Michele G. Sullivan

ST. LOUIS – Despite feeling more emotional distress and disconnection from their families, adolescents who are adopted don't appear to engage in more high-risk behaviors or have worse adult outcomes than nonadopted adolescents, Dr. Cheryl Kodjo reported in a poster at the annual meeting of the Society for Adolescent Medicine.

“The results seem to contradict what many of us believe based on anecdotal observations,” said Dr. Kodjo of the University of Rochester (N.Y.). “I think, however, that they do point up the need for more research into this area.”

Dr. Kodjo's secondary analysis of the National Longitudinal Study of Adolescent Health (Add Health) compared data on the risk behaviors of 18,250 nonadopted and 656 adopted adolescents, obtained in 1994–1995, to their sociobehavioral outcomes as young adults in 2001–2002.

The three-wave Add Health study was launched as a national school-based survey of adolescent behavior. In the first wave, an in-school survey of adolescents from grades 7–12 was carried out in 140 schools during the spring of 1994.

This survey was followed up in 1995 with an in-home interview of each study youth and a principal caregiver.

In the second wave, the adolescents were interviewed again in the home a year later, in 1996.

The third wave of the study occurred during 2001–2002, when the participants were 18–24 years old. By this time, all respondents had left high school for further education, work, or other options. Approximately 10,000 adolescents participated in all three waves.

Dr. Kodjo examined the link between wave 1 risk factors (trying to lose weight; alcohol, marijuana, or other drug use; sexual activity; violence; and suicide attempts) and wave 3 outcomes (diagnosed eating disorder, drug/alcohol treatment, sexually transmitted disease, emergency room injury treatment, and treatment for mental illness), for both the adopted and nonadopted subjects.

She found no significant differences between the two groups in either the frequency of engaging in risk behaviors or the frequency of experiencing an adverse outcome in young adulthood.

Good parenting might be one reason Dr. Kodjo saw no increase in risk behaviors among the adopted adolescents. “Maybe we're just not giving adoptive parents enough credit,” she said in an interview. “It could be that the jobs they are doing in setting limits and enforcing rules effectively keep risk behavior down.”

She noted, however, that the survey did show that adopted adolescents reported more emotional distress and family disconnectedness than their nonadopted counterparts.

ST. LOUIS – Despite feeling more emotional distress and disconnection from their families, adolescents who are adopted don't appear to engage in more high-risk behaviors or have worse adult outcomes than nonadopted adolescents, Dr. Cheryl Kodjo reported in a poster at the annual meeting of the Society for Adolescent Medicine.

“The results seem to contradict what many of us believe based on anecdotal observations,” said Dr. Kodjo of the University of Rochester (N.Y.). “I think, however, that they do point up the need for more research into this area.”

Dr. Kodjo's secondary analysis of the National Longitudinal Study of Adolescent Health (Add Health) compared data on the risk behaviors of 18,250 nonadopted and 656 adopted adolescents, obtained in 1994–1995, to their sociobehavioral outcomes as young adults in 2001–2002.

The three-wave Add Health study was launched as a national school-based survey of adolescent behavior. In the first wave, an in-school survey of adolescents from grades 7–12 was carried out in 140 schools during the spring of 1994.

This survey was followed up in 1995 with an in-home interview of each study youth and a principal caregiver.

In the second wave, the adolescents were interviewed again in the home a year later, in 1996.

The third wave of the study occurred during 2001–2002, when the participants were 18–24 years old. By this time, all respondents had left high school for further education, work, or other options. Approximately 10,000 adolescents participated in all three waves.

Dr. Kodjo examined the link between wave 1 risk factors (trying to lose weight; alcohol, marijuana, or other drug use; sexual activity; violence; and suicide attempts) and wave 3 outcomes (diagnosed eating disorder, drug/alcohol treatment, sexually transmitted disease, emergency room injury treatment, and treatment for mental illness), for both the adopted and nonadopted subjects.

She found no significant differences between the two groups in either the frequency of engaging in risk behaviors or the frequency of experiencing an adverse outcome in young adulthood.

Good parenting might be one reason Dr. Kodjo saw no increase in risk behaviors among the adopted adolescents. “Maybe we're just not giving adoptive parents enough credit,” she said in an interview. “It could be that the jobs they are doing in setting limits and enforcing rules effectively keep risk behavior down.”

She noted, however, that the survey did show that adopted adolescents reported more emotional distress and family disconnectedness than their nonadopted counterparts.

ST. LOUIS – Despite feeling more emotional distress and disconnection from their families, adolescents who are adopted don't appear to engage in more high-risk behaviors or have worse adult outcomes than nonadopted adolescents, Dr. Cheryl Kodjo reported in a poster at the annual meeting of the Society for Adolescent Medicine.

“The results seem to contradict what many of us believe based on anecdotal observations,” said Dr. Kodjo of the University of Rochester (N.Y.). “I think, however, that they do point up the need for more research into this area.”

Dr. Kodjo's secondary analysis of the National Longitudinal Study of Adolescent Health (Add Health) compared data on the risk behaviors of 18,250 nonadopted and 656 adopted adolescents, obtained in 1994–1995, to their sociobehavioral outcomes as young adults in 2001–2002.

The three-wave Add Health study was launched as a national school-based survey of adolescent behavior. In the first wave, an in-school survey of adolescents from grades 7–12 was carried out in 140 schools during the spring of 1994.

This survey was followed up in 1995 with an in-home interview of each study youth and a principal caregiver.

In the second wave, the adolescents were interviewed again in the home a year later, in 1996.

The third wave of the study occurred during 2001–2002, when the participants were 18–24 years old. By this time, all respondents had left high school for further education, work, or other options. Approximately 10,000 adolescents participated in all three waves.

Dr. Kodjo examined the link between wave 1 risk factors (trying to lose weight; alcohol, marijuana, or other drug use; sexual activity; violence; and suicide attempts) and wave 3 outcomes (diagnosed eating disorder, drug/alcohol treatment, sexually transmitted disease, emergency room injury treatment, and treatment for mental illness), for both the adopted and nonadopted subjects.

She found no significant differences between the two groups in either the frequency of engaging in risk behaviors or the frequency of experiencing an adverse outcome in young adulthood.

Good parenting might be one reason Dr. Kodjo saw no increase in risk behaviors among the adopted adolescents. “Maybe we're just not giving adoptive parents enough credit,” she said in an interview. “It could be that the jobs they are doing in setting limits and enforcing rules effectively keep risk behavior down.”

She noted, however, that the survey did show that adopted adolescents reported more emotional distress and family disconnectedness than their nonadopted counterparts.

SAVANNAH, GA. — Brief metronidazole treatment has been associated with a case of reversible autonomic neuropathy in a 15-year-old girl, Lisa Hobson-Webb, M.D., reported in a poster at the annual meeting of the American Association of Electrodiagnostic Medicine.

“This has never been reported in the literature,” said Dr. Hobson-Webb of Wake Forest University, Winston-Salem, N.C. “There are cases of motor or sensory neuropathies after a large dose or an extended treatment period but not any reports of autonomic involvement.”

Dr. Hobson-Webb presented a case study of a 15-year-old black girl who had taken a 3-day course of metronidazole for bacterial vaginitis; she had been unresponsive to a prior course of trimethoprim-sulfamethoxazole. Within 2 weeks of initiating metronidazole treatment, the girl developed such a severe, burning pain in the soles of her feet that she found relief only by keeping her feet and lower legs submerged in buckets of ice water at all times. “She was even sleeping like this,” said Dr. Hobson-Webb.

The patient did not respond to pain medication, including oxycodone.

Examination revealed pitting edema and erythema to the mid-calf bilaterally. When removed from the ice water, the lower legs and feet rapidly became hot and erythematous. Her perception of temperature was reduced to the upper third of the shin bilaterally.

Deep tendon reflexes and strength were maintained. The patient's past medical history was unremarkable, and an examination showed no medical cause for her pain.

Nerve conduction studies showed reduced sensory nerve and compound muscle action potential. Reproducible sympathetic skin potential responses could not be obtained in the right foot, and only diminished responses were seen in the right hand.

“Based on these results, she was diagnosed with a severe sensorimotor and autonomic neuropathy, which was suspected to be a toxic reaction to the metronidazole,” Dr. Hobson-Webb said at the meeting.

The patient was placed on gabapentin and carbamazepine for pain control, and improved over several weeks. After 3 months, her neuropathy had clinically resolved and conduction studies showed normalization of autonomic function.

The mechanism underlying neurotoxicity of metronidazole is unclear. However, Dr. Hobson-Webb said, it's thought to be related to decreased protein synthesis in the nerve.

“We think the drug binds to RNA and decreases protein synthesis. All the case reports on this showed neuropathies with axon loss in myelinated fibers. Why it affected only the autonomic system in this case is hard to say,” she said.

SAVANNAH, GA. — Brief metronidazole treatment has been associated with a case of reversible autonomic neuropathy in a 15-year-old girl, Lisa Hobson-Webb, M.D., reported in a poster at the annual meeting of the American Association of Electrodiagnostic Medicine.

“This has never been reported in the literature,” said Dr. Hobson-Webb of Wake Forest University, Winston-Salem, N.C. “There are cases of motor or sensory neuropathies after a large dose or an extended treatment period but not any reports of autonomic involvement.”

Dr. Hobson-Webb presented a case study of a 15-year-old black girl who had taken a 3-day course of metronidazole for bacterial vaginitis; she had been unresponsive to a prior course of trimethoprim-sulfamethoxazole. Within 2 weeks of initiating metronidazole treatment, the girl developed such a severe, burning pain in the soles of her feet that she found relief only by keeping her feet and lower legs submerged in buckets of ice water at all times. “She was even sleeping like this,” said Dr. Hobson-Webb.

The patient did not respond to pain medication, including oxycodone.

Examination revealed pitting edema and erythema to the mid-calf bilaterally. When removed from the ice water, the lower legs and feet rapidly became hot and erythematous. Her perception of temperature was reduced to the upper third of the shin bilaterally.

Deep tendon reflexes and strength were maintained. The patient's past medical history was unremarkable, and an examination showed no medical cause for her pain.

Nerve conduction studies showed reduced sensory nerve and compound muscle action potential. Reproducible sympathetic skin potential responses could not be obtained in the right foot, and only diminished responses were seen in the right hand.

“Based on these results, she was diagnosed with a severe sensorimotor and autonomic neuropathy, which was suspected to be a toxic reaction to the metronidazole,” Dr. Hobson-Webb said at the meeting.

The patient was placed on gabapentin and carbamazepine for pain control, and improved over several weeks. After 3 months, her neuropathy had clinically resolved and conduction studies showed normalization of autonomic function.

The mechanism underlying neurotoxicity of metronidazole is unclear. However, Dr. Hobson-Webb said, it's thought to be related to decreased protein synthesis in the nerve.

“We think the drug binds to RNA and decreases protein synthesis. All the case reports on this showed neuropathies with axon loss in myelinated fibers. Why it affected only the autonomic system in this case is hard to say,” she said.

SAVANNAH, GA. — Brief metronidazole treatment has been associated with a case of reversible autonomic neuropathy in a 15-year-old girl, Lisa Hobson-Webb, M.D., reported in a poster at the annual meeting of the American Association of Electrodiagnostic Medicine.

“This has never been reported in the literature,” said Dr. Hobson-Webb of Wake Forest University, Winston-Salem, N.C. “There are cases of motor or sensory neuropathies after a large dose or an extended treatment period but not any reports of autonomic involvement.”

Dr. Hobson-Webb presented a case study of a 15-year-old black girl who had taken a 3-day course of metronidazole for bacterial vaginitis; she had been unresponsive to a prior course of trimethoprim-sulfamethoxazole. Within 2 weeks of initiating metronidazole treatment, the girl developed such a severe, burning pain in the soles of her feet that she found relief only by keeping her feet and lower legs submerged in buckets of ice water at all times. “She was even sleeping like this,” said Dr. Hobson-Webb.

The patient did not respond to pain medication, including oxycodone.

Examination revealed pitting edema and erythema to the mid-calf bilaterally. When removed from the ice water, the lower legs and feet rapidly became hot and erythematous. Her perception of temperature was reduced to the upper third of the shin bilaterally.

Deep tendon reflexes and strength were maintained. The patient's past medical history was unremarkable, and an examination showed no medical cause for her pain.

Nerve conduction studies showed reduced sensory nerve and compound muscle action potential. Reproducible sympathetic skin potential responses could not be obtained in the right foot, and only diminished responses were seen in the right hand.

“Based on these results, she was diagnosed with a severe sensorimotor and autonomic neuropathy, which was suspected to be a toxic reaction to the metronidazole,” Dr. Hobson-Webb said at the meeting.

The patient was placed on gabapentin and carbamazepine for pain control, and improved over several weeks. After 3 months, her neuropathy had clinically resolved and conduction studies showed normalization of autonomic function.

The mechanism underlying neurotoxicity of metronidazole is unclear. However, Dr. Hobson-Webb said, it's thought to be related to decreased protein synthesis in the nerve.

“We think the drug binds to RNA and decreases protein synthesis. All the case reports on this showed neuropathies with axon loss in myelinated fibers. Why it affected only the autonomic system in this case is hard to say,” she said.

SAVANNAH, GA. — Even women who have no symptoms of postpartum fecal incontinence can show subtle signs of pudendal nerve injury, Thomas Gregory, M.D., reported in a poster at the annual meeting of the American Association of Electrodiagnostic Medicine.

“There can be detectable evidence of nerve injury in asymptomatic women after a vaginal delivery, and there is evidence of even more injury in women who do have some bowel incontinence post partum,” commented Dr. Gregory of Oregon Health and Science University, Portland.

Because symptoms of fecal incontinence may not manifest for years, the influence of nerve injury sustained in childbirth has been debated, he said. Most previous studies have relied on pudendal nerve terminal motor latency, but this test is abnormal only when the largest, most heavily myelinated nerves are damaged; it does not detect subtle injury.

Needle electromyography (EMG) is a better way to assess this, but the test is difficult to perform on anal sphincter muscles, because these muscles are always contracted to maintain continence. However, a computer program using multi-motor unit action potential analysis can measure important quantitative parameters in these constantly contracted muscles.

Dr. Gregory obtained readings on 71 women (of whom 28 were nulliparous and 43 were primiparous). Of the primiparous women, 23 were asymptomatic at 12 weeks post partum, and 20 reported some level of fecal incontinence by 26-40 weeks post partum.

All primiparous subjects had vaginally delivered a single cephalic fetus with a mean birth weight of 3.495 kg; the mean length of second-stage labor was 75 minutes. There was one operative vaginal delivery in the asymptomatic group, and there were three in the symptomatic group.

Documented at birth were two anal sphincter lacerations in the asymptomatic group and four in the symptomatic group.

All women underwent an ultrasound examination of the anal sphincter. Pudendal nerve terminal motor latency (PNTML) was also assessed. Then, each woman underwent concentric needle EMG of the external anal sphincter. PNTML was not different among the three groups.

Three of the symptomatic women showed evidence of either persistent (noted originally at birth) or occult (not seen originally at birth) sphincter disruption on ultrasound. None of these women were incontinent to solid stool.

However, significant differences were seen between the primiparous and the nulliparous subjects in the motor unit action potentials recorded by EMG.

Both primiparous groups showed increased duration, amplitude, turns, and phases compared to the nulliparous group. These are signs of denervation/reinnervation and indicative of nerve injury. The injuries were probably caused by the compression and stretching of the pudendal nerve during childbirth, Dr. Gregory said.

The symptomatic women showed higher readings in all parameters than the asymptomatic women, indicating that they had experienced a more severe injury.

SAVANNAH, GA. — Even women who have no symptoms of postpartum fecal incontinence can show subtle signs of pudendal nerve injury, Thomas Gregory, M.D., reported in a poster at the annual meeting of the American Association of Electrodiagnostic Medicine.

“There can be detectable evidence of nerve injury in asymptomatic women after a vaginal delivery, and there is evidence of even more injury in women who do have some bowel incontinence post partum,” commented Dr. Gregory of Oregon Health and Science University, Portland.

Because symptoms of fecal incontinence may not manifest for years, the influence of nerve injury sustained in childbirth has been debated, he said. Most previous studies have relied on pudendal nerve terminal motor latency, but this test is abnormal only when the largest, most heavily myelinated nerves are damaged; it does not detect subtle injury.

Needle electromyography (EMG) is a better way to assess this, but the test is difficult to perform on anal sphincter muscles, because these muscles are always contracted to maintain continence. However, a computer program using multi-motor unit action potential analysis can measure important quantitative parameters in these constantly contracted muscles.

Dr. Gregory obtained readings on 71 women (of whom 28 were nulliparous and 43 were primiparous). Of the primiparous women, 23 were asymptomatic at 12 weeks post partum, and 20 reported some level of fecal incontinence by 26-40 weeks post partum.

All primiparous subjects had vaginally delivered a single cephalic fetus with a mean birth weight of 3.495 kg; the mean length of second-stage labor was 75 minutes. There was one operative vaginal delivery in the asymptomatic group, and there were three in the symptomatic group.

Documented at birth were two anal sphincter lacerations in the asymptomatic group and four in the symptomatic group.

All women underwent an ultrasound examination of the anal sphincter. Pudendal nerve terminal motor latency (PNTML) was also assessed. Then, each woman underwent concentric needle EMG of the external anal sphincter. PNTML was not different among the three groups.

Three of the symptomatic women showed evidence of either persistent (noted originally at birth) or occult (not seen originally at birth) sphincter disruption on ultrasound. None of these women were incontinent to solid stool.

However, significant differences were seen between the primiparous and the nulliparous subjects in the motor unit action potentials recorded by EMG.

Both primiparous groups showed increased duration, amplitude, turns, and phases compared to the nulliparous group. These are signs of denervation/reinnervation and indicative of nerve injury. The injuries were probably caused by the compression and stretching of the pudendal nerve during childbirth, Dr. Gregory said.

The symptomatic women showed higher readings in all parameters than the asymptomatic women, indicating that they had experienced a more severe injury.

SAVANNAH, GA. — Even women who have no symptoms of postpartum fecal incontinence can show subtle signs of pudendal nerve injury, Thomas Gregory, M.D., reported in a poster at the annual meeting of the American Association of Electrodiagnostic Medicine.

“There can be detectable evidence of nerve injury in asymptomatic women after a vaginal delivery, and there is evidence of even more injury in women who do have some bowel incontinence post partum,” commented Dr. Gregory of Oregon Health and Science University, Portland.

Because symptoms of fecal incontinence may not manifest for years, the influence of nerve injury sustained in childbirth has been debated, he said. Most previous studies have relied on pudendal nerve terminal motor latency, but this test is abnormal only when the largest, most heavily myelinated nerves are damaged; it does not detect subtle injury.

Needle electromyography (EMG) is a better way to assess this, but the test is difficult to perform on anal sphincter muscles, because these muscles are always contracted to maintain continence. However, a computer program using multi-motor unit action potential analysis can measure important quantitative parameters in these constantly contracted muscles.

Dr. Gregory obtained readings on 71 women (of whom 28 were nulliparous and 43 were primiparous). Of the primiparous women, 23 were asymptomatic at 12 weeks post partum, and 20 reported some level of fecal incontinence by 26-40 weeks post partum.

All primiparous subjects had vaginally delivered a single cephalic fetus with a mean birth weight of 3.495 kg; the mean length of second-stage labor was 75 minutes. There was one operative vaginal delivery in the asymptomatic group, and there were three in the symptomatic group.

Documented at birth were two anal sphincter lacerations in the asymptomatic group and four in the symptomatic group.

All women underwent an ultrasound examination of the anal sphincter. Pudendal nerve terminal motor latency (PNTML) was also assessed. Then, each woman underwent concentric needle EMG of the external anal sphincter. PNTML was not different among the three groups.

Three of the symptomatic women showed evidence of either persistent (noted originally at birth) or occult (not seen originally at birth) sphincter disruption on ultrasound. None of these women were incontinent to solid stool.

However, significant differences were seen between the primiparous and the nulliparous subjects in the motor unit action potentials recorded by EMG.

Both primiparous groups showed increased duration, amplitude, turns, and phases compared to the nulliparous group. These are signs of denervation/reinnervation and indicative of nerve injury. The injuries were probably caused by the compression and stretching of the pudendal nerve during childbirth, Dr. Gregory said.

The symptomatic women showed higher readings in all parameters than the asymptomatic women, indicating that they had experienced a more severe injury.

NEW ORLEANS — Here's one more reason to advise overweight men to shed pounds: Obese men have serum markers of compromised fertility, and men who have fathered children tend to have lower body mass indexes than do those without children.

It's long been established that excess weight can impair female fertility. But a study presented in a poster session at the annual meeting of the Endocrine Society indicates that increasing body mass index (BMI) in males is associated with decreased testosterone and inhibin B levels.

“Lower inhibin B levels are indicative of dysfunction in the seminiferous tubules,” said Eric Pauli, M.D., of the Pennsylvania State University, Hershey. “Our findings indicate that these lower serum inhibin B levels point to decreased tubule function, and that inhibin B might even be a more sensitive way of detecting compromised fertility in men than a semen analysis,” he said.

Dr. Pauli analyzed semen and serum fertility markers in 87 men aged 19–48 years whose BMIs ranged from 16 to 47 kg/m

In addition to providing blood and semen samples, the men had their skinfold thickness measured and underwent testicular examinations to document testicular volume and rule out undiagnosed disease. They also answered questions about paternity status, history of infertility in self or partner, and alcohol and tobacco use.

Blood was tested for inhibin B, FSH, luteinizing hormone, testosterone, and free testosterone. Semen was examined for motility, volume, and concentration.

Almost 70% of the men had a history of paternity; they had lower BMIs (26 kg/m

Patients whose BMIs were around 42.5 kg/m

Men with BMIs of about 42.5 kg/m

There was no association of body fat with luteinizing hormone or with any semen analysis factor. However, lower inhibin B levels were associated with lower sperm motility. Free testosterone was not associated with body fat.

“These guys seem to make normal amounts of sperm, because their sperm count and sperm motility are not different from normal-weight men,” Dr. Pauli said. “However, their inhibin B, which is a marker for normal sperm cell production, is lower, suggesting that their testes make sperm that is in some way dysfunctional. We don't know the nature of this dysfunction, yet.”

NEW ORLEANS — Here's one more reason to advise overweight men to shed pounds: Obese men have serum markers of compromised fertility, and men who have fathered children tend to have lower body mass indexes than do those without children.

It's long been established that excess weight can impair female fertility. But a study presented in a poster session at the annual meeting of the Endocrine Society indicates that increasing body mass index (BMI) in males is associated with decreased testosterone and inhibin B levels.

“Lower inhibin B levels are indicative of dysfunction in the seminiferous tubules,” said Eric Pauli, M.D., of the Pennsylvania State University, Hershey. “Our findings indicate that these lower serum inhibin B levels point to decreased tubule function, and that inhibin B might even be a more sensitive way of detecting compromised fertility in men than a semen analysis,” he said.

Dr. Pauli analyzed semen and serum fertility markers in 87 men aged 19–48 years whose BMIs ranged from 16 to 47 kg/m

In addition to providing blood and semen samples, the men had their skinfold thickness measured and underwent testicular examinations to document testicular volume and rule out undiagnosed disease. They also answered questions about paternity status, history of infertility in self or partner, and alcohol and tobacco use.

Blood was tested for inhibin B, FSH, luteinizing hormone, testosterone, and free testosterone. Semen was examined for motility, volume, and concentration.

Almost 70% of the men had a history of paternity; they had lower BMIs (26 kg/m

Patients whose BMIs were around 42.5 kg/m

Men with BMIs of about 42.5 kg/m

There was no association of body fat with luteinizing hormone or with any semen analysis factor. However, lower inhibin B levels were associated with lower sperm motility. Free testosterone was not associated with body fat.

“These guys seem to make normal amounts of sperm, because their sperm count and sperm motility are not different from normal-weight men,” Dr. Pauli said. “However, their inhibin B, which is a marker for normal sperm cell production, is lower, suggesting that their testes make sperm that is in some way dysfunctional. We don't know the nature of this dysfunction, yet.”

NEW ORLEANS — Here's one more reason to advise overweight men to shed pounds: Obese men have serum markers of compromised fertility, and men who have fathered children tend to have lower body mass indexes than do those without children.

It's long been established that excess weight can impair female fertility. But a study presented in a poster session at the annual meeting of the Endocrine Society indicates that increasing body mass index (BMI) in males is associated with decreased testosterone and inhibin B levels.

“Lower inhibin B levels are indicative of dysfunction in the seminiferous tubules,” said Eric Pauli, M.D., of the Pennsylvania State University, Hershey. “Our findings indicate that these lower serum inhibin B levels point to decreased tubule function, and that inhibin B might even be a more sensitive way of detecting compromised fertility in men than a semen analysis,” he said.

Dr. Pauli analyzed semen and serum fertility markers in 87 men aged 19–48 years whose BMIs ranged from 16 to 47 kg/m

In addition to providing blood and semen samples, the men had their skinfold thickness measured and underwent testicular examinations to document testicular volume and rule out undiagnosed disease. They also answered questions about paternity status, history of infertility in self or partner, and alcohol and tobacco use.

Blood was tested for inhibin B, FSH, luteinizing hormone, testosterone, and free testosterone. Semen was examined for motility, volume, and concentration.

Almost 70% of the men had a history of paternity; they had lower BMIs (26 kg/m

Patients whose BMIs were around 42.5 kg/m

Men with BMIs of about 42.5 kg/m

There was no association of body fat with luteinizing hormone or with any semen analysis factor. However, lower inhibin B levels were associated with lower sperm motility. Free testosterone was not associated with body fat.

“These guys seem to make normal amounts of sperm, because their sperm count and sperm motility are not different from normal-weight men,” Dr. Pauli said. “However, their inhibin B, which is a marker for normal sperm cell production, is lower, suggesting that their testes make sperm that is in some way dysfunctional. We don't know the nature of this dysfunction, yet.”

A program of screening for and treating asymptomatic vaginal infections was associated with a significant reduction in preterm birth and miscarriage in a randomized controlled trial of more than 4,000 women.

Researchers randomized 4,155 pregnant women to receive either screening and treatment or screening and no treatment. The screening was administered at a routine prenatal visit between week 15 and 19 of pregnancy, and the women were screened for bacterial vaginosis, Candida, or Trichomonas vaginalis, or combinations of any of the three, noted Dr. Herbert Kiss and his associates at the University of Vienna, Austria (BMJ 2004;329:371).

About 80% of the women had no vaginal infection; 13% had Candida colonization, 7% had bacterial vaginosis, and 1.5% had a combination of bacterial vaginosis and candidiasis. Three women had a trichomonal infection and two had a combination of bacterial vaginosis and trichomoniasis.

Women in the intervention group who had an infection received the appropriate treatment from their obstetricians. They were evaluated at the next prenatal visit. Those with persistent infection received additional treatment. Screening results for women in the control group were withheld from those obstetricians so that they did not influence her standard prenatal care.

The rate of spontaneous preterm birth was 3% in the intervention group and 5.3% in the control group. The rate of preterm infants weighing 2,500 g or less was significantly lower in the intervention group than in the control group (1.7% vs 3.5%). The number of spontaneous preterm births in the lower weight categories was 50% lower in the intervention group. The rate of late miscarriages was also reduced by 50%.

There were no significant differences between groups in intrauterine death, meconium passage, necrotizing enterocolitis, neonatal sepsis, or neonatal death.

A subgroup analysis showed the greatest treatment effect occurred in the women with a diagnosis of vaginal candidiasis. The number of spontaneous preterm births was almost three times higher in women who were not treated for candidiasis than in those who were treated (20 births vs. 7 births). A much smaller effect was seen in the group with bacterial vaginosis; there were eight spontaneous preterm births in the untreated women and five in the treated women.

Candidiasis has not been associated with preterm birth. However, the researchers suggested, obstetricians who knew their patients had a vaginal infection may have followed them more closely, thus accounting for the good results in the treated group.

In an accompanying editorial, Dr. Anna Alanen agreed that something other than infection treatment probably accounted for the improved outcomes in the intervention group. “The study … is in agreement with most previous studies concerning the failure of antenatal treatment of bacterial vaginosis to prevent preterm birth. The rate of preterm birth was, however, significantly lower in the intervention group, implying that factors connected to the screening program, including the role of candidiasis, deserve further studies.”

A program of screening for and treating asymptomatic vaginal infections was associated with a significant reduction in preterm birth and miscarriage in a randomized controlled trial of more than 4,000 women.

Researchers randomized 4,155 pregnant women to receive either screening and treatment or screening and no treatment. The screening was administered at a routine prenatal visit between week 15 and 19 of pregnancy, and the women were screened for bacterial vaginosis, Candida, or Trichomonas vaginalis, or combinations of any of the three, noted Dr. Herbert Kiss and his associates at the University of Vienna, Austria (BMJ 2004;329:371).

About 80% of the women had no vaginal infection; 13% had Candida colonization, 7% had bacterial vaginosis, and 1.5% had a combination of bacterial vaginosis and candidiasis. Three women had a trichomonal infection and two had a combination of bacterial vaginosis and trichomoniasis.

Women in the intervention group who had an infection received the appropriate treatment from their obstetricians. They were evaluated at the next prenatal visit. Those with persistent infection received additional treatment. Screening results for women in the control group were withheld from those obstetricians so that they did not influence her standard prenatal care.

The rate of spontaneous preterm birth was 3% in the intervention group and 5.3% in the control group. The rate of preterm infants weighing 2,500 g or less was significantly lower in the intervention group than in the control group (1.7% vs 3.5%). The number of spontaneous preterm births in the lower weight categories was 50% lower in the intervention group. The rate of late miscarriages was also reduced by 50%.

There were no significant differences between groups in intrauterine death, meconium passage, necrotizing enterocolitis, neonatal sepsis, or neonatal death.

A subgroup analysis showed the greatest treatment effect occurred in the women with a diagnosis of vaginal candidiasis. The number of spontaneous preterm births was almost three times higher in women who were not treated for candidiasis than in those who were treated (20 births vs. 7 births). A much smaller effect was seen in the group with bacterial vaginosis; there were eight spontaneous preterm births in the untreated women and five in the treated women.

Candidiasis has not been associated with preterm birth. However, the researchers suggested, obstetricians who knew their patients had a vaginal infection may have followed them more closely, thus accounting for the good results in the treated group.

In an accompanying editorial, Dr. Anna Alanen agreed that something other than infection treatment probably accounted for the improved outcomes in the intervention group. “The study … is in agreement with most previous studies concerning the failure of antenatal treatment of bacterial vaginosis to prevent preterm birth. The rate of preterm birth was, however, significantly lower in the intervention group, implying that factors connected to the screening program, including the role of candidiasis, deserve further studies.”

A program of screening for and treating asymptomatic vaginal infections was associated with a significant reduction in preterm birth and miscarriage in a randomized controlled trial of more than 4,000 women.

Researchers randomized 4,155 pregnant women to receive either screening and treatment or screening and no treatment. The screening was administered at a routine prenatal visit between week 15 and 19 of pregnancy, and the women were screened for bacterial vaginosis, Candida, or Trichomonas vaginalis, or combinations of any of the three, noted Dr. Herbert Kiss and his associates at the University of Vienna, Austria (BMJ 2004;329:371).

About 80% of the women had no vaginal infection; 13% had Candida colonization, 7% had bacterial vaginosis, and 1.5% had a combination of bacterial vaginosis and candidiasis. Three women had a trichomonal infection and two had a combination of bacterial vaginosis and trichomoniasis.

Women in the intervention group who had an infection received the appropriate treatment from their obstetricians. They were evaluated at the next prenatal visit. Those with persistent infection received additional treatment. Screening results for women in the control group were withheld from those obstetricians so that they did not influence her standard prenatal care.

The rate of spontaneous preterm birth was 3% in the intervention group and 5.3% in the control group. The rate of preterm infants weighing 2,500 g or less was significantly lower in the intervention group than in the control group (1.7% vs 3.5%). The number of spontaneous preterm births in the lower weight categories was 50% lower in the intervention group. The rate of late miscarriages was also reduced by 50%.

There were no significant differences between groups in intrauterine death, meconium passage, necrotizing enterocolitis, neonatal sepsis, or neonatal death.

A subgroup analysis showed the greatest treatment effect occurred in the women with a diagnosis of vaginal candidiasis. The number of spontaneous preterm births was almost three times higher in women who were not treated for candidiasis than in those who were treated (20 births vs. 7 births). A much smaller effect was seen in the group with bacterial vaginosis; there were eight spontaneous preterm births in the untreated women and five in the treated women.

Candidiasis has not been associated with preterm birth. However, the researchers suggested, obstetricians who knew their patients had a vaginal infection may have followed them more closely, thus accounting for the good results in the treated group.

In an accompanying editorial, Dr. Anna Alanen agreed that something other than infection treatment probably accounted for the improved outcomes in the intervention group. “The study … is in agreement with most previous studies concerning the failure of antenatal treatment of bacterial vaginosis to prevent preterm birth. The rate of preterm birth was, however, significantly lower in the intervention group, implying that factors connected to the screening program, including the role of candidiasis, deserve further studies.”

NEW ORLEANS — Female victims of sexual and physical assault show a high rate of postassault alcohol abuse, which is associated with a more severe course of posttraumatic stress disorder.

Compared with nondrinking women, those with alcohol use disorders (AUD) were significantly more likely to have severe PTSD symptoms, especially intrusion symptoms. Even past alcohol users showed more severe symptoms than did nonusers, Debra Kaysen, Ph.D., said at the annual meeting of the Association for the Advancement of Behavioral Therapy.

Her findings suggest that all assault victims should be carefully screened for both past and present AUD. “My experience is that this is not necessarily done in all cases,” said Dr. Kaysen, of the University of Washington, Seattle. “It's not enough just to ask about current use, because past use is apparently also a risk factor.”

Dr. Kaysen saw 189 women within 2 weeks of either a sexual or physical assault, and 66% (124) of them returned for a 3-month follow-up. The women were young (mean 31 years), and most were black, single, and poor, with 50% making less than $5,000 a year. The women were recruited through local emergency departments, police departments, and community victim services agencies.

Alcohol use and abuse were assessed with the Structured Clinical Interview for DSM-III-R, and PTSD was assessed with the Clinician-Administered PTSD Scale (CAPS).

No symptoms of PTSD were present in 22% of the group. Thirty-five percent of the group showed acute PTSD symptoms 2 weeks after the assault but not at follow-up. Thirty-eight percent showed a chronic course; they were symptomatic at both 2 weeks and 3 months. Delayed onset occurred in 5% of the women; they showed no symptoms at 2 weeks but were symptomatic by the 3-month follow-up.

Most of the women (71%) had no AUD, either current or past. A past history but no acute drinking was found in 17%. Acute AUD occurred in 3%. These women, previously nondrinkers, began drinking at 2 weeks but had stopped by 3 months. Two percent of the group experienced a delayed onset of AUD, 4% had quit drinking in the past but experienced a relapse after the assault, and 2% had a chronic course of AUD.

At the initial visit, women with AUD had the most severe intrusive symptoms—indicated by an average CAPS score of about 26. Women with a past history had a CAPS score of about 22, whereas nondrinkers had a score of about 18.

Symptoms improved at almost the same rate in all of the women over the study period. By 3 months, however, women with current AUD still had more severe intrusive symptoms (CAPS score of 18) than those with a past history of AUD (CAPS score of 15) and those without AUD (CAPS score of 12).

“The women who were drinking got better but never made up the ground they had lost at the very beginning,” Dr. Kaysen said.

She saw a trend toward even worse results in avoidance symptoms among current drinkers. Their average CAPS score fell from about 27 to only 25 by 3 months, compared with a fall from 29 to 23 for those with a past history. The score for nondrinkers fell from 23 to 15.

Because the number of women with current AUD was small, Dr. Kaysen said her results must be interpreted with caution. The combination of PTSD and alcohol use, however, is “clearly potentially devastating” and should spark proactive intervention.

It's important to protect women with acute posttraumatic alcohol use from developing a full-blown alcohol use disorder. “We might think about teaching relapse-prevention skills or using motivational enhancement therapy to prevent the development of alcohol use disorders in those with high-risk drinking” she said.

NEW ORLEANS — Female victims of sexual and physical assault show a high rate of postassault alcohol abuse, which is associated with a more severe course of posttraumatic stress disorder.

Compared with nondrinking women, those with alcohol use disorders (AUD) were significantly more likely to have severe PTSD symptoms, especially intrusion symptoms. Even past alcohol users showed more severe symptoms than did nonusers, Debra Kaysen, Ph.D., said at the annual meeting of the Association for the Advancement of Behavioral Therapy.

Her findings suggest that all assault victims should be carefully screened for both past and present AUD. “My experience is that this is not necessarily done in all cases,” said Dr. Kaysen, of the University of Washington, Seattle. “It's not enough just to ask about current use, because past use is apparently also a risk factor.”

Dr. Kaysen saw 189 women within 2 weeks of either a sexual or physical assault, and 66% (124) of them returned for a 3-month follow-up. The women were young (mean 31 years), and most were black, single, and poor, with 50% making less than $5,000 a year. The women were recruited through local emergency departments, police departments, and community victim services agencies.

Alcohol use and abuse were assessed with the Structured Clinical Interview for DSM-III-R, and PTSD was assessed with the Clinician-Administered PTSD Scale (CAPS).

No symptoms of PTSD were present in 22% of the group. Thirty-five percent of the group showed acute PTSD symptoms 2 weeks after the assault but not at follow-up. Thirty-eight percent showed a chronic course; they were symptomatic at both 2 weeks and 3 months. Delayed onset occurred in 5% of the women; they showed no symptoms at 2 weeks but were symptomatic by the 3-month follow-up.

Most of the women (71%) had no AUD, either current or past. A past history but no acute drinking was found in 17%. Acute AUD occurred in 3%. These women, previously nondrinkers, began drinking at 2 weeks but had stopped by 3 months. Two percent of the group experienced a delayed onset of AUD, 4% had quit drinking in the past but experienced a relapse after the assault, and 2% had a chronic course of AUD.

At the initial visit, women with AUD had the most severe intrusive symptoms—indicated by an average CAPS score of about 26. Women with a past history had a CAPS score of about 22, whereas nondrinkers had a score of about 18.

Symptoms improved at almost the same rate in all of the women over the study period. By 3 months, however, women with current AUD still had more severe intrusive symptoms (CAPS score of 18) than those with a past history of AUD (CAPS score of 15) and those without AUD (CAPS score of 12).

“The women who were drinking got better but never made up the ground they had lost at the very beginning,” Dr. Kaysen said.

She saw a trend toward even worse results in avoidance symptoms among current drinkers. Their average CAPS score fell from about 27 to only 25 by 3 months, compared with a fall from 29 to 23 for those with a past history. The score for nondrinkers fell from 23 to 15.

Because the number of women with current AUD was small, Dr. Kaysen said her results must be interpreted with caution. The combination of PTSD and alcohol use, however, is “clearly potentially devastating” and should spark proactive intervention.

It's important to protect women with acute posttraumatic alcohol use from developing a full-blown alcohol use disorder. “We might think about teaching relapse-prevention skills or using motivational enhancement therapy to prevent the development of alcohol use disorders in those with high-risk drinking” she said.

NEW ORLEANS — Female victims of sexual and physical assault show a high rate of postassault alcohol abuse, which is associated with a more severe course of posttraumatic stress disorder.

Compared with nondrinking women, those with alcohol use disorders (AUD) were significantly more likely to have severe PTSD symptoms, especially intrusion symptoms. Even past alcohol users showed more severe symptoms than did nonusers, Debra Kaysen, Ph.D., said at the annual meeting of the Association for the Advancement of Behavioral Therapy.

Her findings suggest that all assault victims should be carefully screened for both past and present AUD. “My experience is that this is not necessarily done in all cases,” said Dr. Kaysen, of the University of Washington, Seattle. “It's not enough just to ask about current use, because past use is apparently also a risk factor.”

Dr. Kaysen saw 189 women within 2 weeks of either a sexual or physical assault, and 66% (124) of them returned for a 3-month follow-up. The women were young (mean 31 years), and most were black, single, and poor, with 50% making less than $5,000 a year. The women were recruited through local emergency departments, police departments, and community victim services agencies.

Alcohol use and abuse were assessed with the Structured Clinical Interview for DSM-III-R, and PTSD was assessed with the Clinician-Administered PTSD Scale (CAPS).

No symptoms of PTSD were present in 22% of the group. Thirty-five percent of the group showed acute PTSD symptoms 2 weeks after the assault but not at follow-up. Thirty-eight percent showed a chronic course; they were symptomatic at both 2 weeks and 3 months. Delayed onset occurred in 5% of the women; they showed no symptoms at 2 weeks but were symptomatic by the 3-month follow-up.

Most of the women (71%) had no AUD, either current or past. A past history but no acute drinking was found in 17%. Acute AUD occurred in 3%. These women, previously nondrinkers, began drinking at 2 weeks but had stopped by 3 months. Two percent of the group experienced a delayed onset of AUD, 4% had quit drinking in the past but experienced a relapse after the assault, and 2% had a chronic course of AUD.

At the initial visit, women with AUD had the most severe intrusive symptoms—indicated by an average CAPS score of about 26. Women with a past history had a CAPS score of about 22, whereas nondrinkers had a score of about 18.

Symptoms improved at almost the same rate in all of the women over the study period. By 3 months, however, women with current AUD still had more severe intrusive symptoms (CAPS score of 18) than those with a past history of AUD (CAPS score of 15) and those without AUD (CAPS score of 12).

“The women who were drinking got better but never made up the ground they had lost at the very beginning,” Dr. Kaysen said.

She saw a trend toward even worse results in avoidance symptoms among current drinkers. Their average CAPS score fell from about 27 to only 25 by 3 months, compared with a fall from 29 to 23 for those with a past history. The score for nondrinkers fell from 23 to 15.

Because the number of women with current AUD was small, Dr. Kaysen said her results must be interpreted with caution. The combination of PTSD and alcohol use, however, is “clearly potentially devastating” and should spark proactive intervention.

It's important to protect women with acute posttraumatic alcohol use from developing a full-blown alcohol use disorder. “We might think about teaching relapse-prevention skills or using motivational enhancement therapy to prevent the development of alcohol use disorders in those with high-risk drinking” she said.

NEW YORK — Reading performance will return to normal in children who have lagged behind because of hearing impairment associated with chronic middle ear infections, Avishay Golz, M.D., said at the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery Foundation.

“Reading performance is not affected once these children are healed and their hearing is restored,” said Dr. Golz of Ramban Medical Center, Haifa, Israel. “They catch up very rapidly to the same level as children who have never had otologic problems.”

Dr. Golz presented the results of a follow-up study on the reading performance of 75 children with chronic middle ear infection; the same group was the subject of a similar study he conducted 4 years ago.

At that time, the children were in first or second grade; they are now in fifth or sixth grade.

In the initial study, Dr. Golz found that the children with chronic ear infections and associated hearing loss made significantly more mistakes in a reading exercise than their classmates, who were matched for gender, age, socioeconomic status, and culture.

The reading scores were expressed as a percentage of mistakes made out of possible mistakes in the passage.

The children with ear infections scored an average of 15%, compared with an average of 5% for children without infections.

The follow-up study included 75 of the original 80 subjects; the children ranged in age from 10 to 11.7 years. Of this group, 64 no longer had otologic infections and had regained normal hearing. Eleven children still had middle ear disorders, including perforations of the eardrum, middle ear effusion, or infected eardrums. Hearing loss in this group ranged from 24 to 45 dB.

The control group consisted of 60 of the subjects' classmates. All controls had a negative history of middle ear infection and had normal tympanic membranes and normal hearing thresholds.

All children received a complete ear, nose, and throat examination and audiologic assessment; they also received two reading tests 4-6 months apart. Each reading test had a possibly of 220 mistakes; the expected average score was 5%.

The control group scored an average of 3.1% on the test, while the children whose ear infections had resolved scored an average of 3.4% — not a significant difference. The children whose ear problems persisted scored an average of 7% — significantly worse than the scores of either of the other groups.

The unhealed children scored better than they did in the initial study, but the second scores were still worse than what was considered an acceptable average, Dr. Golz pointed out.

“Although the children had improved their performance, this should still be regarded as functionally significant,” he said.

Teachers should be made aware of chronic ear disorders that can affect hearing and impede reading development, as well as other academic areas.

NEW YORK — Reading performance will return to normal in children who have lagged behind because of hearing impairment associated with chronic middle ear infections, Avishay Golz, M.D., said at the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery Foundation.

“Reading performance is not affected once these children are healed and their hearing is restored,” said Dr. Golz of Ramban Medical Center, Haifa, Israel. “They catch up very rapidly to the same level as children who have never had otologic problems.”

Dr. Golz presented the results of a follow-up study on the reading performance of 75 children with chronic middle ear infection; the same group was the subject of a similar study he conducted 4 years ago.

At that time, the children were in first or second grade; they are now in fifth or sixth grade.

In the initial study, Dr. Golz found that the children with chronic ear infections and associated hearing loss made significantly more mistakes in a reading exercise than their classmates, who were matched for gender, age, socioeconomic status, and culture.

The reading scores were expressed as a percentage of mistakes made out of possible mistakes in the passage.

The children with ear infections scored an average of 15%, compared with an average of 5% for children without infections.

The follow-up study included 75 of the original 80 subjects; the children ranged in age from 10 to 11.7 years. Of this group, 64 no longer had otologic infections and had regained normal hearing. Eleven children still had middle ear disorders, including perforations of the eardrum, middle ear effusion, or infected eardrums. Hearing loss in this group ranged from 24 to 45 dB.

The control group consisted of 60 of the subjects' classmates. All controls had a negative history of middle ear infection and had normal tympanic membranes and normal hearing thresholds.

All children received a complete ear, nose, and throat examination and audiologic assessment; they also received two reading tests 4-6 months apart. Each reading test had a possibly of 220 mistakes; the expected average score was 5%.

The control group scored an average of 3.1% on the test, while the children whose ear infections had resolved scored an average of 3.4% — not a significant difference. The children whose ear problems persisted scored an average of 7% — significantly worse than the scores of either of the other groups.

The unhealed children scored better than they did in the initial study, but the second scores were still worse than what was considered an acceptable average, Dr. Golz pointed out.

“Although the children had improved their performance, this should still be regarded as functionally significant,” he said.

Teachers should be made aware of chronic ear disorders that can affect hearing and impede reading development, as well as other academic areas.

NEW YORK — Reading performance will return to normal in children who have lagged behind because of hearing impairment associated with chronic middle ear infections, Avishay Golz, M.D., said at the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery Foundation.

“Reading performance is not affected once these children are healed and their hearing is restored,” said Dr. Golz of Ramban Medical Center, Haifa, Israel. “They catch up very rapidly to the same level as children who have never had otologic problems.”

Dr. Golz presented the results of a follow-up study on the reading performance of 75 children with chronic middle ear infection; the same group was the subject of a similar study he conducted 4 years ago.

At that time, the children were in first or second grade; they are now in fifth or sixth grade.

In the initial study, Dr. Golz found that the children with chronic ear infections and associated hearing loss made significantly more mistakes in a reading exercise than their classmates, who were matched for gender, age, socioeconomic status, and culture.

The reading scores were expressed as a percentage of mistakes made out of possible mistakes in the passage.

The children with ear infections scored an average of 15%, compared with an average of 5% for children without infections.

The follow-up study included 75 of the original 80 subjects; the children ranged in age from 10 to 11.7 years. Of this group, 64 no longer had otologic infections and had regained normal hearing. Eleven children still had middle ear disorders, including perforations of the eardrum, middle ear effusion, or infected eardrums. Hearing loss in this group ranged from 24 to 45 dB.

The control group consisted of 60 of the subjects' classmates. All controls had a negative history of middle ear infection and had normal tympanic membranes and normal hearing thresholds.

All children received a complete ear, nose, and throat examination and audiologic assessment; they also received two reading tests 4-6 months apart. Each reading test had a possibly of 220 mistakes; the expected average score was 5%.

The control group scored an average of 3.1% on the test, while the children whose ear infections had resolved scored an average of 3.4% — not a significant difference. The children whose ear problems persisted scored an average of 7% — significantly worse than the scores of either of the other groups.

The unhealed children scored better than they did in the initial study, but the second scores were still worse than what was considered an acceptable average, Dr. Golz pointed out.

“Although the children had improved their performance, this should still be regarded as functionally significant,” he said.

Teachers should be made aware of chronic ear disorders that can affect hearing and impede reading development, as well as other academic areas.

NEW ORLEANS — Physiologic doses of growth hormone can increase exercise capacity in adults with growth hormone deficiency, as well as improve their body composition and lipid levels, Jostein Hallen, M.D., said at the annual meeting of the Endocrine Society.

The 7% increase in exercise capacity that he found in his placebo-controlled study “is similar to what you would see if you put a similar population on a training program,” said Dr. Hallen of Norwegian University of Sport and Physical Education, Oslo.

The small study included 55 patients with adult-onset growth hormone deficiency; 96% had multiple pituitary hormone deficiencies; 4% had isolated growth hormone deficiency. Mean body mass index for men was 29; the mean BMI for women was 26. Average subject age was 48.5 years.

As many patients were already taking growth hormone, the study began with a 4-month washout period. Then, subjects were randomized to 9 months of placebo or growth hormone. Subjects' therapy was titrated to acheive an insulin-like growth factor-1 (IGF-1) level within the upper normal range for their age and sex. Final mean daily dose was 0.4 mg for men and 0.6 mg for women.

At outset, subject exercise capacity was determined by treadmill, increased until exhaustion occurred. Body composition was measured by dual-energy x-ray absorptiometry. Three quality-of-life scales were completed.

In men who took growth hormone, the mean IGF-1 levels increased from 95 mg/L to 216 mg/L; in women, the mean level increased from 68 mg/L to 186 mg/L. Subjects in the study group lost an average of 1.9 kg of fat and gained 1.8 kg of lean body mass. Their total and LDL cholesterol levels both dropped an average of 0.5 mmol/L.

Compared with placebo, growth hormone treatment increased the subjects' maximal oxygen uptake by 6%. Endurance increased by 7% over baseline in the study group.

There were no significant effects on quality of life, Dr. Hallen said, who is an investigator for Pfizer Inc. The company funded the study and supplied the drug.

NEW ORLEANS — Physiologic doses of growth hormone can increase exercise capacity in adults with growth hormone deficiency, as well as improve their body composition and lipid levels, Jostein Hallen, M.D., said at the annual meeting of the Endocrine Society.

The 7% increase in exercise capacity that he found in his placebo-controlled study “is similar to what you would see if you put a similar population on a training program,” said Dr. Hallen of Norwegian University of Sport and Physical Education, Oslo.

The small study included 55 patients with adult-onset growth hormone deficiency; 96% had multiple pituitary hormone deficiencies; 4% had isolated growth hormone deficiency. Mean body mass index for men was 29; the mean BMI for women was 26. Average subject age was 48.5 years.

As many patients were already taking growth hormone, the study began with a 4-month washout period. Then, subjects were randomized to 9 months of placebo or growth hormone. Subjects' therapy was titrated to acheive an insulin-like growth factor-1 (IGF-1) level within the upper normal range for their age and sex. Final mean daily dose was 0.4 mg for men and 0.6 mg for women.

At outset, subject exercise capacity was determined by treadmill, increased until exhaustion occurred. Body composition was measured by dual-energy x-ray absorptiometry. Three quality-of-life scales were completed.

In men who took growth hormone, the mean IGF-1 levels increased from 95 mg/L to 216 mg/L; in women, the mean level increased from 68 mg/L to 186 mg/L. Subjects in the study group lost an average of 1.9 kg of fat and gained 1.8 kg of lean body mass. Their total and LDL cholesterol levels both dropped an average of 0.5 mmol/L.

Compared with placebo, growth hormone treatment increased the subjects' maximal oxygen uptake by 6%. Endurance increased by 7% over baseline in the study group.

There were no significant effects on quality of life, Dr. Hallen said, who is an investigator for Pfizer Inc. The company funded the study and supplied the drug.

NEW ORLEANS — Physiologic doses of growth hormone can increase exercise capacity in adults with growth hormone deficiency, as well as improve their body composition and lipid levels, Jostein Hallen, M.D., said at the annual meeting of the Endocrine Society.

The 7% increase in exercise capacity that he found in his placebo-controlled study “is similar to what you would see if you put a similar population on a training program,” said Dr. Hallen of Norwegian University of Sport and Physical Education, Oslo.

The small study included 55 patients with adult-onset growth hormone deficiency; 96% had multiple pituitary hormone deficiencies; 4% had isolated growth hormone deficiency. Mean body mass index for men was 29; the mean BMI for women was 26. Average subject age was 48.5 years.

As many patients were already taking growth hormone, the study began with a 4-month washout period. Then, subjects were randomized to 9 months of placebo or growth hormone. Subjects' therapy was titrated to acheive an insulin-like growth factor-1 (IGF-1) level within the upper normal range for their age and sex. Final mean daily dose was 0.4 mg for men and 0.6 mg for women.

At outset, subject exercise capacity was determined by treadmill, increased until exhaustion occurred. Body composition was measured by dual-energy x-ray absorptiometry. Three quality-of-life scales were completed.

In men who took growth hormone, the mean IGF-1 levels increased from 95 mg/L to 216 mg/L; in women, the mean level increased from 68 mg/L to 186 mg/L. Subjects in the study group lost an average of 1.9 kg of fat and gained 1.8 kg of lean body mass. Their total and LDL cholesterol levels both dropped an average of 0.5 mmol/L.

Compared with placebo, growth hormone treatment increased the subjects' maximal oxygen uptake by 6%. Endurance increased by 7% over baseline in the study group.

There were no significant effects on quality of life, Dr. Hallen said, who is an investigator for Pfizer Inc. The company funded the study and supplied the drug.

NEW ORLEANS — Metformin appeared to reverse the features of polycystic ovary syndrome when given to prepubertal girls with a history of low birth weight and precocious puberty in two small randomized studies.

When metformin was withdrawn from these girls after puberty, however, the beneficial changes were reversed within 6 months, Lourdes Ibanez, M.D., said at the annual meeting of the Endocrine Society.

Dr. Ibanez of the University of Barcelona, Spain, reported on two small randomized studies of metformin treatment in girls with a combined history of low birth weight and precocious puberty. The first study randomized 33 prepubertal girls to either no therapy or to 425 mg of metformin daily for 6 months. The second was a randomized crossover trial: 24 postpubertal girls received either no therapy or 850 mg metformin daily for 12 months, after which the groups switched treatments for 6 months.

In the first study, all girls were 8 years old and prepubertal. Birth weight averaged 2.4 kg and BMI, 18.5. All had precocious puberty secondary to exaggerated adrenarche, high circulating levels of interleukin-6 and dehydroepiandrosterone sulfate (DHEAS), and low adiponectin.

In untreated girls, these parameters continued to diverge from normal levels during the 6-month study, Dr. Ibanez said. Their DHEAS levels rose from about 105 μg/dL to 115 μg/dL; interleukin-6 rose from about 1,050 femtogram/mL to 1,100 fg/mL, and adiponectin decreased from about 10.5 μg/mL to 9 μg/mL. The girls continued to increase their abdominal fat over the 6 months, gaining an average of about 300 g.

All these parameters improved in the treated girls, Dr. Ibanez said. In this group, the DHEAS levels remained stable, the interleukin-6 level dropped from about 1,000 fg/mL to abut 800 fg/mL, and the adiponectin increased from about 10 μg/mL to about 11 μg/mL. Abdominal fat decreased in these girls by an average of 300 g.

The crossover trial contained 24 girls who were 6-12 months beyond menarche at the study outset. These girls were also low birth weight (average 2.4 kg). Their average age was 12 years and their average BMI was 21.

All of these girls showed precursor features of polycystic ovary syndrome (PCOS): They had hyperinsulinemia, hyperandrogenemia, increased truncal fat, decreased lean body mass, and dyslipidemia

The girls were randomized to either no treatment or 850 mg of metformin daily for 12 months. At the end of that period, the treated girls stopped therapy, and the untreated girls began therapy.

After 12 months, the untreated girls experienced increases in markers associated with incipient PCOS, Dr. Ibanez said. Their BMI increased from 21 to 21.6; their insulin sensitivity declined; and levels of testosterone, androstenedione, and DHEAS all increased. Their LDL cholesterol and triglycerides increased, while their HDL cholesterol decreased. The girls gained about 2 kg of truncal fat and lost about 1 kg of lean body mass.

Although not fully normalized by the end of 12 moths, these parameters all improved in the treated girls. BMI stayed stable, but the girls lost 0.5 kg of truncal fat and gained about 2 kg of lean body mass. Their insulin sensitivity increased, while their testosterone and androstenedione levels decreased. There was no significant effect on DHEAS.

The girls' lipid levels improved as well, with decreases in LDL cholesterol and triglycerides and an increase in HDL cholesterol.

After 12 months, the groups switched treatments. Within 6 months, the girls who stopped therapy lost almost all of their improvements in weight, hormones, and lipids, while the girls who began therapy made significant gains in these areas.

After 6 months of stopping metformin, the previously treated girls experienced a drop in insulin sensitivity (100% to about 65%) and adiponectin (from 14 μg/mL to 12 μg/mL) and an increase in interleukin-6 (from about 900 fg/mL to 1,300 fg/mL).

After 6 months of treatment, the previously untreated girls experienced an increase in insulin sensitivity (from 60% to about 85%) and adiponectin (from about 12 fg/mL to 13 fg/mL), and a decrease in interleukin-6 (from about 1,400 fg/mL to about 900 fg/mL).

NEW ORLEANS — Metformin appeared to reverse the features of polycystic ovary syndrome when given to prepubertal girls with a history of low birth weight and precocious puberty in two small randomized studies.

When metformin was withdrawn from these girls after puberty, however, the beneficial changes were reversed within 6 months, Lourdes Ibanez, M.D., said at the annual meeting of the Endocrine Society.

Dr. Ibanez of the University of Barcelona, Spain, reported on two small randomized studies of metformin treatment in girls with a combined history of low birth weight and precocious puberty. The first study randomized 33 prepubertal girls to either no therapy or to 425 mg of metformin daily for 6 months. The second was a randomized crossover trial: 24 postpubertal girls received either no therapy or 850 mg metformin daily for 12 months, after which the groups switched treatments for 6 months.

In the first study, all girls were 8 years old and prepubertal. Birth weight averaged 2.4 kg and BMI, 18.5. All had precocious puberty secondary to exaggerated adrenarche, high circulating levels of interleukin-6 and dehydroepiandrosterone sulfate (DHEAS), and low adiponectin.

In untreated girls, these parameters continued to diverge from normal levels during the 6-month study, Dr. Ibanez said. Their DHEAS levels rose from about 105 μg/dL to 115 μg/dL; interleukin-6 rose from about 1,050 femtogram/mL to 1,100 fg/mL, and adiponectin decreased from about 10.5 μg/mL to 9 μg/mL. The girls continued to increase their abdominal fat over the 6 months, gaining an average of about 300 g.

All these parameters improved in the treated girls, Dr. Ibanez said. In this group, the DHEAS levels remained stable, the interleukin-6 level dropped from about 1,000 fg/mL to abut 800 fg/mL, and the adiponectin increased from about 10 μg/mL to about 11 μg/mL. Abdominal fat decreased in these girls by an average of 300 g.

The crossover trial contained 24 girls who were 6-12 months beyond menarche at the study outset. These girls were also low birth weight (average 2.4 kg). Their average age was 12 years and their average BMI was 21.

All of these girls showed precursor features of polycystic ovary syndrome (PCOS): They had hyperinsulinemia, hyperandrogenemia, increased truncal fat, decreased lean body mass, and dyslipidemia

The girls were randomized to either no treatment or 850 mg of metformin daily for 12 months. At the end of that period, the treated girls stopped therapy, and the untreated girls began therapy.

After 12 months, the untreated girls experienced increases in markers associated with incipient PCOS, Dr. Ibanez said. Their BMI increased from 21 to 21.6; their insulin sensitivity declined; and levels of testosterone, androstenedione, and DHEAS all increased. Their LDL cholesterol and triglycerides increased, while their HDL cholesterol decreased. The girls gained about 2 kg of truncal fat and lost about 1 kg of lean body mass.

Although not fully normalized by the end of 12 moths, these parameters all improved in the treated girls. BMI stayed stable, but the girls lost 0.5 kg of truncal fat and gained about 2 kg of lean body mass. Their insulin sensitivity increased, while their testosterone and androstenedione levels decreased. There was no significant effect on DHEAS.

The girls' lipid levels improved as well, with decreases in LDL cholesterol and triglycerides and an increase in HDL cholesterol.

After 12 months, the groups switched treatments. Within 6 months, the girls who stopped therapy lost almost all of their improvements in weight, hormones, and lipids, while the girls who began therapy made significant gains in these areas.

After 6 months of stopping metformin, the previously treated girls experienced a drop in insulin sensitivity (100% to about 65%) and adiponectin (from 14 μg/mL to 12 μg/mL) and an increase in interleukin-6 (from about 900 fg/mL to 1,300 fg/mL).

After 6 months of treatment, the previously untreated girls experienced an increase in insulin sensitivity (from 60% to about 85%) and adiponectin (from about 12 fg/mL to 13 fg/mL), and a decrease in interleukin-6 (from about 1,400 fg/mL to about 900 fg/mL).

NEW ORLEANS — Metformin appeared to reverse the features of polycystic ovary syndrome when given to prepubertal girls with a history of low birth weight and precocious puberty in two small randomized studies.

When metformin was withdrawn from these girls after puberty, however, the beneficial changes were reversed within 6 months, Lourdes Ibanez, M.D., said at the annual meeting of the Endocrine Society.

Dr. Ibanez of the University of Barcelona, Spain, reported on two small randomized studies of metformin treatment in girls with a combined history of low birth weight and precocious puberty. The first study randomized 33 prepubertal girls to either no therapy or to 425 mg of metformin daily for 6 months. The second was a randomized crossover trial: 24 postpubertal girls received either no therapy or 850 mg metformin daily for 12 months, after which the groups switched treatments for 6 months.

In the first study, all girls were 8 years old and prepubertal. Birth weight averaged 2.4 kg and BMI, 18.5. All had precocious puberty secondary to exaggerated adrenarche, high circulating levels of interleukin-6 and dehydroepiandrosterone sulfate (DHEAS), and low adiponectin.

In untreated girls, these parameters continued to diverge from normal levels during the 6-month study, Dr. Ibanez said. Their DHEAS levels rose from about 105 μg/dL to 115 μg/dL; interleukin-6 rose from about 1,050 femtogram/mL to 1,100 fg/mL, and adiponectin decreased from about 10.5 μg/mL to 9 μg/mL. The girls continued to increase their abdominal fat over the 6 months, gaining an average of about 300 g.

All these parameters improved in the treated girls, Dr. Ibanez said. In this group, the DHEAS levels remained stable, the interleukin-6 level dropped from about 1,000 fg/mL to abut 800 fg/mL, and the adiponectin increased from about 10 μg/mL to about 11 μg/mL. Abdominal fat decreased in these girls by an average of 300 g.

The crossover trial contained 24 girls who were 6-12 months beyond menarche at the study outset. These girls were also low birth weight (average 2.4 kg). Their average age was 12 years and their average BMI was 21.

All of these girls showed precursor features of polycystic ovary syndrome (PCOS): They had hyperinsulinemia, hyperandrogenemia, increased truncal fat, decreased lean body mass, and dyslipidemia

The girls were randomized to either no treatment or 850 mg of metformin daily for 12 months. At the end of that period, the treated girls stopped therapy, and the untreated girls began therapy.

After 12 months, the untreated girls experienced increases in markers associated with incipient PCOS, Dr. Ibanez said. Their BMI increased from 21 to 21.6; their insulin sensitivity declined; and levels of testosterone, androstenedione, and DHEAS all increased. Their LDL cholesterol and triglycerides increased, while their HDL cholesterol decreased. The girls gained about 2 kg of truncal fat and lost about 1 kg of lean body mass.

Although not fully normalized by the end of 12 moths, these parameters all improved in the treated girls. BMI stayed stable, but the girls lost 0.5 kg of truncal fat and gained about 2 kg of lean body mass. Their insulin sensitivity increased, while their testosterone and androstenedione levels decreased. There was no significant effect on DHEAS.

The girls' lipid levels improved as well, with decreases in LDL cholesterol and triglycerides and an increase in HDL cholesterol.

After 12 months, the groups switched treatments. Within 6 months, the girls who stopped therapy lost almost all of their improvements in weight, hormones, and lipids, while the girls who began therapy made significant gains in these areas.

After 6 months of stopping metformin, the previously treated girls experienced a drop in insulin sensitivity (100% to about 65%) and adiponectin (from 14 μg/mL to 12 μg/mL) and an increase in interleukin-6 (from about 900 fg/mL to 1,300 fg/mL).

After 6 months of treatment, the previously untreated girls experienced an increase in insulin sensitivity (from 60% to about 85%) and adiponectin (from about 12 fg/mL to 13 fg/mL), and a decrease in interleukin-6 (from about 1,400 fg/mL to about 900 fg/mL).

STOCKHOLM – The brains of bipolar patients show specific regional abnormalities that may be associated with the neurocognitive deficits that bipolar patients exhibit, Jair Soares, M.D., said at the annual meeting of the European College of Neuropsychopharmacology.

It is worth noting, however, that some of these anatomic abnormalities are seen even in the brains of pediatric bipolar patients, so it's unclear whether the changes are neurodevelopmental or neurodegenerative, said Dr. Soares of the University of Texas, San Antonio.

He has collaborated on several brain imaging studies that have consistently identified structural changes in the bipolar brain. Although these studies are small and must be interpreted cautiously, he said, taken together, they paint a picture of a brain that may be fundamentally different from childhood on.

His recently published study of 27 adult bipolar patients (11 untreated and 16 on lithium monotherapy) and 39 healthy controls showed the relationship between the illness, lithium treatment, and cingulate volume. The 11 untreated patients had significantly decreased left anterior cingulate volumes, compared with both the healthy controls and the treated bipolar patients. The cingulate volumes of the treated patients were not different from those of controls (Biol. Psych. 2004;56:467-75).

The cingulate is not the only abnormal area that has been documented in the brains of bipolar patients, Dr. Soares said. The volume of the amygdala and conductivity of the corpus callosum are also abnormal.

In another study of brain anatomy in bipolar subjects, he and his associates examined 24 bipolar patients and 36 healthy controls. Bipolar patients had significantly larger left amygdala volumes compared with controls (J. Psychiatr. Res. 2003;37:287-95).

A 2004 study in which Dr. Soares was involved found lower MRI signal intensity in the corpus callosa of 29 bipolar patients, compared with those of 23 unipolar patients and 36 healthy controls (J. Neurol. Neurosurg. Psych. 2004;75:221-5). “This suggests that there are abnormalities that might reflect abnormal myelination,” he said.

“And this could be responsible for some of the neurocognitive abnormalities that bipolar patients display.”

Bipolar patients also show increased areas of hyperintense abnormalities on MRI scans. “These are very nonspecific abnormalities that are often related to vascular changes. They are very prevalent in late-life depression and in patients with bipolar disorder. These might represent disruptions of specific brain pathways that interconnect areas involved in mood regulation,” he suggested.

Bipolar brains seem to lose gray matter at an accelerated rate.

“We all lose gray matter as we age, but bipolar patients seem to start losing this much earlier,” Dr. Soares said. A 2004 study of 22 bipolar patients and 22 healthy controls, all of middle age, found that age was not associated with gray matter volume in the controls.

In the bipolar patients, however, gray matter volume was inversely related to age (Neuropsychobiology 2001;43:242-7).

“They were losing it at a faster rate as they got older. Because the groups were similar in age this suggests there is a neurodegenerative mechanism in bipolar patients,” he said.

Changes are evident even in the brains of adolescents with bipolar disorder. In a recent study on which he collaborated, investigators measured temporal lobe structures in 16 adolescents with bipolar disorder and 21 healthy controls and found decreased cingulate volumes in the left anterior, left posterior, and right posterior quadrants.

“This is interesting because in the adult study, we only found a change in the left anterior,” Dr. Soares said. “The pediatric study found more extensive cingulate changes.” These results might have been confounded by selection bias, he noted. The bipolar patients in the pediatric study represented early-onset disease, and so might have had a more severe form of the disorder.

Although the brains of adult bipolar patients display an increased amygdala volume, adolescent bipolar brains display a smaller volume, according to a study of both bipolar adolescents and healthy controls (Biol. Psychiatry 2004;56:399-405).

In this study, the left amygdalas of the subjects with bipolar disorder were smaller than those of the controls, a finding that has been replicated in two additional recent studies.

“Why is the amygdala smaller in bipolar children and larger in bipolar adults?” Dr. Soares asked. “What is it in the developmental years that causes this to happen?”

One explanation is that the bipolar brain may fail to control amygdala growth. “In controls, there is an inverse relation in size as the child increases in age.

This might reflect some kind of pruning mechanism in those years” that does not occur in people with bipolar disorder, he said.

There is mounting evidence that lithium treatment may prevent or even reverse some of these changes. The study that showed normal cingulate volumes in bipolar adults on lithium monotherapy and decreased volume in untreated bipolar adults showed lithium's association with an improved anatomic profile.

An earlier study by other investigators looked at the levels of N-acetyl aspartate, a marker of neuronal viability, before and after 4 weeks of lithium therapy both in 12 untreated bipolar patients and 9 healthy controls.

The study found a 5% increase in N-acetyl aspartate concentrations after therapy in both study groups (Biol. Psychiatry 2000;48:1-8).

“Although the studies are small, they do suggest that perhaps lithium has neurotrophic properties that could be preventing or reversing these changes,” he said.

STOCKHOLM – The brains of bipolar patients show specific regional abnormalities that may be associated with the neurocognitive deficits that bipolar patients exhibit, Jair Soares, M.D., said at the annual meeting of the European College of Neuropsychopharmacology.

It is worth noting, however, that some of these anatomic abnormalities are seen even in the brains of pediatric bipolar patients, so it's unclear whether the changes are neurodevelopmental or neurodegenerative, said Dr. Soares of the University of Texas, San Antonio.

He has collaborated on several brain imaging studies that have consistently identified structural changes in the bipolar brain. Although these studies are small and must be interpreted cautiously, he said, taken together, they paint a picture of a brain that may be fundamentally different from childhood on.

His recently published study of 27 adult bipolar patients (11 untreated and 16 on lithium monotherapy) and 39 healthy controls showed the relationship between the illness, lithium treatment, and cingulate volume. The 11 untreated patients had significantly decreased left anterior cingulate volumes, compared with both the healthy controls and the treated bipolar patients. The cingulate volumes of the treated patients were not different from those of controls (Biol. Psych. 2004;56:467-75).

The cingulate is not the only abnormal area that has been documented in the brains of bipolar patients, Dr. Soares said. The volume of the amygdala and conductivity of the corpus callosum are also abnormal.

In another study of brain anatomy in bipolar subjects, he and his associates examined 24 bipolar patients and 36 healthy controls. Bipolar patients had significantly larger left amygdala volumes compared with controls (J. Psychiatr. Res. 2003;37:287-95).

A 2004 study in which Dr. Soares was involved found lower MRI signal intensity in the corpus callosa of 29 bipolar patients, compared with those of 23 unipolar patients and 36 healthy controls (J. Neurol. Neurosurg. Psych. 2004;75:221-5). “This suggests that there are abnormalities that might reflect abnormal myelination,” he said.

“And this could be responsible for some of the neurocognitive abnormalities that bipolar patients display.”

Bipolar patients also show increased areas of hyperintense abnormalities on MRI scans. “These are very nonspecific abnormalities that are often related to vascular changes. They are very prevalent in late-life depression and in patients with bipolar disorder. These might represent disruptions of specific brain pathways that interconnect areas involved in mood regulation,” he suggested.

Bipolar brains seem to lose gray matter at an accelerated rate.

“We all lose gray matter as we age, but bipolar patients seem to start losing this much earlier,” Dr. Soares said. A 2004 study of 22 bipolar patients and 22 healthy controls, all of middle age, found that age was not associated with gray matter volume in the controls.

In the bipolar patients, however, gray matter volume was inversely related to age (Neuropsychobiology 2001;43:242-7).

“They were losing it at a faster rate as they got older. Because the groups were similar in age this suggests there is a neurodegenerative mechanism in bipolar patients,” he said.

Changes are evident even in the brains of adolescents with bipolar disorder. In a recent study on which he collaborated, investigators measured temporal lobe structures in 16 adolescents with bipolar disorder and 21 healthy controls and found decreased cingulate volumes in the left anterior, left posterior, and right posterior quadrants.

“This is interesting because in the adult study, we only found a change in the left anterior,” Dr. Soares said. “The pediatric study found more extensive cingulate changes.” These results might have been confounded by selection bias, he noted. The bipolar patients in the pediatric study represented early-onset disease, and so might have had a more severe form of the disorder.

Although the brains of adult bipolar patients display an increased amygdala volume, adolescent bipolar brains display a smaller volume, according to a study of both bipolar adolescents and healthy controls (Biol. Psychiatry 2004;56:399-405).

In this study, the left amygdalas of the subjects with bipolar disorder were smaller than those of the controls, a finding that has been replicated in two additional recent studies.

“Why is the amygdala smaller in bipolar children and larger in bipolar adults?” Dr. Soares asked. “What is it in the developmental years that causes this to happen?”

One explanation is that the bipolar brain may fail to control amygdala growth. “In controls, there is an inverse relation in size as the child increases in age.

This might reflect some kind of pruning mechanism in those years” that does not occur in people with bipolar disorder, he said.

There is mounting evidence that lithium treatment may prevent or even reverse some of these changes. The study that showed normal cingulate volumes in bipolar adults on lithium monotherapy and decreased volume in untreated bipolar adults showed lithium's association with an improved anatomic profile.

An earlier study by other investigators looked at the levels of N-acetyl aspartate, a marker of neuronal viability, before and after 4 weeks of lithium therapy both in 12 untreated bipolar patients and 9 healthy controls.

The study found a 5% increase in N-acetyl aspartate concentrations after therapy in both study groups (Biol. Psychiatry 2000;48:1-8).

“Although the studies are small, they do suggest that perhaps lithium has neurotrophic properties that could be preventing or reversing these changes,” he said.

STOCKHOLM – The brains of bipolar patients show specific regional abnormalities that may be associated with the neurocognitive deficits that bipolar patients exhibit, Jair Soares, M.D., said at the annual meeting of the European College of Neuropsychopharmacology.

It is worth noting, however, that some of these anatomic abnormalities are seen even in the brains of pediatric bipolar patients, so it's unclear whether the changes are neurodevelopmental or neurodegenerative, said Dr. Soares of the University of Texas, San Antonio.

He has collaborated on several brain imaging studies that have consistently identified structural changes in the bipolar brain. Although these studies are small and must be interpreted cautiously, he said, taken together, they paint a picture of a brain that may be fundamentally different from childhood on.

His recently published study of 27 adult bipolar patients (11 untreated and 16 on lithium monotherapy) and 39 healthy controls showed the relationship between the illness, lithium treatment, and cingulate volume. The 11 untreated patients had significantly decreased left anterior cingulate volumes, compared with both the healthy controls and the treated bipolar patients. The cingulate volumes of the treated patients were not different from those of controls (Biol. Psych. 2004;56:467-75).

The cingulate is not the only abnormal area that has been documented in the brains of bipolar patients, Dr. Soares said. The volume of the amygdala and conductivity of the corpus callosum are also abnormal.

In another study of brain anatomy in bipolar subjects, he and his associates examined 24 bipolar patients and 36 healthy controls. Bipolar patients had significantly larger left amygdala volumes compared with controls (J. Psychiatr. Res. 2003;37:287-95).

A 2004 study in which Dr. Soares was involved found lower MRI signal intensity in the corpus callosa of 29 bipolar patients, compared with those of 23 unipolar patients and 36 healthy controls (J. Neurol. Neurosurg. Psych. 2004;75:221-5). “This suggests that there are abnormalities that might reflect abnormal myelination,” he said.

“And this could be responsible for some of the neurocognitive abnormalities that bipolar patients display.”

Bipolar patients also show increased areas of hyperintense abnormalities on MRI scans. “These are very nonspecific abnormalities that are often related to vascular changes. They are very prevalent in late-life depression and in patients with bipolar disorder. These might represent disruptions of specific brain pathways that interconnect areas involved in mood regulation,” he suggested.

Bipolar brains seem to lose gray matter at an accelerated rate.

“We all lose gray matter as we age, but bipolar patients seem to start losing this much earlier,” Dr. Soares said. A 2004 study of 22 bipolar patients and 22 healthy controls, all of middle age, found that age was not associated with gray matter volume in the controls.

In the bipolar patients, however, gray matter volume was inversely related to age (Neuropsychobiology 2001;43:242-7).

“They were losing it at a faster rate as they got older. Because the groups were similar in age this suggests there is a neurodegenerative mechanism in bipolar patients,” he said.

Changes are evident even in the brains of adolescents with bipolar disorder. In a recent study on which he collaborated, investigators measured temporal lobe structures in 16 adolescents with bipolar disorder and 21 healthy controls and found decreased cingulate volumes in the left anterior, left posterior, and right posterior quadrants.

“This is interesting because in the adult study, we only found a change in the left anterior,” Dr. Soares said. “The pediatric study found more extensive cingulate changes.” These results might have been confounded by selection bias, he noted. The bipolar patients in the pediatric study represented early-onset disease, and so might have had a more severe form of the disorder.

Although the brains of adult bipolar patients display an increased amygdala volume, adolescent bipolar brains display a smaller volume, according to a study of both bipolar adolescents and healthy controls (Biol. Psychiatry 2004;56:399-405).

In this study, the left amygdalas of the subjects with bipolar disorder were smaller than those of the controls, a finding that has been replicated in two additional recent studies.

“Why is the amygdala smaller in bipolar children and larger in bipolar adults?” Dr. Soares asked. “What is it in the developmental years that causes this to happen?”

One explanation is that the bipolar brain may fail to control amygdala growth. “In controls, there is an inverse relation in size as the child increases in age.

This might reflect some kind of pruning mechanism in those years” that does not occur in people with bipolar disorder, he said.

There is mounting evidence that lithium treatment may prevent or even reverse some of these changes. The study that showed normal cingulate volumes in bipolar adults on lithium monotherapy and decreased volume in untreated bipolar adults showed lithium's association with an improved anatomic profile.

An earlier study by other investigators looked at the levels of N-acetyl aspartate, a marker of neuronal viability, before and after 4 weeks of lithium therapy both in 12 untreated bipolar patients and 9 healthy controls.

The study found a 5% increase in N-acetyl aspartate concentrations after therapy in both study groups (Biol. Psychiatry 2000;48:1-8).

“Although the studies are small, they do suggest that perhaps lithium has neurotrophic properties that could be preventing or reversing these changes,” he said.