Mary Ann Moon

An autologous hematopoietic stem cell transplantation technique that achieves lymphoablation without myeloablation proved effective against severe refractory systemic lupus erythematosus in a preliminary study.

Serology, complement, immunomediated hemolysis and thrombocytopenia, thrombotic events, and pulmonary function all improved while preserving renal function in a single-center study of 48 patients. Nonmyeloablative hematopoietic stem cell transplantation (HSCT) significantly improved SLE symptoms and gave patients a 50% probability of 5-year remission, reported Dr. Richard K. Burt of Northwestern University, Chicago, and associates.

These results justify a randomized clinical trial comparing autologous HSCT with standard care, Dr. Burt and his associates said (JAMA 2006;295:527–35).

Fifty “very ill” patients underwent the two-step procedure involving a lupus-specific conditioning regimen to eliminate self-reactive lymphocytes followed by stem cell infusion. All had glomerulonephritis, lung involvement, CNS involvement, vasculitis, myositis, cytopenias, serositis, ulcerative mucocutaneous disease, and/or antiphospholipid syndrome refractory to optimal therapy.

One patient died from pulmonary and cerebral mucormycosis after stem cell mobilization but before transplantation (treatment-related mortality of 2%). A second patient died from active SLE after postponing transplantation.

The remaining 48 patients were followed for a mean of 29 months. Their probability of 5-year survival was 84%, and of disease-free 5-year survival 50%. Measures of serology, complement, and disease activity all remained improved throughout follow-up. Pulmonary function improved; five patients who had been dependent on supplemental oxygen were able to discontinue it.

Of 22 patients, 18 were able to discontinue anticoagulation without subsequent thrombotic events. Renal function remained stable or improved; 16 patients who had nephritis before HSCT were able to discontinue dialysis afterward. Idiopathic thrombocytopenic purpura cleared in five of seven patients. Autoimmune hemolytic anemia cleared in three of five patients.

An autologous hematopoietic stem cell transplantation technique that achieves lymphoablation without myeloablation proved effective against severe refractory systemic lupus erythematosus in a preliminary study.

Serology, complement, immunomediated hemolysis and thrombocytopenia, thrombotic events, and pulmonary function all improved while preserving renal function in a single-center study of 48 patients. Nonmyeloablative hematopoietic stem cell transplantation (HSCT) significantly improved SLE symptoms and gave patients a 50% probability of 5-year remission, reported Dr. Richard K. Burt of Northwestern University, Chicago, and associates.

These results justify a randomized clinical trial comparing autologous HSCT with standard care, Dr. Burt and his associates said (JAMA 2006;295:527–35).

Fifty “very ill” patients underwent the two-step procedure involving a lupus-specific conditioning regimen to eliminate self-reactive lymphocytes followed by stem cell infusion. All had glomerulonephritis, lung involvement, CNS involvement, vasculitis, myositis, cytopenias, serositis, ulcerative mucocutaneous disease, and/or antiphospholipid syndrome refractory to optimal therapy.

One patient died from pulmonary and cerebral mucormycosis after stem cell mobilization but before transplantation (treatment-related mortality of 2%). A second patient died from active SLE after postponing transplantation.

The remaining 48 patients were followed for a mean of 29 months. Their probability of 5-year survival was 84%, and of disease-free 5-year survival 50%. Measures of serology, complement, and disease activity all remained improved throughout follow-up. Pulmonary function improved; five patients who had been dependent on supplemental oxygen were able to discontinue it.

Of 22 patients, 18 were able to discontinue anticoagulation without subsequent thrombotic events. Renal function remained stable or improved; 16 patients who had nephritis before HSCT were able to discontinue dialysis afterward. Idiopathic thrombocytopenic purpura cleared in five of seven patients. Autoimmune hemolytic anemia cleared in three of five patients.

An autologous hematopoietic stem cell transplantation technique that achieves lymphoablation without myeloablation proved effective against severe refractory systemic lupus erythematosus in a preliminary study.

Serology, complement, immunomediated hemolysis and thrombocytopenia, thrombotic events, and pulmonary function all improved while preserving renal function in a single-center study of 48 patients. Nonmyeloablative hematopoietic stem cell transplantation (HSCT) significantly improved SLE symptoms and gave patients a 50% probability of 5-year remission, reported Dr. Richard K. Burt of Northwestern University, Chicago, and associates.

These results justify a randomized clinical trial comparing autologous HSCT with standard care, Dr. Burt and his associates said (JAMA 2006;295:527–35).

Fifty “very ill” patients underwent the two-step procedure involving a lupus-specific conditioning regimen to eliminate self-reactive lymphocytes followed by stem cell infusion. All had glomerulonephritis, lung involvement, CNS involvement, vasculitis, myositis, cytopenias, serositis, ulcerative mucocutaneous disease, and/or antiphospholipid syndrome refractory to optimal therapy.

One patient died from pulmonary and cerebral mucormycosis after stem cell mobilization but before transplantation (treatment-related mortality of 2%). A second patient died from active SLE after postponing transplantation.

The remaining 48 patients were followed for a mean of 29 months. Their probability of 5-year survival was 84%, and of disease-free 5-year survival 50%. Measures of serology, complement, and disease activity all remained improved throughout follow-up. Pulmonary function improved; five patients who had been dependent on supplemental oxygen were able to discontinue it.

Of 22 patients, 18 were able to discontinue anticoagulation without subsequent thrombotic events. Renal function remained stable or improved; 16 patients who had nephritis before HSCT were able to discontinue dialysis afterward. Idiopathic thrombocytopenic purpura cleared in five of seven patients. Autoimmune hemolytic anemia cleared in three of five patients.

Women who have had a baby who died from SIDS are more likely to have preterm birth or intrauterine growth restriction in their next pregnancy than are other women, reported Dr. Gordon C.S. Smith of the University of Cambridge (England) and his associates.

Similarly, women who have had a preterm or small-for-gestational-age (SGA) infant in one pregnancy are more likely to have a baby who dies from SIDS in the next pregnancy.

These associations were discovered in an analysis of large, comprehensive medical databases, and they strongly persisted when the data were adjusted for numerous maternal and demographic factors. However, the associations disappeared when gestational age and intrauterine growth restriction (IUGR) were factored into the analysis. From this finding, the investigators concluded that the link between SIDS and preterm birth/intrauterine growth restriction in other pregnancies is due to an as yet unknown maternal factor that underlies both disorders.

In the analysis, Dr. Smith and his associates reviewed information in a database on all Scottish in-hospital births, another database on all perinatal deaths in Scotland, and a third database on all Scottish birth and death records. They narrowed their study to focus on the records of 258,096 women who had one singleton birth between 1985 and 2001 and a second singleton birth between 1992 and 2001.

There were 332 women whose first infant died from SIDS, and 203 whose second infant died from SIDS, the investigators said (Lancet 2005;366:2107–11).

Women whose first infant died from SIDS were two to three times more likely to have a preterm delivery and two to three times more likely to deliver an SGA infant in the next pregnancy than were other women.

In women whose first delivery was preterm or whose first pregnancy was affected by IUGR, the risk of SIDS was elevated in the baby delivered in the subsequent pregnancy.

“We speculate that the association between SIDS in one pregnancy and obstetric complications in other pregnancies partly explains the tendency for SIDS events to recur,” they said.

Women who have had a baby who died from SIDS are more likely to have preterm birth or intrauterine growth restriction in their next pregnancy than are other women, reported Dr. Gordon C.S. Smith of the University of Cambridge (England) and his associates.

Similarly, women who have had a preterm or small-for-gestational-age (SGA) infant in one pregnancy are more likely to have a baby who dies from SIDS in the next pregnancy.

These associations were discovered in an analysis of large, comprehensive medical databases, and they strongly persisted when the data were adjusted for numerous maternal and demographic factors. However, the associations disappeared when gestational age and intrauterine growth restriction (IUGR) were factored into the analysis. From this finding, the investigators concluded that the link between SIDS and preterm birth/intrauterine growth restriction in other pregnancies is due to an as yet unknown maternal factor that underlies both disorders.

In the analysis, Dr. Smith and his associates reviewed information in a database on all Scottish in-hospital births, another database on all perinatal deaths in Scotland, and a third database on all Scottish birth and death records. They narrowed their study to focus on the records of 258,096 women who had one singleton birth between 1985 and 2001 and a second singleton birth between 1992 and 2001.

There were 332 women whose first infant died from SIDS, and 203 whose second infant died from SIDS, the investigators said (Lancet 2005;366:2107–11).

Women whose first infant died from SIDS were two to three times more likely to have a preterm delivery and two to three times more likely to deliver an SGA infant in the next pregnancy than were other women.

In women whose first delivery was preterm or whose first pregnancy was affected by IUGR, the risk of SIDS was elevated in the baby delivered in the subsequent pregnancy.

“We speculate that the association between SIDS in one pregnancy and obstetric complications in other pregnancies partly explains the tendency for SIDS events to recur,” they said.

Women who have had a baby who died from SIDS are more likely to have preterm birth or intrauterine growth restriction in their next pregnancy than are other women, reported Dr. Gordon C.S. Smith of the University of Cambridge (England) and his associates.

Similarly, women who have had a preterm or small-for-gestational-age (SGA) infant in one pregnancy are more likely to have a baby who dies from SIDS in the next pregnancy.

These associations were discovered in an analysis of large, comprehensive medical databases, and they strongly persisted when the data were adjusted for numerous maternal and demographic factors. However, the associations disappeared when gestational age and intrauterine growth restriction (IUGR) were factored into the analysis. From this finding, the investigators concluded that the link between SIDS and preterm birth/intrauterine growth restriction in other pregnancies is due to an as yet unknown maternal factor that underlies both disorders.

In the analysis, Dr. Smith and his associates reviewed information in a database on all Scottish in-hospital births, another database on all perinatal deaths in Scotland, and a third database on all Scottish birth and death records. They narrowed their study to focus on the records of 258,096 women who had one singleton birth between 1985 and 2001 and a second singleton birth between 1992 and 2001.

There were 332 women whose first infant died from SIDS, and 203 whose second infant died from SIDS, the investigators said (Lancet 2005;366:2107–11).

Women whose first infant died from SIDS were two to three times more likely to have a preterm delivery and two to three times more likely to deliver an SGA infant in the next pregnancy than were other women.

In women whose first delivery was preterm or whose first pregnancy was affected by IUGR, the risk of SIDS was elevated in the baby delivered in the subsequent pregnancy.

“We speculate that the association between SIDS in one pregnancy and obstetric complications in other pregnancies partly explains the tendency for SIDS events to recur,” they said.

Veterans who have seen combat in Iraq use mental health services at a high rate in their first year after returning home, compared with veterans returning from other deployments, reported Dr. Charles W. Hoge of the Walter Reed Army Institute of Research, Silver Spring, Md., and his associates.

About one-third of combat veterans returning from Iraq accessed mental health services during their first year back, most of them within 2 months of returning home. “[These] findings have important implications for estimating the level of mental health services that may be needed in military, Veterans Affairs, and civilian practice settings that care for returning veterans,” Dr. Hoge and his associates noted.

They added that their findings provide “further evidence that the war is burdening the health care system at large” (JAMA 2006;295:1023–32).

Dr. Hoge and his associates conducted what they described as the first analysis of data collected in a mass screening for mental health and other health problems among veterans returning from ground combat operations in Afghanistan and Iraq.

In April 2003, the U.S. Department of Defense mandated that all service members complete a three-page questionnaire upon completion of their deployment. The questionnaire addresses the conditions under which they served and their general health, physical symptoms, mental health concerns, and concerns about exposure to hazardous materials.

Much of the questionnaire is devoted to symptoms of posttraumatic stress disorder, depression, aggression, and suicidal ideation. Veterans are also interviewed by a physician, nurse-practitioner, or physician assistant to determine whether referral for further evaluation and treatment is needed.

The researchers analyzed data from these questionnaires from 303,905 Army soldiers and Marines who returned between May 2003 and April 2004 from deployments in Iraq and nearby areas (73%), Afghanistan (5%), and other locations such as Bosnia and Kosovo (21%). (Percentages do not add to 100 because of rounding.)

Veterans who served in Iraq used inpatient and outpatient mental health services at a higher rate (35% per year) than did veterans deployed to other locations.

The prevalences of mental health problems were consistently higher after service in Iraq than in any other location. “Overall, 19.1% of soldiers and Marines who returned from [Iraq] met the risk criteria for a mental health concern, compared with 11.3% for [Afghanistan] and 8.5% for other locations,” the investigators said.

The prevalence of PTSD in particular was 9.8% in combat veterans who served in Iraq, compared with 4.7% for those who served in Afghanistan and 2.1% for other locations. Of the nearly 22,000 veterans returning from Iraq who screened positive for PTSD, about 80% reported that they had witnessed people being wounded or killed or had discharged their own weapons in direct combat, compared with only 48% of those who screened negative for PTSD.

The investigators did point out that their study probably underestimated the use of mental health services by military personnel. For one thing, mental health problems treated in primary care settings might not be coded under the primarydiagnosis. Also, some service members might receive care from civilians without ties to the military health care system.

Despite those limitations, the study findings “emphasize the fact that the need for mental health services is likely to vary as a function of combat exposure,” the researchers said.

Veterans who screened positive for any mental health concern were significantly more likely to leave the service within 1 year than were those who screened negative for mental health concerns. This confirms that mental health problems associated with combat also have later occupational effects, they said.

Veterans who have seen combat in Iraq use mental health services at a high rate in their first year after returning home, compared with veterans returning from other deployments, reported Dr. Charles W. Hoge of the Walter Reed Army Institute of Research, Silver Spring, Md., and his associates.

About one-third of combat veterans returning from Iraq accessed mental health services during their first year back, most of them within 2 months of returning home. “[These] findings have important implications for estimating the level of mental health services that may be needed in military, Veterans Affairs, and civilian practice settings that care for returning veterans,” Dr. Hoge and his associates noted.

They added that their findings provide “further evidence that the war is burdening the health care system at large” (JAMA 2006;295:1023–32).

Dr. Hoge and his associates conducted what they described as the first analysis of data collected in a mass screening for mental health and other health problems among veterans returning from ground combat operations in Afghanistan and Iraq.

In April 2003, the U.S. Department of Defense mandated that all service members complete a three-page questionnaire upon completion of their deployment. The questionnaire addresses the conditions under which they served and their general health, physical symptoms, mental health concerns, and concerns about exposure to hazardous materials.

Much of the questionnaire is devoted to symptoms of posttraumatic stress disorder, depression, aggression, and suicidal ideation. Veterans are also interviewed by a physician, nurse-practitioner, or physician assistant to determine whether referral for further evaluation and treatment is needed.

The researchers analyzed data from these questionnaires from 303,905 Army soldiers and Marines who returned between May 2003 and April 2004 from deployments in Iraq and nearby areas (73%), Afghanistan (5%), and other locations such as Bosnia and Kosovo (21%). (Percentages do not add to 100 because of rounding.)

Veterans who served in Iraq used inpatient and outpatient mental health services at a higher rate (35% per year) than did veterans deployed to other locations.

The prevalences of mental health problems were consistently higher after service in Iraq than in any other location. “Overall, 19.1% of soldiers and Marines who returned from [Iraq] met the risk criteria for a mental health concern, compared with 11.3% for [Afghanistan] and 8.5% for other locations,” the investigators said.

The prevalence of PTSD in particular was 9.8% in combat veterans who served in Iraq, compared with 4.7% for those who served in Afghanistan and 2.1% for other locations. Of the nearly 22,000 veterans returning from Iraq who screened positive for PTSD, about 80% reported that they had witnessed people being wounded or killed or had discharged their own weapons in direct combat, compared with only 48% of those who screened negative for PTSD.

The investigators did point out that their study probably underestimated the use of mental health services by military personnel. For one thing, mental health problems treated in primary care settings might not be coded under the primarydiagnosis. Also, some service members might receive care from civilians without ties to the military health care system.

Despite those limitations, the study findings “emphasize the fact that the need for mental health services is likely to vary as a function of combat exposure,” the researchers said.

Veterans who screened positive for any mental health concern were significantly more likely to leave the service within 1 year than were those who screened negative for mental health concerns. This confirms that mental health problems associated with combat also have later occupational effects, they said.

Veterans who have seen combat in Iraq use mental health services at a high rate in their first year after returning home, compared with veterans returning from other deployments, reported Dr. Charles W. Hoge of the Walter Reed Army Institute of Research, Silver Spring, Md., and his associates.

About one-third of combat veterans returning from Iraq accessed mental health services during their first year back, most of them within 2 months of returning home. “[These] findings have important implications for estimating the level of mental health services that may be needed in military, Veterans Affairs, and civilian practice settings that care for returning veterans,” Dr. Hoge and his associates noted.

They added that their findings provide “further evidence that the war is burdening the health care system at large” (JAMA 2006;295:1023–32).

Dr. Hoge and his associates conducted what they described as the first analysis of data collected in a mass screening for mental health and other health problems among veterans returning from ground combat operations in Afghanistan and Iraq.

In April 2003, the U.S. Department of Defense mandated that all service members complete a three-page questionnaire upon completion of their deployment. The questionnaire addresses the conditions under which they served and their general health, physical symptoms, mental health concerns, and concerns about exposure to hazardous materials.

Much of the questionnaire is devoted to symptoms of posttraumatic stress disorder, depression, aggression, and suicidal ideation. Veterans are also interviewed by a physician, nurse-practitioner, or physician assistant to determine whether referral for further evaluation and treatment is needed.

The researchers analyzed data from these questionnaires from 303,905 Army soldiers and Marines who returned between May 2003 and April 2004 from deployments in Iraq and nearby areas (73%), Afghanistan (5%), and other locations such as Bosnia and Kosovo (21%). (Percentages do not add to 100 because of rounding.)

Veterans who served in Iraq used inpatient and outpatient mental health services at a higher rate (35% per year) than did veterans deployed to other locations.

The prevalences of mental health problems were consistently higher after service in Iraq than in any other location. “Overall, 19.1% of soldiers and Marines who returned from [Iraq] met the risk criteria for a mental health concern, compared with 11.3% for [Afghanistan] and 8.5% for other locations,” the investigators said.

The prevalence of PTSD in particular was 9.8% in combat veterans who served in Iraq, compared with 4.7% for those who served in Afghanistan and 2.1% for other locations. Of the nearly 22,000 veterans returning from Iraq who screened positive for PTSD, about 80% reported that they had witnessed people being wounded or killed or had discharged their own weapons in direct combat, compared with only 48% of those who screened negative for PTSD.

The investigators did point out that their study probably underestimated the use of mental health services by military personnel. For one thing, mental health problems treated in primary care settings might not be coded under the primarydiagnosis. Also, some service members might receive care from civilians without ties to the military health care system.

Despite those limitations, the study findings “emphasize the fact that the need for mental health services is likely to vary as a function of combat exposure,” the researchers said.

Veterans who screened positive for any mental health concern were significantly more likely to leave the service within 1 year than were those who screened negative for mental health concerns. This confirms that mental health problems associated with combat also have later occupational effects, they said.

Crohn's disease appears to be caused by a weak immune response, not the exaggerated response of a hyperreactive immune system that has long been suspected as the cause, according to Dr. Daniel J. B. Marks, of University College London, and his associates.

The researchers conducted a series of experiments on a small number of patients and control subjects to examine the immunologic underpinnings of Crohn's disease. They concluded that the disease stems from an impaired immune response that allows bacteria in the intestinal contents to accumulate in areas of the bowel. There, some bacteria breach the mucosal barrier of the bowel wall. Their persistence within the tissue results in granuloma formation and a secondary chronic inflammation.

If their theory proves to be correct, it means that current immunosuppressive therapies for the disorder are actually exacerbating the underlying immunodeficiency even as they dampen the secondary intestinal inflammation, Dr. Marks and his associates said (Lancet 2006;367:668–78).

The investigators began by obtaining serial biopsies of the posterior rectal wall in six patients with quiescent Crohn's disease, three with ulcerative colitis, and nine control subjects with noninflammatory bowel disorders. Biopsies also were taken from other locations in the bowel in three more Crohn's patients who had undergone colectomy and in two patients with familial adenomatous polyposis. The procedures confirmed that there was no endoscopic or microscopic evidence of Crohn's lesions.

The biopsies served a second purpose, which was to induce a tiny area of trauma to the bowel wall so that local immune responses could be monitored. The control subjects showed a vigorous inflammatory response at the biopsy sites, with large increases in neutrophils and cells positive for interleukin-8. In contrast, the Crohn's patients showed 79% fewer neutrophils and 63% fewer interleukin-8-positive cells.

To determine whether this abnormal response was localized to the bowel, the researchers then induced a small area of skin trauma by abrading a 3-cm patch on the volar surface of the forearm. Crohn's patients and control subjects showed similar degrees of trauma in these skin lesions and had equivalent levels of C3a, histamine, prostaglandin E₂, and leukotriene B in response to the wounds.

However, neutrophil efflux to the cutaneous wounds was impaired in the Crohn's patients after 5 hours, and was still reduced by half at 24 hours, compared with controls. This indicates that people with Crohn's disease have a generalized constitutional abnormality in their immune response, the investigators said.

Crohn's lesions typically develop at sites within the bowel where bacterial concentrations are highest. “Our present findings suggest that reduced or delayed recruitment of neutrophils to sites at which bacteria penetrate the mucosa might lead to persistence of bacteria and other organic debris in the tissues, possibly within macrophages. Secondary secretion of proinflammatory cytokines, after the failure of initial clearance, could drive the development of chronic inflammation,” they noted.

To assess whether the response to bacteria within bodily tissues was abnormal in patients with Crohn's disease, the researchers then examined the response to subcutaneous injections of heat-killed Escherichia. coli.

The injections yielded vigorous inflammatory responses in all subjects, including pain, erythema, and swelling. Control subjects showed a fivefold increase in blood flow around the lesions at 8 hours and a ninefold increase at 24 hours, which returned to baseline levels within 48 hours. But Crohn's patients showed abnormally low increases in blood flow even though the superficial appearance of the lesions was identical. In particular, Crohn's patients with colonic disease showed a 77% reduction in blood flow, compared with controls; those with ileal disease showed a 50% reduction.

“In 2 patients with ulcerative colitis, blood flow response was greater than that in patients with Crohn's disease and did not show the normal resolution after 48 hours, clearly distinguishing it from the hyporesponsiveness characteristic of Crohn's disease. The inflammatory response was so florid in one patient with ulcerative colitis that we terminated these studies in patients with this condition,” they said.

The investigators then studied whether treatment with the vasodilator sildenafil might correct the deficient blood flow in Crohn's patients. “Oral administration of 50-mg sildenafil to 5 healthy individuals and 10 patients with Crohn's disease at 24 or 48 hours after bacterial injection resulted in marked increases in blood flow,” they noted.

“We propose that the underlying impairment of acute inflammation that predisposes to Crohn's disease can be boosted by a second tier of immune enhancers,” the investigators said. “It might be feasible to introduce interleukin-8 or other proinflammatory stimuli directly into acute lesions, either by direct enteral administration or through synthesis by genetically modified gut organisms, since this cytokine would penetrate the bowel wall only through damaged mucosa.”

In addition, agents such as sildenafil that increase blood flow and proinflammatory drugs also might be useful in healing or preventing lesions.

Crohn's disease appears to be caused by a weak immune response, not the exaggerated response of a hyperreactive immune system that has long been suspected as the cause, according to Dr. Daniel J. B. Marks, of University College London, and his associates.

The researchers conducted a series of experiments on a small number of patients and control subjects to examine the immunologic underpinnings of Crohn's disease. They concluded that the disease stems from an impaired immune response that allows bacteria in the intestinal contents to accumulate in areas of the bowel. There, some bacteria breach the mucosal barrier of the bowel wall. Their persistence within the tissue results in granuloma formation and a secondary chronic inflammation.

If their theory proves to be correct, it means that current immunosuppressive therapies for the disorder are actually exacerbating the underlying immunodeficiency even as they dampen the secondary intestinal inflammation, Dr. Marks and his associates said (Lancet 2006;367:668–78).

The investigators began by obtaining serial biopsies of the posterior rectal wall in six patients with quiescent Crohn's disease, three with ulcerative colitis, and nine control subjects with noninflammatory bowel disorders. Biopsies also were taken from other locations in the bowel in three more Crohn's patients who had undergone colectomy and in two patients with familial adenomatous polyposis. The procedures confirmed that there was no endoscopic or microscopic evidence of Crohn's lesions.

The biopsies served a second purpose, which was to induce a tiny area of trauma to the bowel wall so that local immune responses could be monitored. The control subjects showed a vigorous inflammatory response at the biopsy sites, with large increases in neutrophils and cells positive for interleukin-8. In contrast, the Crohn's patients showed 79% fewer neutrophils and 63% fewer interleukin-8-positive cells.

To determine whether this abnormal response was localized to the bowel, the researchers then induced a small area of skin trauma by abrading a 3-cm patch on the volar surface of the forearm. Crohn's patients and control subjects showed similar degrees of trauma in these skin lesions and had equivalent levels of C3a, histamine, prostaglandin E₂, and leukotriene B in response to the wounds.

However, neutrophil efflux to the cutaneous wounds was impaired in the Crohn's patients after 5 hours, and was still reduced by half at 24 hours, compared with controls. This indicates that people with Crohn's disease have a generalized constitutional abnormality in their immune response, the investigators said.

Crohn's lesions typically develop at sites within the bowel where bacterial concentrations are highest. “Our present findings suggest that reduced or delayed recruitment of neutrophils to sites at which bacteria penetrate the mucosa might lead to persistence of bacteria and other organic debris in the tissues, possibly within macrophages. Secondary secretion of proinflammatory cytokines, after the failure of initial clearance, could drive the development of chronic inflammation,” they noted.

To assess whether the response to bacteria within bodily tissues was abnormal in patients with Crohn's disease, the researchers then examined the response to subcutaneous injections of heat-killed Escherichia. coli.

The injections yielded vigorous inflammatory responses in all subjects, including pain, erythema, and swelling. Control subjects showed a fivefold increase in blood flow around the lesions at 8 hours and a ninefold increase at 24 hours, which returned to baseline levels within 48 hours. But Crohn's patients showed abnormally low increases in blood flow even though the superficial appearance of the lesions was identical. In particular, Crohn's patients with colonic disease showed a 77% reduction in blood flow, compared with controls; those with ileal disease showed a 50% reduction.

“In 2 patients with ulcerative colitis, blood flow response was greater than that in patients with Crohn's disease and did not show the normal resolution after 48 hours, clearly distinguishing it from the hyporesponsiveness characteristic of Crohn's disease. The inflammatory response was so florid in one patient with ulcerative colitis that we terminated these studies in patients with this condition,” they said.

The investigators then studied whether treatment with the vasodilator sildenafil might correct the deficient blood flow in Crohn's patients. “Oral administration of 50-mg sildenafil to 5 healthy individuals and 10 patients with Crohn's disease at 24 or 48 hours after bacterial injection resulted in marked increases in blood flow,” they noted.

“We propose that the underlying impairment of acute inflammation that predisposes to Crohn's disease can be boosted by a second tier of immune enhancers,” the investigators said. “It might be feasible to introduce interleukin-8 or other proinflammatory stimuli directly into acute lesions, either by direct enteral administration or through synthesis by genetically modified gut organisms, since this cytokine would penetrate the bowel wall only through damaged mucosa.”

In addition, agents such as sildenafil that increase blood flow and proinflammatory drugs also might be useful in healing or preventing lesions.

Crohn's disease appears to be caused by a weak immune response, not the exaggerated response of a hyperreactive immune system that has long been suspected as the cause, according to Dr. Daniel J. B. Marks, of University College London, and his associates.

The researchers conducted a series of experiments on a small number of patients and control subjects to examine the immunologic underpinnings of Crohn's disease. They concluded that the disease stems from an impaired immune response that allows bacteria in the intestinal contents to accumulate in areas of the bowel. There, some bacteria breach the mucosal barrier of the bowel wall. Their persistence within the tissue results in granuloma formation and a secondary chronic inflammation.

If their theory proves to be correct, it means that current immunosuppressive therapies for the disorder are actually exacerbating the underlying immunodeficiency even as they dampen the secondary intestinal inflammation, Dr. Marks and his associates said (Lancet 2006;367:668–78).

The investigators began by obtaining serial biopsies of the posterior rectal wall in six patients with quiescent Crohn's disease, three with ulcerative colitis, and nine control subjects with noninflammatory bowel disorders. Biopsies also were taken from other locations in the bowel in three more Crohn's patients who had undergone colectomy and in two patients with familial adenomatous polyposis. The procedures confirmed that there was no endoscopic or microscopic evidence of Crohn's lesions.

The biopsies served a second purpose, which was to induce a tiny area of trauma to the bowel wall so that local immune responses could be monitored. The control subjects showed a vigorous inflammatory response at the biopsy sites, with large increases in neutrophils and cells positive for interleukin-8. In contrast, the Crohn's patients showed 79% fewer neutrophils and 63% fewer interleukin-8-positive cells.

To determine whether this abnormal response was localized to the bowel, the researchers then induced a small area of skin trauma by abrading a 3-cm patch on the volar surface of the forearm. Crohn's patients and control subjects showed similar degrees of trauma in these skin lesions and had equivalent levels of C3a, histamine, prostaglandin E₂, and leukotriene B in response to the wounds.

However, neutrophil efflux to the cutaneous wounds was impaired in the Crohn's patients after 5 hours, and was still reduced by half at 24 hours, compared with controls. This indicates that people with Crohn's disease have a generalized constitutional abnormality in their immune response, the investigators said.

Crohn's lesions typically develop at sites within the bowel where bacterial concentrations are highest. “Our present findings suggest that reduced or delayed recruitment of neutrophils to sites at which bacteria penetrate the mucosa might lead to persistence of bacteria and other organic debris in the tissues, possibly within macrophages. Secondary secretion of proinflammatory cytokines, after the failure of initial clearance, could drive the development of chronic inflammation,” they noted.

To assess whether the response to bacteria within bodily tissues was abnormal in patients with Crohn's disease, the researchers then examined the response to subcutaneous injections of heat-killed Escherichia. coli.

The injections yielded vigorous inflammatory responses in all subjects, including pain, erythema, and swelling. Control subjects showed a fivefold increase in blood flow around the lesions at 8 hours and a ninefold increase at 24 hours, which returned to baseline levels within 48 hours. But Crohn's patients showed abnormally low increases in blood flow even though the superficial appearance of the lesions was identical. In particular, Crohn's patients with colonic disease showed a 77% reduction in blood flow, compared with controls; those with ileal disease showed a 50% reduction.

“In 2 patients with ulcerative colitis, blood flow response was greater than that in patients with Crohn's disease and did not show the normal resolution after 48 hours, clearly distinguishing it from the hyporesponsiveness characteristic of Crohn's disease. The inflammatory response was so florid in one patient with ulcerative colitis that we terminated these studies in patients with this condition,” they said.

The investigators then studied whether treatment with the vasodilator sildenafil might correct the deficient blood flow in Crohn's patients. “Oral administration of 50-mg sildenafil to 5 healthy individuals and 10 patients with Crohn's disease at 24 or 48 hours after bacterial injection resulted in marked increases in blood flow,” they noted.

“We propose that the underlying impairment of acute inflammation that predisposes to Crohn's disease can be boosted by a second tier of immune enhancers,” the investigators said. “It might be feasible to introduce interleukin-8 or other proinflammatory stimuli directly into acute lesions, either by direct enteral administration or through synthesis by genetically modified gut organisms, since this cytokine would penetrate the bowel wall only through damaged mucosa.”

In addition, agents such as sildenafil that increase blood flow and proinflammatory drugs also might be useful in healing or preventing lesions.

Total thyroidectomy can be performed more safely than many clinicians realize, and offers more durable results for people with Grave's disease than do antithyroid drugs or radioiodine, according to Dr. Kaare J. Weber of Mount Sinai School of Medicine, New York, and his associates.

The researchers reviewed the records of all 48 patients who underwent total thyroidectomy for Grave's disease at their hospital between 1993 and 2005. All but 7 of the patients were women, and the mean age was 40 years. All had typical symptoms including palpitations, eye disturbances, anxiety, weight loss, heat intolerance, and tremor.

Of this group, 24 patients had failed on medical therapy with or without radioiodine. Another 12 had refused radioiodine because of concerns about radiation exposure. The remaining 12 chose surgery for assessment of thyroid nodules that were presumed to be related to their disease.

After thyroidectomy and a mean of 40 months of follow-up, there were no recurrences of hyperthyroidism. In contrast, relapse rates of 20%–75% are cited in the literature for medical therapy, Dr. Weber and his associates said (Am. J. Surg. 2006;191:400–5).

Of the 20 patients who had mild or severe ophthalmopathy before surgery, 11 showed marked improvement or resolution of eye disorders and the remaining 9 showed either improvement or stabilization. In contrast, radioiodine treatment has been associated with the onset or exacerbation of ophthalmopathy, they said.

Eight patients (17%) were found to have papillary cancer of the thyroid at surgery. “These patients would not have received appropriate treatment for their coexisting cancer if they were treated only with antithyroid drugs and/or radioiodine,” the investigators noted.

No patients suffered permanent laryngeal nerve injury from the procedure. Complications included three cases of transient hypocalcemia and one case of temporary right vocal cord paralysis. Only one patient developed permanent hypoparathyroidism, and that case “followed a previous failed [thyroid] exploration at another institution,” they said.

“Despite today's methods for a safe thyroidectomy, concern over permanent recurrent laryngeal nerve injury and permanent hypoparathyroidism as a result of the hypervascularity of the thyroid gland prevents some physicians from recommending surgical therapy for Grave's disease,” Dr. Weber and his associates said.

These results demonstrate that total thyroidectomy now can be performed safely, with little of the morbidity and mortality that occurred when the procedure was first developed years ago. In addition, thyroidectomy addresses potentially cancerous nodules, as medical and radioiodine therapies do not, they said.

Total thyroidectomy can be performed more safely than many clinicians realize, and offers more durable results for people with Grave's disease than do antithyroid drugs or radioiodine, according to Dr. Kaare J. Weber of Mount Sinai School of Medicine, New York, and his associates.

The researchers reviewed the records of all 48 patients who underwent total thyroidectomy for Grave's disease at their hospital between 1993 and 2005. All but 7 of the patients were women, and the mean age was 40 years. All had typical symptoms including palpitations, eye disturbances, anxiety, weight loss, heat intolerance, and tremor.

Of this group, 24 patients had failed on medical therapy with or without radioiodine. Another 12 had refused radioiodine because of concerns about radiation exposure. The remaining 12 chose surgery for assessment of thyroid nodules that were presumed to be related to their disease.

After thyroidectomy and a mean of 40 months of follow-up, there were no recurrences of hyperthyroidism. In contrast, relapse rates of 20%–75% are cited in the literature for medical therapy, Dr. Weber and his associates said (Am. J. Surg. 2006;191:400–5).

Of the 20 patients who had mild or severe ophthalmopathy before surgery, 11 showed marked improvement or resolution of eye disorders and the remaining 9 showed either improvement or stabilization. In contrast, radioiodine treatment has been associated with the onset or exacerbation of ophthalmopathy, they said.

Eight patients (17%) were found to have papillary cancer of the thyroid at surgery. “These patients would not have received appropriate treatment for their coexisting cancer if they were treated only with antithyroid drugs and/or radioiodine,” the investigators noted.

No patients suffered permanent laryngeal nerve injury from the procedure. Complications included three cases of transient hypocalcemia and one case of temporary right vocal cord paralysis. Only one patient developed permanent hypoparathyroidism, and that case “followed a previous failed [thyroid] exploration at another institution,” they said.

“Despite today's methods for a safe thyroidectomy, concern over permanent recurrent laryngeal nerve injury and permanent hypoparathyroidism as a result of the hypervascularity of the thyroid gland prevents some physicians from recommending surgical therapy for Grave's disease,” Dr. Weber and his associates said.

These results demonstrate that total thyroidectomy now can be performed safely, with little of the morbidity and mortality that occurred when the procedure was first developed years ago. In addition, thyroidectomy addresses potentially cancerous nodules, as medical and radioiodine therapies do not, they said.

Total thyroidectomy can be performed more safely than many clinicians realize, and offers more durable results for people with Grave's disease than do antithyroid drugs or radioiodine, according to Dr. Kaare J. Weber of Mount Sinai School of Medicine, New York, and his associates.

The researchers reviewed the records of all 48 patients who underwent total thyroidectomy for Grave's disease at their hospital between 1993 and 2005. All but 7 of the patients were women, and the mean age was 40 years. All had typical symptoms including palpitations, eye disturbances, anxiety, weight loss, heat intolerance, and tremor.

Of this group, 24 patients had failed on medical therapy with or without radioiodine. Another 12 had refused radioiodine because of concerns about radiation exposure. The remaining 12 chose surgery for assessment of thyroid nodules that were presumed to be related to their disease.

After thyroidectomy and a mean of 40 months of follow-up, there were no recurrences of hyperthyroidism. In contrast, relapse rates of 20%–75% are cited in the literature for medical therapy, Dr. Weber and his associates said (Am. J. Surg. 2006;191:400–5).

Of the 20 patients who had mild or severe ophthalmopathy before surgery, 11 showed marked improvement or resolution of eye disorders and the remaining 9 showed either improvement or stabilization. In contrast, radioiodine treatment has been associated with the onset or exacerbation of ophthalmopathy, they said.

Eight patients (17%) were found to have papillary cancer of the thyroid at surgery. “These patients would not have received appropriate treatment for their coexisting cancer if they were treated only with antithyroid drugs and/or radioiodine,” the investigators noted.

No patients suffered permanent laryngeal nerve injury from the procedure. Complications included three cases of transient hypocalcemia and one case of temporary right vocal cord paralysis. Only one patient developed permanent hypoparathyroidism, and that case “followed a previous failed [thyroid] exploration at another institution,” they said.

“Despite today's methods for a safe thyroidectomy, concern over permanent recurrent laryngeal nerve injury and permanent hypoparathyroidism as a result of the hypervascularity of the thyroid gland prevents some physicians from recommending surgical therapy for Grave's disease,” Dr. Weber and his associates said.

These results demonstrate that total thyroidectomy now can be performed safely, with little of the morbidity and mortality that occurred when the procedure was first developed years ago. In addition, thyroidectomy addresses potentially cancerous nodules, as medical and radioiodine therapies do not, they said.

High-dose external beam radiotherapy controlled locally advanced, differentiated thyroid cancer in a retrospective study of 42 patients.

There is little information on the efficacy of external beam radiotherapy (EBRT) as adjuvant therapy in such patients. “The relatively low incidence of this malignancy, coupled with its long natural history, has precluded study of various treatment methods in the context of a prospective clinical trial,” said Dr. Kenyon M. Meadows and his associates at the University of Florida, Gainesville.

“Retrospective outcome studies remain the most reliable way of assessing therapeutic efficacy but are hampered by significant heterogeneity in diagnostic evaluation, staging, and treatment strategies that have evolved over time. Accordingly, the indications for EBRT for differentiated thyroid cancer remain poorly defined,” they said.

The 10% of thyroid cancer patients presenting with locally advanced disease are at high risk for local or regional recurrence. Five-year survival is 50%.

The investigators reviewed the records and assessed outcomes in all 42 patients who were treated for advanced or recurrent thyroid cancer with adjuvant high-dose EBRT at their university since April 1962. Median patient age was 58 (Am. J. Otolaryngol. 2006;27:24–8).

Ten patients died from thyroid cancer during a mean follow-up of 7 years and 16 died from unrelated causes. There were no local or regional recurrences at 5 years for patients with no gross residual disease at EBRT and 30% recurrence for those with gross residual disease at EBRT. No recurrences were seen with doses over 64 Gy.

Five-year survival free of distant metastases was 82% in those without metastasis at EBRT.

High-dose external beam radiotherapy controlled locally advanced, differentiated thyroid cancer in a retrospective study of 42 patients.

There is little information on the efficacy of external beam radiotherapy (EBRT) as adjuvant therapy in such patients. “The relatively low incidence of this malignancy, coupled with its long natural history, has precluded study of various treatment methods in the context of a prospective clinical trial,” said Dr. Kenyon M. Meadows and his associates at the University of Florida, Gainesville.

“Retrospective outcome studies remain the most reliable way of assessing therapeutic efficacy but are hampered by significant heterogeneity in diagnostic evaluation, staging, and treatment strategies that have evolved over time. Accordingly, the indications for EBRT for differentiated thyroid cancer remain poorly defined,” they said.

The 10% of thyroid cancer patients presenting with locally advanced disease are at high risk for local or regional recurrence. Five-year survival is 50%.

The investigators reviewed the records and assessed outcomes in all 42 patients who were treated for advanced or recurrent thyroid cancer with adjuvant high-dose EBRT at their university since April 1962. Median patient age was 58 (Am. J. Otolaryngol. 2006;27:24–8).

Ten patients died from thyroid cancer during a mean follow-up of 7 years and 16 died from unrelated causes. There were no local or regional recurrences at 5 years for patients with no gross residual disease at EBRT and 30% recurrence for those with gross residual disease at EBRT. No recurrences were seen with doses over 64 Gy.

Five-year survival free of distant metastases was 82% in those without metastasis at EBRT.

High-dose external beam radiotherapy controlled locally advanced, differentiated thyroid cancer in a retrospective study of 42 patients.

There is little information on the efficacy of external beam radiotherapy (EBRT) as adjuvant therapy in such patients. “The relatively low incidence of this malignancy, coupled with its long natural history, has precluded study of various treatment methods in the context of a prospective clinical trial,” said Dr. Kenyon M. Meadows and his associates at the University of Florida, Gainesville.

“Retrospective outcome studies remain the most reliable way of assessing therapeutic efficacy but are hampered by significant heterogeneity in diagnostic evaluation, staging, and treatment strategies that have evolved over time. Accordingly, the indications for EBRT for differentiated thyroid cancer remain poorly defined,” they said.

The 10% of thyroid cancer patients presenting with locally advanced disease are at high risk for local or regional recurrence. Five-year survival is 50%.

The investigators reviewed the records and assessed outcomes in all 42 patients who were treated for advanced or recurrent thyroid cancer with adjuvant high-dose EBRT at their university since April 1962. Median patient age was 58 (Am. J. Otolaryngol. 2006;27:24–8).

Ten patients died from thyroid cancer during a mean follow-up of 7 years and 16 died from unrelated causes. There were no local or regional recurrences at 5 years for patients with no gross residual disease at EBRT and 30% recurrence for those with gross residual disease at EBRT. No recurrences were seen with doses over 64 Gy.

Five-year survival free of distant metastases was 82% in those without metastasis at EBRT.

Nearly 60 years after exposure to radiation from the atomic bomb explosions in Hiroshima and Nagasaki, survivors remain at increased risk for both malignant and benign thyroid tumors, reported Dr. Misa Imaizumi of Nagasaki (Japan) University, and associates.

There is a significant, linear dose-response relationship: The prevalence of thyroid tumors rises as radiation dose increases. And the dose effects are significantly stronger in people who were exposed as children or adolescents in 1945 than they are in people who were 20 years old or older at that time.

These findings show that “careful examination of the thyroid is still important long after radiation exposure, especially for people exposed at younger ages,” Dr. Imaizumi and associates said (JAMA 2006;295:1011–22).

The researchers conducted what they described as the first comprehensive examinations for thyroid disease in 4,091 survivors of the Hiroshima and Nagasaki bombings. The 1,352 men and 2,739 women had a mean age of 70 years. About half had been within 2 kilometers of the hypocenters of the explosions.

Thyroid diseases were diagnosed at this examination or had been diagnosed previously in 1,833 subjects (44.8%). The prevalence of thyroid disease was significantly higher in women (51.0%) than in men (32.2%).

Malignant thyroid tumors were found in 87 subjects (2.1%), and benign nodules were detected in 207 subjects (5.1%). Another 71 subjects had previously had malignant tumors removed, whereas 43 had previously had benign nodules removed. Thyroid cysts were noted in an additional 324 subjects (7.9%), whereas 589 (14.4%) had mixed-type solid nodules and 321 (7.8%) had nodules for which cytology results were unavailable.

For all of these lesions, the prevalence increased in direct proportion to the degree of radiation exposure. Moreover, the prevalence was highest in people who had been exposed to the atomic bombs' radiation as children or adolescents. The exact reason for this is unknown, but it is likely that children's organs are more sensitive to radiation because of their higher rates of cell proliferation associated with growth, the investigators said.

Autoimmune thyroid diseases were not associated with radiation dose. A total of 1,127 subjects (27.5%) had antithyroid antibodies, 230 (5.6%) had hypothyroidism, and 62 (1.5%) had hyperthyroidism.

In an editorial comment, John D. Boice Jr., Sc.D., of Vanderbilt University in Nashville, Tenn. said, “It is remarkable that a biological effect from a single brief environmental exposure nearly 60 years in the past is still present and can be detected.”

The findings of Dr. Imaizumi and associates show that after radiation exposure, the risk of both malignant and benign thyroid disease “apparently lasts for life,” Dr. Boice said (JAMA 2006;295:1060–2).

Nearly 60 years after exposure to radiation from the atomic bomb explosions in Hiroshima and Nagasaki, survivors remain at increased risk for both malignant and benign thyroid tumors, reported Dr. Misa Imaizumi of Nagasaki (Japan) University, and associates.

There is a significant, linear dose-response relationship: The prevalence of thyroid tumors rises as radiation dose increases. And the dose effects are significantly stronger in people who were exposed as children or adolescents in 1945 than they are in people who were 20 years old or older at that time.

These findings show that “careful examination of the thyroid is still important long after radiation exposure, especially for people exposed at younger ages,” Dr. Imaizumi and associates said (JAMA 2006;295:1011–22).

The researchers conducted what they described as the first comprehensive examinations for thyroid disease in 4,091 survivors of the Hiroshima and Nagasaki bombings. The 1,352 men and 2,739 women had a mean age of 70 years. About half had been within 2 kilometers of the hypocenters of the explosions.

Thyroid diseases were diagnosed at this examination or had been diagnosed previously in 1,833 subjects (44.8%). The prevalence of thyroid disease was significantly higher in women (51.0%) than in men (32.2%).

Malignant thyroid tumors were found in 87 subjects (2.1%), and benign nodules were detected in 207 subjects (5.1%). Another 71 subjects had previously had malignant tumors removed, whereas 43 had previously had benign nodules removed. Thyroid cysts were noted in an additional 324 subjects (7.9%), whereas 589 (14.4%) had mixed-type solid nodules and 321 (7.8%) had nodules for which cytology results were unavailable.

For all of these lesions, the prevalence increased in direct proportion to the degree of radiation exposure. Moreover, the prevalence was highest in people who had been exposed to the atomic bombs' radiation as children or adolescents. The exact reason for this is unknown, but it is likely that children's organs are more sensitive to radiation because of their higher rates of cell proliferation associated with growth, the investigators said.

Autoimmune thyroid diseases were not associated with radiation dose. A total of 1,127 subjects (27.5%) had antithyroid antibodies, 230 (5.6%) had hypothyroidism, and 62 (1.5%) had hyperthyroidism.

In an editorial comment, John D. Boice Jr., Sc.D., of Vanderbilt University in Nashville, Tenn. said, “It is remarkable that a biological effect from a single brief environmental exposure nearly 60 years in the past is still present and can be detected.”

The findings of Dr. Imaizumi and associates show that after radiation exposure, the risk of both malignant and benign thyroid disease “apparently lasts for life,” Dr. Boice said (JAMA 2006;295:1060–2).

Nearly 60 years after exposure to radiation from the atomic bomb explosions in Hiroshima and Nagasaki, survivors remain at increased risk for both malignant and benign thyroid tumors, reported Dr. Misa Imaizumi of Nagasaki (Japan) University, and associates.

There is a significant, linear dose-response relationship: The prevalence of thyroid tumors rises as radiation dose increases. And the dose effects are significantly stronger in people who were exposed as children or adolescents in 1945 than they are in people who were 20 years old or older at that time.

These findings show that “careful examination of the thyroid is still important long after radiation exposure, especially for people exposed at younger ages,” Dr. Imaizumi and associates said (JAMA 2006;295:1011–22).

The researchers conducted what they described as the first comprehensive examinations for thyroid disease in 4,091 survivors of the Hiroshima and Nagasaki bombings. The 1,352 men and 2,739 women had a mean age of 70 years. About half had been within 2 kilometers of the hypocenters of the explosions.

Thyroid diseases were diagnosed at this examination or had been diagnosed previously in 1,833 subjects (44.8%). The prevalence of thyroid disease was significantly higher in women (51.0%) than in men (32.2%).

Malignant thyroid tumors were found in 87 subjects (2.1%), and benign nodules were detected in 207 subjects (5.1%). Another 71 subjects had previously had malignant tumors removed, whereas 43 had previously had benign nodules removed. Thyroid cysts were noted in an additional 324 subjects (7.9%), whereas 589 (14.4%) had mixed-type solid nodules and 321 (7.8%) had nodules for which cytology results were unavailable.

For all of these lesions, the prevalence increased in direct proportion to the degree of radiation exposure. Moreover, the prevalence was highest in people who had been exposed to the atomic bombs' radiation as children or adolescents. The exact reason for this is unknown, but it is likely that children's organs are more sensitive to radiation because of their higher rates of cell proliferation associated with growth, the investigators said.

Autoimmune thyroid diseases were not associated with radiation dose. A total of 1,127 subjects (27.5%) had antithyroid antibodies, 230 (5.6%) had hypothyroidism, and 62 (1.5%) had hyperthyroidism.

In an editorial comment, John D. Boice Jr., Sc.D., of Vanderbilt University in Nashville, Tenn. said, “It is remarkable that a biological effect from a single brief environmental exposure nearly 60 years in the past is still present and can be detected.”

The findings of Dr. Imaizumi and associates show that after radiation exposure, the risk of both malignant and benign thyroid disease “apparently lasts for life,” Dr. Boice said (JAMA 2006;295:1060–2).

The relationship between physicians and the makers of pharmaceuticals and medical devices now is so fraught with conflicts of interest that broad reforms regulating their interactions are essential, according to a group of medical ethics experts.

Industry-sponsored events, the dispensing of free samples and other “gifts” by detail people and drug reps, and lucrative “consultation” agreements are unmistakable ploys by drug and device makers to promote the use of their products. These practices have intensified in recent years to the point that they pose a “serious threat” to both physician integrity and patient welfare, Dr. Troyen A. Brennan of Harvard Medical School, Boston, and his 10 coauthors noted.

Existing guidelines of such groups as the American Medical Association, the American College of Physicians, and the Accreditation Council for Continuing Medical Education “are not sufficiently stringent” and allow both professionalism and patient care to be undermined. “The profession itself must exert much tighter control over the relationships between manufacturers and physicians,” Dr. Brennan and his associates said (JAMA 2006;295:429–33).

The group, whose work was sponsored by the American Board of Internal Medicine Foundation and the Institute on Medicine as a Profession, called for academic medical centers to take the lead in:

▸ Prohibiting all gifts to physicians including free samples, meals, payment for travel, and payment for time spent at meetings.

▸ Strictly regulating industry support of continuing medical education and prohibiting direct funding of CME meetings.

▸ Strictly regulating industry support of research.

▸ Strictly regulating hospital purchases of drugs and medical devices.

▸ Prohibiting faculty from serving on manufacturers' speakers' bureaus and from publishing material ghostwritten by industry employees.

Of the proposed reforms, the prohibition of gifts such as drug and device samples may have the greatest effect on physicians in private practice, if it is enacted.

Most physicians believe that detailers' gifts don't influence their prescribing behavior. But pharmaceutical companies would hardly spend some 90% of their $21 billion marketing budget on these and other practices if the strategies weren't successful in promoting their products, Dr. Brennan and his associates said.

“An overwhelming majority of interactions [with drug and device makers] had negative results on clinical care” in a recent review of the literature, the authors wrote. Prohibiting detailers' visits to physicians' offices will deprive manufacturers of “foot in the door” access that unduly influences physicians' choices of treatment, they added.

Two prominent cardiologists editorialized last year that, unquestionably, there is a powerful and well-organized effort by the pharmaceutical and device industries to co-opt vulnerable physicians (Circulation 2005;111:2552–4).

Dr. Thomas J. Ryan, senior consultant, emeritus chief of cardiology, and professor of medicine at Boston University, and Dr. Roman DeSanctis, emeritus director of clinical cardiology and Evelyn and James Jenks and Paul Dudley White Professor of Medicine, Harvard Medical School, said the resulting egregious professional behavior in medicine is unpardonable, but they also pointed out this behavior did not come about in isolation and has only paralleled changes in the culture and norms of society.

They recommended taking the billions of dollars spent on influencing doctor's prescribing habits and redirecting them to develop new rules of engagement between academic institutions and commercial entities that would undertake to translate policy into practice. They concluded that full disclosure and transparency in medical-industrial relationships should be the rule, not the exception.

But regardless of whether sampling should be eliminated, what goes on in a private practice is beyond the control of academic medical centers and the AMA, said Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, and chief of the cardiology section at the Veterans Affairs Medical Center in Fresno. And the practice simply doesn't exist in many academic institutions, such as UCSF, which neither accepts samples nor allows pharmaceutical representatives in the offices, he added.

Regarding pay for physicians' travel expenses to medical meetings, the editorial writers are ignoring the fact that trainees don't get financial support from their institutions as they once did, and that those institutions don't have the money to send them, said Dr. Deedwania.

Also unrealistic is the notion that CME can survive without industry support, said Dr. John Flack, professor and interim chair of the department of medicine and chief of the division of clinical epidemiology and translational research at Wayne State University, Detroit. “Without industry support, CME will become a thing of the past, because few entities can afford to pay for it.”

Nonetheless, many in the academic community have had a more positive response to the proposals, said Dr. Jordan J. Cohen, one of the JAMA report's coauthors and president of the Association of American Medical Colleges, Washington. The reforms will, of course, meet with resistance because they “represent a big change in practices that have been very widely accepted over a significant time, and frankly there's a significant amount of money in play here. I won't suggest that it would be at all easy to implement these changes, but it is looking possible,” he said.

Dr. David L. Coleman, interim chair of internal medicine at Yale University, New Haven, Conn., applauded Dr. Brennan's group for “stepping forward with a very bold set of recommendations.” Yale has already implemented strict guidelines prohibiting any gifts from industry representatives, any meals funded by industry, and any payment for attending CME meetings. The Yale guidelines are detailed in a report published in February (Acad. Med. 2006;81:154–60).

“I think banning food and gifts makes things a lot easier, frankly,” he said. “It's so nice to walk into a conference and not have to have that awkward conversation with a drug rep, and not have to feel squeamish about possible conflicts of interest.”

Most physicians interviewed agreed heartily with one proposed reform: ghostwriting. This should be controlled or eliminated, because some companies do influence the wording in research manuscripts, and busy investigators may go along with it, said Dr. Deedwania.

The relationship between physicians and the makers of pharmaceuticals and medical devices now is so fraught with conflicts of interest that broad reforms regulating their interactions are essential, according to a group of medical ethics experts.

Industry-sponsored events, the dispensing of free samples and other “gifts” by detail people and drug reps, and lucrative “consultation” agreements are unmistakable ploys by drug and device makers to promote the use of their products. These practices have intensified in recent years to the point that they pose a “serious threat” to both physician integrity and patient welfare, Dr. Troyen A. Brennan of Harvard Medical School, Boston, and his 10 coauthors noted.

Existing guidelines of such groups as the American Medical Association, the American College of Physicians, and the Accreditation Council for Continuing Medical Education “are not sufficiently stringent” and allow both professionalism and patient care to be undermined. “The profession itself must exert much tighter control over the relationships between manufacturers and physicians,” Dr. Brennan and his associates said (JAMA 2006;295:429–33).

The group, whose work was sponsored by the American Board of Internal Medicine Foundation and the Institute on Medicine as a Profession, called for academic medical centers to take the lead in:

▸ Prohibiting all gifts to physicians including free samples, meals, payment for travel, and payment for time spent at meetings.

▸ Strictly regulating industry support of continuing medical education and prohibiting direct funding of CME meetings.

▸ Strictly regulating industry support of research.

▸ Strictly regulating hospital purchases of drugs and medical devices.

▸ Prohibiting faculty from serving on manufacturers' speakers' bureaus and from publishing material ghostwritten by industry employees.

Of the proposed reforms, the prohibition of gifts such as drug and device samples may have the greatest effect on physicians in private practice, if it is enacted.

Most physicians believe that detailers' gifts don't influence their prescribing behavior. But pharmaceutical companies would hardly spend some 90% of their $21 billion marketing budget on these and other practices if the strategies weren't successful in promoting their products, Dr. Brennan and his associates said.

“An overwhelming majority of interactions [with drug and device makers] had negative results on clinical care” in a recent review of the literature, the authors wrote. Prohibiting detailers' visits to physicians' offices will deprive manufacturers of “foot in the door” access that unduly influences physicians' choices of treatment, they added.

Two prominent cardiologists editorialized last year that, unquestionably, there is a powerful and well-organized effort by the pharmaceutical and device industries to co-opt vulnerable physicians (Circulation 2005;111:2552–4).

Dr. Thomas J. Ryan, senior consultant, emeritus chief of cardiology, and professor of medicine at Boston University, and Dr. Roman DeSanctis, emeritus director of clinical cardiology and Evelyn and James Jenks and Paul Dudley White Professor of Medicine, Harvard Medical School, said the resulting egregious professional behavior in medicine is unpardonable, but they also pointed out this behavior did not come about in isolation and has only paralleled changes in the culture and norms of society.

They recommended taking the billions of dollars spent on influencing doctor's prescribing habits and redirecting them to develop new rules of engagement between academic institutions and commercial entities that would undertake to translate policy into practice. They concluded that full disclosure and transparency in medical-industrial relationships should be the rule, not the exception.

But regardless of whether sampling should be eliminated, what goes on in a private practice is beyond the control of academic medical centers and the AMA, said Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, and chief of the cardiology section at the Veterans Affairs Medical Center in Fresno. And the practice simply doesn't exist in many academic institutions, such as UCSF, which neither accepts samples nor allows pharmaceutical representatives in the offices, he added.

Regarding pay for physicians' travel expenses to medical meetings, the editorial writers are ignoring the fact that trainees don't get financial support from their institutions as they once did, and that those institutions don't have the money to send them, said Dr. Deedwania.

Also unrealistic is the notion that CME can survive without industry support, said Dr. John Flack, professor and interim chair of the department of medicine and chief of the division of clinical epidemiology and translational research at Wayne State University, Detroit. “Without industry support, CME will become a thing of the past, because few entities can afford to pay for it.”

Nonetheless, many in the academic community have had a more positive response to the proposals, said Dr. Jordan J. Cohen, one of the JAMA report's coauthors and president of the Association of American Medical Colleges, Washington. The reforms will, of course, meet with resistance because they “represent a big change in practices that have been very widely accepted over a significant time, and frankly there's a significant amount of money in play here. I won't suggest that it would be at all easy to implement these changes, but it is looking possible,” he said.

Dr. David L. Coleman, interim chair of internal medicine at Yale University, New Haven, Conn., applauded Dr. Brennan's group for “stepping forward with a very bold set of recommendations.” Yale has already implemented strict guidelines prohibiting any gifts from industry representatives, any meals funded by industry, and any payment for attending CME meetings. The Yale guidelines are detailed in a report published in February (Acad. Med. 2006;81:154–60).

“I think banning food and gifts makes things a lot easier, frankly,” he said. “It's so nice to walk into a conference and not have to have that awkward conversation with a drug rep, and not have to feel squeamish about possible conflicts of interest.”

Most physicians interviewed agreed heartily with one proposed reform: ghostwriting. This should be controlled or eliminated, because some companies do influence the wording in research manuscripts, and busy investigators may go along with it, said Dr. Deedwania.

The relationship between physicians and the makers of pharmaceuticals and medical devices now is so fraught with conflicts of interest that broad reforms regulating their interactions are essential, according to a group of medical ethics experts.

Industry-sponsored events, the dispensing of free samples and other “gifts” by detail people and drug reps, and lucrative “consultation” agreements are unmistakable ploys by drug and device makers to promote the use of their products. These practices have intensified in recent years to the point that they pose a “serious threat” to both physician integrity and patient welfare, Dr. Troyen A. Brennan of Harvard Medical School, Boston, and his 10 coauthors noted.

Existing guidelines of such groups as the American Medical Association, the American College of Physicians, and the Accreditation Council for Continuing Medical Education “are not sufficiently stringent” and allow both professionalism and patient care to be undermined. “The profession itself must exert much tighter control over the relationships between manufacturers and physicians,” Dr. Brennan and his associates said (JAMA 2006;295:429–33).

The group, whose work was sponsored by the American Board of Internal Medicine Foundation and the Institute on Medicine as a Profession, called for academic medical centers to take the lead in:

▸ Prohibiting all gifts to physicians including free samples, meals, payment for travel, and payment for time spent at meetings.

▸ Strictly regulating industry support of continuing medical education and prohibiting direct funding of CME meetings.

▸ Strictly regulating industry support of research.

▸ Strictly regulating hospital purchases of drugs and medical devices.

▸ Prohibiting faculty from serving on manufacturers' speakers' bureaus and from publishing material ghostwritten by industry employees.

Of the proposed reforms, the prohibition of gifts such as drug and device samples may have the greatest effect on physicians in private practice, if it is enacted.

Most physicians believe that detailers' gifts don't influence their prescribing behavior. But pharmaceutical companies would hardly spend some 90% of their $21 billion marketing budget on these and other practices if the strategies weren't successful in promoting their products, Dr. Brennan and his associates said.

“An overwhelming majority of interactions [with drug and device makers] had negative results on clinical care” in a recent review of the literature, the authors wrote. Prohibiting detailers' visits to physicians' offices will deprive manufacturers of “foot in the door” access that unduly influences physicians' choices of treatment, they added.

Two prominent cardiologists editorialized last year that, unquestionably, there is a powerful and well-organized effort by the pharmaceutical and device industries to co-opt vulnerable physicians (Circulation 2005;111:2552–4).

Dr. Thomas J. Ryan, senior consultant, emeritus chief of cardiology, and professor of medicine at Boston University, and Dr. Roman DeSanctis, emeritus director of clinical cardiology and Evelyn and James Jenks and Paul Dudley White Professor of Medicine, Harvard Medical School, said the resulting egregious professional behavior in medicine is unpardonable, but they also pointed out this behavior did not come about in isolation and has only paralleled changes in the culture and norms of society.

They recommended taking the billions of dollars spent on influencing doctor's prescribing habits and redirecting them to develop new rules of engagement between academic institutions and commercial entities that would undertake to translate policy into practice. They concluded that full disclosure and transparency in medical-industrial relationships should be the rule, not the exception.

But regardless of whether sampling should be eliminated, what goes on in a private practice is beyond the control of academic medical centers and the AMA, said Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, and chief of the cardiology section at the Veterans Affairs Medical Center in Fresno. And the practice simply doesn't exist in many academic institutions, such as UCSF, which neither accepts samples nor allows pharmaceutical representatives in the offices, he added.

Regarding pay for physicians' travel expenses to medical meetings, the editorial writers are ignoring the fact that trainees don't get financial support from their institutions as they once did, and that those institutions don't have the money to send them, said Dr. Deedwania.

Also unrealistic is the notion that CME can survive without industry support, said Dr. John Flack, professor and interim chair of the department of medicine and chief of the division of clinical epidemiology and translational research at Wayne State University, Detroit. “Without industry support, CME will become a thing of the past, because few entities can afford to pay for it.”

Nonetheless, many in the academic community have had a more positive response to the proposals, said Dr. Jordan J. Cohen, one of the JAMA report's coauthors and president of the Association of American Medical Colleges, Washington. The reforms will, of course, meet with resistance because they “represent a big change in practices that have been very widely accepted over a significant time, and frankly there's a significant amount of money in play here. I won't suggest that it would be at all easy to implement these changes, but it is looking possible,” he said.

Dr. David L. Coleman, interim chair of internal medicine at Yale University, New Haven, Conn., applauded Dr. Brennan's group for “stepping forward with a very bold set of recommendations.” Yale has already implemented strict guidelines prohibiting any gifts from industry representatives, any meals funded by industry, and any payment for attending CME meetings. The Yale guidelines are detailed in a report published in February (Acad. Med. 2006;81:154–60).

“I think banning food and gifts makes things a lot easier, frankly,” he said. “It's so nice to walk into a conference and not have to have that awkward conversation with a drug rep, and not have to feel squeamish about possible conflicts of interest.”

Most physicians interviewed agreed heartily with one proposed reform: ghostwriting. This should be controlled or eliminated, because some companies do influence the wording in research manuscripts, and busy investigators may go along with it, said Dr. Deedwania.

Hepatitis B vaccines, hepatitis B immunoglobulin, and a combination of the two all prevent the infection from developing in newborns of mothers who are positive for hepatitis B surface antigen, reported Chuanfang Lee, a clinical pharmacist at Copenhagen University Hospital, and associates.

The researchers conducted a metaanalysis of 26 randomized trials that evaluated vaccine or immunoglobulin effectiveness and included newborns. The average duration of follow-up was 19 months, with a range of 6–60 months.

Compared with placebo or no intervention, hepatitis B vaccination significantly decreased the risk of transmission of the infection from mother to newborn. There was no difference between plasma-derived and recombinant vaccines. “However, more infants who received recombinant vaccine achieved antibody levels to hepatitis surface antigen,” the investigators said (BMJ 2006 Jan. 27 [E-pub doi:10.1136/bmj.38719.435833.7C]).

There was no difference in effectiveness between high-dose and low-dose vaccine, or among different vaccination schedules. “Furthermore, our subgroup analyses did not show a strong association between timing of injection (within 12, 24, or 48 hours [of birth]) and magnitude of effects,” they said.

However, because the number of infants in these trials was small, larger trials are needed to confirm that all doses, schedules, and forms of vaccine are equivalent, the investigators cautioned.

Hepatitis B immunoglobulin also lowered the risk of infection, compared with placebo or no intervention. The vaccine plus immunoglobulin combination was superior to vaccine alone. Few of the trials reported adverse events, so a metaanalysis of adverse events could not be carried out.

Hepatitis B vaccines, hepatitis B immunoglobulin, and a combination of the two all prevent the infection from developing in newborns of mothers who are positive for hepatitis B surface antigen, reported Chuanfang Lee, a clinical pharmacist at Copenhagen University Hospital, and associates.

The researchers conducted a metaanalysis of 26 randomized trials that evaluated vaccine or immunoglobulin effectiveness and included newborns. The average duration of follow-up was 19 months, with a range of 6–60 months.

Compared with placebo or no intervention, hepatitis B vaccination significantly decreased the risk of transmission of the infection from mother to newborn. There was no difference between plasma-derived and recombinant vaccines. “However, more infants who received recombinant vaccine achieved antibody levels to hepatitis surface antigen,” the investigators said (BMJ 2006 Jan. 27 [E-pub doi:10.1136/bmj.38719.435833.7C]).

There was no difference in effectiveness between high-dose and low-dose vaccine, or among different vaccination schedules. “Furthermore, our subgroup analyses did not show a strong association between timing of injection (within 12, 24, or 48 hours [of birth]) and magnitude of effects,” they said.

However, because the number of infants in these trials was small, larger trials are needed to confirm that all doses, schedules, and forms of vaccine are equivalent, the investigators cautioned.

Hepatitis B immunoglobulin also lowered the risk of infection, compared with placebo or no intervention. The vaccine plus immunoglobulin combination was superior to vaccine alone. Few of the trials reported adverse events, so a metaanalysis of adverse events could not be carried out.

Hepatitis B vaccines, hepatitis B immunoglobulin, and a combination of the two all prevent the infection from developing in newborns of mothers who are positive for hepatitis B surface antigen, reported Chuanfang Lee, a clinical pharmacist at Copenhagen University Hospital, and associates.

The researchers conducted a metaanalysis of 26 randomized trials that evaluated vaccine or immunoglobulin effectiveness and included newborns. The average duration of follow-up was 19 months, with a range of 6–60 months.

Compared with placebo or no intervention, hepatitis B vaccination significantly decreased the risk of transmission of the infection from mother to newborn. There was no difference between plasma-derived and recombinant vaccines. “However, more infants who received recombinant vaccine achieved antibody levels to hepatitis surface antigen,” the investigators said (BMJ 2006 Jan. 27 [E-pub doi:10.1136/bmj.38719.435833.7C]).

There was no difference in effectiveness between high-dose and low-dose vaccine, or among different vaccination schedules. “Furthermore, our subgroup analyses did not show a strong association between timing of injection (within 12, 24, or 48 hours [of birth]) and magnitude of effects,” they said.

However, because the number of infants in these trials was small, larger trials are needed to confirm that all doses, schedules, and forms of vaccine are equivalent, the investigators cautioned.

Hepatitis B immunoglobulin also lowered the risk of infection, compared with placebo or no intervention. The vaccine plus immunoglobulin combination was superior to vaccine alone. Few of the trials reported adverse events, so a metaanalysis of adverse events could not be carried out.

Total thyroidectomy can be performed more safely than many clinicians realize, and offers more durable results for people with Grave's disease than do antithyroid drugs or radioiodine, according to Dr. Kaare J. Weber of Mount Sinai School of Medicine, New York, and his associates.

The researchers reviewed the records of all 48 patients who underwent total thyroidectomy for Grave's disease at their hospital between 1993 and 2005. All but seven of the patients were women, and the mean age was 40 years. All had typical symptoms including palpitations, eye disturbances, anxiety, weight loss, heat intolerance, and tremor.

Of this group, 24 patients had failed on medical therapy with or without radioiodine. Another 12 had refused radioiodine because of concerns about radiation exposure. The remaining 12 chose surgery for assessment of thyroid nodules that were presumed to be related to their disease.

After thyroidectomy and a mean of 40 months of follow-up, there were no recurrences of hyperthyroidism. In contrast, relapse rates of 20%–75% are cited in the literature for medical therapy, Dr. Weber and his associates said (Am. J. Surg. 2006;191:400–5).

Of the 20 patients who had mild or severe ophthalmopathy before surgery, 11 showed marked improvement or resolution of eye disorders and the remaining 9 showed either improvement or stabilization. In contrast, radioiodine treatment has been associated with the onset or exacerbation of ophthalmopathy, they said.

Eight patients (17%) were found to have papillary cancer of the thyroid at surgery. “These patients would not have received appropriate treatment for their coexisting cancer if they were treated only with antithyroid drugs and/or radioiodine,” the investigators noted.

No patients suffered permanent laryngeal nerve injury from the procedure. Complications included three cases of transient hypocalcemia and one case of temporary right vocal cord paralysis. Only one patient developed permanent hypoparathyroidism, and that case “followed a previous failed [thyroid] exploration at another institution,” they said.

“Despite today's methods for a safe thyroidectomy, concern over permanent recurrent laryngeal nerve injury and permanent hypoparathyroidism as a result of the hypervascularity of the thyroid gland prevents some physicians from recommending surgical therapy for Grave's disease,” Dr. Weber and his associates said.

These results demonstrate that total thyroidectomy now can be performed safely, with little of the morbidity and mortality that occurred when the procedure was first developed years ago.

In addition, thyroidectomy addresses potentially cancerous nodules, as medical and radioiodine therapies do not, they said.

Total thyroidectomy can be performed more safely than many clinicians realize, and offers more durable results for people with Grave's disease than do antithyroid drugs or radioiodine, according to Dr. Kaare J. Weber of Mount Sinai School of Medicine, New York, and his associates.

The researchers reviewed the records of all 48 patients who underwent total thyroidectomy for Grave's disease at their hospital between 1993 and 2005. All but seven of the patients were women, and the mean age was 40 years. All had typical symptoms including palpitations, eye disturbances, anxiety, weight loss, heat intolerance, and tremor.

Of this group, 24 patients had failed on medical therapy with or without radioiodine. Another 12 had refused radioiodine because of concerns about radiation exposure. The remaining 12 chose surgery for assessment of thyroid nodules that were presumed to be related to their disease.

After thyroidectomy and a mean of 40 months of follow-up, there were no recurrences of hyperthyroidism. In contrast, relapse rates of 20%–75% are cited in the literature for medical therapy, Dr. Weber and his associates said (Am. J. Surg. 2006;191:400–5).

Of the 20 patients who had mild or severe ophthalmopathy before surgery, 11 showed marked improvement or resolution of eye disorders and the remaining 9 showed either improvement or stabilization. In contrast, radioiodine treatment has been associated with the onset or exacerbation of ophthalmopathy, they said.

Eight patients (17%) were found to have papillary cancer of the thyroid at surgery. “These patients would not have received appropriate treatment for their coexisting cancer if they were treated only with antithyroid drugs and/or radioiodine,” the investigators noted.

No patients suffered permanent laryngeal nerve injury from the procedure. Complications included three cases of transient hypocalcemia and one case of temporary right vocal cord paralysis. Only one patient developed permanent hypoparathyroidism, and that case “followed a previous failed [thyroid] exploration at another institution,” they said.

“Despite today's methods for a safe thyroidectomy, concern over permanent recurrent laryngeal nerve injury and permanent hypoparathyroidism as a result of the hypervascularity of the thyroid gland prevents some physicians from recommending surgical therapy for Grave's disease,” Dr. Weber and his associates said.

These results demonstrate that total thyroidectomy now can be performed safely, with little of the morbidity and mortality that occurred when the procedure was first developed years ago.

In addition, thyroidectomy addresses potentially cancerous nodules, as medical and radioiodine therapies do not, they said.

Total thyroidectomy can be performed more safely than many clinicians realize, and offers more durable results for people with Grave's disease than do antithyroid drugs or radioiodine, according to Dr. Kaare J. Weber of Mount Sinai School of Medicine, New York, and his associates.

The researchers reviewed the records of all 48 patients who underwent total thyroidectomy for Grave's disease at their hospital between 1993 and 2005. All but seven of the patients were women, and the mean age was 40 years. All had typical symptoms including palpitations, eye disturbances, anxiety, weight loss, heat intolerance, and tremor.

Of this group, 24 patients had failed on medical therapy with or without radioiodine. Another 12 had refused radioiodine because of concerns about radiation exposure. The remaining 12 chose surgery for assessment of thyroid nodules that were presumed to be related to their disease.

After thyroidectomy and a mean of 40 months of follow-up, there were no recurrences of hyperthyroidism. In contrast, relapse rates of 20%–75% are cited in the literature for medical therapy, Dr. Weber and his associates said (Am. J. Surg. 2006;191:400–5).

Of the 20 patients who had mild or severe ophthalmopathy before surgery, 11 showed marked improvement or resolution of eye disorders and the remaining 9 showed either improvement or stabilization. In contrast, radioiodine treatment has been associated with the onset or exacerbation of ophthalmopathy, they said.

Eight patients (17%) were found to have papillary cancer of the thyroid at surgery. “These patients would not have received appropriate treatment for their coexisting cancer if they were treated only with antithyroid drugs and/or radioiodine,” the investigators noted.

No patients suffered permanent laryngeal nerve injury from the procedure. Complications included three cases of transient hypocalcemia and one case of temporary right vocal cord paralysis. Only one patient developed permanent hypoparathyroidism, and that case “followed a previous failed [thyroid] exploration at another institution,” they said.

“Despite today's methods for a safe thyroidectomy, concern over permanent recurrent laryngeal nerve injury and permanent hypoparathyroidism as a result of the hypervascularity of the thyroid gland prevents some physicians from recommending surgical therapy for Grave's disease,” Dr. Weber and his associates said.

These results demonstrate that total thyroidectomy now can be performed safely, with little of the morbidity and mortality that occurred when the procedure was first developed years ago.

In addition, thyroidectomy addresses potentially cancerous nodules, as medical and radioiodine therapies do not, they said.