. ZYVOX has not been studied in the treatment of decubitus ulcers.
IMPORTANT SAFETY CONSIDERATIONS
ZYVOX formulations are contraindicated for use in patients who have known hypersensitivity to linezolid or any of the other product components.
ZYVOX should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g. phenelzine, isocarboxazid) or within 2 weeks of taking any such medicinal product.
Unless patients are monitored for potential increases in blood pressure, ZYVOX should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis and/or patients taking any of the following types of medications: directly and indirectly acting sympathomimetic agents (e.g. pseudoephedrine), vasopressive agents (e.g. epinephrine, norepinephrine), and dopaminergic agents (e.g. dopamine, dobutamine).
Unless patients are carefully observed for signs and/or symptoms of serotonin syndrome, ZYVOX should not be administered to patients with carcinoid syndrome and/or patients taking any of the following medications: serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine, or buspirone.
Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been reported in patients receiving ZYVOX. In cases where the outcome is known, when ZYVOX was discontinued, the affected hematologic parameters have risen toward pretreatment levels. Complete blood counts should be monitored weekly in patients who receive ZYVOX, particularly in those who receive ZYVOX for longer than 2 weeks, those with preexisting myelosuppression, those receiving concomitant drugs that produce bone marrow suppression, or those with a chronic infection who have received previous or concomitant antibiotic therapy. Discontinuation of therapy with ZYVOX should be considered in patients who develop or have worsening myelosuppression.
ZYVOX is not approved and should not be used for the treatment of patients with catheter-related bloodstream infections or catheter-site infections.
In an open-label investigational study in seriously ill patients with intravascular catheter-related infections, an imbalance in mortality was seen in patients treated with ZYVOX compared with vancomycin/dicloxacillin/oxacillin. While causality has not been established, mortality was higher in patients treated with ZYVOX who were infected with Gram-negative organisms alone, with both Gram-positive and Gram-negative organisms, or who had no infection when they entered the study. Patients with Gram-positive infections had no difference in mortality.
ZYVOX has no clinical activity against Gram-negative pathogens and is not indicated for the treatment of Gram-negative infections. It is critical that specific Gram-negative therapy be initiated immediately if a concomitant Gram-negative pathogen is documented or suspected.
Lactic acidosis has been reported with the use of ZYVOX. In reported cases, patients experienced repeated episodes of nausea and vomiting. Patients who develop recurrent nausea or vomiting, unexplained acidosis, or a low bicarbonate level while receiving ZYVOX should receive immediate medical evaluation.
Spontaneous reports of serotonin syndrome associated with the coadministration of ZYVOX and serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs), have been reported. Where administration of ZYVOX and concomitant serotonergic agents is clinically appropriate, patients should be closely observed for signs and symptoms of serotonin syndrome such as cognitive dysfunction, hyperpyrexia, hyperreflexia, and incoordination. If signs or symptoms occur, physicians should consider discontinuation of either one or both agents.
Peripheral and optic neuropathy have been reported in patients treated with ZYVOX, primarily those patients treated for longer than the maximum recommended duration of 28 days. In cases of optic neuropathy that progressed to loss of vision, patients were treated for extended periods beyond the maximum recommended duration. Visual blurring has been reported in some patients treated with ZYVOX for less than 28 days.
If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, blurred vision, or visual field defect, prompt ophthalmic evaluation is recommended. Visual function should be monitored in all patients taking ZYVOX for extended periods (3 months) and in all patients reporting new visual symptoms regardless of length of therapy with ZYVOX. If peripheral or optic neuropathy occurs, the continued use of ZYVOX in these patients should be weighed against the potential risks.
Convulsions have been reported in patients when treated with ZYVOX. In some of these cases, a history of seizures or risk factors for seizures was reported.
The most commonly reported adverse events in adults across clinical trials were nausea, headache, and diarrhea.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZYVOX and other antibacterial drugs, ZYVOX should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Clostridium difficile –associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including ZYVOX, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C difficile . C difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C difficile , and surgical evaluation should be instituted as clinically indicated.
ZYVOX INDICATIONS
ZYVOX® (linezolid) is indicated in the treatment of the following infections caused by susceptible strains of the designated microorganisms:
Nosocomial pneumonia caused by Staphylococcus aureus(methicillin-susceptible and -resistant strains) or Streptococcus pneumoniae(including multidrug-resistant strains [MDRSP]). MDRSP refers to isolates resistant to 2 or more of the following antibiotics: penicillin, second-generation cephalosporins, macrolides, tetracycline, and trimethoprim/sulfamethoxazole.
Complicated skin and skin structure infections, including diabetic foot infections, without concomitant osteomyelitis, caused by Staphylococcus aureus (methicillin-susceptible and -resistant strains), Streptococcus pyogenes, or Streptococcus agalactiae. ZYVOX has not been studied in the treatment of decubitus ulcers.
IMPORTANT SAFETY CONSIDERATIONS
ZYVOX formulations are contraindicated for use in patients who have known hypersensitivity to linezolid or any of the other product components.
ZYVOX should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g. phenelzine, isocarboxazid) or within 2 weeks of taking any such medicinal product.
Unless patients are monitored for potential increases in blood pressure, ZYVOX should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis and/or patients taking any of the following types of medications: directly and indirectly acting sympathomimetic agents (e.g. pseudoephedrine), vasopressive agents (e.g. epinephrine, norepinephrine), and dopaminergic agents (e.g. dopamine, dobutamine).
Unless patients are carefully observed for signs and/or symptoms of serotonin syndrome, ZYVOX should not be administered to patients with carcinoid syndrome and/or patients taking any of the following medications: serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine, or buspirone.
Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been reported in patients receiving ZYVOX. In cases where the outcome is known, when ZYVOX was discontinued, the affected hematologic parameters have risen toward pretreatment levels. Complete blood counts should be monitored weekly in patients who receive ZYVOX, particularly in those who receive ZYVOX for longer than 2 weeks, those with preexisting myelosuppression, those receiving concomitant drugs that produce bone marrow suppression, or those with a chronic infection who have received previous or concomitant antibiotic therapy. Discontinuation of therapy with ZYVOX should be considered in patients who develop or have worsening myelosuppression.
ZYVOX is not approved and should not be used for the treatment of patients with catheter-related bloodstream infections or catheter-site infections.
In an open-label investigational study in seriously ill patients with intravascular catheter-related infections, an imbalance in mortality was seen in patients treated with ZYVOX compared with vancomycin/dicloxacillin/oxacillin. While causality has not been established, mortality was higher in patients treated with ZYVOX who were infected with Gram-negative organisms alone, with both Gram-positive and Gram-negative organisms, or who had no infection when they entered the study. Patients with Gram-positive infections had no difference in mortality.
ZYVOX has no clinical activity against Gram-negative pathogens and is not indicated for the treatment of Gram-negative infections. It is critical that specific Gram-negative therapy be initiated immediately if a concomitant Gram-negative pathogen is documented or suspected.
Lactic acidosis has been reported with the use of ZYVOX. In reported cases, patients experienced repeated episodes of nausea and vomiting. Patients who develop recurrent nausea or vomiting, unexplained acidosis, or a low bicarbonate level while receiving ZYVOX should receive immediate medical evaluation.
Spontaneous reports of serotonin syndrome associated with the coadministration of ZYVOX and serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs), have been reported. Where administration of ZYVOX and concomitant serotonergic agents is clinically appropriate, patients should be closely observed for signs and symptoms of serotonin syndrome such as cognitive dysfunction, hyperpyrexia, hyperreflexia, and incoordination. If signs or symptoms occur, physicians should consider discontinuation of either one or both agents.
Peripheral and optic neuropathy have been reported in patients treated with ZYVOX, primarily those patients treated for longer than the maximum recommended duration of 28 days. In cases of optic neuropathy that progressed to loss of vision, patients were treated for extended periods beyond the maximum recommended duration. Visual blurring has been reported in some patients treated with ZYVOX for less than 28 days.
If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, blurred vision, or visual field defect, prompt ophthalmic evaluation is recommended. Visual function should be monitored in all patients taking ZYVOX for extended periods (3 months) and in all patients reporting new visual symptoms regardless of length of therapy with ZYVOX. If peripheral or optic neuropathy occurs, the continued use of ZYVOX in these patients should be weighed against the potential risks.
Convulsions have been reported in patients when treated with ZYVOX. In some of these cases, a history of seizures or risk factors for seizures was reported.
The most commonly reported adverse events in adults across clinical trials were nausea, headache, and diarrhea.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZYVOX and other antibacterial drugs, ZYVOX should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Clostridium difficile –associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including ZYVOX, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C difficile . C difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C difficile , and surgical evaluation should be instituted as clinically indicated.
North American breakthrough for dialysis patients
http://www.physorg.com/printnews.php?newsid=147001312
North American breakthrough for dialysis patients
Suffering from end-stage renal disease (ESRD), a growing number of patients at the Centre hospitalier de l'Université de Montréal (CHUM), have become the beneficiaries of a North American breakthrough: high efficacy hemodiafiltration (HDF).
An extracorporeal blood purification technique, HDF is indicated for ESRD patients. Since the HDF unit was introduced in CHUM's Nephrology section, preliminary results show a clear advantage of high efficacy HDF over conventional hemodialysis in several areas, including the following:
-- Improved removal of uremic toxins;
-- Decreased number of hospitalization days;
-- A better tolerance for patients;
-- Minimizes the state of chronic inflammation that too often may lead to complications over a long course of dialysis;
-- Diminished need for certain medications.
-- Increased biocompatibility across the blood-dialysis system interface.
"Conventional hemodialysis continues to save lives, but we now have the technology to improve the lot of dialysis patients," says Dr. Rénee Lévesque, nephologist and lead physician in the HDF program at CHUM, and a professor with the medical faculty of the Université de Montréal. "At CHUM, we're proud to soon be accepting a cohort of forty patients undergoing HDF." Dr. Lévesque added that the CHUM Nephrology section is putting much efforts behind the new process, and hopes that one day soon all dialysis patients will be treated in this fashion.
Recent retrospective clinical data indicate that HDF reduces the mortality rates of dialysis patients and randomized studies are under way to provide clear proof of increased survival rates for patients. Among these, the CONTRAST study compares hemodialysis with online hemodiafiltration HDF in overall performance relative to cardiovascular morbidity and mortality. The study seeks to recruit seven hundred test subjects and follow them over a three-year period. CHUM is the only medical centre in North America to take part in this study, currently the largest in terms of the size of the randomized cohort.
Hemodiafiltration : the best of both worlds
HDF combines the elements of two processes, conventional hemodialysis (HD) and hemofiltration (HF). Renal replacement therapy for ESRD is based on two processes: diffusion and convection.
Conventional HD is diffusive; blood is circulated in an artificial kidney machine on one side of a semi-permeable membrane, while a special dialysis fluid is circulated on the other side. Small molecules of metabolic waste seep out into a dialysis solution flowing in the opposite direction on the other side of the membrane, mimicking the kidneys and washing wastes and toxins out of the bloodstream. One major toxin is urea. HD is the most widely used renal replacement function technology for ESRD.
Hemofiltration (HF) or ultrafiltration is exclusively convective, forcing blood through a filter under high pressure. The principle consists of applying a hydrostatic pressure gradient (high pressure on one side, low pressure on the other) across the membrane or filter. This results in an ultrafiltrate (water and electrolytes) on the other side. The quantity of ultrafiltrate lost in this process must be compensated by a matching infusion of replacement fluid. HF is used primarily in continuous mode and in acute care or intensive care.
In HDF, the diffusive component of HD is combined with the convective component of HF. As is the case in HF, the excessive loss of liquid must be compensated by the reinfusion of a sterile and apyrogenic (not producing fever) fluid. Recent developments have led to the "on-line" production of large volumes of ultrapure liquid of high quality. This has led to higher quality physicochemical and microbiological properties in these solutions, in comparison with HD.
Some statistics on the treatment of end-stage renal disease:
-- At the end of 2003, there were 29,551 Canadians undergoing renal substitution treatment and that number is expected to double over the next ten years;
-- Among that number, 61 % were in dialysis. Of these patients, 81 % were in hemodialysis and 19 % followed a regiment of peritoneal dialysis, e.g. from the abdomen.
Source: Université de Montréal Hospital Centre
North American breakthrough for dialysis patients
Suffering from end-stage renal disease (ESRD), a growing number of patients at the Centre hospitalier de l'Université de Montréal (CHUM), have become the beneficiaries of a North American breakthrough: high efficacy hemodiafiltration (HDF).
An extracorporeal blood purification technique, HDF is indicated for ESRD patients. Since the HDF unit was introduced in CHUM's Nephrology section, preliminary results show a clear advantage of high efficacy HDF over conventional hemodialysis in several areas, including the following:
-- Improved removal of uremic toxins;
-- Decreased number of hospitalization days;
-- A better tolerance for patients;
-- Minimizes the state of chronic inflammation that too often may lead to complications over a long course of dialysis;
-- Diminished need for certain medications.
-- Increased biocompatibility across the blood-dialysis system interface.
"Conventional hemodialysis continues to save lives, but we now have the technology to improve the lot of dialysis patients," says Dr. Rénee Lévesque, nephologist and lead physician in the HDF program at CHUM, and a professor with the medical faculty of the Université de Montréal. "At CHUM, we're proud to soon be accepting a cohort of forty patients undergoing HDF." Dr. Lévesque added that the CHUM Nephrology section is putting much efforts behind the new process, and hopes that one day soon all dialysis patients will be treated in this fashion.
Recent retrospective clinical data indicate that HDF reduces the mortality rates of dialysis patients and randomized studies are under way to provide clear proof of increased survival rates for patients. Among these, the CONTRAST study compares hemodialysis with online hemodiafiltration HDF in overall performance relative to cardiovascular morbidity and mortality. The study seeks to recruit seven hundred test subjects and follow them over a three-year period. CHUM is the only medical centre in North America to take part in this study, currently the largest in terms of the size of the randomized cohort.
Hemodiafiltration : the best of both worlds
HDF combines the elements of two processes, conventional hemodialysis (HD) and hemofiltration (HF). Renal replacement therapy for ESRD is based on two processes: diffusion and convection.
Conventional HD is diffusive; blood is circulated in an artificial kidney machine on one side of a semi-permeable membrane, while a special dialysis fluid is circulated on the other side. Small molecules of metabolic waste seep out into a dialysis solution flowing in the opposite direction on the other side of the membrane, mimicking the kidneys and washing wastes and toxins out of the bloodstream. One major toxin is urea. HD is the most widely used renal replacement function technology for ESRD.
Hemofiltration (HF) or ultrafiltration is exclusively convective, forcing blood through a filter under high pressure. The principle consists of applying a hydrostatic pressure gradient (high pressure on one side, low pressure on the other) across the membrane or filter. This results in an ultrafiltrate (water and electrolytes) on the other side. The quantity of ultrafiltrate lost in this process must be compensated by a matching infusion of replacement fluid. HF is used primarily in continuous mode and in acute care or intensive care.
In HDF, the diffusive component of HD is combined with the convective component of HF. As is the case in HF, the excessive loss of liquid must be compensated by the reinfusion of a sterile and apyrogenic (not producing fever) fluid. Recent developments have led to the "on-line" production of large volumes of ultrapure liquid of high quality. This has led to higher quality physicochemical and microbiological properties in these solutions, in comparison with HD.
Some statistics on the treatment of end-stage renal disease:
-- At the end of 2003, there were 29,551 Canadians undergoing renal substitution treatment and that number is expected to double over the next ten years;
-- Among that number, 61 % were in dialysis. Of these patients, 81 % were in hemodialysis and 19 % followed a regiment of peritoneal dialysis, e.g. from the abdomen.
Source: Université de Montréal Hospital Centre
Wednesday, December 10, 2008
Diabetes causes more amputations than landmines
December 8, 2008
The condition now accounts for 70 per cent of all lower limb amputations
Dr Thomas Stuttaford
Mohandas Gandhi was known as Mahatma, or “great soul”, because he combined patriotism with moral teaching, reform and a horror of violence, consumerism and class, caste or racial discrimination.
Gandhi would have welcomed the support given to the World Diabetes Foundation (WDF) and the World Health Organisation (WHO) by Handicap International. That is the French charitable organisation that has been awarded a Nobel prize for its work with people left crippled and handicapped in Vietnam, Cambodia and other countries by landmines.
Exploding hidden landmines remain a considerable danger, but one that has been overtaken by diabetes as a reason for the amputation of younger people's legs around the world. Diabetes now accounts for 70 per cent of all lower limb amputations. Hence the decision of Handicap International, while continuing to work in Vietnam, Cambodia and other former war zones, to add to its agenda the WDF campaign to reduce the incidence and improve the treatment of diabetes in developing countries.
The loss of a lower limb in a working man usually heralds the loss of the family's livelihood so that poverty becomes inevitable. Locally made artificial lower limbs are satisfactory for walking but rarely adequate for hard manual work.
RELATED LINKS
Temporary castration for prostate cancer sufferers
Back pain causing a lack of sleep
Are injectable self-tans safe?
The WDF's expertise helps in the formation of partnerships to deal with diabetes in the developing world. It unites the various people and organisations interested in raising the awareness of the lifestyle changes needed to prevent diabetes and the need for prompt diagnosis and treatment. Earlier treatment of diabetic foot complications would prevent 85 per cent of amputations.
Currently 40,000 legs are amputated in India each year. Last week doctors, health workers and journalists gathered in Bangalore and Madras. In Bangalore they visited the vascular surgical unit at the Bhagwan Jain hospital. The unit, led by Dr Kalkunte Suresh, is financed by the WDF, the WHO, Handicap International and several local philanthropists. It runs a footcare division that organises local clinics that screen people in surrounding villages for diabetes and the first signs of nerve damage that could desensitise their feet so that they become vulnerable to minor injury.
The clinics also raise public awareness of the lifestyle changes needed to reduce the incidence of diabetes and its complications. Dr Suresh, the director of the scheme and of the hospital's vascular surgical unit, said that diabetic foot complications were increasing and that someone with diabetes in India was 25 times more likely to have a leg amputated than someone without it.
Dr Suresh added that doctors trained in the developed world associate foot complications including gangrene and amputation with elderly or obese, under-exercised patients. This is not so in India. There, the most common cause for a crisis leading to gangrene and amputation was more likely to be precipitated by diabetic nerve damage than deteriorating arterial blood flow.
The Indian patients who need amputation are often aged only around 35 to 45, a time in the manual worker's life when he has maximal domestic responsibilities and is probably providing for several generations. Most of Dr Suresh's patients who had leg amputations were not overweight but lean, tough and muscular agricultural workers.
Gandhi, delegates were reminded, taught that India lives in its villages, and in order to bring about change it was necessary to change the way that village people think.
Dr Suresh and his team, when spreading the message about diabetic prevention and treatment, rely on well -respected local people - popular village postmen or bus drivers are ideal - to educate their fellow villagers about the signs and symptoms of early diabetes, the need for foot care, and the importance of wearing shoes in and out of the house (more feet are injured indoors than in the fields).
All these aspects of diabetes can be taught in the villages by troupes of enthusiastic street performers acting out short plays and singing traditional folk songs, modified to spell out the methods of prevention and treatment of diabetes.
While India watched and mourned the atrocities in Mumbai, the delegates moved to Madras. There they visited the projects the WDF has established with the Pabolu Ogirala and Sriram Charitable Trust. It aims to combat eye problems in diabetic patients, who are twice as likely to develop them as non-diabetic people. Fifty per cent of all diabetic people develop some degree of diabetic eye disease.
www.worlddiabetesfoundation.org
The condition now accounts for 70 per cent of all lower limb amputations
Dr Thomas Stuttaford
Mohandas Gandhi was known as Mahatma, or “great soul”, because he combined patriotism with moral teaching, reform and a horror of violence, consumerism and class, caste or racial discrimination.
Gandhi would have welcomed the support given to the World Diabetes Foundation (WDF) and the World Health Organisation (WHO) by Handicap International. That is the French charitable organisation that has been awarded a Nobel prize for its work with people left crippled and handicapped in Vietnam, Cambodia and other countries by landmines.
Exploding hidden landmines remain a considerable danger, but one that has been overtaken by diabetes as a reason for the amputation of younger people's legs around the world. Diabetes now accounts for 70 per cent of all lower limb amputations. Hence the decision of Handicap International, while continuing to work in Vietnam, Cambodia and other former war zones, to add to its agenda the WDF campaign to reduce the incidence and improve the treatment of diabetes in developing countries.
The loss of a lower limb in a working man usually heralds the loss of the family's livelihood so that poverty becomes inevitable. Locally made artificial lower limbs are satisfactory for walking but rarely adequate for hard manual work.
RELATED LINKS
Temporary castration for prostate cancer sufferers
Back pain causing a lack of sleep
Are injectable self-tans safe?
The WDF's expertise helps in the formation of partnerships to deal with diabetes in the developing world. It unites the various people and organisations interested in raising the awareness of the lifestyle changes needed to prevent diabetes and the need for prompt diagnosis and treatment. Earlier treatment of diabetic foot complications would prevent 85 per cent of amputations.
Currently 40,000 legs are amputated in India each year. Last week doctors, health workers and journalists gathered in Bangalore and Madras. In Bangalore they visited the vascular surgical unit at the Bhagwan Jain hospital. The unit, led by Dr Kalkunte Suresh, is financed by the WDF, the WHO, Handicap International and several local philanthropists. It runs a footcare division that organises local clinics that screen people in surrounding villages for diabetes and the first signs of nerve damage that could desensitise their feet so that they become vulnerable to minor injury.
The clinics also raise public awareness of the lifestyle changes needed to reduce the incidence of diabetes and its complications. Dr Suresh, the director of the scheme and of the hospital's vascular surgical unit, said that diabetic foot complications were increasing and that someone with diabetes in India was 25 times more likely to have a leg amputated than someone without it.
Dr Suresh added that doctors trained in the developed world associate foot complications including gangrene and amputation with elderly or obese, under-exercised patients. This is not so in India. There, the most common cause for a crisis leading to gangrene and amputation was more likely to be precipitated by diabetic nerve damage than deteriorating arterial blood flow.
The Indian patients who need amputation are often aged only around 35 to 45, a time in the manual worker's life when he has maximal domestic responsibilities and is probably providing for several generations. Most of Dr Suresh's patients who had leg amputations were not overweight but lean, tough and muscular agricultural workers.
Gandhi, delegates were reminded, taught that India lives in its villages, and in order to bring about change it was necessary to change the way that village people think.
Dr Suresh and his team, when spreading the message about diabetic prevention and treatment, rely on well -respected local people - popular village postmen or bus drivers are ideal - to educate their fellow villagers about the signs and symptoms of early diabetes, the need for foot care, and the importance of wearing shoes in and out of the house (more feet are injured indoors than in the fields).
All these aspects of diabetes can be taught in the villages by troupes of enthusiastic street performers acting out short plays and singing traditional folk songs, modified to spell out the methods of prevention and treatment of diabetes.
While India watched and mourned the atrocities in Mumbai, the delegates moved to Madras. There they visited the projects the WDF has established with the Pabolu Ogirala and Sriram Charitable Trust. It aims to combat eye problems in diabetic patients, who are twice as likely to develop them as non-diabetic people. Fifty per cent of all diabetic people develop some degree of diabetic eye disease.
www.worlddiabetesfoundation.org
Salt 'as bad as cigarettes'
12/10/08 7:01 PM
AAPDecember 03, 2008 03:36pm
Health & Lifestyle
AUSTRALIANS are consuming too much salt, say nutritionists who blame not only fast food but also
healthier alternatives such as canned vegetables and baked beans.
Less than 5 per cent of all sausages and beef burgers sold in the nation's supermarkets contained
acceptable levels of salt, a Nutrition Society of Australia conference has also heard.
Jacqui Webster, a senior project manager based at Sydney's The George Institute for International
Health, said Australians were consuming well over the maximum recommended intake of six grams
of salt a day.
"Despite being aware of the adverse health effects of salt, most Australian consumers are taking little
action to reduce their intake,'' Ms Webster told the conference.
"Consuming too much salt, or sodium, can lead to serious health problems including high blood
pressure, cardiovascular disease, stroke, osteoporosis and stomach cancer.
"There is also some evidence that it adds to the severity of asthma symptoms.''
Ms Webster said the 2007 Australian National Children's Nutrition and Physical Activity Survey
showed boys were consuming around 9g of salt daily, while girls came in at the maximum 6g.
She said it was also likely that many adults consumed in excess of the 9g of salt each day.
Ms Webster said foods contributing to high salt diet included bread, processed meats, baked beans,
canned vegetables, table sauces, some breakfast cereals and fast food.
Research in the UK showed processed foods accounted for 75 per cent of salt in a person's diet, with
10 per cent from natural foods like fish and vegetables.
The remaining 15 per cent was salt added at the table or during cooking.
Given the dire health consequences, Ms Webster said reducing salt in the diet should be "considered
on the same level of importance as reducing obesity, alcohol and tobacco consumption''.
Leading nutritionists from around Australia and the world are attending the conference in Adelaide.
AAPDecember 03, 2008 03:36pm
Health & Lifestyle
AUSTRALIANS are consuming too much salt, say nutritionists who blame not only fast food but also
healthier alternatives such as canned vegetables and baked beans.
Less than 5 per cent of all sausages and beef burgers sold in the nation's supermarkets contained
acceptable levels of salt, a Nutrition Society of Australia conference has also heard.
Jacqui Webster, a senior project manager based at Sydney's The George Institute for International
Health, said Australians were consuming well over the maximum recommended intake of six grams
of salt a day.
"Despite being aware of the adverse health effects of salt, most Australian consumers are taking little
action to reduce their intake,'' Ms Webster told the conference.
"Consuming too much salt, or sodium, can lead to serious health problems including high blood
pressure, cardiovascular disease, stroke, osteoporosis and stomach cancer.
"There is also some evidence that it adds to the severity of asthma symptoms.''
Ms Webster said the 2007 Australian National Children's Nutrition and Physical Activity Survey
showed boys were consuming around 9g of salt daily, while girls came in at the maximum 6g.
She said it was also likely that many adults consumed in excess of the 9g of salt each day.
Ms Webster said foods contributing to high salt diet included bread, processed meats, baked beans,
canned vegetables, table sauces, some breakfast cereals and fast food.
Research in the UK showed processed foods accounted for 75 per cent of salt in a person's diet, with
10 per cent from natural foods like fish and vegetables.
The remaining 15 per cent was salt added at the table or during cooking.
Given the dire health consequences, Ms Webster said reducing salt in the diet should be "considered
on the same level of importance as reducing obesity, alcohol and tobacco consumption''.
Leading nutritionists from around Australia and the world are attending the conference in Adelaide.
The Pain May Be Real, but the Scan Is Deceiving
Cheryl Weinstein’s left knee bothered her for years, but when it started clicking and hurting when she straightened it, she told her internist that something was definitely wrong.
The Evidence Gap
Diagnosing the Wrong Problem
Articles in this series, are exploring medical treatments used despite scant proof that they work and are examining steps toward medicine based on evidence.
Previous Articles in the Series »
Multimedia
Dartmouth-Hitchcock Medical Center
It was the start of her medical odyssey, a journey that led her to specialists, physical therapy, Internet searches and, finally, an M.R.I. scan that showed a torn cartilage and convinced her that her only hope for relief was to have surgery to repair it. But in fact, fixing the torn cartilage that was picked up on the scan was not going to solve her problem, which, eventually, she found was caused by arthritis.
Scans — more sensitive and easily available than ever — are increasingly finding abnormalities that may not be the cause of the problem for which they are blamed. It’s an issue particularly for the millions of people who go to doctors’ offices in pain.
The scans are expensive — Medicare and its beneficiaries pay about $750 to $950 for an M.R.I. scan of a knee or back, for example. Many doctors own their own scanners, which can provide an incentive to offer scans to their patients.
And so, in what is often an irresistible feedback loop, patients who are in pain often demand scans hoping to find out what is wrong, doctors are tempted to offer scans to those patients, and then, once a scan is done, it is common for doctors and patients to assume that any abnormalities found are the reason for the pain.
But in many cases it is just not known whether what is seen on a scan is the cause of the pain. The problem is that all too often, no one knows what is normal.
“A patient comes in because he’s in pain,” said Dr. Nelda Wray, a senior research scientist at the Methodist Institute for Technology in Houston. “We see something in a scan, and we assume causation. But we have no idea of the prevalence of the abnormality in routine populations.”
Now, as more and more people have scans for everything from headaches to foot aches, more are left in a medical lurch, or with unnecessary or sometimes even harmful treatments, including surgery.
“Every time we get a new technology that provides insights into structures we didn’t encounter before, we end up saying, ‘Oh, my God, look at all those abnormalities.’ They might be dangerous,” said Dr. David Felson, a professor of medicine and epidemiology at Boston University Medical School. “Some are, some aren’t, but it ends up leading to a lot of care that’s unnecessary.”
That was what almost happened with Mrs. Weinstein, an active, athletic 64-year-old who lives in New London, N.H. And it was her great fortune to finally visit a surgeon who told her so. He told her bluntly that her pain was caused by arthritis, not the torn cartilage.
No one had told her that before, Mrs. Weinstein said, and looking back on her quest to get a scan and get the cartilage fixed, she shook her head in dismay. There’s no surgical procedure short of a knee replacement that will help, and she’s not ready for a knee replacement.
“I feel that I have come full circle,” she said. “I will cope on my own with this knee.”
In fact, Mrs. Weinstein was also lucky because her problem was with her knee. It’s one of only two body parts — the other is the back — where there are good data on abnormalities that turn up in people who feel just fine, indicating that the abnormalities may not be so abnormal after all.
But even the data on knees comes from just one study, and researchers say the problem is far from fixed. It is difficult to conduct scans on people who feel fine — most do not want to spend time in an M.R.I. machine, and CT scans require that people be exposed to radiation. But that leaves patients and doctors in an untenable situation.
“It’s a concern, isn’t it?” said Dr. Jeffrey Jarvik, a professor of radiology and neurosurgery at the University of Washington. “We are trying to fix things that shouldn’t be fixed.”
As a rheumatologist, Dr. Felson saw patient after patient with knee pain, many of whom had already had scans. And he was becoming concerned about their findings.
Often, a scan would show that a person with arthritis had a torn meniscus, cartilage that stabilizes the knee. And often the result was surgery — orthopedic surgeons do more meniscus surgery than any other operation. But, Dr. Felson wondered, was the torn cartilage an injury causing pain or was the arthritis causing pain and the tear a consequence of arthritis?
That led Dr. Felson and his colleagues to do the first and so far the only large study of knees, asking what is normal. It involved M.R.I. scans on 991 people ages 50 to 90. Some had knee pain, others did not.
On Sept. 11, Dr. Felson and his colleagues published their results in The New England Journal of Medicine: meniscal tears were just as common in people with knee arthritis who did not complain of pain as they were in people with knee arthritis who did have pain. They tended to occur along with arthritis and were a part of the disease process itself. And so repairing the tears would not eliminate the pain.
“The rule is, as you get older, you will get a meniscal tear,” Dr. Felson said. “It’s a function of aging and disease. If you are a 60-year-old guy, the chance that you have a meniscal tear is 40 percent.”
It is a result that paralleled what spine researchers found over the past decade in what is perhaps the best evidence on what shows up on scans of healthy people. “If you’re going to look at a spine, you need to know what that spine might look like in a normal patient,” said Dr. Michael Modic, chairman of the Neurological Institute at the Cleveland Clinic.
After Dr. Modic and others scanned hundreds of asymptomatic people, they learned abnormalities were common.
“Somewhere between 20 and 25 percent of people who climb into a scanner will have a herniated disk,” Dr. Modic said. As many as 60 percent of healthy adults with no back pain, he said, have degenerative changes in their spines.
Those findings made Dr. Modic ask: Why do a scan in the first place? There are some who may benefit from surgery, but does it make sense to routinely do scans for nearly everyone with back pain? After all, one-third of herniated disks disappear on their own in six weeks, and two-thirds in six months.
And surgeons use symptoms and a physical examination to identify patients who would be helped by operations. What extra medical help does a scan provide? So Dr. Modic did another study, this time with 250 patients. All had M.R.I. scans when they first arrived complaining of back pain or shooting pains down their leg, which can be caused by a herniated disc pressing on a nerve in the spine. And all had scans again six weeks later. Sixty percent had herniated disks, the scans showed.
Dr. Modic gave the results to only half of the patients and their doctors — the others had no idea what the M.R.I.’s revealed. Dr. Modic knew, though.
In 13 percent of the patients, the second scan showed that the herniated disk had become bigger or a new herniated disk had appeared. In 15 percent, the herniated disk had disappeared. But there was no relationship between the scan findings at six weeks and patients’ symptoms. Some continued to complain of pain even though their herniated disk had disappeared; others said they felt better even though their herniation had grown bigger.
The question, though, was whether it helped the patients and their doctors to know what the M.R.I.’s had found. And the answer, Dr. Modic reported, is that it did not. The patients who knew recovered no faster than those who did not know. However, Dr. Modic said, there was one effect of being told — patients felt worse about themselves when they knew they had a bulging disk.
“If I tell you that you have a degenerated disk, basically I’m telling you you’re ugly,” Dr. Modic said.
Scans, he said, are presurgical tools, not screening tools. A scan can help a surgeon before he or she operates, but it does not help with a diagnosis.
“If a patient has back or leg pain, they should be treated conservatively for at least eight weeks,” Dr. Modic said, meaning that they take pain relievers and go about their normal lives. “Then you should do imaging only if you are going to do surgery.”
That message can be a hard sell, he acknowledged. “A lot of people are driven by wanting to have imaging,” Dr. Modic said. “They are miserable as hell, they can’t work, they can’t sit. We look at you and say, ‘We think you have a herniated disk. We say the natural history is that you will get better. You should go through six to eight weeks of conservative management.’ ”
At the Partners Healthcare System in Boston, spine experts have the same struggle to convince patients that an M.R.I. scan is not necessarily desirable, said Dr. Scott Gazelle, director of radiology there.
“The consensus is that you are a surgical candidate or not based on your history and physical findings, not on imaging findings,” he said.
Dr. Gazelle had a chance last year to test his own convictions. He had the classic symptoms of a herniated disk — shooting pains down his left leg, a numb foot and difficulty walking.
Dr. Gazelle went to see his primary-care doctor but, he said, “I didn’t get an M.R.I.” That decision, he added, “was the right thing to do.”
About three months later, he had recovered on his own.
In 1998, two medical scientists, writing in The Lancet, proposed what sounded like a radical idea. Instead of simply providing patients and their doctors with the results of an X-ray or an M.R.I. scan, he said, radiologists should put the findings in context. For example, they wrote, if a scan showed advanced disk deterioration, the report should say, “Roughly 40 percent of patients with this finding do not have back pain so the finding may be unrelated.”
It is an idea that only would work for back pain, because that is the one area where radiologists have enough data. But it made eminent sense to Dr. Jarvik. “It gives referring physicians some sort of context,” he said.
So, a few years ago, with some trepidation, his radiology group starting including epidemiological data in their reports. “We thought, ‘What’s going to be the reaction among referring physicians?’ ” Dr. Jarvik said. Their fear was that doctors would start choosing other places for M.R.I.’s and that Dr. Jarvik’s group would lose business.
Because of the way the university’s records are kept, it’s hard to know whether the new reporting system had that effect, Dr. Jarvik said. But he was heartened by the responses of some doctors, like Dr. Sohail Mirza, who recently moved to Dartmouth Medical School.
“We often see patients who have already had M.R.I. scans,” Dr. Mirza said. “They are fixated on the abnormality and come to a surgeon to try to get the abnormality fixed. They’ll come in with the report in hand.”
The new sort of report, Dr. Mirza said, was “very helpful information to have when talking to patients and very helpful for patients to help them understand that the abnormalities were not catastrophic findings.”
Others, like Dr. Modic, are hesitant about reporting epidemiology along with a patient’s scan findings.
“It’s an interesting idea,” he said. But, he added: “The problem isn’t what happens after they get their imaging. It’s that they get the imaging in the first place.”
That was what happened with Mrs. Weinstein.
When she started looking up her symptoms on the Internet, she decided she probably had a meniscus tear. “I was very forceful in asking for an M.R.I.,” she said.
And when the scan showed that her meniscus was torn, she went to a surgeon expecting an operation.
He X-rayed her knee and told her she had arthritis. Then, Mrs. Weinstein said, the surgeon looked at her and said, “Let me get this straight. Are you here for a knee replacement?”
She said no, of course not. She skis, she does aerobics, she was nowhere near ready for something so drastic.
Then the surgeon told her that there was no point in repairing her meniscus because that was not her problem. And if he repaired the cartilage, her arthritic bones would just grind it down again.
For now, Mrs. Weinstein says she is finished with her medical odyssey.
“I continue to live with this, whatever they call it, this arthritic knee,” she said.
The Evidence Gap
Diagnosing the Wrong Problem
Articles in this series, are exploring medical treatments used despite scant proof that they work and are examining steps toward medicine based on evidence.
Previous Articles in the Series »
Multimedia
Dartmouth-Hitchcock Medical Center
It was the start of her medical odyssey, a journey that led her to specialists, physical therapy, Internet searches and, finally, an M.R.I. scan that showed a torn cartilage and convinced her that her only hope for relief was to have surgery to repair it. But in fact, fixing the torn cartilage that was picked up on the scan was not going to solve her problem, which, eventually, she found was caused by arthritis.
Scans — more sensitive and easily available than ever — are increasingly finding abnormalities that may not be the cause of the problem for which they are blamed. It’s an issue particularly for the millions of people who go to doctors’ offices in pain.
The scans are expensive — Medicare and its beneficiaries pay about $750 to $950 for an M.R.I. scan of a knee or back, for example. Many doctors own their own scanners, which can provide an incentive to offer scans to their patients.
And so, in what is often an irresistible feedback loop, patients who are in pain often demand scans hoping to find out what is wrong, doctors are tempted to offer scans to those patients, and then, once a scan is done, it is common for doctors and patients to assume that any abnormalities found are the reason for the pain.
But in many cases it is just not known whether what is seen on a scan is the cause of the pain. The problem is that all too often, no one knows what is normal.
“A patient comes in because he’s in pain,” said Dr. Nelda Wray, a senior research scientist at the Methodist Institute for Technology in Houston. “We see something in a scan, and we assume causation. But we have no idea of the prevalence of the abnormality in routine populations.”
Now, as more and more people have scans for everything from headaches to foot aches, more are left in a medical lurch, or with unnecessary or sometimes even harmful treatments, including surgery.
“Every time we get a new technology that provides insights into structures we didn’t encounter before, we end up saying, ‘Oh, my God, look at all those abnormalities.’ They might be dangerous,” said Dr. David Felson, a professor of medicine and epidemiology at Boston University Medical School. “Some are, some aren’t, but it ends up leading to a lot of care that’s unnecessary.”
That was what almost happened with Mrs. Weinstein, an active, athletic 64-year-old who lives in New London, N.H. And it was her great fortune to finally visit a surgeon who told her so. He told her bluntly that her pain was caused by arthritis, not the torn cartilage.
No one had told her that before, Mrs. Weinstein said, and looking back on her quest to get a scan and get the cartilage fixed, she shook her head in dismay. There’s no surgical procedure short of a knee replacement that will help, and she’s not ready for a knee replacement.
“I feel that I have come full circle,” she said. “I will cope on my own with this knee.”
In fact, Mrs. Weinstein was also lucky because her problem was with her knee. It’s one of only two body parts — the other is the back — where there are good data on abnormalities that turn up in people who feel just fine, indicating that the abnormalities may not be so abnormal after all.
But even the data on knees comes from just one study, and researchers say the problem is far from fixed. It is difficult to conduct scans on people who feel fine — most do not want to spend time in an M.R.I. machine, and CT scans require that people be exposed to radiation. But that leaves patients and doctors in an untenable situation.
“It’s a concern, isn’t it?” said Dr. Jeffrey Jarvik, a professor of radiology and neurosurgery at the University of Washington. “We are trying to fix things that shouldn’t be fixed.”
As a rheumatologist, Dr. Felson saw patient after patient with knee pain, many of whom had already had scans. And he was becoming concerned about their findings.
Often, a scan would show that a person with arthritis had a torn meniscus, cartilage that stabilizes the knee. And often the result was surgery — orthopedic surgeons do more meniscus surgery than any other operation. But, Dr. Felson wondered, was the torn cartilage an injury causing pain or was the arthritis causing pain and the tear a consequence of arthritis?
That led Dr. Felson and his colleagues to do the first and so far the only large study of knees, asking what is normal. It involved M.R.I. scans on 991 people ages 50 to 90. Some had knee pain, others did not.
On Sept. 11, Dr. Felson and his colleagues published their results in The New England Journal of Medicine: meniscal tears were just as common in people with knee arthritis who did not complain of pain as they were in people with knee arthritis who did have pain. They tended to occur along with arthritis and were a part of the disease process itself. And so repairing the tears would not eliminate the pain.
“The rule is, as you get older, you will get a meniscal tear,” Dr. Felson said. “It’s a function of aging and disease. If you are a 60-year-old guy, the chance that you have a meniscal tear is 40 percent.”
It is a result that paralleled what spine researchers found over the past decade in what is perhaps the best evidence on what shows up on scans of healthy people. “If you’re going to look at a spine, you need to know what that spine might look like in a normal patient,” said Dr. Michael Modic, chairman of the Neurological Institute at the Cleveland Clinic.
After Dr. Modic and others scanned hundreds of asymptomatic people, they learned abnormalities were common.
“Somewhere between 20 and 25 percent of people who climb into a scanner will have a herniated disk,” Dr. Modic said. As many as 60 percent of healthy adults with no back pain, he said, have degenerative changes in their spines.
Those findings made Dr. Modic ask: Why do a scan in the first place? There are some who may benefit from surgery, but does it make sense to routinely do scans for nearly everyone with back pain? After all, one-third of herniated disks disappear on their own in six weeks, and two-thirds in six months.
And surgeons use symptoms and a physical examination to identify patients who would be helped by operations. What extra medical help does a scan provide? So Dr. Modic did another study, this time with 250 patients. All had M.R.I. scans when they first arrived complaining of back pain or shooting pains down their leg, which can be caused by a herniated disc pressing on a nerve in the spine. And all had scans again six weeks later. Sixty percent had herniated disks, the scans showed.
Dr. Modic gave the results to only half of the patients and their doctors — the others had no idea what the M.R.I.’s revealed. Dr. Modic knew, though.
In 13 percent of the patients, the second scan showed that the herniated disk had become bigger or a new herniated disk had appeared. In 15 percent, the herniated disk had disappeared. But there was no relationship between the scan findings at six weeks and patients’ symptoms. Some continued to complain of pain even though their herniated disk had disappeared; others said they felt better even though their herniation had grown bigger.
The question, though, was whether it helped the patients and their doctors to know what the M.R.I.’s had found. And the answer, Dr. Modic reported, is that it did not. The patients who knew recovered no faster than those who did not know. However, Dr. Modic said, there was one effect of being told — patients felt worse about themselves when they knew they had a bulging disk.
“If I tell you that you have a degenerated disk, basically I’m telling you you’re ugly,” Dr. Modic said.
Scans, he said, are presurgical tools, not screening tools. A scan can help a surgeon before he or she operates, but it does not help with a diagnosis.
“If a patient has back or leg pain, they should be treated conservatively for at least eight weeks,” Dr. Modic said, meaning that they take pain relievers and go about their normal lives. “Then you should do imaging only if you are going to do surgery.”
That message can be a hard sell, he acknowledged. “A lot of people are driven by wanting to have imaging,” Dr. Modic said. “They are miserable as hell, they can’t work, they can’t sit. We look at you and say, ‘We think you have a herniated disk. We say the natural history is that you will get better. You should go through six to eight weeks of conservative management.’ ”
At the Partners Healthcare System in Boston, spine experts have the same struggle to convince patients that an M.R.I. scan is not necessarily desirable, said Dr. Scott Gazelle, director of radiology there.
“The consensus is that you are a surgical candidate or not based on your history and physical findings, not on imaging findings,” he said.
Dr. Gazelle had a chance last year to test his own convictions. He had the classic symptoms of a herniated disk — shooting pains down his left leg, a numb foot and difficulty walking.
Dr. Gazelle went to see his primary-care doctor but, he said, “I didn’t get an M.R.I.” That decision, he added, “was the right thing to do.”
About three months later, he had recovered on his own.
In 1998, two medical scientists, writing in The Lancet, proposed what sounded like a radical idea. Instead of simply providing patients and their doctors with the results of an X-ray or an M.R.I. scan, he said, radiologists should put the findings in context. For example, they wrote, if a scan showed advanced disk deterioration, the report should say, “Roughly 40 percent of patients with this finding do not have back pain so the finding may be unrelated.”
It is an idea that only would work for back pain, because that is the one area where radiologists have enough data. But it made eminent sense to Dr. Jarvik. “It gives referring physicians some sort of context,” he said.
So, a few years ago, with some trepidation, his radiology group starting including epidemiological data in their reports. “We thought, ‘What’s going to be the reaction among referring physicians?’ ” Dr. Jarvik said. Their fear was that doctors would start choosing other places for M.R.I.’s and that Dr. Jarvik’s group would lose business.
Because of the way the university’s records are kept, it’s hard to know whether the new reporting system had that effect, Dr. Jarvik said. But he was heartened by the responses of some doctors, like Dr. Sohail Mirza, who recently moved to Dartmouth Medical School.
“We often see patients who have already had M.R.I. scans,” Dr. Mirza said. “They are fixated on the abnormality and come to a surgeon to try to get the abnormality fixed. They’ll come in with the report in hand.”
The new sort of report, Dr. Mirza said, was “very helpful information to have when talking to patients and very helpful for patients to help them understand that the abnormalities were not catastrophic findings.”
Others, like Dr. Modic, are hesitant about reporting epidemiology along with a patient’s scan findings.
“It’s an interesting idea,” he said. But, he added: “The problem isn’t what happens after they get their imaging. It’s that they get the imaging in the first place.”
That was what happened with Mrs. Weinstein.
When she started looking up her symptoms on the Internet, she decided she probably had a meniscus tear. “I was very forceful in asking for an M.R.I.,” she said.
And when the scan showed that her meniscus was torn, she went to a surgeon expecting an operation.
He X-rayed her knee and told her she had arthritis. Then, Mrs. Weinstein said, the surgeon looked at her and said, “Let me get this straight. Are you here for a knee replacement?”
She said no, of course not. She skis, she does aerobics, she was nowhere near ready for something so drastic.
Then the surgeon told her that there was no point in repairing her meniscus because that was not her problem. And if he repaired the cartilage, her arthritic bones would just grind it down again.
For now, Mrs. Weinstein says she is finished with her medical odyssey.
“I continue to live with this, whatever they call it, this arthritic knee,” she said.
Study: 4 Out of 5 Doctors Don’t Get Enough Exercise
By Amanda MacMillan
As a health writer, people often ask me if I’ve changed my lifestyle to become a healthier person. Do I eat healthier, work out more, and actually put to use any of those nifty tips I learn about every day?
For a long time, my response was, “No—I still have all the same bad habits; now I just feel guiltier about them.”
I did eventually get involved in fitness and running, partially thanks to my job. But I still find it hard to squeeze in a workout most days, even though I know how important it is to my long-term health.
Turns out, I’m probably not the only health-related professional who feels that way. Most doctors, who know the dangers of inactivity more than anyone, don’t get enough exercise, according to a study published this month in the British Journal of Sports Medicine.
Almost 80% of doctors fall short
Researchers at the United Kingdom’s Bedford Hospital NHS Trust surveyed 61 hospital physicians and found that only 21% get the recommended 30 minutes of moderate exercise at least five days a week—that’s less than half of the 44% of the overall population in the same age group who claim to meet this goal. Those who didn’t blamed lack of time, lack of motivation, or lack of workout facilities. (Doctors with an on-site gym at their hospital didn’t fare any better than those without, however. In fact, a third of them didn’t even know it existed!)
Other good habits had seemed to rub off on the junior doctors, who had an average age of 27 and an average BMI of 23.5 (considered normal weight): They weighed less and smoked less than the national average, and only 7% drank more than the recommended weekly amount of alcohol. As for their abysmal exercise habits, many had been more active in school—and had only become couch potatoes after they started their jobs.
What does it mean for us?
While the study was done on British hospital doctors (as opposed to, say, American primary-care physicians), coauthor Lampson Fan, MBBS, is willing to bet that findings would be similar elsewhere: “In both the U.K. and U.S., doctors are under the influence of the same stresses,” he says. “In many ways, it’s probably worse in the U.S. as the doctors there are working on average 30 hours more [a week] than those in the U.K.”
While I can’t say I’m shocked at these results, the numbers are quite disheartening. If doctors, whose responsibility it should be to promote good health, can’t find time to exercise, what hope is there for others out there with demanding schedules—lawyers, truck drivers, working moms, or people who have taken on a second job?
Previous research has shown that doctors who exercise are more likely to counsel their patients to do the same, and that patients are more willing to try exercising when their doctors disclose their own personal workout habits. Think about it: If an out-of-shape doctor pleaded with you to get more exercise, how seriously could you take him knowing that he’s not getting enough himself?
Dr. Lampson recommends that health-care institutions do more to promote physical activity among employees, such as sponsoring organized exercise classes, team sports, and discounts with local gyms. If doctors can get passionate about exercise, hopefully they’ll pass on that excitement to their patients—or at least set a good example.
Does the physical fitness of your doctor matter to you? Have you ever been motivated—or discouraged—by the health of a physician?
As a health writer, people often ask me if I’ve changed my lifestyle to become a healthier person. Do I eat healthier, work out more, and actually put to use any of those nifty tips I learn about every day?
For a long time, my response was, “No—I still have all the same bad habits; now I just feel guiltier about them.”
I did eventually get involved in fitness and running, partially thanks to my job. But I still find it hard to squeeze in a workout most days, even though I know how important it is to my long-term health.
Turns out, I’m probably not the only health-related professional who feels that way. Most doctors, who know the dangers of inactivity more than anyone, don’t get enough exercise, according to a study published this month in the British Journal of Sports Medicine.
Almost 80% of doctors fall short
Researchers at the United Kingdom’s Bedford Hospital NHS Trust surveyed 61 hospital physicians and found that only 21% get the recommended 30 minutes of moderate exercise at least five days a week—that’s less than half of the 44% of the overall population in the same age group who claim to meet this goal. Those who didn’t blamed lack of time, lack of motivation, or lack of workout facilities. (Doctors with an on-site gym at their hospital didn’t fare any better than those without, however. In fact, a third of them didn’t even know it existed!)
Other good habits had seemed to rub off on the junior doctors, who had an average age of 27 and an average BMI of 23.5 (considered normal weight): They weighed less and smoked less than the national average, and only 7% drank more than the recommended weekly amount of alcohol. As for their abysmal exercise habits, many had been more active in school—and had only become couch potatoes after they started their jobs.
What does it mean for us?
While the study was done on British hospital doctors (as opposed to, say, American primary-care physicians), coauthor Lampson Fan, MBBS, is willing to bet that findings would be similar elsewhere: “In both the U.K. and U.S., doctors are under the influence of the same stresses,” he says. “In many ways, it’s probably worse in the U.S. as the doctors there are working on average 30 hours more [a week] than those in the U.K.”
While I can’t say I’m shocked at these results, the numbers are quite disheartening. If doctors, whose responsibility it should be to promote good health, can’t find time to exercise, what hope is there for others out there with demanding schedules—lawyers, truck drivers, working moms, or people who have taken on a second job?
Previous research has shown that doctors who exercise are more likely to counsel their patients to do the same, and that patients are more willing to try exercising when their doctors disclose their own personal workout habits. Think about it: If an out-of-shape doctor pleaded with you to get more exercise, how seriously could you take him knowing that he’s not getting enough himself?
Dr. Lampson recommends that health-care institutions do more to promote physical activity among employees, such as sponsoring organized exercise classes, team sports, and discounts with local gyms. If doctors can get passionate about exercise, hopefully they’ll pass on that excitement to their patients—or at least set a good example.
Does the physical fitness of your doctor matter to you? Have you ever been motivated—or discouraged—by the health of a physician?
Half-Dose Flu Shots Work In Adults, Study Finds
Half-Dose Flu Shots Work In Adults, Study Finds
By Lindsey Tanner, AP Medical Writer
posted: 09 December 2008 03:59 pm ET
CHICAGO — Half-dose flu shots are effective in adults, especially in women and those younger than 50, and offer a viable way to stretch supplies during vaccine shortages, a government study found.
The strategy also might be an option during hard economic times since lower doses likely would mean cheaper shots, said Vanderbilt University vaccine expert Dr. Kathryn Edwards, who wasn't involved in the study. And the lower dosage could open doors to vaccinating people in poor countries where flu shots are little used, she said.
Even so, Edwards said giving half-dose flu shots isn't ready for prime time. It's still experimental and hasn't been approved by federal authorities.
The study involved 1,114 adults aged 18 to 64. It's the first to test half-dose flu shots in those aged 50 and older during a single flu season, 2004-05. The results among younger adults echo previous research, said lead author Dr. Renata Engler of Walter Reed Army Medical Center.
The government-funded study appears in Monday's Archives of Internal Medicine.
"Traditionally, vaccine programs have followed a 'one-size-fits-all' approach," Engler said. That means everyone gets the same dose and during shortages, supplies are more likely to run out.
If the study results are confirmed through additional research, Engler said, half-doses could be given to large numbers of adults, enabling more people to get vaccinated.
That's important because while influenza is often underestimated, the federal Centers for Disease Control and Prevention says each year the disease is responsible for about 36,000 deaths and 200,000 hospitalizations nationwide.
In the study, participants were randomly chosen to get full- or half-dose flu shots in late 2004 in the Washington D.C. area. The researchers measured blood levels of antibodies to flu virus before vaccination and 21 days afterward.
After the shots, similar numbers of adults of all ages, including men and women, had antibody levels considered adequate to protect against the flu.
The 18-to-49 age group and women had the highest antibody levels. That adds to evidence that women may be more sensitive to some vaccines than men.
Dr. Ronald Hershow, an infectious disease specialist at the University of Illinois's Chicago campus, noted that while half-doses produced an adequate immune response, full doses produced a stronger response. And there's evidence that stronger immune responses provide better protection against disease, he said.
Still, the study authors argued that from a public health standpoint, it would be better to vaccinate many people with lower doses than fewer people with full doses when vaccine supplies are scarce.
There were few reports of flu-like illnesses among the study volunteers, but the number of people of all ages with those symptoms was similar in both the full-dose and half-dose groups.
Engler noted that because adults in their 60s and older are more vulnerable to flu complications, more research is needed to be sure that half-doses are adequate for them.
The study was done during the vaccine shortage in the winter of 2004-05 when contamination was found at a major vaccine supplier's plant in Britain.
Now, there are five licensed flu vaccine manufacturers, making shortages in the near future unlikely. Still, Dr. Joseph Bresee, the CDC's flu chief, said the study provides useful information just in case.
Flu season starts in the fall and this year is off to a pretty typical start, with low levels of disease nationwide, Bresee said.
"It's still a good time to get a vaccine," Bresee said.
By Lindsey Tanner, AP Medical Writer
posted: 09 December 2008 03:59 pm ET
CHICAGO — Half-dose flu shots are effective in adults, especially in women and those younger than 50, and offer a viable way to stretch supplies during vaccine shortages, a government study found.
The strategy also might be an option during hard economic times since lower doses likely would mean cheaper shots, said Vanderbilt University vaccine expert Dr. Kathryn Edwards, who wasn't involved in the study. And the lower dosage could open doors to vaccinating people in poor countries where flu shots are little used, she said.
Even so, Edwards said giving half-dose flu shots isn't ready for prime time. It's still experimental and hasn't been approved by federal authorities.
The study involved 1,114 adults aged 18 to 64. It's the first to test half-dose flu shots in those aged 50 and older during a single flu season, 2004-05. The results among younger adults echo previous research, said lead author Dr. Renata Engler of Walter Reed Army Medical Center.
The government-funded study appears in Monday's Archives of Internal Medicine.
"Traditionally, vaccine programs have followed a 'one-size-fits-all' approach," Engler said. That means everyone gets the same dose and during shortages, supplies are more likely to run out.
If the study results are confirmed through additional research, Engler said, half-doses could be given to large numbers of adults, enabling more people to get vaccinated.
That's important because while influenza is often underestimated, the federal Centers for Disease Control and Prevention says each year the disease is responsible for about 36,000 deaths and 200,000 hospitalizations nationwide.
In the study, participants were randomly chosen to get full- or half-dose flu shots in late 2004 in the Washington D.C. area. The researchers measured blood levels of antibodies to flu virus before vaccination and 21 days afterward.
After the shots, similar numbers of adults of all ages, including men and women, had antibody levels considered adequate to protect against the flu.
The 18-to-49 age group and women had the highest antibody levels. That adds to evidence that women may be more sensitive to some vaccines than men.
Dr. Ronald Hershow, an infectious disease specialist at the University of Illinois's Chicago campus, noted that while half-doses produced an adequate immune response, full doses produced a stronger response. And there's evidence that stronger immune responses provide better protection against disease, he said.
Still, the study authors argued that from a public health standpoint, it would be better to vaccinate many people with lower doses than fewer people with full doses when vaccine supplies are scarce.
There were few reports of flu-like illnesses among the study volunteers, but the number of people of all ages with those symptoms was similar in both the full-dose and half-dose groups.
Engler noted that because adults in their 60s and older are more vulnerable to flu complications, more research is needed to be sure that half-doses are adequate for them.
The study was done during the vaccine shortage in the winter of 2004-05 when contamination was found at a major vaccine supplier's plant in Britain.
Now, there are five licensed flu vaccine manufacturers, making shortages in the near future unlikely. Still, Dr. Joseph Bresee, the CDC's flu chief, said the study provides useful information just in case.
Flu season starts in the fall and this year is off to a pretty typical start, with low levels of disease nationwide, Bresee said.
"It's still a good time to get a vaccine," Bresee said.
Thursday, November 6, 2008
Human trials to begin on 'diabetes cure' after terminally ill mice are returned to health
Human trials to begin on 'diabetes cure' after terminally ill mice are returned to health
By NOEL YOUNG
Last updated at 23:30 14 March 2008
Most diabetes sufferers could be cured within four years if a revolutionary treatment involving the BCG vaccine works, scientists said yesterday.
A human clinical trial with hopes of finding a cure for type 1 diabetes is to start at a leading American research hospital using BCG, universally given for many years in Britain to prevent tuberculosis.
If all goes well in later trials, the treatment could be approved for ordinary patients in four years.
Volunteer patients are now being enrolled for the trial at at Massachusetts General Hospital in Boston.
The aim is to find out whether promising results obtained by Dr Denise Faustman in mouse studies can be applied to human diabetes.
Her studies have shown that mice with a form of diabetes closely resembling type 1 diabetes in humans can be cured. “Hundreds of mice were involved in a number of experiments over a period of years," said Dr Faustman.
"All were suffering from type 1 diabetes with only about two weeks to live."
“They started improving within days after the first injection of BCG was given, and were eventually free of diabetes."
The vaccine destroyed abnormal white blood cells obstructing the production of insulin, which is needed to prevent diabetes, she said.
The first step in the human study is to determine whether the same strategy using BCG vaccination can be used to modify the abnormal autoimmune cells present in type 1 diabetes, sometimes called “juvenile-onset” diabetes.
“We are pleased to be starting human clinical trials,” said Dr Faustman.
“We are making the step from curing diabetes in mice to determining whether it will work in men and women with diabetes.”
Mouse blood is very similar to human blood and a clue as to whether the vaccine programme is working could be available within months of the start of the trial.
“One of the beautie of this is that BCG is a drug that has been tried and tested for 80 years, “ said Dr Faustman.
“There is no multi- million-dollar drug approval pipeline. It is a generic drug and will be cheap to administer if it works for humans.”
Type 1 diabetes usually starts during childhood or adolescence when a person's immune system attacks and destroys the insulin-producing cells in the pancreas.
Complications can include kidney failure, blindness, amputations, heart disease, and strokes. The risk of complications is closely linked to the elevated blood sugar levels.
Maintaining near-normal sugar levels requires life-long demands on the patient, including frequent blood sugar monitoring and at least three daily injections of insulin or use of an insulin pump, along with restrictive diets.
Dr Faustman, a diabetes researcher for 15 years, realised that reversing Type 1 diabetes would require a drug that killed the bad white blood cells.
Going over years of records, she identified BCG, one of whose side effects in combatting TB is that it does just that.
Type two diabetes, which is an adult-onset illness often linked to obesity, is a different disease and not likely to be affected by the American trial.
By NOEL YOUNG
Last updated at 23:30 14 March 2008
Most diabetes sufferers could be cured within four years if a revolutionary treatment involving the BCG vaccine works, scientists said yesterday.
A human clinical trial with hopes of finding a cure for type 1 diabetes is to start at a leading American research hospital using BCG, universally given for many years in Britain to prevent tuberculosis.
If all goes well in later trials, the treatment could be approved for ordinary patients in four years.
Volunteer patients are now being enrolled for the trial at at Massachusetts General Hospital in Boston.
The aim is to find out whether promising results obtained by Dr Denise Faustman in mouse studies can be applied to human diabetes.
Her studies have shown that mice with a form of diabetes closely resembling type 1 diabetes in humans can be cured. “Hundreds of mice were involved in a number of experiments over a period of years," said Dr Faustman.
"All were suffering from type 1 diabetes with only about two weeks to live."
“They started improving within days after the first injection of BCG was given, and were eventually free of diabetes."
The vaccine destroyed abnormal white blood cells obstructing the production of insulin, which is needed to prevent diabetes, she said.
The first step in the human study is to determine whether the same strategy using BCG vaccination can be used to modify the abnormal autoimmune cells present in type 1 diabetes, sometimes called “juvenile-onset” diabetes.
“We are pleased to be starting human clinical trials,” said Dr Faustman.
“We are making the step from curing diabetes in mice to determining whether it will work in men and women with diabetes.”
Mouse blood is very similar to human blood and a clue as to whether the vaccine programme is working could be available within months of the start of the trial.
“One of the beautie of this is that BCG is a drug that has been tried and tested for 80 years, “ said Dr Faustman.
“There is no multi- million-dollar drug approval pipeline. It is a generic drug and will be cheap to administer if it works for humans.”
Type 1 diabetes usually starts during childhood or adolescence when a person's immune system attacks and destroys the insulin-producing cells in the pancreas.
Complications can include kidney failure, blindness, amputations, heart disease, and strokes. The risk of complications is closely linked to the elevated blood sugar levels.
Maintaining near-normal sugar levels requires life-long demands on the patient, including frequent blood sugar monitoring and at least three daily injections of insulin or use of an insulin pump, along with restrictive diets.
Dr Faustman, a diabetes researcher for 15 years, realised that reversing Type 1 diabetes would require a drug that killed the bad white blood cells.
Going over years of records, she identified BCG, one of whose side effects in combatting TB is that it does just that.
Type two diabetes, which is an adult-onset illness often linked to obesity, is a different disease and not likely to be affected by the American trial.
Diabetes breakthrough
Diabetes breakthrough
Toronto scientists cure disease in mice
Tom Blackwell, National Post
Published: Friday, December 15, 2006
In a discovery that has stunned even those behind it, scientists at a Toronto hospital say they have proof the body's nervous system helps trigger diabetes, opening the door to a potential near-cure of the disease that affects millions of Canadians.
Diabetic mice became healthy virtually overnight after researchers injected a substance to counteract the effect of malfunctioning pain neurons in the pancreas.
"I couldn't believe it," said Dr. Michael Salter, a pain expert at the Hospital for Sick Children and one of the scientists. "Mice with diabetes suddenly didn't have diabetes any more."
The researchers caution they have yet to confirm their findings in people, but say they expect results from human studies within a year or so. Any treatment that may emerge to help at least some patients would likely be years away from hitting the market.
But the excitement of the team from Sick Kids, whose work is being published today in the journal Cell, is almost palpable.
"I've never seen anything like it," said Dr. Hans Michael Dosch, an immunologist at the hospital and a leader of the studies. "In my career, this is unique."
Their conclusions upset conventional wisdom that Type 1 diabetes, the most serious form of the illness that typically first appears in childhood, was solely caused by auto-immune responses -- the body's immune system turning on itself.
They also conclude that there are far more similarities than previously thought between Type 1 and Type 2 diabetes, and that nerves likely play a role in other chronic inflammatory conditions, such as asthma and Crohn's disease.
The "paradigm-changing" study opens "a novel, exciting door to address one of the diseases with large societal impact," said Dr. Christian Stohler, a leading U.S. pain specialist and dean of dentistry at the University of Maryland, who has reviewed the work.
"The treatment and diagnosis of neuropathic diseases is poised to take a dramatic leap forward because of the impressive research."
About two million Canadians suffer from diabetes, 10% of them with Type 1, contributing to 41,000 deaths a year.
Insulin replacement therapy is the only treatment of Type 1, and cannot prevent many of the side effects, from heart attacks to kidney failure.
In Type 1 diabetes, the pancreas does not produce enough insulin to shift glucose into the cells that need it. In Type 2 diabetes, the insulin that is produced is not used effectively -- something called insulin resistance -- also resulting in poor absorption of glucose.
The problems stem partly from inflammation -- and eventual death -- of insulin-producing islet cells in the pancreas.
Dr. Dosch had concluded in a 1999 paper that there were surprising similarities between diabetes and multiple sclerosis, a central nervous system disease. His interest was also piqued by the presence around the insulin-producing islets of an "enormous" number of nerves, pain neurons primarily used to signal the brain that tissue has been damaged.
Suspecting a link between the nerves and diabetes, he and Dr. Salter used an old experimental trick -- injecting capsaicin, the active ingredient in hot chili peppers, to kill the pancreatic sensory nerves in mice that had an equivalent of Type 1 diabetes.
"Then we had the biggest shock of our lives," Dr. Dosch said. Almost immediately, the islets began producing insulin normally "It was a shock ? really out of left field, because nothing in the literature was saying anything about this."
It turns out the nerves secrete neuropeptides that are instrumental in the proper functioning of the islets. Further study by the team, which also involved the University of Calgary and the Jackson Laboratory in Maine, found that the nerves in diabetic mice were releasing too little of the neuropeptides, resulting in a "vicious cycle" of stress on the islets.
So next they injected the neuropeptide "substance P" in the pancreases of diabetic mice, a demanding task given the tiny size of the rodent organs. The results were dramatic.
The islet inflammation cleared up and the diabetes was gone. Some have remained in that state for as long as four months, with just one injection.
They also discovered that their treatments curbed the insulin resistance that is the hallmark of Type 2 diabetes, and that insulin resistance is a major factor in Type 1 diabetes, suggesting the two illnesses are quite similar.
While pain scientists have been receptive to the research, immunologists have voiced skepticism at the idea of the nervous system playing such a major role in the disease. Editors of Cell put the Toronto researchers through vigorous review to prove the validity of their conclusions, though an editorial in the publication gives a positive review of the work.
"It will no doubt cause a great deal of consternation," said Dr. Salter about his paper.
The researchers are now setting out to confirm that the connection between sensory nerves and diabetes holds true in humans. If it does, they will see if their treatments have the same effects on people as they did on mice.
Nothing is for sure, but "there is a great deal of promise," Dr. Salter said.
Copyright © 2007 CanWest Interactive, a division of CanWest MediaWorks Publications, Inc.. All rights reserved.
Toronto scientists cure disease in mice
Tom Blackwell, National Post
Published: Friday, December 15, 2006
In a discovery that has stunned even those behind it, scientists at a Toronto hospital say they have proof the body's nervous system helps trigger diabetes, opening the door to a potential near-cure of the disease that affects millions of Canadians.
Diabetic mice became healthy virtually overnight after researchers injected a substance to counteract the effect of malfunctioning pain neurons in the pancreas.
"I couldn't believe it," said Dr. Michael Salter, a pain expert at the Hospital for Sick Children and one of the scientists. "Mice with diabetes suddenly didn't have diabetes any more."
The researchers caution they have yet to confirm their findings in people, but say they expect results from human studies within a year or so. Any treatment that may emerge to help at least some patients would likely be years away from hitting the market.
But the excitement of the team from Sick Kids, whose work is being published today in the journal Cell, is almost palpable.
"I've never seen anything like it," said Dr. Hans Michael Dosch, an immunologist at the hospital and a leader of the studies. "In my career, this is unique."
Their conclusions upset conventional wisdom that Type 1 diabetes, the most serious form of the illness that typically first appears in childhood, was solely caused by auto-immune responses -- the body's immune system turning on itself.
They also conclude that there are far more similarities than previously thought between Type 1 and Type 2 diabetes, and that nerves likely play a role in other chronic inflammatory conditions, such as asthma and Crohn's disease.
The "paradigm-changing" study opens "a novel, exciting door to address one of the diseases with large societal impact," said Dr. Christian Stohler, a leading U.S. pain specialist and dean of dentistry at the University of Maryland, who has reviewed the work.
"The treatment and diagnosis of neuropathic diseases is poised to take a dramatic leap forward because of the impressive research."
About two million Canadians suffer from diabetes, 10% of them with Type 1, contributing to 41,000 deaths a year.
Insulin replacement therapy is the only treatment of Type 1, and cannot prevent many of the side effects, from heart attacks to kidney failure.
In Type 1 diabetes, the pancreas does not produce enough insulin to shift glucose into the cells that need it. In Type 2 diabetes, the insulin that is produced is not used effectively -- something called insulin resistance -- also resulting in poor absorption of glucose.
The problems stem partly from inflammation -- and eventual death -- of insulin-producing islet cells in the pancreas.
Dr. Dosch had concluded in a 1999 paper that there were surprising similarities between diabetes and multiple sclerosis, a central nervous system disease. His interest was also piqued by the presence around the insulin-producing islets of an "enormous" number of nerves, pain neurons primarily used to signal the brain that tissue has been damaged.
Suspecting a link between the nerves and diabetes, he and Dr. Salter used an old experimental trick -- injecting capsaicin, the active ingredient in hot chili peppers, to kill the pancreatic sensory nerves in mice that had an equivalent of Type 1 diabetes.
"Then we had the biggest shock of our lives," Dr. Dosch said. Almost immediately, the islets began producing insulin normally "It was a shock ? really out of left field, because nothing in the literature was saying anything about this."
It turns out the nerves secrete neuropeptides that are instrumental in the proper functioning of the islets. Further study by the team, which also involved the University of Calgary and the Jackson Laboratory in Maine, found that the nerves in diabetic mice were releasing too little of the neuropeptides, resulting in a "vicious cycle" of stress on the islets.
So next they injected the neuropeptide "substance P" in the pancreases of diabetic mice, a demanding task given the tiny size of the rodent organs. The results were dramatic.
The islet inflammation cleared up and the diabetes was gone. Some have remained in that state for as long as four months, with just one injection.
They also discovered that their treatments curbed the insulin resistance that is the hallmark of Type 2 diabetes, and that insulin resistance is a major factor in Type 1 diabetes, suggesting the two illnesses are quite similar.
While pain scientists have been receptive to the research, immunologists have voiced skepticism at the idea of the nervous system playing such a major role in the disease. Editors of Cell put the Toronto researchers through vigorous review to prove the validity of their conclusions, though an editorial in the publication gives a positive review of the work.
"It will no doubt cause a great deal of consternation," said Dr. Salter about his paper.
The researchers are now setting out to confirm that the connection between sensory nerves and diabetes holds true in humans. If it does, they will see if their treatments have the same effects on people as they did on mice.
Nothing is for sure, but "there is a great deal of promise," Dr. Salter said.
Copyright © 2007 CanWest Interactive, a division of CanWest MediaWorks Publications, Inc.. All rights reserved.
Wednesday, October 29, 2008
Copper door handles and taps kill 95% of superbugs in hospitals
Copper door handles and taps kill 95% of superbugs in hospitals
By Fiona Macrae
Last updated at 1:34 AM on 29th October 2008
Hope: Copper taps, toilet seats and push plates on doors all but eliminated common bugs, the study found
Making door handles, taps and light switches from copper could help the country beat superbugs, scientists say.
A study found that copper fittings rapidly killed bugs on hospital wards, succeeding where other infection control measures failed.
In the trial at Selly Oak hospital, in Birmingham, copper taps, toilet seats and push plates on doors all but eliminated common bugs.
It is thought the metal 'suffocates' germs, preventing them breathing. It may also stop them from feeding and destroy their DNA.
Lab tests show that the metal kills off the deadly MRSA and C difficile superbugs.
It also kills other dangerous germs, including the flu virus and the E coli food poisoning bug.
Although the number of cases of MRSA and C difficile is falling, the two bugs still claim thousands of lives a year.
During the ten-week trial on a medical ward, a set of taps, a lavatory seat and a push plate on an entrance door were replaced with copper versions. They were swabbed twice a day for bugs and the results compared with a traditional tap, lavatory seat and push plate elsewhere in the ward.
The copper items had up to 95 per cent fewer bugs on their surface whenever they were tested, a U.S. conference on antibiotics heard yesterday.
Professor Tom Elliott, the lead researcher and a consultant microbiologist at the hospital, said: 'The findings of 90 to 95 per cent killing of those organisms, even after a busy day on a medical ward with items being touched by numerous people, is remarkable.
'I have been a consultant microbiologist for several decades. This is the first time I have seen anything like copper in terms of the effect it will have in the environment.
'It may well offer us another mechanism for trying to defeat the spread of infection.'
Researcher Professor Peter Lambert, of Aston University, Birmingham, said: 'The numbers decreased always on copper but not on the steel surfaces.'
If further hospital-based trials prove as successful, the researchers would like copper fixtures and fittings installed in hospitals around the country.
Doorknobs, taps, light switches, toilet seats and handles and bathroom 'grab rails' could all be ripped out and replaced with copper versions.
Making door handles, taps and light switches from copper could help the country beat superbugs, scientists say
Although it is usually thought to be an expensive metal, copper is actually a similar price to stainless steel, the researchers said. Nursing homes and even our houses could also benefit from the metal's ability to wipe out dangerous bugs.
The healing power of copper has been recognised for thousands of years.
More than 4,000 years ago, the Egyptians used it to sterilise wounds and drinking water and the Aztecs treated skin conditions with the metal.
The ancient Greeks also knew of its benefits. Hippocrates, sometimes called 'the father of medicine', noted that it could be used to treat leg ulcers.
Today, copper is a common constituent in medicines including antiseptic and antifungal creams. It is also believed to have anti-inflammatory properties. Many of those with arthritis wear copper bangles.
Although they provide relief to many, there is no scientific evidence that they work.
Copper is present in our diet in trace amounts and plays an important role in the formation of red blood cells and in keeping our blood vessels, nerves and bones healthy.
The research was funded by the copper industry.
By Fiona Macrae
Last updated at 1:34 AM on 29th October 2008
Hope: Copper taps, toilet seats and push plates on doors all but eliminated common bugs, the study found
Making door handles, taps and light switches from copper could help the country beat superbugs, scientists say.
A study found that copper fittings rapidly killed bugs on hospital wards, succeeding where other infection control measures failed.
In the trial at Selly Oak hospital, in Birmingham, copper taps, toilet seats and push plates on doors all but eliminated common bugs.
It is thought the metal 'suffocates' germs, preventing them breathing. It may also stop them from feeding and destroy their DNA.
Lab tests show that the metal kills off the deadly MRSA and C difficile superbugs.
It also kills other dangerous germs, including the flu virus and the E coli food poisoning bug.
Although the number of cases of MRSA and C difficile is falling, the two bugs still claim thousands of lives a year.
During the ten-week trial on a medical ward, a set of taps, a lavatory seat and a push plate on an entrance door were replaced with copper versions. They were swabbed twice a day for bugs and the results compared with a traditional tap, lavatory seat and push plate elsewhere in the ward.
The copper items had up to 95 per cent fewer bugs on their surface whenever they were tested, a U.S. conference on antibiotics heard yesterday.
Professor Tom Elliott, the lead researcher and a consultant microbiologist at the hospital, said: 'The findings of 90 to 95 per cent killing of those organisms, even after a busy day on a medical ward with items being touched by numerous people, is remarkable.
'I have been a consultant microbiologist for several decades. This is the first time I have seen anything like copper in terms of the effect it will have in the environment.
'It may well offer us another mechanism for trying to defeat the spread of infection.'
Researcher Professor Peter Lambert, of Aston University, Birmingham, said: 'The numbers decreased always on copper but not on the steel surfaces.'
If further hospital-based trials prove as successful, the researchers would like copper fixtures and fittings installed in hospitals around the country.
Doorknobs, taps, light switches, toilet seats and handles and bathroom 'grab rails' could all be ripped out and replaced with copper versions.
Making door handles, taps and light switches from copper could help the country beat superbugs, scientists say
Although it is usually thought to be an expensive metal, copper is actually a similar price to stainless steel, the researchers said. Nursing homes and even our houses could also benefit from the metal's ability to wipe out dangerous bugs.
The healing power of copper has been recognised for thousands of years.
More than 4,000 years ago, the Egyptians used it to sterilise wounds and drinking water and the Aztecs treated skin conditions with the metal.
The ancient Greeks also knew of its benefits. Hippocrates, sometimes called 'the father of medicine', noted that it could be used to treat leg ulcers.
Today, copper is a common constituent in medicines including antiseptic and antifungal creams. It is also believed to have anti-inflammatory properties. Many of those with arthritis wear copper bangles.
Although they provide relief to many, there is no scientific evidence that they work.
Copper is present in our diet in trace amounts and plays an important role in the formation of red blood cells and in keeping our blood vessels, nerves and bones healthy.
The research was funded by the copper industry.
Tuesday, October 28, 2008
Sudden Cardiac Death No. 1 Risk for Patients on Dialysis
Sudden Cardiac Death No. 1 Risk for Patients on Dialysis
Study: Inflammation, malnutrition identified as key risk factors
By Eric Vohr
Johns Hopkins Medicine
In a 10-year study of more than a thousand kidney failure patients, sudden cardiac death emerged as the No. 1 cause of death for patients on dialysis, according to a Johns Hopkins researcher.
The study, already published online and appearing in the Nov. 2 issue of Kidney International, identified systemic inflammatory response and malnutrition as key risk factors for the fatal heart attacks.
"This is believed to be the first time anyone has taken a rigorous prospective look at why so many patients on dialysis die from sudden cardiac death, and the results could help doctors identify those at highest risk and potentially save lives," said Rulan S. Parekh, associate professor in the Department of Nephrology at the Johns Hopkins University School of Medicine.
Parekh and her team gathered their data from a cohort of 1,041 end-stage renal disease patients on dialysis who were part of Choices for Healthy Outcomes in Caring for ESRD, known as CHOICE. In a 9.5-year period, 658 of this group died. The largest number of these deaths, 146, was the result of sudden cardiac death, or SDC — in this case, unexpected deaths that occurred outside the hospital setting.
The researchers then looked at previously recorded blood test results from 122 of these 146 sudden cardiac death patients to search for a possible relationship between the deaths and levels of high-sensitivity C-reactive (hsCRP), interleukin-6 (IL-6) and albumin. The proteins IL-6 and hsCRP are both markers for widespread blood vessel and organ inflammation, while low albumin levels are associated with malnutrition.
Results showed that patients with high levels of either hsCRP or IL-6 were twice as likely to die from sudden cardiac death as those with low levels of these proteins. Low albumin levels were associated with a 1.35 times increase in the risk of dying of sudden cardiac death when compared with high levels, according to Parekh. In addition, those with low levels of albumin and high levels of hsCRP were four times more likely to die of sudden cardiac death than those with high levels of albumin and low levels of hsCRP.
"These results tell us that ESRD patients with low albumin and/or high levels of IL-6 and hsCRP are at a significantly higher risk of SCD," Parekh said.
The half-million people in the United States with ESRD are 10 to 100 times more likely than the general public to die from cardiovascular disease, depending on age, according to Parekh. They have an annual mortality rate of more than 20 percent, and one-fifth of these deaths are attributed to sudden cardiac death.
Systemic inflammatory response is common with ESRD patients and occurs when the body responds to an infectious or noninfectious attack. Parekh said that because those with kidney failure are quite ill, the chance of infection and chronic inflammation is higher. Also common with ESRD patients is malnutrition from the stress of kidney failure, loss of appetite and a highly restricted diet; compounding the issue, she said, is that Medicare does not cover oral nutritional supplements.
"When people think of heart attacks, they think of cholesterol and obesity," Parekh said, "but these are risk factors for hardening of the arteries and are not directly linked to sudden heart death among patients on dialysis."
Other researchers from Johns Hopkins who contributed to this study are Neil R. Powe, Josef Coresh, Lucy A. Meoni, Bernard G. Jaar and Nancy E. Fink, all of the School of Medicine; and Michael J. Klag, W.H. Linda Kao and Laura C. Plantinga, all of the Bloomberg School of Public Health.
Study: Inflammation, malnutrition identified as key risk factors
By Eric Vohr
Johns Hopkins Medicine
In a 10-year study of more than a thousand kidney failure patients, sudden cardiac death emerged as the No. 1 cause of death for patients on dialysis, according to a Johns Hopkins researcher.
The study, already published online and appearing in the Nov. 2 issue of Kidney International, identified systemic inflammatory response and malnutrition as key risk factors for the fatal heart attacks.
"This is believed to be the first time anyone has taken a rigorous prospective look at why so many patients on dialysis die from sudden cardiac death, and the results could help doctors identify those at highest risk and potentially save lives," said Rulan S. Parekh, associate professor in the Department of Nephrology at the Johns Hopkins University School of Medicine.
Parekh and her team gathered their data from a cohort of 1,041 end-stage renal disease patients on dialysis who were part of Choices for Healthy Outcomes in Caring for ESRD, known as CHOICE. In a 9.5-year period, 658 of this group died. The largest number of these deaths, 146, was the result of sudden cardiac death, or SDC — in this case, unexpected deaths that occurred outside the hospital setting.
The researchers then looked at previously recorded blood test results from 122 of these 146 sudden cardiac death patients to search for a possible relationship between the deaths and levels of high-sensitivity C-reactive (hsCRP), interleukin-6 (IL-6) and albumin. The proteins IL-6 and hsCRP are both markers for widespread blood vessel and organ inflammation, while low albumin levels are associated with malnutrition.
Results showed that patients with high levels of either hsCRP or IL-6 were twice as likely to die from sudden cardiac death as those with low levels of these proteins. Low albumin levels were associated with a 1.35 times increase in the risk of dying of sudden cardiac death when compared with high levels, according to Parekh. In addition, those with low levels of albumin and high levels of hsCRP were four times more likely to die of sudden cardiac death than those with high levels of albumin and low levels of hsCRP.
"These results tell us that ESRD patients with low albumin and/or high levels of IL-6 and hsCRP are at a significantly higher risk of SCD," Parekh said.
The half-million people in the United States with ESRD are 10 to 100 times more likely than the general public to die from cardiovascular disease, depending on age, according to Parekh. They have an annual mortality rate of more than 20 percent, and one-fifth of these deaths are attributed to sudden cardiac death.
Systemic inflammatory response is common with ESRD patients and occurs when the body responds to an infectious or noninfectious attack. Parekh said that because those with kidney failure are quite ill, the chance of infection and chronic inflammation is higher. Also common with ESRD patients is malnutrition from the stress of kidney failure, loss of appetite and a highly restricted diet; compounding the issue, she said, is that Medicare does not cover oral nutritional supplements.
"When people think of heart attacks, they think of cholesterol and obesity," Parekh said, "but these are risk factors for hardening of the arteries and are not directly linked to sudden heart death among patients on dialysis."
Other researchers from Johns Hopkins who contributed to this study are Neil R. Powe, Josef Coresh, Lucy A. Meoni, Bernard G. Jaar and Nancy E. Fink, all of the School of Medicine; and Michael J. Klag, W.H. Linda Kao and Laura C. Plantinga, all of the Bloomberg School of Public Health.
A Rise in Kidney Stones Is Seen in U.S. Children
October 28, 2008
A Rise in Kidney Stones Is Seen in U.S. Children
By LAURIE TARKAN
To the great surprise of parents, kidney stones, once considered a disorder of middle age, are now showing up in children as young as 5 or 6.
While there are no reliable data on the number of cases, pediatric urologists and nephrologists across the country say they are seeing a steep rise in young patients. Some hospitals have opened pediatric kidney stone clinics.
“The older doctors would say in the ’70s and ’80s, they’d see a kid with a stone once every few months,” said Dr. Caleb P. Nelson, a urology instructor at Harvard Medical School who is co-director of the new kidney stone center at Children’s Hospital Boston. “Now we see kids once a week or less.”
Dr. John C. Pope IV, an associate professor of urologic surgery and pediatrics at the Monroe Carell Jr. Children’s Hospital at Vanderbilt in Nashville, said, “When we tell parents, most say they’ve never heard of a kid with a kidney stone and think something is terribly wrong with their child.”
In China recently, many children who drank milk tainted with melamine — a toxic chemical illegally added to watered-down milk to inflate the protein count — developed kidney stones.
The increase in the United States is attributed to a host of factors, including a food additive that is both legal and ubiquitous: salt.
Though most of the research on kidney stones comes from adult studies, experts believe it can be applied to children. Those studies have found that dietary factors are the leading cause of kidney stones, which are crystallizations of several substances in the urine. Stones form when these substances become too concentrated.
Forty to 65 percent of kidney stones are formed when oxalate, a byproduct of certain foods, binds to calcium in the urine. (Other common types include calcium phosphate stones and uric acid stones.) And the two biggest risk factors for this binding process are not drinking enough fluids and eating too much salt; both increase the amount of calcium and oxalate in the urine.
Excess salt has to be excreted through the kidneys, but salt binds to calcium on its way out, creating a greater concentration of calcium in the urine and the kidneys.
“What we’ve really seen is an increase in the salt load in children’s diet,” said Dr. Bruce L. Slaughenhoupt, co-director of pediatric urology and of the pediatric kidney stone clinic at the University of Wisconsin. He and other experts mentioned not just salty chips and French fries, but also processed foods like sandwich meats; canned soups; packaged meals; and even sports drinks like Gatorade, which are so popular among schoolchildren they are now sold in child-friendly juice boxes.
Children also tend not to drink enough water. “They don’t want to go to the bathroom at school; they don’t have time, so they drink less,” said Dr. Alicia Neu, medical director of pediatric nephrology and the pediatric stone clinic at Johns Hopkins Children’s Center in Baltimore. Instead, they are likely to drink only once they’re thirsty — but that may be too little, too late, especially for children who play sports or are just active.
“Drinking more water is the most important step in the prevention of kidney stones,” Dr. Neu said.
The incidence of kidney stones in adults has also been rising, especially in women, and experts say they see more adults in their 20s and 30s with stones; in the past, it was more common in adults in their 40s and 50s.
“It’s no longer a middle-aged disease,” Dr. Nelson said. “Most of us suspect what we’re seeing in children is the spillover of the overall increase in the whole population.”
The median age of children with stones is about 10.
Many experts say the rise in obesity is contributing to kidney stones in children as well as adults. But not all stone centers are seeing overweight children, and having a healthy weight does not preclude kidney stones. “Of the school-age and adolescent kids we’ve seen, most of them appear to be reasonably fit, active kids,” Dr. Nelson said. “We’re not seeing a parade of overweight Nintendo players.”
Dr. Slaughenhoupt has seen more overweight children at his clinic. “We haven’t compared our data yet,” he said, “but my sense is that children with stones are bigger, and some of them are morbidly obese.”
Dr. Pope, in Nashville, agreed. His hospital lies in the so-called stone belt, a swath of Southern states with a higher incidence of kidney stones, and he said doctors there saw two to three new pediatric cases a week.
“There’s no question in my mind that it is largely dietary and directly related to the childhood obesity epidemic,” he said.
Fifty to 60 percent of children with kidney stones have a family history of the disease. “If you have a family history, it’s important to recognize your kids are at risk at some point in their life,” Dr. Nelson said. “That means instilling lifelong habits of good hydration, balanced diet, and avoiding processed high-salt, high-fat foods.”
There is also evidence that sucrose, found in sodas, can also increase risk of stones, as can high-protein weight-loss diets, which are growing in popularity among teenagers.
A common misconception is that people with kidney stones should avoid calcium. In fact, dairy products have been shown to reduce the risk of stones, because the dietary calcium binds with oxalate before it is absorbed by the body, preventing it from getting into the kidneys.
Children with kidney stones can experience severe pain in their side or stomach when a stone is passing through the narrow ureter through which urine travels from the kidneys to the bladder. Younger children may have a more vague pain or stomachache, making the condition harder to diagnose. Children may feel sick to their stomach, and often there is blood in the urine.
One Saturday last February, 11-year-old Tessa Cesario of Frederick, Md., began having back pains. An aspiring ballerina who dances en pointe five nights a week, she was used to occasional aches and strains. But this one was so intense that her parents took her to the doctor.
The pediatrician ordered an X-ray, and when he phoned with the results, her parents were astonished.
“I was afraid he was calling to say she pulled something and wouldn’t be able to dance,” said her mother, Theresa Cesario. Instead, they were told that Tessa had a kidney stone.
“I thought older men get kidney stones, not kids,” Ms. Cesario said.
The treatment for kidney stones is similar in children and adults. Doctors try to let the stone pass, but if it is too large, if it blocks the flow of urine or if there is a sign of infection, it is removed through one of two types of minimally invasive surgery.
Shock-wave lithotripsy is a noninvasive procedure that uses high-energy sound waves to blast the stones into fragments that are then more easily passed. In ureteroscopy, an endoscope is inserted through the ureter to retrieve or obliterate the stone.
Tessa Cesario is taking a wait-and-see approach. Her stone is not budging, so her parents are putting off surgery until they can work it into her dance schedule. In the meantime, she has vastly reduced her salt intake by cutting back on sandwich meats, processed soups and chips.
And, her mother said, “she drinks a ton more water.”
Copyright 2008 The New York Times Company
A Rise in Kidney Stones Is Seen in U.S. Children
By LAURIE TARKAN
To the great surprise of parents, kidney stones, once considered a disorder of middle age, are now showing up in children as young as 5 or 6.
While there are no reliable data on the number of cases, pediatric urologists and nephrologists across the country say they are seeing a steep rise in young patients. Some hospitals have opened pediatric kidney stone clinics.
“The older doctors would say in the ’70s and ’80s, they’d see a kid with a stone once every few months,” said Dr. Caleb P. Nelson, a urology instructor at Harvard Medical School who is co-director of the new kidney stone center at Children’s Hospital Boston. “Now we see kids once a week or less.”
Dr. John C. Pope IV, an associate professor of urologic surgery and pediatrics at the Monroe Carell Jr. Children’s Hospital at Vanderbilt in Nashville, said, “When we tell parents, most say they’ve never heard of a kid with a kidney stone and think something is terribly wrong with their child.”
In China recently, many children who drank milk tainted with melamine — a toxic chemical illegally added to watered-down milk to inflate the protein count — developed kidney stones.
The increase in the United States is attributed to a host of factors, including a food additive that is both legal and ubiquitous: salt.
Though most of the research on kidney stones comes from adult studies, experts believe it can be applied to children. Those studies have found that dietary factors are the leading cause of kidney stones, which are crystallizations of several substances in the urine. Stones form when these substances become too concentrated.
Forty to 65 percent of kidney stones are formed when oxalate, a byproduct of certain foods, binds to calcium in the urine. (Other common types include calcium phosphate stones and uric acid stones.) And the two biggest risk factors for this binding process are not drinking enough fluids and eating too much salt; both increase the amount of calcium and oxalate in the urine.
Excess salt has to be excreted through the kidneys, but salt binds to calcium on its way out, creating a greater concentration of calcium in the urine and the kidneys.
“What we’ve really seen is an increase in the salt load in children’s diet,” said Dr. Bruce L. Slaughenhoupt, co-director of pediatric urology and of the pediatric kidney stone clinic at the University of Wisconsin. He and other experts mentioned not just salty chips and French fries, but also processed foods like sandwich meats; canned soups; packaged meals; and even sports drinks like Gatorade, which are so popular among schoolchildren they are now sold in child-friendly juice boxes.
Children also tend not to drink enough water. “They don’t want to go to the bathroom at school; they don’t have time, so they drink less,” said Dr. Alicia Neu, medical director of pediatric nephrology and the pediatric stone clinic at Johns Hopkins Children’s Center in Baltimore. Instead, they are likely to drink only once they’re thirsty — but that may be too little, too late, especially for children who play sports or are just active.
“Drinking more water is the most important step in the prevention of kidney stones,” Dr. Neu said.
The incidence of kidney stones in adults has also been rising, especially in women, and experts say they see more adults in their 20s and 30s with stones; in the past, it was more common in adults in their 40s and 50s.
“It’s no longer a middle-aged disease,” Dr. Nelson said. “Most of us suspect what we’re seeing in children is the spillover of the overall increase in the whole population.”
The median age of children with stones is about 10.
Many experts say the rise in obesity is contributing to kidney stones in children as well as adults. But not all stone centers are seeing overweight children, and having a healthy weight does not preclude kidney stones. “Of the school-age and adolescent kids we’ve seen, most of them appear to be reasonably fit, active kids,” Dr. Nelson said. “We’re not seeing a parade of overweight Nintendo players.”
Dr. Slaughenhoupt has seen more overweight children at his clinic. “We haven’t compared our data yet,” he said, “but my sense is that children with stones are bigger, and some of them are morbidly obese.”
Dr. Pope, in Nashville, agreed. His hospital lies in the so-called stone belt, a swath of Southern states with a higher incidence of kidney stones, and he said doctors there saw two to three new pediatric cases a week.
“There’s no question in my mind that it is largely dietary and directly related to the childhood obesity epidemic,” he said.
Fifty to 60 percent of children with kidney stones have a family history of the disease. “If you have a family history, it’s important to recognize your kids are at risk at some point in their life,” Dr. Nelson said. “That means instilling lifelong habits of good hydration, balanced diet, and avoiding processed high-salt, high-fat foods.”
There is also evidence that sucrose, found in sodas, can also increase risk of stones, as can high-protein weight-loss diets, which are growing in popularity among teenagers.
A common misconception is that people with kidney stones should avoid calcium. In fact, dairy products have been shown to reduce the risk of stones, because the dietary calcium binds with oxalate before it is absorbed by the body, preventing it from getting into the kidneys.
Children with kidney stones can experience severe pain in their side or stomach when a stone is passing through the narrow ureter through which urine travels from the kidneys to the bladder. Younger children may have a more vague pain or stomachache, making the condition harder to diagnose. Children may feel sick to their stomach, and often there is blood in the urine.
One Saturday last February, 11-year-old Tessa Cesario of Frederick, Md., began having back pains. An aspiring ballerina who dances en pointe five nights a week, she was used to occasional aches and strains. But this one was so intense that her parents took her to the doctor.
The pediatrician ordered an X-ray, and when he phoned with the results, her parents were astonished.
“I was afraid he was calling to say she pulled something and wouldn’t be able to dance,” said her mother, Theresa Cesario. Instead, they were told that Tessa had a kidney stone.
“I thought older men get kidney stones, not kids,” Ms. Cesario said.
The treatment for kidney stones is similar in children and adults. Doctors try to let the stone pass, but if it is too large, if it blocks the flow of urine or if there is a sign of infection, it is removed through one of two types of minimally invasive surgery.
Shock-wave lithotripsy is a noninvasive procedure that uses high-energy sound waves to blast the stones into fragments that are then more easily passed. In ureteroscopy, an endoscope is inserted through the ureter to retrieve or obliterate the stone.
Tessa Cesario is taking a wait-and-see approach. Her stone is not budging, so her parents are putting off surgery until they can work it into her dance schedule. In the meantime, she has vastly reduced her salt intake by cutting back on sandwich meats, processed soups and chips.
And, her mother said, “she drinks a ton more water.”
Copyright 2008 The New York Times Company
Sunday, October 26, 2008
'Flying syringe' mosquitos funded by Bill Gates
'Flying syringe' mosquitos, other ideas get Gates funding
The Bill and Melinda Gates Foundation awarded 100,000 dollars each on Wednesday to scientists in 22 countries including funding for a Japanese proposal to turn mosquitos into "flying syringes" delivering vaccines.
The charitable foundation created by the founder of software giant Microsoft said in a statement that the grants were designed to "explore bold and largely unproven ways to improve global health."
The grants were awarded for research into preventing or curing infectious diseases such as HIV/AIDS and tuberculosis and limiting the emergence of drug resistance.
They are the first round of funding for the Gates Foundation's "Grand Challenges Explorations," a five-year 100-million-dollar initiative to "promote innovative ideas in global health."
The funding was directed to projects that "fall outside current scientific paradigms and could lead to significant advances if successful," the Gates Foundation statement said.
"We were hoping this program would level the playing field so anyone with a transformational idea could more quickly assess its potential for the benefit of global health," said Tachi Yamada, president of global health at the Gates Foundation.
The Gates Foundation said 104 grants were awarded from nearly 4,000 proposals. The recipients included universities, nonprofit organizations, government agencies, and six private companies.
"It was so hard for reviewers to champion just one great idea that we selected almost twice as many projects for funding as we had initially planned," Yamada said.
Among the proposals receiving funding was one from Hiroyuki Matsuoka at Jichi Medical University in Japan.
"(Matsuoka) thinks it may be possible to turn mosquitoes that normally transmit disease into 'flying syringes,' so that when they bite humans they deliver vaccines," the Gates Foundation said.
It said Pattamaporn Kittayapong at Mahidol University in Thailand received a grant to "explore new approaches for controlling dengue fever by studying bacteria with natural abilities to limit the disease."
Founded in 1994, the Seattle, Washington-based Gates Foundation is the largest private philanthropical organization in the world.
© 2008 AFP
This news is brought to you by PhysOrg.com
The Bill and Melinda Gates Foundation awarded 100,000 dollars each on Wednesday to scientists in 22 countries including funding for a Japanese proposal to turn mosquitos into "flying syringes" delivering vaccines.
The charitable foundation created by the founder of software giant Microsoft said in a statement that the grants were designed to "explore bold and largely unproven ways to improve global health."
The grants were awarded for research into preventing or curing infectious diseases such as HIV/AIDS and tuberculosis and limiting the emergence of drug resistance.
They are the first round of funding for the Gates Foundation's "Grand Challenges Explorations," a five-year 100-million-dollar initiative to "promote innovative ideas in global health."
The funding was directed to projects that "fall outside current scientific paradigms and could lead to significant advances if successful," the Gates Foundation statement said.
"We were hoping this program would level the playing field so anyone with a transformational idea could more quickly assess its potential for the benefit of global health," said Tachi Yamada, president of global health at the Gates Foundation.
The Gates Foundation said 104 grants were awarded from nearly 4,000 proposals. The recipients included universities, nonprofit organizations, government agencies, and six private companies.
"It was so hard for reviewers to champion just one great idea that we selected almost twice as many projects for funding as we had initially planned," Yamada said.
Among the proposals receiving funding was one from Hiroyuki Matsuoka at Jichi Medical University in Japan.
"(Matsuoka) thinks it may be possible to turn mosquitoes that normally transmit disease into 'flying syringes,' so that when they bite humans they deliver vaccines," the Gates Foundation said.
It said Pattamaporn Kittayapong at Mahidol University in Thailand received a grant to "explore new approaches for controlling dengue fever by studying bacteria with natural abilities to limit the disease."
Founded in 1994, the Seattle, Washington-based Gates Foundation is the largest private philanthropical organization in the world.
© 2008 AFP
This news is brought to you by PhysOrg.com
Saturday, October 25, 2008
Even mild sleep apnea increases cardiovascular risk
Public release date: 24-Oct-2008
Contact: Keely Savoie
ksavoie@thoracic.org
212-315-8620
American Thoracic Society
Even mild sleep apnea increases cardiovascular risk
People with even minimally symptomatic obstructive sleep apnea (OSA) may be at increased risk for cardiovascular disease because of impaired endothelial function and increased arterial stiffness, according to a study from the Oxford Centre for Respiratory Medicine in the UK.
"It was previously known that people with OSA severe enough to affect their daytime alertness and manifest in other ways are at increased risk of cardiovascular disease, but this finding suggests that many more people—some of whom may be completely unaware that they even have OSA—are at risk than previously thought," said lead author of the study, Malcolm Kohler, M.D.
The study will be published in the first issue for November of the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.
"Only one out of approximately five subjects with [clinically defined OSA] complains of excessive daytime sleepiness in population studies," wrote Geraldo Lorenzi-Filho, M.D., Ph.D. in an editorial in the same issue of the Journal. "[I]t is now recognized that OSA triggers a cascade of biological reactions, including increased sympathetic activity, systemic inflammation, oxidative stress, and metabolic alterations that are potentially harmful to the cardiovascular system."
To determine the exact nature of some of these effects, Dr. Kohler and colleagues performed a controlled, cross-sectional study to assess differences in endothelial function (often a harbinger for cardiovascular problems to come), arterial stiffness and blood pressure in patients with minimally symptomatic OSA. They compared 64 patients who had proven OSA to matched control subjects without OSA.
Their findings suggested that minimally symptomatic OSA is a cardiovascular risk factor to a degree not previously known.
"In our study, the augmentation index, a measure of central arterial stiffness that independently predicts cardiovascular events in high-risk populations, was significantly higher in patients with minimally symptomatic OSA compared to matched controls," said Dr. Kohler. "We also found impaired endothelial function as indicated by decreased vascular reactivity of their arteries compared to control subjects without OSA."
The difference in arterial stiffness between OSA patients and control subjects, Dr. Kohler said was "comparable in size to the effect seen after four weeks' continuous positive airway pressure (CPAP) therapy in patients with moderate to severe symptomatic OSA."
This suggests that asymptomatic or minimally symptomatic patients with OSA may enjoy a cardiovascular benefit from CPAP therapy.
Dr.Kohler and colleagues from the Oxford Centre for Respiratory Medicine are currently investigating the effects of 6 month CPAP therapy on arterial stiffness and endothelial function as part of an international randomized controlled trial (Multicentre Obstructive Sleep Apnoea Interventional Cardiovascular Trial; MOSAIC) which will show the impact of CPAP therapy on cardiovascular risk in patients with minimally symptomatic OSA.
###
Full Text of Original Article Available Here: http://www.thoracic.org/sections/publications/press-releases/resources/110108Kohler.pdf
Full Text of Original Editorial Available Here: http://www.thoracic.org/sections/publications/press-releases/resources/OSAed110108.pdf
Contact: Keely Savoie
ksavoie@thoracic.org
212-315-8620
American Thoracic Society
Even mild sleep apnea increases cardiovascular risk
People with even minimally symptomatic obstructive sleep apnea (OSA) may be at increased risk for cardiovascular disease because of impaired endothelial function and increased arterial stiffness, according to a study from the Oxford Centre for Respiratory Medicine in the UK.
"It was previously known that people with OSA severe enough to affect their daytime alertness and manifest in other ways are at increased risk of cardiovascular disease, but this finding suggests that many more people—some of whom may be completely unaware that they even have OSA—are at risk than previously thought," said lead author of the study, Malcolm Kohler, M.D.
The study will be published in the first issue for November of the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.
"Only one out of approximately five subjects with [clinically defined OSA] complains of excessive daytime sleepiness in population studies," wrote Geraldo Lorenzi-Filho, M.D., Ph.D. in an editorial in the same issue of the Journal. "[I]t is now recognized that OSA triggers a cascade of biological reactions, including increased sympathetic activity, systemic inflammation, oxidative stress, and metabolic alterations that are potentially harmful to the cardiovascular system."
To determine the exact nature of some of these effects, Dr. Kohler and colleagues performed a controlled, cross-sectional study to assess differences in endothelial function (often a harbinger for cardiovascular problems to come), arterial stiffness and blood pressure in patients with minimally symptomatic OSA. They compared 64 patients who had proven OSA to matched control subjects without OSA.
Their findings suggested that minimally symptomatic OSA is a cardiovascular risk factor to a degree not previously known.
"In our study, the augmentation index, a measure of central arterial stiffness that independently predicts cardiovascular events in high-risk populations, was significantly higher in patients with minimally symptomatic OSA compared to matched controls," said Dr. Kohler. "We also found impaired endothelial function as indicated by decreased vascular reactivity of their arteries compared to control subjects without OSA."
The difference in arterial stiffness between OSA patients and control subjects, Dr. Kohler said was "comparable in size to the effect seen after four weeks' continuous positive airway pressure (CPAP) therapy in patients with moderate to severe symptomatic OSA."
This suggests that asymptomatic or minimally symptomatic patients with OSA may enjoy a cardiovascular benefit from CPAP therapy.
Dr.Kohler and colleagues from the Oxford Centre for Respiratory Medicine are currently investigating the effects of 6 month CPAP therapy on arterial stiffness and endothelial function as part of an international randomized controlled trial (Multicentre Obstructive Sleep Apnoea Interventional Cardiovascular Trial; MOSAIC) which will show the impact of CPAP therapy on cardiovascular risk in patients with minimally symptomatic OSA.
###
Full Text of Original Article Available Here: http://www.thoracic.org/sections/publications/press-releases/resources/110108Kohler.pdf
Full Text of Original Editorial Available Here: http://www.thoracic.org/sections/publications/press-releases/resources/OSAed110108.pdf
Scientists create organic wires for use inside the human body
Trendwatch
By Rick C. Hodgin
Friday, October 24, 2008 11:30
Baltimore (MD) - Research chemists at Johns Hopkins University (JHU) have developed a water-soluble, organic, self-assembling electronic wire suitable for use inside the human body. Derived from carbon materials, the lightweight, flexible wires can power pacemakers, reconnect damaged nerve tissues, while also interacting with real electronic device that could augment or stimulate organic function. But do not worry, for this is only step one of the long process of turning us all into Borg-like drones.
Inter-cellular wiring
The self-assembly process produces wires which are notably thinner than a human hair. They can be manufactured so small, in fact, that they could interact with individual cells. And therein lies significant potential for paralytics.
Researchers believe a procedure could eventually be developed whereby the severed portions of nerve fibers are reconnected with these new organic wires. Such patients could theoretically regain at least some of their former mobility, if not all of it, once the science is perfected and applied.
In fact, John D. Tovar, assistant professor, Department of Chemistry at Zanvyl Krieger School of Arts and Sciences, spoke of this very possibility. He said, "Can we use these materials to guide electrical current at the nanoscale? Can we use them to regulate cell-to-cell communication as a prelude to re-engineering neural networks or damaged spinal cords? These are the kinds of questions we are looking forward to being able to address and answer in the coming years."
The big prize
As Tovar indicates, perhaps the biggest benefit from this research is the mechanism which now exists. This team essentially overcame all of the problems associated with developing this kind of application. And now, they've presented unto the world what will be just another tool in a researcher's arsenal.
No longer will other scientists in other labs have to ponder over how they could create self-assembling wires for their needs. Now they can simply operate from within the mindset, "If we used their self-assembling wires here, then this new ability would be possible. Yes, it's all so clear now."
Summary
In short, with this powerful new ability added to the scientist's “toolbox,” now they can think in terms of the goal or destination rather than how to go about building the road to get there. Somebody else has done the hard work. And now, the application of the thing should quickly move to the realm of "Oh, how extremely beneficial. Thank you so much, doctor."
By Rick C. Hodgin
Friday, October 24, 2008 11:30
Baltimore (MD) - Research chemists at Johns Hopkins University (JHU) have developed a water-soluble, organic, self-assembling electronic wire suitable for use inside the human body. Derived from carbon materials, the lightweight, flexible wires can power pacemakers, reconnect damaged nerve tissues, while also interacting with real electronic device that could augment or stimulate organic function. But do not worry, for this is only step one of the long process of turning us all into Borg-like drones.
Inter-cellular wiring
The self-assembly process produces wires which are notably thinner than a human hair. They can be manufactured so small, in fact, that they could interact with individual cells. And therein lies significant potential for paralytics.
Researchers believe a procedure could eventually be developed whereby the severed portions of nerve fibers are reconnected with these new organic wires. Such patients could theoretically regain at least some of their former mobility, if not all of it, once the science is perfected and applied.
In fact, John D. Tovar, assistant professor, Department of Chemistry at Zanvyl Krieger School of Arts and Sciences, spoke of this very possibility. He said, "Can we use these materials to guide electrical current at the nanoscale? Can we use them to regulate cell-to-cell communication as a prelude to re-engineering neural networks or damaged spinal cords? These are the kinds of questions we are looking forward to being able to address and answer in the coming years."
The big prize
As Tovar indicates, perhaps the biggest benefit from this research is the mechanism which now exists. This team essentially overcame all of the problems associated with developing this kind of application. And now, they've presented unto the world what will be just another tool in a researcher's arsenal.
No longer will other scientists in other labs have to ponder over how they could create self-assembling wires for their needs. Now they can simply operate from within the mindset, "If we used their self-assembling wires here, then this new ability would be possible. Yes, it's all so clear now."
Summary
In short, with this powerful new ability added to the scientist's “toolbox,” now they can think in terms of the goal or destination rather than how to go about building the road to get there. Somebody else has done the hard work. And now, the application of the thing should quickly move to the realm of "Oh, how extremely beneficial. Thank you so much, doctor."
Culprit unmasked in multiple myeloma
PDF link to the article
Culprit unmasked in multiple myeloma
Multiple myeloma is caused by the
recently discovered Kaposi’s sarcoma-
associated herpesvirus, US
researchers have found (Science
1997;276:1851-4). Multiple myeloma
is the second most common type of
blood cancer in the US. Research had
focused on why it develops in only
25% of patients with a precursor
condition (MGUS). The researchers
believe that both MGUS and the
virus, which infects the dendritic cells
in the bone marrow, may be needed
for multiple myeloma. The virus
does not infect the actual cancer cells,
leading researchers to suspect that it
causes cancer by producing a protein
(interleukin-6) that stimulates the
growth of myeloma cells.
News and analysis
14827 Sept 1/97 CMAJ /Page505
CAN MED ASSOC J • SEPT. 1, 1997; 157 (5) 505
In the news...
Culprit unmasked in multiple myeloma
Multiple myeloma is caused by the
recently discovered Kaposi’s sarcoma-
associated herpesvirus, US
researchers have found (Science
1997;276:1851-4). Multiple myeloma
is the second most common type of
blood cancer in the US. Research had
focused on why it develops in only
25% of patients with a precursor
condition (MGUS). The researchers
believe that both MGUS and the
virus, which infects the dendritic cells
in the bone marrow, may be needed
for multiple myeloma. The virus
does not infect the actual cancer cells,
leading researchers to suspect that it
causes cancer by producing a protein
(interleukin-6) that stimulates the
growth of myeloma cells.
News and analysis
14827 Sept 1/97 CMAJ /Page505
CAN MED ASSOC J • SEPT. 1, 1997; 157 (5) 505
In the news...
Friday, October 24, 2008
Medline article on Multiple Myeloma
Medline Link
From the article:
Exams and Tests
Blood tests can help diagnose this disease. Such tests may include:
Blood chemistry (CHEM 20) shows increased levels of calcium, total protein, and abnormal kidney function.
Complete blood count (CBC) reveals low number of red and white blood cells and platelets.
Freelite diagnostic assay measures immunoglobulin pieces called light chains.
Protein electrophoresis - serum is abnormal.
From the article:
Exams and Tests
Blood tests can help diagnose this disease. Such tests may include:
Blood chemistry (CHEM 20) shows increased levels of calcium, total protein, and abnormal kidney function.
Complete blood count (CBC) reveals low number of red and white blood cells and platelets.
Freelite diagnostic assay measures immunoglobulin pieces called light chains.
Protein electrophoresis - serum is abnormal.
Multiple Myeloma: Recognition and Management
Multiple Myeloma: Recognition and Management
Link to the page.
Link to the page.
What is Multiple Myeloma? How Is It Treated?
What is Multiple Myeloma? How Is It Treated?
What is multiple myeloma?
Multiple myeloma (say: mull-tip-ul my-el-oh-ma) is a kind of cancer. It's caused when cells in the bone, called "plasma cells," grow too much. When this happens, the plasma cells kill the bone around them. The plasma cells also make too much of something called "immunoglobulins." The immunoglobulins cause problems in the blood.
What causes myeloma?
We don't know what causes myeloma. This cancer usually happens in people older than 55 years of age. Slightly more men than women get it. It doesn't usually run in families. Myeloma is more common in blacks than in whites. Fertilizers and insecticides might cause myeloma. This may be why myeloma is more common in farmers.
How does my doctor know I have myeloma?
Several tests can tell if you have myeloma. First, you'll need x-rays to check the areas where you feel pain. Your doctor might take some blood tests. One test measures the kind of immunoglobulins in your blood. Other tests tell if you're anemic (low iron in your blood), if your calcium level is high and how well your kidneys are working.
If the myeloma is in a later stage, you may need more tests. Your doctor might want you to have a magnetic resonance imaging scan of your bones (also called an MRI scan). This scan shows if the myeloma is in your spine.
The only way to be sure you have myeloma is if your doctor uses a needle to take a very small sample of the inside of a bone. This is called "bone marrow aspiration." It can be done in your doctor's office. This procedure hurts a little, but no special care is needed afterward.
How is myeloma treated?
There is no cure for myeloma. However, medicines can help with the pain and make you feel better. You need treatment if you have severe pain, broken bones, a low blood count, many infections or kidney damage. Even with treatment, sometimes your symptoms will be better and sometimes they'll be worse. The two medicines most often used are melphalan (brand name: Alkeran) and prednisone (a steroid medicine).
If you have multiple myeloma, you should try to stay active. Staying active helps keep the calcium in your bones instead of in your blood. Keeping calcium in your bones helps keep your bones strong. You should eat a balanced diet and drink plenty of fluids, too.
Are there side effects of myeloma medicine?
Yes, as with most cancer medicines. You and your doctors will keep an eye on your side effects. You'll probably have blood tests about once a month while you're taking the medicines. When melphalan kills the cancer cells, it also kills some of your body's "good" cells. These good cells are in your bones, lungs and skin. You'll probably lose some hair, but it will grow back after you stop taking the medicine. However, if you have fever, bleeding (like nosebleeds or bleeding gums or bruising), a skin rash or a cough that doesn't go away, call your doctor right away. These are the more serious side effects of melphalan. While you're taking melphalan, you must not get pregnant. Melphalan might hurt the baby.
If the cancer doesn't respond to melphalan and prednisone, your doctor may talk with you about other treatments. These include other medicines, radiation treatments or a bone marrow transplant.
Where can I get more information about multiple myeloma?
You can get information about multiple myeloma from the following group:
The International Myeloma Foundation (IMF)
2129 Stanley Hills Dr.
Los Angeles, CA 90046
Telephone: 1-800-452-CURE (1-800-452-2873)
Internet: http://www.myeloma.org
This handout provides a general overview on this topic and may not apply to everyone. To find out if this handout applies to you and to get more information on this subject, talk to your family doctor.
Visit familydoctor.org for information on this and many other health-related topics.
Copyright © 1999 by the American Academy of Family Physicians.
Permission is granted to print and photocopy this material for nonprofit educational uses. Written permission is required for all other uses, including electronic uses.
What is multiple myeloma?
Multiple myeloma (say: mull-tip-ul my-el-oh-ma) is a kind of cancer. It's caused when cells in the bone, called "plasma cells," grow too much. When this happens, the plasma cells kill the bone around them. The plasma cells also make too much of something called "immunoglobulins." The immunoglobulins cause problems in the blood.
What causes myeloma?
We don't know what causes myeloma. This cancer usually happens in people older than 55 years of age. Slightly more men than women get it. It doesn't usually run in families. Myeloma is more common in blacks than in whites. Fertilizers and insecticides might cause myeloma. This may be why myeloma is more common in farmers.
How does my doctor know I have myeloma?
Several tests can tell if you have myeloma. First, you'll need x-rays to check the areas where you feel pain. Your doctor might take some blood tests. One test measures the kind of immunoglobulins in your blood. Other tests tell if you're anemic (low iron in your blood), if your calcium level is high and how well your kidneys are working.
If the myeloma is in a later stage, you may need more tests. Your doctor might want you to have a magnetic resonance imaging scan of your bones (also called an MRI scan). This scan shows if the myeloma is in your spine.
The only way to be sure you have myeloma is if your doctor uses a needle to take a very small sample of the inside of a bone. This is called "bone marrow aspiration." It can be done in your doctor's office. This procedure hurts a little, but no special care is needed afterward.
How is myeloma treated?
There is no cure for myeloma. However, medicines can help with the pain and make you feel better. You need treatment if you have severe pain, broken bones, a low blood count, many infections or kidney damage. Even with treatment, sometimes your symptoms will be better and sometimes they'll be worse. The two medicines most often used are melphalan (brand name: Alkeran) and prednisone (a steroid medicine).
If you have multiple myeloma, you should try to stay active. Staying active helps keep the calcium in your bones instead of in your blood. Keeping calcium in your bones helps keep your bones strong. You should eat a balanced diet and drink plenty of fluids, too.
Are there side effects of myeloma medicine?
Yes, as with most cancer medicines. You and your doctors will keep an eye on your side effects. You'll probably have blood tests about once a month while you're taking the medicines. When melphalan kills the cancer cells, it also kills some of your body's "good" cells. These good cells are in your bones, lungs and skin. You'll probably lose some hair, but it will grow back after you stop taking the medicine. However, if you have fever, bleeding (like nosebleeds or bleeding gums or bruising), a skin rash or a cough that doesn't go away, call your doctor right away. These are the more serious side effects of melphalan. While you're taking melphalan, you must not get pregnant. Melphalan might hurt the baby.
If the cancer doesn't respond to melphalan and prednisone, your doctor may talk with you about other treatments. These include other medicines, radiation treatments or a bone marrow transplant.
Where can I get more information about multiple myeloma?
You can get information about multiple myeloma from the following group:
The International Myeloma Foundation (IMF)
2129 Stanley Hills Dr.
Los Angeles, CA 90046
Telephone: 1-800-452-CURE (1-800-452-2873)
Internet: http://www.myeloma.org
This handout provides a general overview on this topic and may not apply to everyone. To find out if this handout applies to you and to get more information on this subject, talk to your family doctor.
Visit familydoctor.org for information on this and many other health-related topics.
Copyright © 1999 by the American Academy of Family Physicians.
Permission is granted to print and photocopy this material for nonprofit educational uses. Written permission is required for all other uses, including electronic uses.
Mass. General transplant method prevents organ rejection
HARVARD UNIVERSITY, MASS GENERAL
Mass. General transplant method prevents organ rejection
By Patricia Wen, Globe Staff
A Massachusetts General Hospital research team is reporting a major advance in the years-long effort to overcome the rejection of organ transplants.
Four out of five patients who underwent an experimental kidney transplant were able to stop taking powerful immunosuppressive drugs, and they have so far lived between 15 months and almost five years without experiencing rejection. At the time of their transplant, the patients received bone marrow from the same donor.
The report in tomorrow's New England Journal of Medicine is considered particularly significant because the patients received kidneys that were different from their own tissue type. Transplants of such mismatched organs are the most common, and the most likely to be rejected, even when patients take immunosuppressive drugs.
One of the five patients rejected the kidney during the experimental program, and researchers ultimately concluded that was due to an unexpected antibody reaction. The team later tweaked their protocol to include a new drug to prevent such a scenario from happening again.
Dr. David H. Sachs, a 66-year-old Harvard Medical School professor who has spent his career trying to induce tolerance for organ transplants, said he was encouraged by his team's "initial success" with the procedure.
"While we need to study this approach in a larger group of patients before it is ready for broad clinical use, this is the first time that tolerance to a series of mismatched transplants has been intentionally and successfully induced," said Sachs, who co-authored the study with two transplant surgeons, Dr. Tatsuo Kawai and Dr. Benedict Cosimi, as well as a dozen other researchers at Mass. General.
Sachs, director of Mass. General's Transplantation Biology Research Center, has long believed that a donor's bone marrow -- from which immune cells originate -- could play a pivotal role in giving transplant patients "induced tolerance" to a donated organ.
Under Sachs' approach, five days prior to transplant surgery, patients begin low-dose chemotherapy to kill off some of their own marrow cells and make room for the injection of the donor's bone marrow.
The patients also receive a drug and radiation to the thymus to eliminate a type of immune system cell, known as a T cell, that typically attacks any tissue perceived as foreign.
On the day of the procedure, surgeons attach the new kidney while injecting the donor's bone marrow into a blood vessel in the patient's arm. The donor's bone marrow mixes with the patient's, creating a temporary state called "mixed chimerism." This tricks the patient's immune system into recognizing for years -- and possibly forever -- the donated organ as part of the "self."
After the surgery, the immune system is still in a period of adjustment, and doctors give patients anti-rejection drugs that are gradually tapered off. Most patients were off the drugs by the ninth month.
Sachs first tried this approach successfully on mice, pigs, then monkeys. In 1998, he won approval to try his treatment on a select group of Mass. General patients with severe kidney failure, all of whom were offered matching kidneys from close relatives. When these six patients did well, Sachs moved on to the most ambitious test of his method, trying it out on patients with mismatched donors.
Sachs' study represents a pivotal moment in organ transplantation, organ transplant researchers say. It shows that it may be feasible to eliminate immunosuppressive drugs with their debilitating side effects, such as skin warts, cataracts and increased risks of heart disease, diabetes and serious infections. Also, patients may no longer need to live with the fear of organ rejection. Within 10 years, half of all transplanted kidneys fail because of chronic rejection, a bleak predicament in this era of organ shortages.
"This is landmark work," said Dr. Joshua Miller, an organ transplant researcher from Northwestern University's Feinberg School of Medicine in Chicago. "It gives us hope that recipients of organ transplants will be relieved of being on chronic immunosuppressive drugs for the rest of their lives."
Researchers cautioned, though, that only the healthiest patients may be able to endure the rigorous pre-transplant treatments.
Mass. General transplant method prevents organ rejection
By Patricia Wen, Globe Staff
A Massachusetts General Hospital research team is reporting a major advance in the years-long effort to overcome the rejection of organ transplants.
Four out of five patients who underwent an experimental kidney transplant were able to stop taking powerful immunosuppressive drugs, and they have so far lived between 15 months and almost five years without experiencing rejection. At the time of their transplant, the patients received bone marrow from the same donor.
The report in tomorrow's New England Journal of Medicine is considered particularly significant because the patients received kidneys that were different from their own tissue type. Transplants of such mismatched organs are the most common, and the most likely to be rejected, even when patients take immunosuppressive drugs.
One of the five patients rejected the kidney during the experimental program, and researchers ultimately concluded that was due to an unexpected antibody reaction. The team later tweaked their protocol to include a new drug to prevent such a scenario from happening again.
Dr. David H. Sachs, a 66-year-old Harvard Medical School professor who has spent his career trying to induce tolerance for organ transplants, said he was encouraged by his team's "initial success" with the procedure.
"While we need to study this approach in a larger group of patients before it is ready for broad clinical use, this is the first time that tolerance to a series of mismatched transplants has been intentionally and successfully induced," said Sachs, who co-authored the study with two transplant surgeons, Dr. Tatsuo Kawai and Dr. Benedict Cosimi, as well as a dozen other researchers at Mass. General.
Sachs, director of Mass. General's Transplantation Biology Research Center, has long believed that a donor's bone marrow -- from which immune cells originate -- could play a pivotal role in giving transplant patients "induced tolerance" to a donated organ.
Under Sachs' approach, five days prior to transplant surgery, patients begin low-dose chemotherapy to kill off some of their own marrow cells and make room for the injection of the donor's bone marrow.
The patients also receive a drug and radiation to the thymus to eliminate a type of immune system cell, known as a T cell, that typically attacks any tissue perceived as foreign.
On the day of the procedure, surgeons attach the new kidney while injecting the donor's bone marrow into a blood vessel in the patient's arm. The donor's bone marrow mixes with the patient's, creating a temporary state called "mixed chimerism." This tricks the patient's immune system into recognizing for years -- and possibly forever -- the donated organ as part of the "self."
After the surgery, the immune system is still in a period of adjustment, and doctors give patients anti-rejection drugs that are gradually tapered off. Most patients were off the drugs by the ninth month.
Sachs first tried this approach successfully on mice, pigs, then monkeys. In 1998, he won approval to try his treatment on a select group of Mass. General patients with severe kidney failure, all of whom were offered matching kidneys from close relatives. When these six patients did well, Sachs moved on to the most ambitious test of his method, trying it out on patients with mismatched donors.
Sachs' study represents a pivotal moment in organ transplantation, organ transplant researchers say. It shows that it may be feasible to eliminate immunosuppressive drugs with their debilitating side effects, such as skin warts, cataracts and increased risks of heart disease, diabetes and serious infections. Also, patients may no longer need to live with the fear of organ rejection. Within 10 years, half of all transplanted kidneys fail because of chronic rejection, a bleak predicament in this era of organ shortages.
"This is landmark work," said Dr. Joshua Miller, an organ transplant researcher from Northwestern University's Feinberg School of Medicine in Chicago. "It gives us hope that recipients of organ transplants will be relieved of being on chronic immunosuppressive drugs for the rest of their lives."
Researchers cautioned, though, that only the healthiest patients may be able to endure the rigorous pre-transplant treatments.
HLA-Mismatched Renal Transplantation without Maintenance Immunosuppression
New England Journal of Medicine
Link to the full Article
PubMed Citation
SUMMARY
Five patients with end-stage renal disease received combined bone marrow and kidney transplants from HLA single-haplotype mismatched living related donors, with the use of a nonmyeloablative preparative regimen. Transient chimerism and reversible capillary leak syndrome developed in all recipients. Irreversible humoral rejection occurred in one patient. In the other four recipients, it was possible to discontinue all immunosuppressive therapy 9 to 14 months after the transplantation, and renal function has remained stable for 2.0 to 5.3 years since transplantation. The T cells from these four recipients, tested in vitro, showed donor-specific unresponsiveness and in specimens from allograft biopsies, obtained after withdrawal of immunosuppressive therapy, there were high levels of P3 (FOXP3) messenger RNA (mRNA) but not granzyme B mRNA.
Link to the full Article
PubMed Citation
SUMMARY
Five patients with end-stage renal disease received combined bone marrow and kidney transplants from HLA single-haplotype mismatched living related donors, with the use of a nonmyeloablative preparative regimen. Transient chimerism and reversible capillary leak syndrome developed in all recipients. Irreversible humoral rejection occurred in one patient. In the other four recipients, it was possible to discontinue all immunosuppressive therapy 9 to 14 months after the transplantation, and renal function has remained stable for 2.0 to 5.3 years since transplantation. The T cells from these four recipients, tested in vitro, showed donor-specific unresponsiveness and in specimens from allograft biopsies, obtained after withdrawal of immunosuppressive therapy, there were high levels of P3 (FOXP3) messenger RNA (mRNA) but not granzyme B mRNA.
Scientist triumphs after setback in kidney transplant method
Rejecting defeat
Scientist triumphs after setback in kidney transplant method
By Patricia Wen, Globe Staff | January 24, 2008
Dr. David H. Sachs was full of optimism when the third patient in his $1 million study was wheeled into the recovery room at Massachusetts General Hospital after an experimental kidney transplant.
The first two patients had thrived, adding credibility to an unorthodox idea that Sachs had pioneered over his career, that transplanting a donor's bone marrow along with the kidney could solve the problem of organ rejection, sparing patients a lifetime of powerful antirejection drugs.
But 10 days after the third patient's surgery, Sachs's phone rang at his spacious lab overlooking Boston Harbor. A colleague reported that William Andrews, a 43-year-old father of two, was rejecting the kidney.
Sachs and his research team remember the darkness of the ensuing months in 2003, when they abruptly suspended their transplants for nearly two years. Andrews was demoralized and on dialysis, his sister's donated kidney seemingly wasted. Over and over, Sachs paced the corridors of his lab asking himself, "What did we miss?"
Today, capping a comeback from the crisis, Sachs and his team are reporting that they unraveled the explanation for Andrews's rejection. After they tweaked their protocol, adding a drug to avert what happened to Andrews, two new patients have thrived without the long-term need for antirejection drugs, according to a paper published in the New England Journal of Medicine.
Overall, four of Sachs's five patients have experienced no organ rejection, a particularly striking accomplishment because they all received kidneys that were different from their own tissue type. Transplants of such mismatched organs are the most common and the most likely to be rejected, even when patients take immunosuppressive drugs.
"I had confidence we would figure it out," said the 66-year-old Harvard Medical School professor, who has dedicated more than three decades to conquering organ rejection. He said the results restored his faith that his once-radical idea will eventually become mainstream, making organ transplants safer and more available.
Transplant surgeons said Sachs's study represents a pivotal moment in organ transplantation, demonstrating that it is feasible to eliminate immunosuppressive drugs with their debilitating side effects, such as skin warts, cataracts, and increased risks of heart disease, diabetes, and serious infections. If the results are borne out in a larger group of patients, the Mass. General technique has the potential to help transplant recipients live longer. Within 10 years, half of all transplanted organs fail because of chronic rejection, a bleak predicament in this era of organ shortages.
"This is landmark work," said Dr. Joshua Miller, an organ transplant researcher at Northwestern University's Feinberg School of Medicine in Chicago.
Other researchers cautioned that only the healthiest patients may be able to endure the rigorous treatments, including chemotherapy and radiation, that precede the transplant.
Andrews said that going through the experimental protocol was not easy and that being an example of a failed case was even harder. But he sees his difficult experience as a contribution to medical research, saying how impressed he was that the Mass. General staff worked tirelessly on his case.
"They did not want to accept defeat," said Andrews, who ultimately received a replacement kidney in 2004 using conventional treatment with antirejection drugs.
Sachs is no stranger to the emotional roller coaster of experimental medicine and the intellectual nimbleness required to overcome setbacks. Since he was a young Harvard medical student in the mid-1960s, hearing his first lecture on organ transplantation, Sachs has set out to tackle "the most important problem that could be solved." In his mind, that was the persistent problem of organ rejection.
Sachs, director of the Transplantation Biology Research Center at Mass. General, had faith that a donor's bone marrow, from which immune cells originate, could play a pivotal role in giving transplant patients "induced tolerance" to a donated organ.
Under Sachs's approach, five days prior to transplant surgery, patients begin to undergo low-dose chemotherapy to kill off some of their marrow cells and make room for injection of the donor's bone marrow.
The patients also receive a drug and radiation to the thymus to eliminate a type of immune system cell, known as a T cell, that typically attacks any tissue perceived as foreign.
On the day of the procedure, surgeons attach the new kidney while injecting the donor's bone marrow into a blood vessel in the patient's arm. The donor's bone marrow mixes with the patient's, creating a temporary state called mixed chimerism. This tricks the patient's immune system into recognizing for years - and possibly forever - the donated organ as part of the self.
After the surgery, the immune system is still in a period of adjustment, and doctors give patients antirejection drugs that are gradually tapered off. Most patients were off the drugs by the ninth month.
Sachs first tried this approach successfully on mice, pigs, then monkeys. In 1998, he won approval to try his treatment on a select group of Mass. General patients with severe kidney failure, all of whom were offered matching kidneys from close relatives. When these six patients did well, Sachs moved on to the most ambitious test of his method, trying it out on patients with mismatched donors.
Starting in 2002, the method worked nearly flawlessly on Jennifer Searl, 28, a librarian from Peabody, and Christopher McMahon, 26, a retail store manager from Tewskbury.
Sachs and his colleagues felt something close to restrained euphoria. At a New Year's Eve party in 2002, Sachs and the chief surgeon on the research team, Dr. Benedict Cosimi, who share a small boat that they years ago named "Tolerance," gave a toast to the initial success of the experiment.
Then in October 2003, Andrews, a software engineer with polycystic kidney disease, went in for his experimental procedure. When the surgery was complete, spirits were high.
"Everybody thought it was a success," Andrews recalled.
But within two weeks of the surgery, Dr. Tatsuo Kawai, one of Sach's research colleagues, was handed test results showing that Andrews's urine output had dropped and that his blood contained high levels of toxins. An ultrasound scan showed the new organ was losing blood flow.
"The kidney's rejecting," Kawai remembered saying to himself.
He phoned Sachs, who was in his lab at one of Mass. General's research facilities in the Charlestown Navy Yard, with the news.
"It hurt," Sachs recalled. "You want to see everyone succeed."
For several months, Sachs and his team tried various drugs on Andrews, hoping to reverse the rejection. But by spring 2004, doctors began dialysis, conceding defeat in saving Andrews's new kidney. Because of the failure, Andrews was no longer eligible for another try with the experimental treatment.
The outcome for Andrews hit everyone on the research team hard.
"It was the lowest moment," Sachs recalled.
He said these studies put "people's lives in your hands" and are full of unpredictability.
Sachs and his dozen colleagues on the project began brainstorming about what went wrong, trying to salvage a lesson, if not Andrews's kidney. After intensive study, they concluded that another type of immune cell, the B cells, played a critical role in his organ rejection. They theorized that Andrews's body harbored B cells that ultimately produced antibodies against his sister's kidney, a scenario they did not anticipate because B cells had played no role in organ rejection in any of their previous studies.
To prevent rejection in new cases, the team revised the protocol to give all patients a drug prior to surgery that depletes B cells. Before they could proceed with the study, they had to win approvals from several regulatory agencies, which ensure patient safety.
Meanwhile, Sachs was delighted when he heard that Andrews's cousin had stepped forward to offer a kidney.
In August 2004, that conventional transplant surgery went smoothly, and Andrews went back to work "feeling great," while accepting his fate of being on antirejection drugs.
By 2005, the regulatory agencies approved the revised plan. In February 2005, surgeons operated on Derek Besenfelder, 28, a communications specialist from Los Angeles, and then in January 2006, they did transplant surgery on Matthew Knowles, 48, of Marshfield. Both have returned to their normal lives.
"I'm in perfect health," said Knowles, a supervisor for a gas company. "I don't take a pill a day. It's a miracle."
The four successful transplant patients have so far lived between 15 months and nearly five years without antirejection drugs.
Other researchers are also experimenting with ways to create permanent tolerance to donated organs, using slightly different approaches. Today's New England Journal includes two case studies from these other groups.
Sachs hopes to expand the study to include 20 new patients with mismatched donors. His greatest hope is that someday his novel treatment will extend to other organs.
"It's a wonderful feeling when you see people returning to their normal lives," he said.
Patricia Wen can be reached at wen@globe.com.
http://www.boston.com/news/local/articles/2008/01/24/rejecting_defeat?mode=PF
Scientist triumphs after setback in kidney transplant method
By Patricia Wen, Globe Staff | January 24, 2008
Dr. David H. Sachs was full of optimism when the third patient in his $1 million study was wheeled into the recovery room at Massachusetts General Hospital after an experimental kidney transplant.
The first two patients had thrived, adding credibility to an unorthodox idea that Sachs had pioneered over his career, that transplanting a donor's bone marrow along with the kidney could solve the problem of organ rejection, sparing patients a lifetime of powerful antirejection drugs.
But 10 days after the third patient's surgery, Sachs's phone rang at his spacious lab overlooking Boston Harbor. A colleague reported that William Andrews, a 43-year-old father of two, was rejecting the kidney.
Sachs and his research team remember the darkness of the ensuing months in 2003, when they abruptly suspended their transplants for nearly two years. Andrews was demoralized and on dialysis, his sister's donated kidney seemingly wasted. Over and over, Sachs paced the corridors of his lab asking himself, "What did we miss?"
Today, capping a comeback from the crisis, Sachs and his team are reporting that they unraveled the explanation for Andrews's rejection. After they tweaked their protocol, adding a drug to avert what happened to Andrews, two new patients have thrived without the long-term need for antirejection drugs, according to a paper published in the New England Journal of Medicine.
Overall, four of Sachs's five patients have experienced no organ rejection, a particularly striking accomplishment because they all received kidneys that were different from their own tissue type. Transplants of such mismatched organs are the most common and the most likely to be rejected, even when patients take immunosuppressive drugs.
"I had confidence we would figure it out," said the 66-year-old Harvard Medical School professor, who has dedicated more than three decades to conquering organ rejection. He said the results restored his faith that his once-radical idea will eventually become mainstream, making organ transplants safer and more available.
Transplant surgeons said Sachs's study represents a pivotal moment in organ transplantation, demonstrating that it is feasible to eliminate immunosuppressive drugs with their debilitating side effects, such as skin warts, cataracts, and increased risks of heart disease, diabetes, and serious infections. If the results are borne out in a larger group of patients, the Mass. General technique has the potential to help transplant recipients live longer. Within 10 years, half of all transplanted organs fail because of chronic rejection, a bleak predicament in this era of organ shortages.
"This is landmark work," said Dr. Joshua Miller, an organ transplant researcher at Northwestern University's Feinberg School of Medicine in Chicago.
Other researchers cautioned that only the healthiest patients may be able to endure the rigorous treatments, including chemotherapy and radiation, that precede the transplant.
Andrews said that going through the experimental protocol was not easy and that being an example of a failed case was even harder. But he sees his difficult experience as a contribution to medical research, saying how impressed he was that the Mass. General staff worked tirelessly on his case.
"They did not want to accept defeat," said Andrews, who ultimately received a replacement kidney in 2004 using conventional treatment with antirejection drugs.
Sachs is no stranger to the emotional roller coaster of experimental medicine and the intellectual nimbleness required to overcome setbacks. Since he was a young Harvard medical student in the mid-1960s, hearing his first lecture on organ transplantation, Sachs has set out to tackle "the most important problem that could be solved." In his mind, that was the persistent problem of organ rejection.
Sachs, director of the Transplantation Biology Research Center at Mass. General, had faith that a donor's bone marrow, from which immune cells originate, could play a pivotal role in giving transplant patients "induced tolerance" to a donated organ.
Under Sachs's approach, five days prior to transplant surgery, patients begin to undergo low-dose chemotherapy to kill off some of their marrow cells and make room for injection of the donor's bone marrow.
The patients also receive a drug and radiation to the thymus to eliminate a type of immune system cell, known as a T cell, that typically attacks any tissue perceived as foreign.
On the day of the procedure, surgeons attach the new kidney while injecting the donor's bone marrow into a blood vessel in the patient's arm. The donor's bone marrow mixes with the patient's, creating a temporary state called mixed chimerism. This tricks the patient's immune system into recognizing for years - and possibly forever - the donated organ as part of the self.
After the surgery, the immune system is still in a period of adjustment, and doctors give patients antirejection drugs that are gradually tapered off. Most patients were off the drugs by the ninth month.
Sachs first tried this approach successfully on mice, pigs, then monkeys. In 1998, he won approval to try his treatment on a select group of Mass. General patients with severe kidney failure, all of whom were offered matching kidneys from close relatives. When these six patients did well, Sachs moved on to the most ambitious test of his method, trying it out on patients with mismatched donors.
Starting in 2002, the method worked nearly flawlessly on Jennifer Searl, 28, a librarian from Peabody, and Christopher McMahon, 26, a retail store manager from Tewskbury.
Sachs and his colleagues felt something close to restrained euphoria. At a New Year's Eve party in 2002, Sachs and the chief surgeon on the research team, Dr. Benedict Cosimi, who share a small boat that they years ago named "Tolerance," gave a toast to the initial success of the experiment.
Then in October 2003, Andrews, a software engineer with polycystic kidney disease, went in for his experimental procedure. When the surgery was complete, spirits were high.
"Everybody thought it was a success," Andrews recalled.
But within two weeks of the surgery, Dr. Tatsuo Kawai, one of Sach's research colleagues, was handed test results showing that Andrews's urine output had dropped and that his blood contained high levels of toxins. An ultrasound scan showed the new organ was losing blood flow.
"The kidney's rejecting," Kawai remembered saying to himself.
He phoned Sachs, who was in his lab at one of Mass. General's research facilities in the Charlestown Navy Yard, with the news.
"It hurt," Sachs recalled. "You want to see everyone succeed."
For several months, Sachs and his team tried various drugs on Andrews, hoping to reverse the rejection. But by spring 2004, doctors began dialysis, conceding defeat in saving Andrews's new kidney. Because of the failure, Andrews was no longer eligible for another try with the experimental treatment.
The outcome for Andrews hit everyone on the research team hard.
"It was the lowest moment," Sachs recalled.
He said these studies put "people's lives in your hands" and are full of unpredictability.
Sachs and his dozen colleagues on the project began brainstorming about what went wrong, trying to salvage a lesson, if not Andrews's kidney. After intensive study, they concluded that another type of immune cell, the B cells, played a critical role in his organ rejection. They theorized that Andrews's body harbored B cells that ultimately produced antibodies against his sister's kidney, a scenario they did not anticipate because B cells had played no role in organ rejection in any of their previous studies.
To prevent rejection in new cases, the team revised the protocol to give all patients a drug prior to surgery that depletes B cells. Before they could proceed with the study, they had to win approvals from several regulatory agencies, which ensure patient safety.
Meanwhile, Sachs was delighted when he heard that Andrews's cousin had stepped forward to offer a kidney.
In August 2004, that conventional transplant surgery went smoothly, and Andrews went back to work "feeling great," while accepting his fate of being on antirejection drugs.
By 2005, the regulatory agencies approved the revised plan. In February 2005, surgeons operated on Derek Besenfelder, 28, a communications specialist from Los Angeles, and then in January 2006, they did transplant surgery on Matthew Knowles, 48, of Marshfield. Both have returned to their normal lives.
"I'm in perfect health," said Knowles, a supervisor for a gas company. "I don't take a pill a day. It's a miracle."
The four successful transplant patients have so far lived between 15 months and nearly five years without antirejection drugs.
Other researchers are also experimenting with ways to create permanent tolerance to donated organs, using slightly different approaches. Today's New England Journal includes two case studies from these other groups.
Sachs hopes to expand the study to include 20 new patients with mismatched donors. His greatest hope is that someday his novel treatment will extend to other organs.
"It's a wonderful feeling when you see people returning to their normal lives," he said.
Patricia Wen can be reached at wen@globe.com.
http://www.boston.com/news/local/articles/2008/01/24/rejecting_defeat?mode=PF
Avoiding Organ Rejection
Avoiding Organ Rejection
Audio
Professor Megan Sykes, Harvard University
One of the biggest breakthroughs in the transplantation field has been the discovery of immuno-suppressants. These are drugs that can partially switch off the immune system to prevent it from rejecting what the body sees as foreign tissue or non-self in a donor organ. But this comes at a cost because the drugs are quite toxic and immuno-suppressed patients are also quite vulnerable to infections and cancers.
Instead scientists have been searching for ways to persuade the immune system to accept the new foreign tissue in a donor organ as its own. Harvard’s professor Megan Sykes and her colleagues have now managed to do that by giving patients a partial bone marrow transplant collected from the same donor as the kidney they’re receiving. Somehow the new bone marrow re-educates the immune system so that it ignores the new kidney and the patients no longer require any kind of immuno-suppression.
Megan - Since the very first time allogeneic transplants were performed, that means transplants that were done one individual to another, we’ve known that there is this rejection response that will destroy the graft unless something is done to prevent it. So the success of allogeneic transplantation in patients in the last quarter century or so has depended on the use of immuno-suppressant drugs that suppress the immune system in a way that prevents the rejection of the graft.
Chris - There are some consequences of doing that though, aren’t there?
Megan - Yes. The trouble with that is these immuno-suppressive drugs suppress all immune responses so that the immune system is very generally compromised. What that means is that the recipient is predisposed to developing infections and also cancers, diseases because it turns out the immune system is needed to protect us from developing cancers. These are very serious side-effects and in addition there are a number of metabolic side-effects associated with these drugs and other unpleasant side-effects that people would like to avoid.
Chris - Why can’t we re-programme the immune system to try to ignore what we’re putting into the body and say ‘this kidney I’m putting in is friend, not foe, don’t attack it?’
Megan - Well, that’s exactly what we have been attempting to do for quite a long time now and that we seem to have achieved in a small group of patients in a pilot study. The approach that we have used involves use of bone marrow which contains cells that can form all of the blood-forming cells in the body. It’s been known for quite some years now that if bone marrow of two different individuals exists in one recipient that the donor bone marrow will educate the immune system in a way that allows the immune system to regard the donor as self and so the situation that you just described is created. Any graft from that same donor is ignored because it looks like self. The immune system has been educated to think that graft is self.
Chris - So what you’re saying is that if you gave someone a kidney transplant, if you gave them a bone marrow transplant at the same time you can change what the immune system recognises as friend and foe.
Megan - That’s right. That’s the idea. Now what I’ve just described has been well-established in animal models for a while now and we have a pretty good understanding of how it works in the animal models. The problem is, how do you go to an animal model from patients? Patients who get organ transplants in general do quite well early on, especially in the first two years. Another problem that I haven’t mentioned yet with organs transplants that are performed is that despite all the chronic non-specific immuno-suppressive therapy there’s a late phase of graft rejection called chronic rejection that really hasn’t been improved by all this immuno-suppressive therapy so many grafts are lost in the 5, 10, 15 year period. If we had this state where the immune system is re-educated as we’ve described, not only would we not need immuno-suppressive drugs but this more chronic type of rejection would also be prevented.
Chris - Could you talk us through, step-by-step, what you did in the pilot study with these patients?
Megan - Yes. What it involves is giving the recipient some chemotherapy but at a dose that that is well below the dose that is used in a conventional bone marrow transplant and giving the drug that is the antibody that causes depletion of the rejecting lymphocytes, the T cells in the recipient and also affects the T cells in the donor bone marrow graft.
Chris - So you end up with a patient who, for a while at least has got 2 types of bone marrow. They’ve got the donor who’s going to give them, say the kidney, and they’ve got their own bone marrow as well.
Megan - Right, that’s exactly right.
Chris - Then you put in the donor organ and at that time the immune system now is being told because the bone marrow is the same, don’t reject this organ.
Megan - Right, so the kidney and the bone marrow are given at the same time and the bone marrow is present in the circulation for a period of just a few weeks. Together the bone marrow derived cells in the kidney itself are doing some complex things that we’re still trying to understand to re-educate the immune system and allow it to regard the kidney as self.
Chris - In the patients that you’ve tested this on so far what’s been the outcome and are things still working for them now?
Megan - We’ve done five patients in this pilot study and four of them are currently doing very well. They’ve been off immuno-suppression for a number of years. One is approaching five years. Their kidneys are being accepted despite the lack of any immuno-suppressant drugs.
Chris - So you’ve proved that this can work, at least on a small scale, with kidney transplants. What about other organs, livers, hearts, lungs things like that.
Megan - The timing of the protocol is such that the organs and the bone marrow need to be transplanted at exactly the same time. Yet the preparation of the recipient has to begin five or six days beforehand. You need to know ahead of time that you’re going to do the transplant. At the moment this protocol limits us to live donors and the types of organs that are transplanted from living donors right now include kidneys, partial livers and sometimes lungs but hearts at the moment would not be relevant with this protocol. However, the overall idea does work in animal models for any type of graft from the donor. One of the things that we’re working on in our animal models is modifying the regiment so that it will be possible to time it in a way that any organ can be transplanted.
February 2008
Audio
Professor Megan Sykes, Harvard University
One of the biggest breakthroughs in the transplantation field has been the discovery of immuno-suppressants. These are drugs that can partially switch off the immune system to prevent it from rejecting what the body sees as foreign tissue or non-self in a donor organ. But this comes at a cost because the drugs are quite toxic and immuno-suppressed patients are also quite vulnerable to infections and cancers.
Instead scientists have been searching for ways to persuade the immune system to accept the new foreign tissue in a donor organ as its own. Harvard’s professor Megan Sykes and her colleagues have now managed to do that by giving patients a partial bone marrow transplant collected from the same donor as the kidney they’re receiving. Somehow the new bone marrow re-educates the immune system so that it ignores the new kidney and the patients no longer require any kind of immuno-suppression.
Megan - Since the very first time allogeneic transplants were performed, that means transplants that were done one individual to another, we’ve known that there is this rejection response that will destroy the graft unless something is done to prevent it. So the success of allogeneic transplantation in patients in the last quarter century or so has depended on the use of immuno-suppressant drugs that suppress the immune system in a way that prevents the rejection of the graft.
Chris - There are some consequences of doing that though, aren’t there?
Megan - Yes. The trouble with that is these immuno-suppressive drugs suppress all immune responses so that the immune system is very generally compromised. What that means is that the recipient is predisposed to developing infections and also cancers, diseases because it turns out the immune system is needed to protect us from developing cancers. These are very serious side-effects and in addition there are a number of metabolic side-effects associated with these drugs and other unpleasant side-effects that people would like to avoid.
Chris - Why can’t we re-programme the immune system to try to ignore what we’re putting into the body and say ‘this kidney I’m putting in is friend, not foe, don’t attack it?’
Megan - Well, that’s exactly what we have been attempting to do for quite a long time now and that we seem to have achieved in a small group of patients in a pilot study. The approach that we have used involves use of bone marrow which contains cells that can form all of the blood-forming cells in the body. It’s been known for quite some years now that if bone marrow of two different individuals exists in one recipient that the donor bone marrow will educate the immune system in a way that allows the immune system to regard the donor as self and so the situation that you just described is created. Any graft from that same donor is ignored because it looks like self. The immune system has been educated to think that graft is self.
Chris - So what you’re saying is that if you gave someone a kidney transplant, if you gave them a bone marrow transplant at the same time you can change what the immune system recognises as friend and foe.
Megan - That’s right. That’s the idea. Now what I’ve just described has been well-established in animal models for a while now and we have a pretty good understanding of how it works in the animal models. The problem is, how do you go to an animal model from patients? Patients who get organ transplants in general do quite well early on, especially in the first two years. Another problem that I haven’t mentioned yet with organs transplants that are performed is that despite all the chronic non-specific immuno-suppressive therapy there’s a late phase of graft rejection called chronic rejection that really hasn’t been improved by all this immuno-suppressive therapy so many grafts are lost in the 5, 10, 15 year period. If we had this state where the immune system is re-educated as we’ve described, not only would we not need immuno-suppressive drugs but this more chronic type of rejection would also be prevented.
Chris - Could you talk us through, step-by-step, what you did in the pilot study with these patients?
Megan - Yes. What it involves is giving the recipient some chemotherapy but at a dose that that is well below the dose that is used in a conventional bone marrow transplant and giving the drug that is the antibody that causes depletion of the rejecting lymphocytes, the T cells in the recipient and also affects the T cells in the donor bone marrow graft.
Chris - So you end up with a patient who, for a while at least has got 2 types of bone marrow. They’ve got the donor who’s going to give them, say the kidney, and they’ve got their own bone marrow as well.
Megan - Right, that’s exactly right.
Chris - Then you put in the donor organ and at that time the immune system now is being told because the bone marrow is the same, don’t reject this organ.
Megan - Right, so the kidney and the bone marrow are given at the same time and the bone marrow is present in the circulation for a period of just a few weeks. Together the bone marrow derived cells in the kidney itself are doing some complex things that we’re still trying to understand to re-educate the immune system and allow it to regard the kidney as self.
Chris - In the patients that you’ve tested this on so far what’s been the outcome and are things still working for them now?
Megan - We’ve done five patients in this pilot study and four of them are currently doing very well. They’ve been off immuno-suppression for a number of years. One is approaching five years. Their kidneys are being accepted despite the lack of any immuno-suppressant drugs.
Chris - So you’ve proved that this can work, at least on a small scale, with kidney transplants. What about other organs, livers, hearts, lungs things like that.
Megan - The timing of the protocol is such that the organs and the bone marrow need to be transplanted at exactly the same time. Yet the preparation of the recipient has to begin five or six days beforehand. You need to know ahead of time that you’re going to do the transplant. At the moment this protocol limits us to live donors and the types of organs that are transplanted from living donors right now include kidneys, partial livers and sometimes lungs but hearts at the moment would not be relevant with this protocol. However, the overall idea does work in animal models for any type of graft from the donor. One of the things that we’re working on in our animal models is modifying the regiment so that it will be possible to time it in a way that any organ can be transplanted.
February 2008
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