Robert Finn

SANTA MONICA, CALIF. — Fertility-sparing trachelectomy is a safe and effective option for carefully selected women with cervical cancer, Dr. John H. Shepherd reported at the biennial meeting of the International Gynecologic Cancer Society.

In a case series of 141 women treated with this surgery between 1994 and 2006, so far there have been 69 pregnancies, 33 live births, and only 4 recurrences of cancer, said Dr. Shepherd of St. Bartholomew's Hospital, London.

According to Dr. Shepherd, the principle of the operation is to remove the cervix, the lower cervical tissue up to the uterine isthmus, and the upper 2 cm of the vagina. The procedure preserves the body of the uterus. “Our standard is to put in a cervical cerclage—or we can call it an isthmic cerclage—into the remaining isthmus before performing a vaginal-isthmic anastomosis and restoring the continuity of the birth canal,” he said.

The procedure is appropriate for women whose cancer is in stage Ia2, stage Ib1, and for selected cases that are at stage IIa. In addition to the stage, consideration should be given to the size of the tumor, its pathology and grade, the age of the woman, the status of her lymph nodes and whether there has been lymphovascular space invasion, her fertility status, any comorbidities, and, of course, her wishes.

Among the 141 women who elected the procedure, the average age was 31 years. Almost all—98%—had stage Ib1 disease. Two of the women had stage Ia2 disease with poor prognoses, and one had stage IIa disease. About one-third of the women had lymphovascular space invasion. Histologic type was squamous in 64% of the women, adenocarcinoma in 31%, adenosquamous in 3%, and other in 3% (percentages exceed 100% because of rounding).

After final pathology, physicians recommended completion treatment for 19 of the women (13%), with most opting for chemotherapy and radiotherapy. One woman with a single positive lymph node refused completion treatment, went on to have a child, and has had no recurrences after 3 years. Two patients with close margins also refused completion treatment.

There have been relatively few surgical complications, and Dr. Shepherd said that even those few have declined as the surgical team ascended the learning curve. Ureteric damage and uterine perforation were the most common perioperative complications. Two of the three cases of ureteric damage were caused by extensive microscopic disease involving the bladder that was not detected prior to surgery. Both uterine perforations were caused by overzealous insertion of cervical sounds.

Other complications included seven cases of isthmic stenosis, five cases of temporary thigh numbness, four cases of stitch expulsion, and three cases of amenorrhea. In all, there were 24 women with fertility issues after surgery. Among these were the seven women with isthmic stenosis, who required dilatation; two cases of apareunia, probably psychosexual in nature; three cases of endometriosis; and six cases that required in vitro fertilization.

So far there have been 33 pregnancies among 24 of the 141 women in the series. Of the 27 miscarriages, 16 occurred in the first trimester and 11 occurred in the second. At the time of Dr. Shepherd's talk, four additional women have become pregnant.

“We have a significant prematurity rate, [approximately one-fourth of which] I would regard as severe prematurity [24–31 weeks],” Dr. Shepherd said. “This is probably related to the extent of the surgery we decided to carry out up to the isthmus.” An additional fourth of the women delivered between 32 and 35 weeks, and the remaining 50% delivered successfully by classical cesarean section at 36–38 weeks.

“Premature delivery we believe is initiated by premature spontaneous rupture of membranes, and this is due to the absence of a cervical plug leading to ascending infection,” he said. “We would recommend that antibiotics in the second trimester should be considered.”

SANTA MONICA, CALIF. — Fertility-sparing trachelectomy is a safe and effective option for carefully selected women with cervical cancer, Dr. John H. Shepherd reported at the biennial meeting of the International Gynecologic Cancer Society.

In a case series of 141 women treated with this surgery between 1994 and 2006, so far there have been 69 pregnancies, 33 live births, and only 4 recurrences of cancer, said Dr. Shepherd of St. Bartholomew's Hospital, London.

According to Dr. Shepherd, the principle of the operation is to remove the cervix, the lower cervical tissue up to the uterine isthmus, and the upper 2 cm of the vagina. The procedure preserves the body of the uterus. “Our standard is to put in a cervical cerclage—or we can call it an isthmic cerclage—into the remaining isthmus before performing a vaginal-isthmic anastomosis and restoring the continuity of the birth canal,” he said.

The procedure is appropriate for women whose cancer is in stage Ia2, stage Ib1, and for selected cases that are at stage IIa. In addition to the stage, consideration should be given to the size of the tumor, its pathology and grade, the age of the woman, the status of her lymph nodes and whether there has been lymphovascular space invasion, her fertility status, any comorbidities, and, of course, her wishes.

Among the 141 women who elected the procedure, the average age was 31 years. Almost all—98%—had stage Ib1 disease. Two of the women had stage Ia2 disease with poor prognoses, and one had stage IIa disease. About one-third of the women had lymphovascular space invasion. Histologic type was squamous in 64% of the women, adenocarcinoma in 31%, adenosquamous in 3%, and other in 3% (percentages exceed 100% because of rounding).

After final pathology, physicians recommended completion treatment for 19 of the women (13%), with most opting for chemotherapy and radiotherapy. One woman with a single positive lymph node refused completion treatment, went on to have a child, and has had no recurrences after 3 years. Two patients with close margins also refused completion treatment.

There have been relatively few surgical complications, and Dr. Shepherd said that even those few have declined as the surgical team ascended the learning curve. Ureteric damage and uterine perforation were the most common perioperative complications. Two of the three cases of ureteric damage were caused by extensive microscopic disease involving the bladder that was not detected prior to surgery. Both uterine perforations were caused by overzealous insertion of cervical sounds.

Other complications included seven cases of isthmic stenosis, five cases of temporary thigh numbness, four cases of stitch expulsion, and three cases of amenorrhea. In all, there were 24 women with fertility issues after surgery. Among these were the seven women with isthmic stenosis, who required dilatation; two cases of apareunia, probably psychosexual in nature; three cases of endometriosis; and six cases that required in vitro fertilization.

So far there have been 33 pregnancies among 24 of the 141 women in the series. Of the 27 miscarriages, 16 occurred in the first trimester and 11 occurred in the second. At the time of Dr. Shepherd's talk, four additional women have become pregnant.

“We have a significant prematurity rate, [approximately one-fourth of which] I would regard as severe prematurity [24–31 weeks],” Dr. Shepherd said. “This is probably related to the extent of the surgery we decided to carry out up to the isthmus.” An additional fourth of the women delivered between 32 and 35 weeks, and the remaining 50% delivered successfully by classical cesarean section at 36–38 weeks.

“Premature delivery we believe is initiated by premature spontaneous rupture of membranes, and this is due to the absence of a cervical plug leading to ascending infection,” he said. “We would recommend that antibiotics in the second trimester should be considered.”

SANTA MONICA, CALIF. — Fertility-sparing trachelectomy is a safe and effective option for carefully selected women with cervical cancer, Dr. John H. Shepherd reported at the biennial meeting of the International Gynecologic Cancer Society.

In a case series of 141 women treated with this surgery between 1994 and 2006, so far there have been 69 pregnancies, 33 live births, and only 4 recurrences of cancer, said Dr. Shepherd of St. Bartholomew's Hospital, London.

According to Dr. Shepherd, the principle of the operation is to remove the cervix, the lower cervical tissue up to the uterine isthmus, and the upper 2 cm of the vagina. The procedure preserves the body of the uterus. “Our standard is to put in a cervical cerclage—or we can call it an isthmic cerclage—into the remaining isthmus before performing a vaginal-isthmic anastomosis and restoring the continuity of the birth canal,” he said.

The procedure is appropriate for women whose cancer is in stage Ia2, stage Ib1, and for selected cases that are at stage IIa. In addition to the stage, consideration should be given to the size of the tumor, its pathology and grade, the age of the woman, the status of her lymph nodes and whether there has been lymphovascular space invasion, her fertility status, any comorbidities, and, of course, her wishes.

Among the 141 women who elected the procedure, the average age was 31 years. Almost all—98%—had stage Ib1 disease. Two of the women had stage Ia2 disease with poor prognoses, and one had stage IIa disease. About one-third of the women had lymphovascular space invasion. Histologic type was squamous in 64% of the women, adenocarcinoma in 31%, adenosquamous in 3%, and other in 3% (percentages exceed 100% because of rounding).

After final pathology, physicians recommended completion treatment for 19 of the women (13%), with most opting for chemotherapy and radiotherapy. One woman with a single positive lymph node refused completion treatment, went on to have a child, and has had no recurrences after 3 years. Two patients with close margins also refused completion treatment.

There have been relatively few surgical complications, and Dr. Shepherd said that even those few have declined as the surgical team ascended the learning curve. Ureteric damage and uterine perforation were the most common perioperative complications. Two of the three cases of ureteric damage were caused by extensive microscopic disease involving the bladder that was not detected prior to surgery. Both uterine perforations were caused by overzealous insertion of cervical sounds.

Other complications included seven cases of isthmic stenosis, five cases of temporary thigh numbness, four cases of stitch expulsion, and three cases of amenorrhea. In all, there were 24 women with fertility issues after surgery. Among these were the seven women with isthmic stenosis, who required dilatation; two cases of apareunia, probably psychosexual in nature; three cases of endometriosis; and six cases that required in vitro fertilization.

So far there have been 33 pregnancies among 24 of the 141 women in the series. Of the 27 miscarriages, 16 occurred in the first trimester and 11 occurred in the second. At the time of Dr. Shepherd's talk, four additional women have become pregnant.

“We have a significant prematurity rate, [approximately one-fourth of which] I would regard as severe prematurity [24–31 weeks],” Dr. Shepherd said. “This is probably related to the extent of the surgery we decided to carry out up to the isthmus.” An additional fourth of the women delivered between 32 and 35 weeks, and the remaining 50% delivered successfully by classical cesarean section at 36–38 weeks.

“Premature delivery we believe is initiated by premature spontaneous rupture of membranes, and this is due to the absence of a cervical plug leading to ascending infection,” he said. “We would recommend that antibiotics in the second trimester should be considered.”

Adherence to a Mediterranean diet is associated with reduced risk for Alzheimer's disease, and supplementation with omega-3 fatty acids appears to slow the progression of mild forms of the disease, according to two separate studies appearing in Archives of Neurology.

In a case-control study involving 1,984 people (average age 76.3 years), a greater degree of adherence to the Mediterranean diet was associated with a significantly lower risk of Alzheimer's disease, according to the article, which appeared online on Oct. 9, 2006. The investigators, led by Dr. Nikolaos Scarmeas of Columbia University in New York, assessed adherence to the Mediterranean diet on a 9-point scale (Arch. Neurol. 2006 [Epub doi10.1001/archneur.63.12.noc60109]).

Participants were questioned extensively about their diets over the previous year, and points could be accumulated for eating more than the median amount of fish, vegetables, legumes, and cereals; for eating less than the median amount of dairy, meat, and fat; and for drinking a moderate amount of alcohol.

Compared with people whose diets scored in the lower third of similarity to the Mediterranean diet, those with diets in the upper third were 69% less likely to have Alzheimer's. These results were adjusted for many factors, including age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, smoking, body mass index, and history of stroke, diabetes, hypertension, heart disease, and lipid levels.

The investigators found it noteworthy that their inclusion of a long list of vascular variables did not change the risk analysis. This finding indicates that the effect of the Mediterranean diet on Alzheimer's disease risk may be mediated by nonvascular mechanisms such as oxidation or inflammation. Indeed, other studies have determined that components of the Mediterranean diet decrease markers of oxidative stress and inflammation.

The investigators acknowledged that there may be several alternative explanations for their findings. For example, degree of adherence to the Mediterranean diet could represent a consequence and not a cause of Alzheimer's disease.

The study on omega-3 fatty acids, published in the October 2006 issue of Archives of Neurology, was a randomized, placebo-controlled, double-blind clinical trial involving 204 people with Alzheimer's. Investigators at the Karolinska Institute, Stockholm, led by Dr. Yvonne Freund-Levi, randomized patients to receive 1.7 g of docosahexaenoic acid (DHA) and 0.6 g of eicosapentaenoic acid (EPA) or placebo daily for 6 months. At the end of 6 months, patients in both arms received the omega-3 fatty acids daily for an additional 6 months (Arch. Neurol. 2006;63:1402–8).

After the first 6 months there was no statistically significant difference between the two groups on the two measures of cognitive decline–the Mini-Mental State Examination (MMSE) and the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-COG).

However, when investigators examined a subset of the patients–32 patients with very mild Alzheimer's disease–those receiving omega-3 fatty acid supplementation showed no decline in MMSE scores over 6 months, while the ones receiving placebo had a statistically significant decline.

Furthermore, during the next 6 months, when patients in the group formerly receiving placebo were switched to omega-3 supplementation, they had a similar slowing in cognitive decline.

The findings from this controlled trial are in agreement with results from earlier epidemiologic studies suggesting that a high intake of DHA-rich fish reduces the risk of developing Alzheimer's disease.

Although it is not known why omega-3 fatty acids may interfere with the progression of Alzheimer's disease, the investigators suggested that the anti-inflammatory effects of these agents may play a role.

Other epidemiologic evidence suggests that there may be a critical period of about 2 years before the onset of dementia during which the brain may be especially sensitive to anti-inflammatory agents.

The investigators cautioned, however, that their findings “cannot serve as a basis for general recommendations for treatment of [Alzheimer's disease] with dietary DHA-rich fish oil preparations,” and that larger studies in patients with mild cognitive impairment are needed.

Adherence to a Mediterranean diet is associated with reduced risk for Alzheimer's disease, and supplementation with omega-3 fatty acids appears to slow the progression of mild forms of the disease, according to two separate studies appearing in Archives of Neurology.

In a case-control study involving 1,984 people (average age 76.3 years), a greater degree of adherence to the Mediterranean diet was associated with a significantly lower risk of Alzheimer's disease, according to the article, which appeared online on Oct. 9, 2006. The investigators, led by Dr. Nikolaos Scarmeas of Columbia University in New York, assessed adherence to the Mediterranean diet on a 9-point scale (Arch. Neurol. 2006 [Epub doi10.1001/archneur.63.12.noc60109]).

Participants were questioned extensively about their diets over the previous year, and points could be accumulated for eating more than the median amount of fish, vegetables, legumes, and cereals; for eating less than the median amount of dairy, meat, and fat; and for drinking a moderate amount of alcohol.

Compared with people whose diets scored in the lower third of similarity to the Mediterranean diet, those with diets in the upper third were 69% less likely to have Alzheimer's. These results were adjusted for many factors, including age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, smoking, body mass index, and history of stroke, diabetes, hypertension, heart disease, and lipid levels.

The investigators found it noteworthy that their inclusion of a long list of vascular variables did not change the risk analysis. This finding indicates that the effect of the Mediterranean diet on Alzheimer's disease risk may be mediated by nonvascular mechanisms such as oxidation or inflammation. Indeed, other studies have determined that components of the Mediterranean diet decrease markers of oxidative stress and inflammation.

The investigators acknowledged that there may be several alternative explanations for their findings. For example, degree of adherence to the Mediterranean diet could represent a consequence and not a cause of Alzheimer's disease.

The study on omega-3 fatty acids, published in the October 2006 issue of Archives of Neurology, was a randomized, placebo-controlled, double-blind clinical trial involving 204 people with Alzheimer's. Investigators at the Karolinska Institute, Stockholm, led by Dr. Yvonne Freund-Levi, randomized patients to receive 1.7 g of docosahexaenoic acid (DHA) and 0.6 g of eicosapentaenoic acid (EPA) or placebo daily for 6 months. At the end of 6 months, patients in both arms received the omega-3 fatty acids daily for an additional 6 months (Arch. Neurol. 2006;63:1402–8).

After the first 6 months there was no statistically significant difference between the two groups on the two measures of cognitive decline–the Mini-Mental State Examination (MMSE) and the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-COG).

However, when investigators examined a subset of the patients–32 patients with very mild Alzheimer's disease–those receiving omega-3 fatty acid supplementation showed no decline in MMSE scores over 6 months, while the ones receiving placebo had a statistically significant decline.

Furthermore, during the next 6 months, when patients in the group formerly receiving placebo were switched to omega-3 supplementation, they had a similar slowing in cognitive decline.

The findings from this controlled trial are in agreement with results from earlier epidemiologic studies suggesting that a high intake of DHA-rich fish reduces the risk of developing Alzheimer's disease.

Although it is not known why omega-3 fatty acids may interfere with the progression of Alzheimer's disease, the investigators suggested that the anti-inflammatory effects of these agents may play a role.

Other epidemiologic evidence suggests that there may be a critical period of about 2 years before the onset of dementia during which the brain may be especially sensitive to anti-inflammatory agents.

The investigators cautioned, however, that their findings “cannot serve as a basis for general recommendations for treatment of [Alzheimer's disease] with dietary DHA-rich fish oil preparations,” and that larger studies in patients with mild cognitive impairment are needed.

Adherence to a Mediterranean diet is associated with reduced risk for Alzheimer's disease, and supplementation with omega-3 fatty acids appears to slow the progression of mild forms of the disease, according to two separate studies appearing in Archives of Neurology.

In a case-control study involving 1,984 people (average age 76.3 years), a greater degree of adherence to the Mediterranean diet was associated with a significantly lower risk of Alzheimer's disease, according to the article, which appeared online on Oct. 9, 2006. The investigators, led by Dr. Nikolaos Scarmeas of Columbia University in New York, assessed adherence to the Mediterranean diet on a 9-point scale (Arch. Neurol. 2006 [Epub doi10.1001/archneur.63.12.noc60109]).

Participants were questioned extensively about their diets over the previous year, and points could be accumulated for eating more than the median amount of fish, vegetables, legumes, and cereals; for eating less than the median amount of dairy, meat, and fat; and for drinking a moderate amount of alcohol.

Compared with people whose diets scored in the lower third of similarity to the Mediterranean diet, those with diets in the upper third were 69% less likely to have Alzheimer's. These results were adjusted for many factors, including age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, smoking, body mass index, and history of stroke, diabetes, hypertension, heart disease, and lipid levels.

The investigators found it noteworthy that their inclusion of a long list of vascular variables did not change the risk analysis. This finding indicates that the effect of the Mediterranean diet on Alzheimer's disease risk may be mediated by nonvascular mechanisms such as oxidation or inflammation. Indeed, other studies have determined that components of the Mediterranean diet decrease markers of oxidative stress and inflammation.

The investigators acknowledged that there may be several alternative explanations for their findings. For example, degree of adherence to the Mediterranean diet could represent a consequence and not a cause of Alzheimer's disease.

The study on omega-3 fatty acids, published in the October 2006 issue of Archives of Neurology, was a randomized, placebo-controlled, double-blind clinical trial involving 204 people with Alzheimer's. Investigators at the Karolinska Institute, Stockholm, led by Dr. Yvonne Freund-Levi, randomized patients to receive 1.7 g of docosahexaenoic acid (DHA) and 0.6 g of eicosapentaenoic acid (EPA) or placebo daily for 6 months. At the end of 6 months, patients in both arms received the omega-3 fatty acids daily for an additional 6 months (Arch. Neurol. 2006;63:1402–8).

After the first 6 months there was no statistically significant difference between the two groups on the two measures of cognitive decline–the Mini-Mental State Examination (MMSE) and the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-COG).

However, when investigators examined a subset of the patients–32 patients with very mild Alzheimer's disease–those receiving omega-3 fatty acid supplementation showed no decline in MMSE scores over 6 months, while the ones receiving placebo had a statistically significant decline.

Furthermore, during the next 6 months, when patients in the group formerly receiving placebo were switched to omega-3 supplementation, they had a similar slowing in cognitive decline.

The findings from this controlled trial are in agreement with results from earlier epidemiologic studies suggesting that a high intake of DHA-rich fish reduces the risk of developing Alzheimer's disease.

Although it is not known why omega-3 fatty acids may interfere with the progression of Alzheimer's disease, the investigators suggested that the anti-inflammatory effects of these agents may play a role.

Other epidemiologic evidence suggests that there may be a critical period of about 2 years before the onset of dementia during which the brain may be especially sensitive to anti-inflammatory agents.

The investigators cautioned, however, that their findings “cannot serve as a basis for general recommendations for treatment of [Alzheimer's disease] with dietary DHA-rich fish oil preparations,” and that larger studies in patients with mild cognitive impairment are needed.

ATLANTA — Current sets of criteria for diagnosing metabolic syndrome fail to identify many African American patients at increased risk of cardiovascular disease and diabetes, said Dr. Anne E. Sumner in a presentation given at a meeting sponsored by the International Society on Hypertension in Blacks.

The three sets of diagnostic criteria currently in use all list triglyceride levels in excess of 150 mg/dL as one sign that a patient has the metabolic syndrome. But studies show that even obese and insulin-resistant African Americans can have low triglyceride levels, Dr. Sumner, a diabetes expert at the National Institutes of Health, said in her presentation.

“The inclusion of triglyceride [levels] in the metabolic syndrome leads to the exclusion of a significant proportion of insulin-resistant African Americans,” Dr. Sumner said. Excluding elevated triglycerides from the metabolic syndrome criteria would “lead to the inclusion of a significant proportion of insulin-resistant African Americans.”

Dr. Sumner relied on several clinical studies to support her conclusion. Data from the National Health and Nutrition Examination Survey (NHANES) show that both African American men and women have a significantly higher prevalence of cardiovascular disease and diabetes than do whites. Despite that, NHANES data show that African American men and women at all body-mass index levels have lower rates of metabolic syndrome than do whites.

Dr. Sumner emphasized that the data supporting her comments are preliminary and have not yet been peer reviewed.

Preliminary results from the Triglyceride and Cardiovascular Risk in African Americans (TARA) study, for which Dr. Sumner is a principal investigator, show that even African Americans with very high BMIs and very high levels of insulin resistance can have very low levels of triglycerides.

She pointed in particular to 2 women among the 210 African Americans so far enrolled in the study. One has a BMI of 55 kg/m

Of the African Americans in the study, 30% are insulin resistant, but only 2% have elevated triglycerides. In comparison, data from other studies show that about 60% of whites with insulin resistance have elevated triglycerides.

Dr. Sumner obtained similar results from her as-yet-unpublished analysis of NHANES data. She examined data from a cohort of 2,804 persons, aged 20–70, composed of 569 non-Hispanic blacks, 1,485 non-Hispanic whites, and 750 Mexican Americans. She divided the entire cohort into thirds based on their homeostasis model assessment (HOMA) scores, a surrogate for insulin resistance. Of the patients with the highest HOMA scores, the blacks had significantly lower triglyceride levels than either the whites or the Mexican Americans. This held true for both men and women as well as for individuals who were obese, overweight, and of normal weight.

Although triglyceride levels do have a direct relationship with insulin resistance, the absence of high triglyceride levels in African Americans does not mean the absence of insulin resistance. Therefore, any system that relies on triglyceride levels as a marker for insulin resistance risks underdiagnosis in African Americans.

“In blacks, the danger of underdiagnosis is the lost opportunity for the prevention of diseases related to insulin resistance, particularly diabetes and heart disease,” Dr. Sumner said.

She suggested that the solution is to develop criteria for “triglyceride-absent metabolic syndrome” to be used in African Americans and to test prospectively whether requiring just two of the four remaining criteria (waist circumference, hypertension, low HDL cholesterol, and high fasting glucose) for diagnosis of metabolic syndrome would accurately predict the onset of diabetes or cardiovascular disease.

For the individuals in her TARA study, the definition of metabolic syndrome developed by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) results in a prevalence of 11%, a sensitivity of 21%, and a specificity of 97%. On the other hand, using the triglyceride-absent definition, the prevalence would be 30%, the sensitivity would be 53%, and the specificity would be 81%.

“I felt this [triglyceride-absent definition] was a minimalist approach to the changing of the metabolic syndrome with the smallest perturbation,” Dr. Sumner said.

ATLANTA — Current sets of criteria for diagnosing metabolic syndrome fail to identify many African American patients at increased risk of cardiovascular disease and diabetes, said Dr. Anne E. Sumner in a presentation given at a meeting sponsored by the International Society on Hypertension in Blacks.

The three sets of diagnostic criteria currently in use all list triglyceride levels in excess of 150 mg/dL as one sign that a patient has the metabolic syndrome. But studies show that even obese and insulin-resistant African Americans can have low triglyceride levels, Dr. Sumner, a diabetes expert at the National Institutes of Health, said in her presentation.

“The inclusion of triglyceride [levels] in the metabolic syndrome leads to the exclusion of a significant proportion of insulin-resistant African Americans,” Dr. Sumner said. Excluding elevated triglycerides from the metabolic syndrome criteria would “lead to the inclusion of a significant proportion of insulin-resistant African Americans.”

Dr. Sumner relied on several clinical studies to support her conclusion. Data from the National Health and Nutrition Examination Survey (NHANES) show that both African American men and women have a significantly higher prevalence of cardiovascular disease and diabetes than do whites. Despite that, NHANES data show that African American men and women at all body-mass index levels have lower rates of metabolic syndrome than do whites.

Dr. Sumner emphasized that the data supporting her comments are preliminary and have not yet been peer reviewed.

Preliminary results from the Triglyceride and Cardiovascular Risk in African Americans (TARA) study, for which Dr. Sumner is a principal investigator, show that even African Americans with very high BMIs and very high levels of insulin resistance can have very low levels of triglycerides.

She pointed in particular to 2 women among the 210 African Americans so far enrolled in the study. One has a BMI of 55 kg/m

Of the African Americans in the study, 30% are insulin resistant, but only 2% have elevated triglycerides. In comparison, data from other studies show that about 60% of whites with insulin resistance have elevated triglycerides.

Dr. Sumner obtained similar results from her as-yet-unpublished analysis of NHANES data. She examined data from a cohort of 2,804 persons, aged 20–70, composed of 569 non-Hispanic blacks, 1,485 non-Hispanic whites, and 750 Mexican Americans. She divided the entire cohort into thirds based on their homeostasis model assessment (HOMA) scores, a surrogate for insulin resistance. Of the patients with the highest HOMA scores, the blacks had significantly lower triglyceride levels than either the whites or the Mexican Americans. This held true for both men and women as well as for individuals who were obese, overweight, and of normal weight.

Although triglyceride levels do have a direct relationship with insulin resistance, the absence of high triglyceride levels in African Americans does not mean the absence of insulin resistance. Therefore, any system that relies on triglyceride levels as a marker for insulin resistance risks underdiagnosis in African Americans.

“In blacks, the danger of underdiagnosis is the lost opportunity for the prevention of diseases related to insulin resistance, particularly diabetes and heart disease,” Dr. Sumner said.

She suggested that the solution is to develop criteria for “triglyceride-absent metabolic syndrome” to be used in African Americans and to test prospectively whether requiring just two of the four remaining criteria (waist circumference, hypertension, low HDL cholesterol, and high fasting glucose) for diagnosis of metabolic syndrome would accurately predict the onset of diabetes or cardiovascular disease.

For the individuals in her TARA study, the definition of metabolic syndrome developed by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) results in a prevalence of 11%, a sensitivity of 21%, and a specificity of 97%. On the other hand, using the triglyceride-absent definition, the prevalence would be 30%, the sensitivity would be 53%, and the specificity would be 81%.

“I felt this [triglyceride-absent definition] was a minimalist approach to the changing of the metabolic syndrome with the smallest perturbation,” Dr. Sumner said.

ATLANTA — Current sets of criteria for diagnosing metabolic syndrome fail to identify many African American patients at increased risk of cardiovascular disease and diabetes, said Dr. Anne E. Sumner in a presentation given at a meeting sponsored by the International Society on Hypertension in Blacks.

The three sets of diagnostic criteria currently in use all list triglyceride levels in excess of 150 mg/dL as one sign that a patient has the metabolic syndrome. But studies show that even obese and insulin-resistant African Americans can have low triglyceride levels, Dr. Sumner, a diabetes expert at the National Institutes of Health, said in her presentation.

“The inclusion of triglyceride [levels] in the metabolic syndrome leads to the exclusion of a significant proportion of insulin-resistant African Americans,” Dr. Sumner said. Excluding elevated triglycerides from the metabolic syndrome criteria would “lead to the inclusion of a significant proportion of insulin-resistant African Americans.”

Dr. Sumner relied on several clinical studies to support her conclusion. Data from the National Health and Nutrition Examination Survey (NHANES) show that both African American men and women have a significantly higher prevalence of cardiovascular disease and diabetes than do whites. Despite that, NHANES data show that African American men and women at all body-mass index levels have lower rates of metabolic syndrome than do whites.

Dr. Sumner emphasized that the data supporting her comments are preliminary and have not yet been peer reviewed.

Preliminary results from the Triglyceride and Cardiovascular Risk in African Americans (TARA) study, for which Dr. Sumner is a principal investigator, show that even African Americans with very high BMIs and very high levels of insulin resistance can have very low levels of triglycerides.

She pointed in particular to 2 women among the 210 African Americans so far enrolled in the study. One has a BMI of 55 kg/m

Of the African Americans in the study, 30% are insulin resistant, but only 2% have elevated triglycerides. In comparison, data from other studies show that about 60% of whites with insulin resistance have elevated triglycerides.

Dr. Sumner obtained similar results from her as-yet-unpublished analysis of NHANES data. She examined data from a cohort of 2,804 persons, aged 20–70, composed of 569 non-Hispanic blacks, 1,485 non-Hispanic whites, and 750 Mexican Americans. She divided the entire cohort into thirds based on their homeostasis model assessment (HOMA) scores, a surrogate for insulin resistance. Of the patients with the highest HOMA scores, the blacks had significantly lower triglyceride levels than either the whites or the Mexican Americans. This held true for both men and women as well as for individuals who were obese, overweight, and of normal weight.

Although triglyceride levels do have a direct relationship with insulin resistance, the absence of high triglyceride levels in African Americans does not mean the absence of insulin resistance. Therefore, any system that relies on triglyceride levels as a marker for insulin resistance risks underdiagnosis in African Americans.

“In blacks, the danger of underdiagnosis is the lost opportunity for the prevention of diseases related to insulin resistance, particularly diabetes and heart disease,” Dr. Sumner said.

She suggested that the solution is to develop criteria for “triglyceride-absent metabolic syndrome” to be used in African Americans and to test prospectively whether requiring just two of the four remaining criteria (waist circumference, hypertension, low HDL cholesterol, and high fasting glucose) for diagnosis of metabolic syndrome would accurately predict the onset of diabetes or cardiovascular disease.

For the individuals in her TARA study, the definition of metabolic syndrome developed by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) results in a prevalence of 11%, a sensitivity of 21%, and a specificity of 97%. On the other hand, using the triglyceride-absent definition, the prevalence would be 30%, the sensitivity would be 53%, and the specificity would be 81%.

“I felt this [triglyceride-absent definition] was a minimalist approach to the changing of the metabolic syndrome with the smallest perturbation,” Dr. Sumner said.

Diacerein has advantages over placebo and nonsteroidal anti-inflammatory drugs in treating hip and knee osteoarthritis, according to a new meta-analysis.

Diacerein is a member of the symptomatic slow-acting drugs in osteoarthritis group. They are of interest because they reduce cartilage degradation while improving symptoms. They tend to start working slowly, but they have a prolonged residual effect after treatment is stopped.

For the meta-analysis, published in the Sept. 25, 2006, issue of Archives of Internal Medicine, Dr. Bernhard Rintelen and colleagues from the Lower Austrian Center for Rheumatology, Stockerau, Austria, analyzed 19 randomized controlled trials involving a total of 2,637 patients (Arch. Intern. Med. 2006;166:1899–906).

Eight of the trials were placebo controlled, while 11 had active controls, which mainly compared diacerein with nonsteroidal anti-inflammatory drugs (NSAIDs).

During the active treatment phase, diacerein was significantly superior to placebo in reducing pain and improving function, with a Glass score (standardized mean difference) of 1.50, the authors wrote. NSAIDs showed similar efficacy to diacerein during active treatment, but at treatment end, diacerein's efficacy lasted up to 3 months longer, whereas NSAIDs did not (Glass score of 2.06).

Diacerein seemed well tolerated, even after long-term use. The most common adverse event was mild to moderate diarrhea, starting in early treatment and resolving during continuing therapy. The only other frequent adverse event was darker-than-normal urine, which had no clinical significance. There were no statistically significant differences between diacerein and NSAIDs in tolerability, though patients taking NSAIDs had a greater number of severe events. Diacerein is marketed as Artrodar in India, Europe, and Latin America. It is not yet available in the United States.

Diacerein has advantages over placebo and nonsteroidal anti-inflammatory drugs in treating hip and knee osteoarthritis, according to a new meta-analysis.

Diacerein is a member of the symptomatic slow-acting drugs in osteoarthritis group. They are of interest because they reduce cartilage degradation while improving symptoms. They tend to start working slowly, but they have a prolonged residual effect after treatment is stopped.

For the meta-analysis, published in the Sept. 25, 2006, issue of Archives of Internal Medicine, Dr. Bernhard Rintelen and colleagues from the Lower Austrian Center for Rheumatology, Stockerau, Austria, analyzed 19 randomized controlled trials involving a total of 2,637 patients (Arch. Intern. Med. 2006;166:1899–906).

Eight of the trials were placebo controlled, while 11 had active controls, which mainly compared diacerein with nonsteroidal anti-inflammatory drugs (NSAIDs).

During the active treatment phase, diacerein was significantly superior to placebo in reducing pain and improving function, with a Glass score (standardized mean difference) of 1.50, the authors wrote. NSAIDs showed similar efficacy to diacerein during active treatment, but at treatment end, diacerein's efficacy lasted up to 3 months longer, whereas NSAIDs did not (Glass score of 2.06).

Diacerein seemed well tolerated, even after long-term use. The most common adverse event was mild to moderate diarrhea, starting in early treatment and resolving during continuing therapy. The only other frequent adverse event was darker-than-normal urine, which had no clinical significance. There were no statistically significant differences between diacerein and NSAIDs in tolerability, though patients taking NSAIDs had a greater number of severe events. Diacerein is marketed as Artrodar in India, Europe, and Latin America. It is not yet available in the United States.

Diacerein has advantages over placebo and nonsteroidal anti-inflammatory drugs in treating hip and knee osteoarthritis, according to a new meta-analysis.

Diacerein is a member of the symptomatic slow-acting drugs in osteoarthritis group. They are of interest because they reduce cartilage degradation while improving symptoms. They tend to start working slowly, but they have a prolonged residual effect after treatment is stopped.

For the meta-analysis, published in the Sept. 25, 2006, issue of Archives of Internal Medicine, Dr. Bernhard Rintelen and colleagues from the Lower Austrian Center for Rheumatology, Stockerau, Austria, analyzed 19 randomized controlled trials involving a total of 2,637 patients (Arch. Intern. Med. 2006;166:1899–906).

Eight of the trials were placebo controlled, while 11 had active controls, which mainly compared diacerein with nonsteroidal anti-inflammatory drugs (NSAIDs).

During the active treatment phase, diacerein was significantly superior to placebo in reducing pain and improving function, with a Glass score (standardized mean difference) of 1.50, the authors wrote. NSAIDs showed similar efficacy to diacerein during active treatment, but at treatment end, diacerein's efficacy lasted up to 3 months longer, whereas NSAIDs did not (Glass score of 2.06).

Diacerein seemed well tolerated, even after long-term use. The most common adverse event was mild to moderate diarrhea, starting in early treatment and resolving during continuing therapy. The only other frequent adverse event was darker-than-normal urine, which had no clinical significance. There were no statistically significant differences between diacerein and NSAIDs in tolerability, though patients taking NSAIDs had a greater number of severe events. Diacerein is marketed as Artrodar in India, Europe, and Latin America. It is not yet available in the United States.

A reinterpretation of data from a 1988 study of Vietnam veterans has determined that their lifetime occurrence of posttraumatic stress disorder is far lower than previously thought.

The reinterpreted analysis suggests that only 19% of those veterans had a lifetime occurrence of PTSD, and that 9% were suffering from the disorder at the time of the study, which was 11–12 years after the war. The original study, based on a representative sample of 1,200 veterans, calculated a lifetime occurrence of 31%, with 15% suffering from the disorder when they were interviewed.

The National Vietnam Veterans Readjustment Study (NVVRS) relied on self-reports by the veterans on whether they experienced traumatic events, and used the DSM-III-R definition of PTSD. The new study used DSM-IV criteria and estimated exposure to traumatic events by using independent sources, such as military personnel files, military archives, and newspaper and historical accounts (Science 2006;313:979–82).

Bruce P. Dohrenwend, Ph.D., of Columbia University, New York, and colleagues applied these new estimates of military exposure to 260 of the veterans who participated in the original study. As in the original study, the investigators found a strong dose-response relationship between combat exposure and the occurrence of PTSD.

They attributed the lower estimates of PTSD occurrence to two factors. First, they eliminated individuals in whom the index traumatic event occurred before or after their service in Vietnam. Second, whereas current DSM-IV criteria for PTSD require at least some degree of social impairment to establish a diagnosis, DSM-III-R criteria in the original study had no such requirement.

Critics of the original study charged that the 31% lifetime occurrence of PTSD could not possibly be accurate, because only 15% of Vietnam veterans served in combat roles. And they said that the veterans' recall of their exposure to traumatic events could not be relied on, suggesting that access to veterans' benefits provided a motive for falsification.

The investigators involved in the reanalysis disputed both of those explanations. In comparing the self-reports of combat exposure with their objective measures, they found little evidence that the veterans falsified or exaggerated their experiences, they wrote.

For example, of the individuals judged to have low exposure to war zone stress by objective measures, 97% self-reported low exposure and only 3% reported high exposure. And of the individuals judged to have very high stress exposure by objective measures, 72% self-reported high exposure and 28% reported low exposure.

Furthermore, even though the conflict in Vietnam has been described as a “low-intensity” war for U.S. forces, it was not a conventional war with assurances of safety behind the front lines. Some military histories estimate that at least half of the veterans who served in Vietnam or its environs were involved in combat and could have been exposed to traumatic events.

“The message from the NVVRS has been that the Vietnam War took a severe psychological toll on U.S. veterans. Our results provide compelling reasons to take this message seriously,” the authors wrote. Furthermore, they pointed out, similarities exist between the combat experience in Vietnam at that time and in Iraq now.

“Both have been wars without fronts, in which it is often difficult to tell peaceful civilians from enemy combatants,” they wrotes. “What has been, and can still be, learned about PTSD and Vietnam veterans should be applicable to understanding the psychological risks to U.S. veterans of the war in Iraq.”

A reinterpretation of data from a 1988 study of Vietnam veterans has determined that their lifetime occurrence of posttraumatic stress disorder is far lower than previously thought.

The reinterpreted analysis suggests that only 19% of those veterans had a lifetime occurrence of PTSD, and that 9% were suffering from the disorder at the time of the study, which was 11–12 years after the war. The original study, based on a representative sample of 1,200 veterans, calculated a lifetime occurrence of 31%, with 15% suffering from the disorder when they were interviewed.

The National Vietnam Veterans Readjustment Study (NVVRS) relied on self-reports by the veterans on whether they experienced traumatic events, and used the DSM-III-R definition of PTSD. The new study used DSM-IV criteria and estimated exposure to traumatic events by using independent sources, such as military personnel files, military archives, and newspaper and historical accounts (Science 2006;313:979–82).

Bruce P. Dohrenwend, Ph.D., of Columbia University, New York, and colleagues applied these new estimates of military exposure to 260 of the veterans who participated in the original study. As in the original study, the investigators found a strong dose-response relationship between combat exposure and the occurrence of PTSD.

They attributed the lower estimates of PTSD occurrence to two factors. First, they eliminated individuals in whom the index traumatic event occurred before or after their service in Vietnam. Second, whereas current DSM-IV criteria for PTSD require at least some degree of social impairment to establish a diagnosis, DSM-III-R criteria in the original study had no such requirement.

Critics of the original study charged that the 31% lifetime occurrence of PTSD could not possibly be accurate, because only 15% of Vietnam veterans served in combat roles. And they said that the veterans' recall of their exposure to traumatic events could not be relied on, suggesting that access to veterans' benefits provided a motive for falsification.

The investigators involved in the reanalysis disputed both of those explanations. In comparing the self-reports of combat exposure with their objective measures, they found little evidence that the veterans falsified or exaggerated their experiences, they wrote.

For example, of the individuals judged to have low exposure to war zone stress by objective measures, 97% self-reported low exposure and only 3% reported high exposure. And of the individuals judged to have very high stress exposure by objective measures, 72% self-reported high exposure and 28% reported low exposure.

Furthermore, even though the conflict in Vietnam has been described as a “low-intensity” war for U.S. forces, it was not a conventional war with assurances of safety behind the front lines. Some military histories estimate that at least half of the veterans who served in Vietnam or its environs were involved in combat and could have been exposed to traumatic events.

“The message from the NVVRS has been that the Vietnam War took a severe psychological toll on U.S. veterans. Our results provide compelling reasons to take this message seriously,” the authors wrote. Furthermore, they pointed out, similarities exist between the combat experience in Vietnam at that time and in Iraq now.

“Both have been wars without fronts, in which it is often difficult to tell peaceful civilians from enemy combatants,” they wrotes. “What has been, and can still be, learned about PTSD and Vietnam veterans should be applicable to understanding the psychological risks to U.S. veterans of the war in Iraq.”

A reinterpretation of data from a 1988 study of Vietnam veterans has determined that their lifetime occurrence of posttraumatic stress disorder is far lower than previously thought.

The reinterpreted analysis suggests that only 19% of those veterans had a lifetime occurrence of PTSD, and that 9% were suffering from the disorder at the time of the study, which was 11–12 years after the war. The original study, based on a representative sample of 1,200 veterans, calculated a lifetime occurrence of 31%, with 15% suffering from the disorder when they were interviewed.

The National Vietnam Veterans Readjustment Study (NVVRS) relied on self-reports by the veterans on whether they experienced traumatic events, and used the DSM-III-R definition of PTSD. The new study used DSM-IV criteria and estimated exposure to traumatic events by using independent sources, such as military personnel files, military archives, and newspaper and historical accounts (Science 2006;313:979–82).

Bruce P. Dohrenwend, Ph.D., of Columbia University, New York, and colleagues applied these new estimates of military exposure to 260 of the veterans who participated in the original study. As in the original study, the investigators found a strong dose-response relationship between combat exposure and the occurrence of PTSD.

They attributed the lower estimates of PTSD occurrence to two factors. First, they eliminated individuals in whom the index traumatic event occurred before or after their service in Vietnam. Second, whereas current DSM-IV criteria for PTSD require at least some degree of social impairment to establish a diagnosis, DSM-III-R criteria in the original study had no such requirement.

Critics of the original study charged that the 31% lifetime occurrence of PTSD could not possibly be accurate, because only 15% of Vietnam veterans served in combat roles. And they said that the veterans' recall of their exposure to traumatic events could not be relied on, suggesting that access to veterans' benefits provided a motive for falsification.

The investigators involved in the reanalysis disputed both of those explanations. In comparing the self-reports of combat exposure with their objective measures, they found little evidence that the veterans falsified or exaggerated their experiences, they wrote.

For example, of the individuals judged to have low exposure to war zone stress by objective measures, 97% self-reported low exposure and only 3% reported high exposure. And of the individuals judged to have very high stress exposure by objective measures, 72% self-reported high exposure and 28% reported low exposure.

Furthermore, even though the conflict in Vietnam has been described as a “low-intensity” war for U.S. forces, it was not a conventional war with assurances of safety behind the front lines. Some military histories estimate that at least half of the veterans who served in Vietnam or its environs were involved in combat and could have been exposed to traumatic events.

“The message from the NVVRS has been that the Vietnam War took a severe psychological toll on U.S. veterans. Our results provide compelling reasons to take this message seriously,” the authors wrote. Furthermore, they pointed out, similarities exist between the combat experience in Vietnam at that time and in Iraq now.

“Both have been wars without fronts, in which it is often difficult to tell peaceful civilians from enemy combatants,” they wrotes. “What has been, and can still be, learned about PTSD and Vietnam veterans should be applicable to understanding the psychological risks to U.S. veterans of the war in Iraq.”

A whole-virion vaccine for the H5N1 avian influenza virus produces acceptable levels of immunity even at low doses, researchers found in a preliminary study.

The vaccine, developed at the Sinovac Biotech Co. in Beijing, seems to be effective when delivered in two 10-mcg doses 28 days apart. A different whole-virion vaccine required two 90-mcg doses, and a split-virion vaccine required two 30-mcg doses.

Given current manufacturing constraints, supplies of that split-virion vaccine would be limited to about 225 million people, far lower than worldwide demand in the event of an avian flu pandemic. A much greater number of people could be treated if the new dosage-sparing vaccine is found effective in larger clinical trials.

Dr. Jiangtao Lin of the Chinese-Japanese Friendship Hospital, Beijing, and colleagues reported on a placebo-controlled, double-blind, phase I trial of 120 volunteers aged 18–60 years. The participants were given either two injections of placebo or two injections of an inactivated, whole-virion influenza A (H5N1) vaccine at four doses between 1.25 mcg and 10 mcg. Aluminum hydroxide was added as an adjuvant, a practice previously shown to reduce the dosage needed to produce immunogenicity.

Although all four doses produced immune responses, the 10-mcg dose produced 78% seropositivity, significantly higher than that produced by the other doses (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140–6736(06)69294–5]).

No serious adverse events were reported at any dose level up to 56 days after the first injection. Local and systemic reactions were all rated as mild and transient. Pain at the injection site in the deltoid muscle was more frequently reported in the vaccine groups than in the placebo group, but there were no significant differences in systemic reactions, the most common of which were fever, headache, myalgia, and nausea.

In an accompanying editorial, Dr. Iain Stephenson, of the Leicester (England) Royal Infirmary, noted that vaccination will be central to any response to an avian flu pandemic (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140–6736(06)69340–9]). The 1918 influenza pandemic—also derived from an avian virus—caused up to 50 million deaths. Dr. Stephenson said that the dose-sparing approach described by Dr. Lin could be crucial for obtaining a global supply of the vaccine.

He also noted that earlier whole-virion vaccines were associated with febrile reactions, especially in children. Although larger clinical trials will be necessary before widespread immunization, Dr. Stephenson said a modest amount of reactogenicity might be acceptable in the face of the threat of a global pandemic.

The authors of the study acknowledged that funding came from the Sinovac Biotech Co., which had a role in both study design and monitoring. They said the company had no role in data collection or in writing the report.

A whole-virion vaccine for the H5N1 avian influenza virus produces acceptable levels of immunity even at low doses, researchers found in a preliminary study.

The vaccine, developed at the Sinovac Biotech Co. in Beijing, seems to be effective when delivered in two 10-mcg doses 28 days apart. A different whole-virion vaccine required two 90-mcg doses, and a split-virion vaccine required two 30-mcg doses.

Given current manufacturing constraints, supplies of that split-virion vaccine would be limited to about 225 million people, far lower than worldwide demand in the event of an avian flu pandemic. A much greater number of people could be treated if the new dosage-sparing vaccine is found effective in larger clinical trials.

Dr. Jiangtao Lin of the Chinese-Japanese Friendship Hospital, Beijing, and colleagues reported on a placebo-controlled, double-blind, phase I trial of 120 volunteers aged 18–60 years. The participants were given either two injections of placebo or two injections of an inactivated, whole-virion influenza A (H5N1) vaccine at four doses between 1.25 mcg and 10 mcg. Aluminum hydroxide was added as an adjuvant, a practice previously shown to reduce the dosage needed to produce immunogenicity.

Although all four doses produced immune responses, the 10-mcg dose produced 78% seropositivity, significantly higher than that produced by the other doses (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140–6736(06)69294–5]).

No serious adverse events were reported at any dose level up to 56 days after the first injection. Local and systemic reactions were all rated as mild and transient. Pain at the injection site in the deltoid muscle was more frequently reported in the vaccine groups than in the placebo group, but there were no significant differences in systemic reactions, the most common of which were fever, headache, myalgia, and nausea.

In an accompanying editorial, Dr. Iain Stephenson, of the Leicester (England) Royal Infirmary, noted that vaccination will be central to any response to an avian flu pandemic (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140–6736(06)69340–9]). The 1918 influenza pandemic—also derived from an avian virus—caused up to 50 million deaths. Dr. Stephenson said that the dose-sparing approach described by Dr. Lin could be crucial for obtaining a global supply of the vaccine.

He also noted that earlier whole-virion vaccines were associated with febrile reactions, especially in children. Although larger clinical trials will be necessary before widespread immunization, Dr. Stephenson said a modest amount of reactogenicity might be acceptable in the face of the threat of a global pandemic.

The authors of the study acknowledged that funding came from the Sinovac Biotech Co., which had a role in both study design and monitoring. They said the company had no role in data collection or in writing the report.

A whole-virion vaccine for the H5N1 avian influenza virus produces acceptable levels of immunity even at low doses, researchers found in a preliminary study.

The vaccine, developed at the Sinovac Biotech Co. in Beijing, seems to be effective when delivered in two 10-mcg doses 28 days apart. A different whole-virion vaccine required two 90-mcg doses, and a split-virion vaccine required two 30-mcg doses.

Given current manufacturing constraints, supplies of that split-virion vaccine would be limited to about 225 million people, far lower than worldwide demand in the event of an avian flu pandemic. A much greater number of people could be treated if the new dosage-sparing vaccine is found effective in larger clinical trials.

Dr. Jiangtao Lin of the Chinese-Japanese Friendship Hospital, Beijing, and colleagues reported on a placebo-controlled, double-blind, phase I trial of 120 volunteers aged 18–60 years. The participants were given either two injections of placebo or two injections of an inactivated, whole-virion influenza A (H5N1) vaccine at four doses between 1.25 mcg and 10 mcg. Aluminum hydroxide was added as an adjuvant, a practice previously shown to reduce the dosage needed to produce immunogenicity.

Although all four doses produced immune responses, the 10-mcg dose produced 78% seropositivity, significantly higher than that produced by the other doses (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140–6736(06)69294–5]).

No serious adverse events were reported at any dose level up to 56 days after the first injection. Local and systemic reactions were all rated as mild and transient. Pain at the injection site in the deltoid muscle was more frequently reported in the vaccine groups than in the placebo group, but there were no significant differences in systemic reactions, the most common of which were fever, headache, myalgia, and nausea.

In an accompanying editorial, Dr. Iain Stephenson, of the Leicester (England) Royal Infirmary, noted that vaccination will be central to any response to an avian flu pandemic (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140–6736(06)69340–9]). The 1918 influenza pandemic—also derived from an avian virus—caused up to 50 million deaths. Dr. Stephenson said that the dose-sparing approach described by Dr. Lin could be crucial for obtaining a global supply of the vaccine.

He also noted that earlier whole-virion vaccines were associated with febrile reactions, especially in children. Although larger clinical trials will be necessary before widespread immunization, Dr. Stephenson said a modest amount of reactogenicity might be acceptable in the face of the threat of a global pandemic.

The authors of the study acknowledged that funding came from the Sinovac Biotech Co., which had a role in both study design and monitoring. They said the company had no role in data collection or in writing the report.

A whole-virion vaccine for the H5N1 avian influenza virus produces acceptable levels of immunity even at low doses, researchers found in a preliminary study.

Developed at the Sinovac Biotech Co. in Beijing, the vaccine appears to be effective when delivered in two 10-mcg doses 28 days apart. A different whole-virion vaccine required two 90-mcg doses, and a split-virion vaccine required two 30-mcg doses.

Given current manufacturing constraints, supplies of that split-virion vaccine would be limited to about 225 million people, far lower than worldwide demand in the event of an avian flu pandemic. A much greater number of people could be treated if the new dosage-sparing vaccine is found effective in larger clinical trials.

Dr. Jiangtao Lin of the Chinese-Japanese Friendship Hospital, Beijing, and colleagues reported on a placebo-controlled, double-blind, phase I trial of 120 volunteers aged 18–60 years. The participants were given either two injections of placebo or two injections of an inactivated, whole-virion influenza A (H5N1) vaccine at four doses between 1.25 mcg and 10 mcg. Aluminum hydroxide was added as an adjuvant, a practice previously shown to reduce the dosage needed to produce immunogenicity.

All four doses produced immune responses, but the 10-mcg dose produced 78% seropositivity, which was significantly higher than that produced by the other doses (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140-6736(06)69294-5]).

No serious adverse events were reported at any dose level up to 56 days after the first injection. Local and systemic reactions were all rated as mild and transient. Pain at the injection site in the deltoid muscle was more frequently reported in the vaccine groups than in the placebo group, but there were no significant differences in systemic reactions, the most common of which were fever, headache, myalgia, and nausea.

In an editorial, Dr. Iain Stephenson, of the Leicester (England) Royal Infirmary, noted that vaccination will be central to any response to an avian flu pandemic (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140-6736(06)69340-9]). The 1918 influenza pandemic—also derived from an avian virus—caused up to 50 million deaths.

Dr. Stephenson said that the dose-sparing approach described by Dr. Lin could be crucial for obtaining a global supply of the vaccine.

He also noted that earlier whole-virion vaccines were associated with febrile reactions, especially in children. Although larger clinical trials will certainly be necessary before widespread immunization, Dr. Stephenson suggested that a modest amount of reactogenicity might be acceptable in the face of the threat of a worldwide pandemic.

The authors of the study acknowledged that funding came from the Sinovac Biotech Co., which had a role in both study design and monitoring. They said the company had no role in data collection or in the writing of the report.

A whole-virion vaccine for the H5N1 avian influenza virus produces acceptable levels of immunity even at low doses, researchers found in a preliminary study.

Developed at the Sinovac Biotech Co. in Beijing, the vaccine appears to be effective when delivered in two 10-mcg doses 28 days apart. A different whole-virion vaccine required two 90-mcg doses, and a split-virion vaccine required two 30-mcg doses.

Given current manufacturing constraints, supplies of that split-virion vaccine would be limited to about 225 million people, far lower than worldwide demand in the event of an avian flu pandemic. A much greater number of people could be treated if the new dosage-sparing vaccine is found effective in larger clinical trials.

Dr. Jiangtao Lin of the Chinese-Japanese Friendship Hospital, Beijing, and colleagues reported on a placebo-controlled, double-blind, phase I trial of 120 volunteers aged 18–60 years. The participants were given either two injections of placebo or two injections of an inactivated, whole-virion influenza A (H5N1) vaccine at four doses between 1.25 mcg and 10 mcg. Aluminum hydroxide was added as an adjuvant, a practice previously shown to reduce the dosage needed to produce immunogenicity.

All four doses produced immune responses, but the 10-mcg dose produced 78% seropositivity, which was significantly higher than that produced by the other doses (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140-6736(06)69294-5]).

No serious adverse events were reported at any dose level up to 56 days after the first injection. Local and systemic reactions were all rated as mild and transient. Pain at the injection site in the deltoid muscle was more frequently reported in the vaccine groups than in the placebo group, but there were no significant differences in systemic reactions, the most common of which were fever, headache, myalgia, and nausea.

In an editorial, Dr. Iain Stephenson, of the Leicester (England) Royal Infirmary, noted that vaccination will be central to any response to an avian flu pandemic (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140-6736(06)69340-9]). The 1918 influenza pandemic—also derived from an avian virus—caused up to 50 million deaths.

Dr. Stephenson said that the dose-sparing approach described by Dr. Lin could be crucial for obtaining a global supply of the vaccine.

He also noted that earlier whole-virion vaccines were associated with febrile reactions, especially in children. Although larger clinical trials will certainly be necessary before widespread immunization, Dr. Stephenson suggested that a modest amount of reactogenicity might be acceptable in the face of the threat of a worldwide pandemic.

The authors of the study acknowledged that funding came from the Sinovac Biotech Co., which had a role in both study design and monitoring. They said the company had no role in data collection or in the writing of the report.

A whole-virion vaccine for the H5N1 avian influenza virus produces acceptable levels of immunity even at low doses, researchers found in a preliminary study.

Developed at the Sinovac Biotech Co. in Beijing, the vaccine appears to be effective when delivered in two 10-mcg doses 28 days apart. A different whole-virion vaccine required two 90-mcg doses, and a split-virion vaccine required two 30-mcg doses.

Given current manufacturing constraints, supplies of that split-virion vaccine would be limited to about 225 million people, far lower than worldwide demand in the event of an avian flu pandemic. A much greater number of people could be treated if the new dosage-sparing vaccine is found effective in larger clinical trials.

Dr. Jiangtao Lin of the Chinese-Japanese Friendship Hospital, Beijing, and colleagues reported on a placebo-controlled, double-blind, phase I trial of 120 volunteers aged 18–60 years. The participants were given either two injections of placebo or two injections of an inactivated, whole-virion influenza A (H5N1) vaccine at four doses between 1.25 mcg and 10 mcg. Aluminum hydroxide was added as an adjuvant, a practice previously shown to reduce the dosage needed to produce immunogenicity.

All four doses produced immune responses, but the 10-mcg dose produced 78% seropositivity, which was significantly higher than that produced by the other doses (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140-6736(06)69294-5]).

No serious adverse events were reported at any dose level up to 56 days after the first injection. Local and systemic reactions were all rated as mild and transient. Pain at the injection site in the deltoid muscle was more frequently reported in the vaccine groups than in the placebo group, but there were no significant differences in systemic reactions, the most common of which were fever, headache, myalgia, and nausea.

In an editorial, Dr. Iain Stephenson, of the Leicester (England) Royal Infirmary, noted that vaccination will be central to any response to an avian flu pandemic (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140-6736(06)69340-9]). The 1918 influenza pandemic—also derived from an avian virus—caused up to 50 million deaths.

Dr. Stephenson said that the dose-sparing approach described by Dr. Lin could be crucial for obtaining a global supply of the vaccine.

He also noted that earlier whole-virion vaccines were associated with febrile reactions, especially in children. Although larger clinical trials will certainly be necessary before widespread immunization, Dr. Stephenson suggested that a modest amount of reactogenicity might be acceptable in the face of the threat of a worldwide pandemic.

The authors of the study acknowledged that funding came from the Sinovac Biotech Co., which had a role in both study design and monitoring. They said the company had no role in data collection or in the writing of the report.

SAN FRANCISCO — “It's a pretty exciting time for drug development in osteoporosis,” Dr. Deborah Sellmeyer said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

While joking that her information was “sourced from Google and rumor and various investment brochures,” Dr. Sellmeyer, director of the Center for Osteoporosis at the university, listed some of the osteoporosis drugs in the pipeline.

A fracture trial for a full-length version of parathyroid hormone (PTH [1-84]) has been completed, and a new drug application (NDA) was submitted to the Food and Drug Administration in July 2005.

Meanwhile, inhaled-powder and oral forms of PTH are in phase I and phase II trials, and at least one PTH analogue is in phase III. “Everyone's looking for the magic combination that will be able to replicate the PTH skeletal effect and get rid of the hypercalcemic effect,” Dr. Sellmeyer said.

Oral calcitonin preparations are in phase I and phase II. And low-dose and ultralow-dose estrogen remain fertile areas of research. The hope is that these preparations will replicate the beneficial bone effects of estrogen while avoiding its harmful vascular effects. While two low-dose patches and one low-dose pill have already been approved for the prevention of osteoporosis and for the treatment of vasomotor symptoms, no fracture data are yet available.

Zoledronic acid, a once-a-year intravenous bisphosphonate, is currently approved for hypercalcemia of malignancy and is now in a phase III trial to determine whether it prevents osteoporotic fractures. This agent is likely to benefit people who cannot tolerate oral bisphosphonates, people in assisted-living situations, and people who have difficulty remembering to take medication.

There are several new selective estrogen receptor modulators under development, with three—lasofoxifene, bazedoxifene, and arzoxifene—in phase III or beyond. An NDA for lasofoxifene was submitted to the FDA in 2004, but the manufacturer apparently received a nonapprovable letter in September 2005, putting the drug in limbo. An NDA for bazedoxifene was submitted in 2006 for the prevention of osteoporosis, and an NDA is planned for 2007 for a combination of bazedoxifene and estrogen for osteoporosis treatment and possible premenopausal use. Results from a phase III trial of arzoxifene are not expected until 2010.

Tibolone is a drug that “likes every steroid receptor it ever met,” in Dr. Sellmeyer's words. Its three metabolites separately have affinities for estrogen, progesterone, and androgen receptors. A recently completed 24-month prevention trial in 90 women showed no difference in vaginal spotting between tibolone and placebo. Interestingly, the women taking placebo experienced a 12% weight gain, while the women taking tibolone experienced no average weight gain. A multinational fracture study involving 4,000 women is expected to conclude sometime in 2006.

It's been known for decades that strontium improves bone mineral density (BMD), but it was never developed for osteoporosis prevention or treatment because it's a nonpatentable chemical element. Recently, however, a proprietary formulation of strontium—strontium ranelate—has shown some promise. A granular form has already been approved for use in Europe and the United Kingdom, and a once-a-day pill finished a phase I trial in September 2005. Strontium ranelate is likely to complicate interpretation of BMD testing, since it has a higher density than calcium.

Denosumab, also known as AMG 162, is a monoclonal antibody that appears to decrease bone resorption. Currently in a phase III fracture trial on postmenopausal women, denosumab will require two subcutaneous injections per year.

Isosorbide mononitrate, long used for the pain of angina, appears to improve several bone markers in postmenopausal women. A BMD trial is currently underway.

β-Blockers constitute another class of drugs that may well have bone effects. Most epidemiologic studies associate use of β-blockers with increases in BMD and decreases in fractures. Randomized trials are needed to determine whether β-blockers actually have a place in osteoporosis prevention or treatment.

Finally, there are several new agents with previously untried mechanisms of action in the pipeline. Among them are selective androgen receptor modulators, cathepsin K inhibitors, and calcilytics. All are in early-phase studies for osteoporosis.

SAN FRANCISCO — “It's a pretty exciting time for drug development in osteoporosis,” Dr. Deborah Sellmeyer said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

While joking that her information was “sourced from Google and rumor and various investment brochures,” Dr. Sellmeyer, director of the Center for Osteoporosis at the university, listed some of the osteoporosis drugs in the pipeline.

A fracture trial for a full-length version of parathyroid hormone (PTH [1-84]) has been completed, and a new drug application (NDA) was submitted to the Food and Drug Administration in July 2005.

Meanwhile, inhaled-powder and oral forms of PTH are in phase I and phase II trials, and at least one PTH analogue is in phase III. “Everyone's looking for the magic combination that will be able to replicate the PTH skeletal effect and get rid of the hypercalcemic effect,” Dr. Sellmeyer said.

Oral calcitonin preparations are in phase I and phase II. And low-dose and ultralow-dose estrogen remain fertile areas of research. The hope is that these preparations will replicate the beneficial bone effects of estrogen while avoiding its harmful vascular effects. While two low-dose patches and one low-dose pill have already been approved for the prevention of osteoporosis and for the treatment of vasomotor symptoms, no fracture data are yet available.

Zoledronic acid, a once-a-year intravenous bisphosphonate, is currently approved for hypercalcemia of malignancy and is now in a phase III trial to determine whether it prevents osteoporotic fractures. This agent is likely to benefit people who cannot tolerate oral bisphosphonates, people in assisted-living situations, and people who have difficulty remembering to take medication.

There are several new selective estrogen receptor modulators under development, with three—lasofoxifene, bazedoxifene, and arzoxifene—in phase III or beyond. An NDA for lasofoxifene was submitted to the FDA in 2004, but the manufacturer apparently received a nonapprovable letter in September 2005, putting the drug in limbo. An NDA for bazedoxifene was submitted in 2006 for the prevention of osteoporosis, and an NDA is planned for 2007 for a combination of bazedoxifene and estrogen for osteoporosis treatment and possible premenopausal use. Results from a phase III trial of arzoxifene are not expected until 2010.

Tibolone is a drug that “likes every steroid receptor it ever met,” in Dr. Sellmeyer's words. Its three metabolites separately have affinities for estrogen, progesterone, and androgen receptors. A recently completed 24-month prevention trial in 90 women showed no difference in vaginal spotting between tibolone and placebo. Interestingly, the women taking placebo experienced a 12% weight gain, while the women taking tibolone experienced no average weight gain. A multinational fracture study involving 4,000 women is expected to conclude sometime in 2006.

It's been known for decades that strontium improves bone mineral density (BMD), but it was never developed for osteoporosis prevention or treatment because it's a nonpatentable chemical element. Recently, however, a proprietary formulation of strontium—strontium ranelate—has shown some promise. A granular form has already been approved for use in Europe and the United Kingdom, and a once-a-day pill finished a phase I trial in September 2005. Strontium ranelate is likely to complicate interpretation of BMD testing, since it has a higher density than calcium.

Denosumab, also known as AMG 162, is a monoclonal antibody that appears to decrease bone resorption. Currently in a phase III fracture trial on postmenopausal women, denosumab will require two subcutaneous injections per year.

Isosorbide mononitrate, long used for the pain of angina, appears to improve several bone markers in postmenopausal women. A BMD trial is currently underway.

β-Blockers constitute another class of drugs that may well have bone effects. Most epidemiologic studies associate use of β-blockers with increases in BMD and decreases in fractures. Randomized trials are needed to determine whether β-blockers actually have a place in osteoporosis prevention or treatment.

Finally, there are several new agents with previously untried mechanisms of action in the pipeline. Among them are selective androgen receptor modulators, cathepsin K inhibitors, and calcilytics. All are in early-phase studies for osteoporosis.

SAN FRANCISCO — “It's a pretty exciting time for drug development in osteoporosis,” Dr. Deborah Sellmeyer said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

While joking that her information was “sourced from Google and rumor and various investment brochures,” Dr. Sellmeyer, director of the Center for Osteoporosis at the university, listed some of the osteoporosis drugs in the pipeline.

A fracture trial for a full-length version of parathyroid hormone (PTH [1-84]) has been completed, and a new drug application (NDA) was submitted to the Food and Drug Administration in July 2005.

Meanwhile, inhaled-powder and oral forms of PTH are in phase I and phase II trials, and at least one PTH analogue is in phase III. “Everyone's looking for the magic combination that will be able to replicate the PTH skeletal effect and get rid of the hypercalcemic effect,” Dr. Sellmeyer said.

Oral calcitonin preparations are in phase I and phase II. And low-dose and ultralow-dose estrogen remain fertile areas of research. The hope is that these preparations will replicate the beneficial bone effects of estrogen while avoiding its harmful vascular effects. While two low-dose patches and one low-dose pill have already been approved for the prevention of osteoporosis and for the treatment of vasomotor symptoms, no fracture data are yet available.

Zoledronic acid, a once-a-year intravenous bisphosphonate, is currently approved for hypercalcemia of malignancy and is now in a phase III trial to determine whether it prevents osteoporotic fractures. This agent is likely to benefit people who cannot tolerate oral bisphosphonates, people in assisted-living situations, and people who have difficulty remembering to take medication.

There are several new selective estrogen receptor modulators under development, with three—lasofoxifene, bazedoxifene, and arzoxifene—in phase III or beyond. An NDA for lasofoxifene was submitted to the FDA in 2004, but the manufacturer apparently received a nonapprovable letter in September 2005, putting the drug in limbo. An NDA for bazedoxifene was submitted in 2006 for the prevention of osteoporosis, and an NDA is planned for 2007 for a combination of bazedoxifene and estrogen for osteoporosis treatment and possible premenopausal use. Results from a phase III trial of arzoxifene are not expected until 2010.

Tibolone is a drug that “likes every steroid receptor it ever met,” in Dr. Sellmeyer's words. Its three metabolites separately have affinities for estrogen, progesterone, and androgen receptors. A recently completed 24-month prevention trial in 90 women showed no difference in vaginal spotting between tibolone and placebo. Interestingly, the women taking placebo experienced a 12% weight gain, while the women taking tibolone experienced no average weight gain. A multinational fracture study involving 4,000 women is expected to conclude sometime in 2006.

It's been known for decades that strontium improves bone mineral density (BMD), but it was never developed for osteoporosis prevention or treatment because it's a nonpatentable chemical element. Recently, however, a proprietary formulation of strontium—strontium ranelate—has shown some promise. A granular form has already been approved for use in Europe and the United Kingdom, and a once-a-day pill finished a phase I trial in September 2005. Strontium ranelate is likely to complicate interpretation of BMD testing, since it has a higher density than calcium.

Denosumab, also known as AMG 162, is a monoclonal antibody that appears to decrease bone resorption. Currently in a phase III fracture trial on postmenopausal women, denosumab will require two subcutaneous injections per year.

Isosorbide mononitrate, long used for the pain of angina, appears to improve several bone markers in postmenopausal women. A BMD trial is currently underway.

β-Blockers constitute another class of drugs that may well have bone effects. Most epidemiologic studies associate use of β-blockers with increases in BMD and decreases in fractures. Randomized trials are needed to determine whether β-blockers actually have a place in osteoporosis prevention or treatment.

Finally, there are several new agents with previously untried mechanisms of action in the pipeline. Among them are selective androgen receptor modulators, cathepsin K inhibitors, and calcilytics. All are in early-phase studies for osteoporosis.

SAN FRANCISCO — Azithromycin had no influence on the clinical course of pityriasis rosea, according to a small randomized controlled trial presented at the annual meeting of the Pediatric Academic Societies.

The etiologic agent for pityriasis rosea, an acute inflammatory skin disease common in children and adolescents, is unknown. But a study published in 2000 reported complete resolution of symptoms in 73% of patients treated with erythromycin (J. Am. Acad. Dermatol. 2000;42:241–4).

Dr. Ahdi Amer and Dr. Howard Fischer, both of the Wayne State University, Detroit, treated 49 children an average of 1.5 weeks after a diagnosis of pityriasis rosea. The children, aged 2–18, were randomly assigned to receive a 5-day course of azithromycin or placebo, they said in a poster presentation at the meeting, sponsored by the American Pediatric Society, the Society for Pediatric Research, the Ambulatory Pediatric Association, and the American Academy of Pediatrics.

A total of 15 patients in the azithromycin group (60%) and 10 patients in the placebo group (42%) had complete resolution of symptoms within 2 weeks. Seven patients in each group had partial resolution. There were three treatment failures in the azithromycin group and seven in the placebo group. None of these differences between groups was statistically significant. Complete resolution was defined by previous lesions that were neither scaly nor raised, and the appearance of no new lesions. In patients who experienced a decrease in lesion number, scaliness, or thickness were considered to have a partial resolution.

There were no statistically significant differences in the proportion of patients with residual hyperpigmentation or hypopigmentation. Two patients in the treatment group reported stomachache and another two reported diarrhea while receiving azithromycin.

SAN FRANCISCO — Azithromycin had no influence on the clinical course of pityriasis rosea, according to a small randomized controlled trial presented at the annual meeting of the Pediatric Academic Societies.

The etiologic agent for pityriasis rosea, an acute inflammatory skin disease common in children and adolescents, is unknown. But a study published in 2000 reported complete resolution of symptoms in 73% of patients treated with erythromycin (J. Am. Acad. Dermatol. 2000;42:241–4).

Dr. Ahdi Amer and Dr. Howard Fischer, both of the Wayne State University, Detroit, treated 49 children an average of 1.5 weeks after a diagnosis of pityriasis rosea. The children, aged 2–18, were randomly assigned to receive a 5-day course of azithromycin or placebo, they said in a poster presentation at the meeting, sponsored by the American Pediatric Society, the Society for Pediatric Research, the Ambulatory Pediatric Association, and the American Academy of Pediatrics.

A total of 15 patients in the azithromycin group (60%) and 10 patients in the placebo group (42%) had complete resolution of symptoms within 2 weeks. Seven patients in each group had partial resolution. There were three treatment failures in the azithromycin group and seven in the placebo group. None of these differences between groups was statistically significant. Complete resolution was defined by previous lesions that were neither scaly nor raised, and the appearance of no new lesions. In patients who experienced a decrease in lesion number, scaliness, or thickness were considered to have a partial resolution.

There were no statistically significant differences in the proportion of patients with residual hyperpigmentation or hypopigmentation. Two patients in the treatment group reported stomachache and another two reported diarrhea while receiving azithromycin.

SAN FRANCISCO — Azithromycin had no influence on the clinical course of pityriasis rosea, according to a small randomized controlled trial presented at the annual meeting of the Pediatric Academic Societies.

The etiologic agent for pityriasis rosea, an acute inflammatory skin disease common in children and adolescents, is unknown. But a study published in 2000 reported complete resolution of symptoms in 73% of patients treated with erythromycin (J. Am. Acad. Dermatol. 2000;42:241–4).

Dr. Ahdi Amer and Dr. Howard Fischer, both of the Wayne State University, Detroit, treated 49 children an average of 1.5 weeks after a diagnosis of pityriasis rosea. The children, aged 2–18, were randomly assigned to receive a 5-day course of azithromycin or placebo, they said in a poster presentation at the meeting, sponsored by the American Pediatric Society, the Society for Pediatric Research, the Ambulatory Pediatric Association, and the American Academy of Pediatrics.

A total of 15 patients in the azithromycin group (60%) and 10 patients in the placebo group (42%) had complete resolution of symptoms within 2 weeks. Seven patients in each group had partial resolution. There were three treatment failures in the azithromycin group and seven in the placebo group. None of these differences between groups was statistically significant. Complete resolution was defined by previous lesions that were neither scaly nor raised, and the appearance of no new lesions. In patients who experienced a decrease in lesion number, scaliness, or thickness were considered to have a partial resolution.

There were no statistically significant differences in the proportion of patients with residual hyperpigmentation or hypopigmentation. Two patients in the treatment group reported stomachache and another two reported diarrhea while receiving azithromycin.

A whole-virion vaccine for the H5N1 avian influenza virus produces acceptable levels of immunity even at low doses, researchers found in a preliminary study.

Developed at the Sinovac Biotech Co. in Beijing, the vaccine appears to be effective when delivered in two 10-mcg doses 28 days apart. A different whole-virion vaccine required two 90-mcg doses, and a split-virion vaccine required two 30-mcg doses.

Given current manufacturing constraints, supplies of that split-virion vaccine would be limited to about 225 million people, far lower than worldwide demand in the event of an avian flu pandemic. A much greater number of people could be treated if the new dosage-sparing vaccine is found effective in larger clinical trials.

Dr. Jiangtao Lin of the Chinese-Japanese Friendship Hospital, Beijing, and colleagues reported on a placebo-controlled, double-blind, phase I trial of 120 volunteers aged 18–60 years. The participants were given either two injections of placebo or two injections of an inactivated, whole-virion influenza A (H5N1) vaccine at four doses between 1.25 mcg and 10 mcg.

Aluminum hydroxide was added as an adjuvant, a practice previously shown to reduce the dosage needed to produce immunogenicity.

Although all four doses produced immune responses, the 10-mcg dose produced 78% seropositivity, significantly higher than that produced by the other doses (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140–6736(06)69294–5]).

No serious adverse events were reported at any dose level up to 56 days after the first injection. Local and systemic reactions were all rated as mild and transient.

Pain at the injection site in the deltoid muscle was more frequently reported in the vaccine groups than in the placebo group, but there were no significant differences in systemic reactions, the most common of which were fever, headache, myalgia, and nausea.

In an accompanying editorial, Dr. Iain Stephenson, of the Leicester (England) Royal Infirmary, noted that vaccination will be central to any response to an avian flu pandemic (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140–6736(06)69340–9]). The 1918 influenza pandemic—also derived from an avian virus—caused up to 50 million deaths. Dr. Stephenson said that the dose-sparing approach described by Dr. Lin could be crucial for obtaining a global supply of the vaccine.

He also noted that earlier whole-virion vaccines were associated with febrile reactions, especially in children.

Although larger clinical trials will certainly be necessary before widespread immunization, Dr. Stephenson suggested that a modest amount of reactogenicity might be acceptable in the face of the threat of a worldwide pandemic.

The authors of the study acknowledged that funding came from the Sinovac Biotech Co., which had a role in both study design and monitoring. They said the company had no role in data collection or in writing the report.

A whole-virion vaccine for the H5N1 avian influenza virus produces acceptable levels of immunity even at low doses, researchers found in a preliminary study.

Developed at the Sinovac Biotech Co. in Beijing, the vaccine appears to be effective when delivered in two 10-mcg doses 28 days apart. A different whole-virion vaccine required two 90-mcg doses, and a split-virion vaccine required two 30-mcg doses.

Given current manufacturing constraints, supplies of that split-virion vaccine would be limited to about 225 million people, far lower than worldwide demand in the event of an avian flu pandemic. A much greater number of people could be treated if the new dosage-sparing vaccine is found effective in larger clinical trials.

Dr. Jiangtao Lin of the Chinese-Japanese Friendship Hospital, Beijing, and colleagues reported on a placebo-controlled, double-blind, phase I trial of 120 volunteers aged 18–60 years. The participants were given either two injections of placebo or two injections of an inactivated, whole-virion influenza A (H5N1) vaccine at four doses between 1.25 mcg and 10 mcg.

Aluminum hydroxide was added as an adjuvant, a practice previously shown to reduce the dosage needed to produce immunogenicity.

Although all four doses produced immune responses, the 10-mcg dose produced 78% seropositivity, significantly higher than that produced by the other doses (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140–6736(06)69294–5]).

No serious adverse events were reported at any dose level up to 56 days after the first injection. Local and systemic reactions were all rated as mild and transient.

Pain at the injection site in the deltoid muscle was more frequently reported in the vaccine groups than in the placebo group, but there were no significant differences in systemic reactions, the most common of which were fever, headache, myalgia, and nausea.

In an accompanying editorial, Dr. Iain Stephenson, of the Leicester (England) Royal Infirmary, noted that vaccination will be central to any response to an avian flu pandemic (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140–6736(06)69340–9]). The 1918 influenza pandemic—also derived from an avian virus—caused up to 50 million deaths. Dr. Stephenson said that the dose-sparing approach described by Dr. Lin could be crucial for obtaining a global supply of the vaccine.

He also noted that earlier whole-virion vaccines were associated with febrile reactions, especially in children.

Although larger clinical trials will certainly be necessary before widespread immunization, Dr. Stephenson suggested that a modest amount of reactogenicity might be acceptable in the face of the threat of a worldwide pandemic.

The authors of the study acknowledged that funding came from the Sinovac Biotech Co., which had a role in both study design and monitoring. They said the company had no role in data collection or in writing the report.

A whole-virion vaccine for the H5N1 avian influenza virus produces acceptable levels of immunity even at low doses, researchers found in a preliminary study.

Developed at the Sinovac Biotech Co. in Beijing, the vaccine appears to be effective when delivered in two 10-mcg doses 28 days apart. A different whole-virion vaccine required two 90-mcg doses, and a split-virion vaccine required two 30-mcg doses.

Given current manufacturing constraints, supplies of that split-virion vaccine would be limited to about 225 million people, far lower than worldwide demand in the event of an avian flu pandemic. A much greater number of people could be treated if the new dosage-sparing vaccine is found effective in larger clinical trials.

Dr. Jiangtao Lin of the Chinese-Japanese Friendship Hospital, Beijing, and colleagues reported on a placebo-controlled, double-blind, phase I trial of 120 volunteers aged 18–60 years. The participants were given either two injections of placebo or two injections of an inactivated, whole-virion influenza A (H5N1) vaccine at four doses between 1.25 mcg and 10 mcg.

Aluminum hydroxide was added as an adjuvant, a practice previously shown to reduce the dosage needed to produce immunogenicity.

Although all four doses produced immune responses, the 10-mcg dose produced 78% seropositivity, significantly higher than that produced by the other doses (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140–6736(06)69294–5]).

No serious adverse events were reported at any dose level up to 56 days after the first injection. Local and systemic reactions were all rated as mild and transient.

Pain at the injection site in the deltoid muscle was more frequently reported in the vaccine groups than in the placebo group, but there were no significant differences in systemic reactions, the most common of which were fever, headache, myalgia, and nausea.

In an accompanying editorial, Dr. Iain Stephenson, of the Leicester (England) Royal Infirmary, noted that vaccination will be central to any response to an avian flu pandemic (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140–6736(06)69340–9]). The 1918 influenza pandemic—also derived from an avian virus—caused up to 50 million deaths. Dr. Stephenson said that the dose-sparing approach described by Dr. Lin could be crucial for obtaining a global supply of the vaccine.

He also noted that earlier whole-virion vaccines were associated with febrile reactions, especially in children.

Although larger clinical trials will certainly be necessary before widespread immunization, Dr. Stephenson suggested that a modest amount of reactogenicity might be acceptable in the face of the threat of a worldwide pandemic.

The authors of the study acknowledged that funding came from the Sinovac Biotech Co., which had a role in both study design and monitoring. They said the company had no role in data collection or in writing the report.