Michele G. Sullivan

Women who are considering the risks and benefits of hormone therapy should be informed of the link between hormones and a decreased risk of diabetes, especially if they are at risk for the disorder, according to Dr. Wulf Utian, executive director of the North American Menopause Society, in Cleveland.

“While hormone therapy [HT] is not indicated for the prevention of diabetes, women with diabetes risk factors who are considering it for a valid indication should understand the evidence in this area,” Dr. Utian said in an interview. “For these women, the link between HT and diabetes might fall on the benefit side of the equation.”

NAMs' newly revised position statement on hypertension is the group's first to review this evidence, Dr. Utian said. “In 2004 [when NAMS issued its last position paper], there were not enough data to address this issue.

Since then, a number of published studies have shown the same link between HT and a decreased incidence of diabetes.”

The paper reviewed three studies on the subject, granting Class I status to the evidence presented in each one: two subanalyses of the Women's Health Initiative (WHI) and one subanalysis of the Heart and Estrogen/Progestin Replacement Study (HERS).

The first of the WHI studies, published in 2004, examined the effect of HT on diabetes development in the 16,600 women included in the estrogen/progestin arm (Diabetologia 2004;47:1175–87).

After 5 years of follow-up, women in the active group were 21% less likely to develop diabetes than those in the placebo group (277 cases vs. 324 cases—a significant difference).

The numbers achieved greater significance when the analysis was restricted to the small subgroup of women who remained compliant with therapy throughout the follow-up period. In this group, the decreased risk was 33%.

The difference seemed to be driven by steady improvements in fasting glucose and insulin resistance in the active group, the authors wrote. The risk ratios remained unchanged after adjusting for body mass index (BMI) and waist circumference.

Insulin resistance and glucose level were also the driving forces behind the smaller risk reductions seen among women in WHI's estrogen-only arm (Diabetologia 2006;49:459–68).

This study included 9,712 women (about 1,000 were excluded from the analysis because of a baseline diagnosis of diabetes).

At year 6, women in the active group were 12% less likely to have developed diabetes than those in the placebo group (a rate of 8.3% vs. a rate of 9.3%). This difference was not significant in the overall group, but became highly so in the smaller group of women who were compliant with therapy through the study's end. These women were 27% less likely to develop diabetes than the placebo group.

Again, adjusting for BMI and waist circumference did not account for the difference, the authors said. Instead, the risk reduction seemed to be related to improvements in fasting glucose and insulin resistance. These were significant within the first year of therapy and then waned in the overall group, but remained significant in the compliant group.

The final study, a subanalysis of the HERS data, confirmed HT's beneficial effect on diabetes development in women with preexisting coronary heart disease. The subanalysis followed 2,029 patients who did not have diabetes at baseline (Ann. Intern. Med. 2003;138:1–9).

At 4 years' follow-up, the incidence of diabetes in patients in the active group was 6.2%, compared with 9.5% in patients in the placebo group—a significant risk reduction of 35%. The authors concluded that in this group, 30 was the number needed to treat to prevent 1 case of diabetes.

The risk differential was related to significantly higher fasting glucose levels in the placebo group; these levels remained stable in the active group.

There was no association of decreased diabetes with the active group's modest decreases in BMI or waist circumference.

More research is necessary to further define HT's impact on diabetes, Dr. Utian said.

In the meantime, patients who are at risk of diabetes should receive lifestyle counseling in addition to information about the hormone/diabetes link. “We need to focus on healthy living, diet, exercise, and moderation in alcohol.

“If patients would comply with those recommendations, they would be much more beneficial than any hormone therapy,” he noted.

Women who are considering the risks and benefits of hormone therapy should be informed of the link between hormones and a decreased risk of diabetes, especially if they are at risk for the disorder, according to Dr. Wulf Utian, executive director of the North American Menopause Society, in Cleveland.

“While hormone therapy [HT] is not indicated for the prevention of diabetes, women with diabetes risk factors who are considering it for a valid indication should understand the evidence in this area,” Dr. Utian said in an interview. “For these women, the link between HT and diabetes might fall on the benefit side of the equation.”

NAMs' newly revised position statement on hypertension is the group's first to review this evidence, Dr. Utian said. “In 2004 [when NAMS issued its last position paper], there were not enough data to address this issue.

Since then, a number of published studies have shown the same link between HT and a decreased incidence of diabetes.”

The paper reviewed three studies on the subject, granting Class I status to the evidence presented in each one: two subanalyses of the Women's Health Initiative (WHI) and one subanalysis of the Heart and Estrogen/Progestin Replacement Study (HERS).

The first of the WHI studies, published in 2004, examined the effect of HT on diabetes development in the 16,600 women included in the estrogen/progestin arm (Diabetologia 2004;47:1175–87).

After 5 years of follow-up, women in the active group were 21% less likely to develop diabetes than those in the placebo group (277 cases vs. 324 cases—a significant difference).

The numbers achieved greater significance when the analysis was restricted to the small subgroup of women who remained compliant with therapy throughout the follow-up period. In this group, the decreased risk was 33%.

The difference seemed to be driven by steady improvements in fasting glucose and insulin resistance in the active group, the authors wrote. The risk ratios remained unchanged after adjusting for body mass index (BMI) and waist circumference.

Insulin resistance and glucose level were also the driving forces behind the smaller risk reductions seen among women in WHI's estrogen-only arm (Diabetologia 2006;49:459–68).

This study included 9,712 women (about 1,000 were excluded from the analysis because of a baseline diagnosis of diabetes).

At year 6, women in the active group were 12% less likely to have developed diabetes than those in the placebo group (a rate of 8.3% vs. a rate of 9.3%). This difference was not significant in the overall group, but became highly so in the smaller group of women who were compliant with therapy through the study's end. These women were 27% less likely to develop diabetes than the placebo group.

Again, adjusting for BMI and waist circumference did not account for the difference, the authors said. Instead, the risk reduction seemed to be related to improvements in fasting glucose and insulin resistance. These were significant within the first year of therapy and then waned in the overall group, but remained significant in the compliant group.

The final study, a subanalysis of the HERS data, confirmed HT's beneficial effect on diabetes development in women with preexisting coronary heart disease. The subanalysis followed 2,029 patients who did not have diabetes at baseline (Ann. Intern. Med. 2003;138:1–9).

At 4 years' follow-up, the incidence of diabetes in patients in the active group was 6.2%, compared with 9.5% in patients in the placebo group—a significant risk reduction of 35%. The authors concluded that in this group, 30 was the number needed to treat to prevent 1 case of diabetes.

The risk differential was related to significantly higher fasting glucose levels in the placebo group; these levels remained stable in the active group.

There was no association of decreased diabetes with the active group's modest decreases in BMI or waist circumference.

More research is necessary to further define HT's impact on diabetes, Dr. Utian said.

In the meantime, patients who are at risk of diabetes should receive lifestyle counseling in addition to information about the hormone/diabetes link. “We need to focus on healthy living, diet, exercise, and moderation in alcohol.

“If patients would comply with those recommendations, they would be much more beneficial than any hormone therapy,” he noted.

Women who are considering the risks and benefits of hormone therapy should be informed of the link between hormones and a decreased risk of diabetes, especially if they are at risk for the disorder, according to Dr. Wulf Utian, executive director of the North American Menopause Society, in Cleveland.

“While hormone therapy [HT] is not indicated for the prevention of diabetes, women with diabetes risk factors who are considering it for a valid indication should understand the evidence in this area,” Dr. Utian said in an interview. “For these women, the link between HT and diabetes might fall on the benefit side of the equation.”

NAMs' newly revised position statement on hypertension is the group's first to review this evidence, Dr. Utian said. “In 2004 [when NAMS issued its last position paper], there were not enough data to address this issue.

Since then, a number of published studies have shown the same link between HT and a decreased incidence of diabetes.”

The paper reviewed three studies on the subject, granting Class I status to the evidence presented in each one: two subanalyses of the Women's Health Initiative (WHI) and one subanalysis of the Heart and Estrogen/Progestin Replacement Study (HERS).

The first of the WHI studies, published in 2004, examined the effect of HT on diabetes development in the 16,600 women included in the estrogen/progestin arm (Diabetologia 2004;47:1175–87).

After 5 years of follow-up, women in the active group were 21% less likely to develop diabetes than those in the placebo group (277 cases vs. 324 cases—a significant difference).

The numbers achieved greater significance when the analysis was restricted to the small subgroup of women who remained compliant with therapy throughout the follow-up period. In this group, the decreased risk was 33%.

The difference seemed to be driven by steady improvements in fasting glucose and insulin resistance in the active group, the authors wrote. The risk ratios remained unchanged after adjusting for body mass index (BMI) and waist circumference.

Insulin resistance and glucose level were also the driving forces behind the smaller risk reductions seen among women in WHI's estrogen-only arm (Diabetologia 2006;49:459–68).

This study included 9,712 women (about 1,000 were excluded from the analysis because of a baseline diagnosis of diabetes).

At year 6, women in the active group were 12% less likely to have developed diabetes than those in the placebo group (a rate of 8.3% vs. a rate of 9.3%). This difference was not significant in the overall group, but became highly so in the smaller group of women who were compliant with therapy through the study's end. These women were 27% less likely to develop diabetes than the placebo group.

Again, adjusting for BMI and waist circumference did not account for the difference, the authors said. Instead, the risk reduction seemed to be related to improvements in fasting glucose and insulin resistance. These were significant within the first year of therapy and then waned in the overall group, but remained significant in the compliant group.

The final study, a subanalysis of the HERS data, confirmed HT's beneficial effect on diabetes development in women with preexisting coronary heart disease. The subanalysis followed 2,029 patients who did not have diabetes at baseline (Ann. Intern. Med. 2003;138:1–9).

At 4 years' follow-up, the incidence of diabetes in patients in the active group was 6.2%, compared with 9.5% in patients in the placebo group—a significant risk reduction of 35%. The authors concluded that in this group, 30 was the number needed to treat to prevent 1 case of diabetes.

The risk differential was related to significantly higher fasting glucose levels in the placebo group; these levels remained stable in the active group.

There was no association of decreased diabetes with the active group's modest decreases in BMI or waist circumference.

More research is necessary to further define HT's impact on diabetes, Dr. Utian said.

In the meantime, patients who are at risk of diabetes should receive lifestyle counseling in addition to information about the hormone/diabetes link. “We need to focus on healthy living, diet, exercise, and moderation in alcohol.

“If patients would comply with those recommendations, they would be much more beneficial than any hormone therapy,” he noted.

PITTSBURGH – Topiramate appears to be a good choice for preventing pediatric migraine, including basilar migraine, researchers reported at the annual meeting of the Child Neurology Society.

The drug was approved for treatment of adult migraine in 2004, and is used off label for pediatric migraine, said Dr. Marcus Cruz of St. Christopher's Hospital for Children, Philadelphia. “However, the availability of sufficient data to support the effectiveness, tolerability, and adequate dose is scarce and not yet well supported,” he said.

Dr. Cruz retrospectively examined the use of topiramate as a migraine prophylactic in 37 children (mean age 14 years). Most of the group (81%) experienced migraine without aura; 11% had migraine with aura, and the rest of the children had abdominal, ophthalmoplegic, or catamenial migraine.

For 21 patients, topiramate was the first-line prophylactic therapy; for the rest, it was an add-on drug.

Most of the children (65%) had an excellent or good response to topiramate. Before treatment, the children had an average of 15 headaches per month; after treatment, that number decreased to about three per month.

Eight children had side effects, including cognitive effects (four), drowsiness (three), and paresthesias (one). All four patients who experienced cognitive side effects were switched to another medication. There was a direct correlation between dosage and side effects, Dr. Cruz noted. Children taking more than 2 mg/kg per day were significantly more likely to have adverse effects than were children taking less than 2 mg/kg per day.

Topiramate is also effective in preventing basilar-type migraine in children, said Dr. Donald Lewis, of Eastern Virginia Medical School, Norfolk. In a small, parallel-group study, the drug significantly reduced the total number of headache days per month, although it did not affect the duration or pain level of any headaches that still occurred.

Basilar migraine affects up to 19% of children with migraine, and is characterized by episodes of intense dizziness, vertigo, visual disturbances, ataxia, and diplopia, followed by pain.

Dr. Lewis' study included 14 children aged 6–18 years who received either 25 mg or 100 mg of topiramate per day. At baseline, the children had a median of five migraines per month.

After reaching their target dosage and entering a maintenance phase, 100% of children in the 25-mg/day group and 71% of those in the 100- mg/day group experienced a reduction in all migraine days of at least 50% per month (a median decrease from 4.5 days to 1.5 days), Dr. Lewis said.

The drug also significantly reduced the number of days with basilar migraines in each group from a median of 3 days to 0.6 days per month. Neither dosage had a significant effect on the duration or intensity of any migraines that occurred during treatment, however.

The study was supported by a research grant from Ortho-McNeil Neurologics Inc.

PITTSBURGH – Topiramate appears to be a good choice for preventing pediatric migraine, including basilar migraine, researchers reported at the annual meeting of the Child Neurology Society.

The drug was approved for treatment of adult migraine in 2004, and is used off label for pediatric migraine, said Dr. Marcus Cruz of St. Christopher's Hospital for Children, Philadelphia. “However, the availability of sufficient data to support the effectiveness, tolerability, and adequate dose is scarce and not yet well supported,” he said.

Dr. Cruz retrospectively examined the use of topiramate as a migraine prophylactic in 37 children (mean age 14 years). Most of the group (81%) experienced migraine without aura; 11% had migraine with aura, and the rest of the children had abdominal, ophthalmoplegic, or catamenial migraine.

For 21 patients, topiramate was the first-line prophylactic therapy; for the rest, it was an add-on drug.

Most of the children (65%) had an excellent or good response to topiramate. Before treatment, the children had an average of 15 headaches per month; after treatment, that number decreased to about three per month.

Eight children had side effects, including cognitive effects (four), drowsiness (three), and paresthesias (one). All four patients who experienced cognitive side effects were switched to another medication. There was a direct correlation between dosage and side effects, Dr. Cruz noted. Children taking more than 2 mg/kg per day were significantly more likely to have adverse effects than were children taking less than 2 mg/kg per day.

Topiramate is also effective in preventing basilar-type migraine in children, said Dr. Donald Lewis, of Eastern Virginia Medical School, Norfolk. In a small, parallel-group study, the drug significantly reduced the total number of headache days per month, although it did not affect the duration or pain level of any headaches that still occurred.

Basilar migraine affects up to 19% of children with migraine, and is characterized by episodes of intense dizziness, vertigo, visual disturbances, ataxia, and diplopia, followed by pain.

Dr. Lewis' study included 14 children aged 6–18 years who received either 25 mg or 100 mg of topiramate per day. At baseline, the children had a median of five migraines per month.

After reaching their target dosage and entering a maintenance phase, 100% of children in the 25-mg/day group and 71% of those in the 100- mg/day group experienced a reduction in all migraine days of at least 50% per month (a median decrease from 4.5 days to 1.5 days), Dr. Lewis said.

The drug also significantly reduced the number of days with basilar migraines in each group from a median of 3 days to 0.6 days per month. Neither dosage had a significant effect on the duration or intensity of any migraines that occurred during treatment, however.

The study was supported by a research grant from Ortho-McNeil Neurologics Inc.

PITTSBURGH – Topiramate appears to be a good choice for preventing pediatric migraine, including basilar migraine, researchers reported at the annual meeting of the Child Neurology Society.

The drug was approved for treatment of adult migraine in 2004, and is used off label for pediatric migraine, said Dr. Marcus Cruz of St. Christopher's Hospital for Children, Philadelphia. “However, the availability of sufficient data to support the effectiveness, tolerability, and adequate dose is scarce and not yet well supported,” he said.

Dr. Cruz retrospectively examined the use of topiramate as a migraine prophylactic in 37 children (mean age 14 years). Most of the group (81%) experienced migraine without aura; 11% had migraine with aura, and the rest of the children had abdominal, ophthalmoplegic, or catamenial migraine.

For 21 patients, topiramate was the first-line prophylactic therapy; for the rest, it was an add-on drug.

Most of the children (65%) had an excellent or good response to topiramate. Before treatment, the children had an average of 15 headaches per month; after treatment, that number decreased to about three per month.

Eight children had side effects, including cognitive effects (four), drowsiness (three), and paresthesias (one). All four patients who experienced cognitive side effects were switched to another medication. There was a direct correlation between dosage and side effects, Dr. Cruz noted. Children taking more than 2 mg/kg per day were significantly more likely to have adverse effects than were children taking less than 2 mg/kg per day.

Topiramate is also effective in preventing basilar-type migraine in children, said Dr. Donald Lewis, of Eastern Virginia Medical School, Norfolk. In a small, parallel-group study, the drug significantly reduced the total number of headache days per month, although it did not affect the duration or pain level of any headaches that still occurred.

Basilar migraine affects up to 19% of children with migraine, and is characterized by episodes of intense dizziness, vertigo, visual disturbances, ataxia, and diplopia, followed by pain.

Dr. Lewis' study included 14 children aged 6–18 years who received either 25 mg or 100 mg of topiramate per day. At baseline, the children had a median of five migraines per month.

After reaching their target dosage and entering a maintenance phase, 100% of children in the 25-mg/day group and 71% of those in the 100- mg/day group experienced a reduction in all migraine days of at least 50% per month (a median decrease from 4.5 days to 1.5 days), Dr. Lewis said.

The drug also significantly reduced the number of days with basilar migraines in each group from a median of 3 days to 0.6 days per month. Neither dosage had a significant effect on the duration or intensity of any migraines that occurred during treatment, however.

The study was supported by a research grant from Ortho-McNeil Neurologics Inc.

HOT SPRINGS, VA. — Placental growth factor, an angiogenic factor normally elevated in early pregnancy, may be a valuable biomarker for detecting pregnancies destined to become preeclamptic, Dr. Ramsey Unal said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

Vascular growth factors are essential in creating and maintaining the placenta, said Dr. Unal, a resident at the Medical University of South Carolina, Charleston. Both placental growth factor (PIGF) and vascular endothelial growth factor (VEGF) are higher in early pregnancy and decrease as delivery approaches. Another factor, soluble FMS-like tyrosine kinase 1 (sFlt1), increases later in pregnancy and binds both PIGF and VEGF, decreasing their bioavailability as the pregnancy nears term.

“Normal pregnancy is a balancing act in angiogenesis,” Dr. Unal said. “At the beginning, during placentation, you have a proangiogenic state and toward the end, in preparation for delivery; you shift to an antiangiogenic state. In preeclampsia, we think the shift happens too early and is too exaggerated.”

Dr. Unal investigated the utility of using second-trimester PIGF and sFLT1 levels as predictors of preeclampsia. If the levels were already abnormal in the second trimester, she reasoned, they could easily be included in the quad screen to flag women at risk for preeclampsia.

Her retrospective study included 64 women: 21 of them developed preeclampsia and were delivered for that reason, 34 were healthy women with uncomplicated term deliveries, and 9 had chronic, prepregnancy hypertension. All the women had singleton pregnancies. Dr. Unal performed enzyme-linked immunosorbent assay testing for PIGF and sFLT1 on stored quad screen serum samples obtained from these women at 16–24 weeks' gestation.

PIGF was significantly lower in the group that went on to develop preeclampsia than it was in the normal control group, she said (mean 85.3 pg/mL vs. 133 pg/mL). There were no significant differences in sFLT1 levels between the groups. However, women with chronic hypertension had slightly, though not significantly, lower sFLT1 levels than did normal controls—an interesting relationship, Dr. Unal said. “Preeclampsia is a disease of the placenta, and hypertension can also cause placenta problems.”

PIGF levels could easily be drawn from quad screen sera, adding yet another valuable biomarker to the routine screen. “But we need a large, prospective trial before any recommendations can be made,” she said.

HOT SPRINGS, VA. — Placental growth factor, an angiogenic factor normally elevated in early pregnancy, may be a valuable biomarker for detecting pregnancies destined to become preeclamptic, Dr. Ramsey Unal said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

Vascular growth factors are essential in creating and maintaining the placenta, said Dr. Unal, a resident at the Medical University of South Carolina, Charleston. Both placental growth factor (PIGF) and vascular endothelial growth factor (VEGF) are higher in early pregnancy and decrease as delivery approaches. Another factor, soluble FMS-like tyrosine kinase 1 (sFlt1), increases later in pregnancy and binds both PIGF and VEGF, decreasing their bioavailability as the pregnancy nears term.

“Normal pregnancy is a balancing act in angiogenesis,” Dr. Unal said. “At the beginning, during placentation, you have a proangiogenic state and toward the end, in preparation for delivery; you shift to an antiangiogenic state. In preeclampsia, we think the shift happens too early and is too exaggerated.”

Dr. Unal investigated the utility of using second-trimester PIGF and sFLT1 levels as predictors of preeclampsia. If the levels were already abnormal in the second trimester, she reasoned, they could easily be included in the quad screen to flag women at risk for preeclampsia.

Her retrospective study included 64 women: 21 of them developed preeclampsia and were delivered for that reason, 34 were healthy women with uncomplicated term deliveries, and 9 had chronic, prepregnancy hypertension. All the women had singleton pregnancies. Dr. Unal performed enzyme-linked immunosorbent assay testing for PIGF and sFLT1 on stored quad screen serum samples obtained from these women at 16–24 weeks' gestation.

PIGF was significantly lower in the group that went on to develop preeclampsia than it was in the normal control group, she said (mean 85.3 pg/mL vs. 133 pg/mL). There were no significant differences in sFLT1 levels between the groups. However, women with chronic hypertension had slightly, though not significantly, lower sFLT1 levels than did normal controls—an interesting relationship, Dr. Unal said. “Preeclampsia is a disease of the placenta, and hypertension can also cause placenta problems.”

PIGF levels could easily be drawn from quad screen sera, adding yet another valuable biomarker to the routine screen. “But we need a large, prospective trial before any recommendations can be made,” she said.

HOT SPRINGS, VA. — Placental growth factor, an angiogenic factor normally elevated in early pregnancy, may be a valuable biomarker for detecting pregnancies destined to become preeclamptic, Dr. Ramsey Unal said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

Vascular growth factors are essential in creating and maintaining the placenta, said Dr. Unal, a resident at the Medical University of South Carolina, Charleston. Both placental growth factor (PIGF) and vascular endothelial growth factor (VEGF) are higher in early pregnancy and decrease as delivery approaches. Another factor, soluble FMS-like tyrosine kinase 1 (sFlt1), increases later in pregnancy and binds both PIGF and VEGF, decreasing their bioavailability as the pregnancy nears term.

“Normal pregnancy is a balancing act in angiogenesis,” Dr. Unal said. “At the beginning, during placentation, you have a proangiogenic state and toward the end, in preparation for delivery; you shift to an antiangiogenic state. In preeclampsia, we think the shift happens too early and is too exaggerated.”

Dr. Unal investigated the utility of using second-trimester PIGF and sFLT1 levels as predictors of preeclampsia. If the levels were already abnormal in the second trimester, she reasoned, they could easily be included in the quad screen to flag women at risk for preeclampsia.

Her retrospective study included 64 women: 21 of them developed preeclampsia and were delivered for that reason, 34 were healthy women with uncomplicated term deliveries, and 9 had chronic, prepregnancy hypertension. All the women had singleton pregnancies. Dr. Unal performed enzyme-linked immunosorbent assay testing for PIGF and sFLT1 on stored quad screen serum samples obtained from these women at 16–24 weeks' gestation.

PIGF was significantly lower in the group that went on to develop preeclampsia than it was in the normal control group, she said (mean 85.3 pg/mL vs. 133 pg/mL). There were no significant differences in sFLT1 levels between the groups. However, women with chronic hypertension had slightly, though not significantly, lower sFLT1 levels than did normal controls—an interesting relationship, Dr. Unal said. “Preeclampsia is a disease of the placenta, and hypertension can also cause placenta problems.”

PIGF levels could easily be drawn from quad screen sera, adding yet another valuable biomarker to the routine screen. “But we need a large, prospective trial before any recommendations can be made,” she said.

RIVIERA MAYA, MEXICO — A perimortem cesarean delivery should be performed within 5 minutes of maternal cardiac arrest to maximize survival chances for both the fetus and its mother, presenters said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“I've done it a dozen times in 28 years, and it's probably the most frightening thing you will ever encounter,” said Dr. John Marx, chair of emergency medicine at the Carolinas Medical Center, Charlotte, N.C. “It is the fastest, hardest decision making you will ever do.”

Only about 300 cases of perimortem cesarean section have been reported in the literature, and many of these were confounded by inadequate reporting of time from maternal injury, drawing into question whether the fetus had any chance of survival.

A 2005 review identified 38 cases since 1986 in which the procedure was appropriately documented, and supported it for two reasons: to save the life of a viable fetus and/or to maximize maternal response to resuscitation (AJOG 2005;192:1916–21).

The indication for maternal salvage is a rather new thought, said Dr. Bernard Gonik, the Fann S. Srer Chair of Perinatal Medicine at Wayne State University, Detroit. “There are data indicating that the procedure can dramatically improve maternal cardiac output by emptying the uterus so that it's not pressing on the vena cava and inhibiting return. This can improve cardiac output by 25%.”

The pregnant uterus consumes a large amount of maternal blood, causing gravid women to become anoxic much more quickly during a crisis. “That's another reason to add C-section to your resuscitation efforts,” Dr. Gonik said.

The 2005 review included resuscitation information for 22 women; 12 of them showed profoundly increased response after the procedure. Of 20 potentially salvageable mothers, 13 were discharged from the hospital in good condition.

Time is the most critical factor when a pregnant woman with a gestationally viable fetus arrests, both physicians said. “The earlier you deliver, the more likely you are to have a neurologically intact baby,” Dr. Gonik said, noting that the review indicated that 98% of babies born within 5 minutes of maternal arrest were neurologically intact.

Dr. Marx agreed. “If you get the fetus out within 5 minutes you have a good chance not only for it to survive but to have good neurologic outcome. If you wait 15 minutes, the chance of survival and good neurologic outcome is dim. I'm not sure which is worse from a legal perspective: to wind up with a baby who will never, ever be OK, or to wind up with a dead fetus.”

Difficult decisions abound in this kind of situation, both men said. The patient will not be physically or mentally able to give informed consent, and very often, no kin are available to help in that regard. Opinions differ on the importance of accurately assessing gestational age, which is best done via ultrasound. Dr. Marx advised against performing the procedure to try and save a fetus of less than 24 weeks. But some audience members commented that fetal age is irrelevant, since the primary indication should be to maximize maternal outcome.

A similar discussion arose around fetal heart rate: Whereas a good rate is a deciding factor for some physicians, others proceed with the delivery regardless of the rate, in the hopes of saving the mother's life.

“My counterpoint would be this,” Dr. Marx said. “Turning the mother onto her left side 50 to 30 degrees should help considerably in maximizing maternal response [by decreasing pressure on the inferior vena cava]. Secondly, if we think the fetus has no chance of survival, we may end up doing a thoracotomy on the mother, cross-clamping to eliminate any blood lost to the uterus. We want to be very, very cautious about delivering a fetus that is only semi-viable. That's the conundrum.”

The procedure demands a team effort by the most experienced people available. “You call obstetrics, you call surgery, and you call people who have expert ultrasound capabilities if you don't have them,” Dr. Marx said. “And this is not a procedure for a third-year medical student. You want the most competent person in the room, whether it's the obstetrician or the emergency physician.”

The delivery is a midline crash vertical incision “from stem to stern” through all tissue levels of the anterior uterus. “If the placenta is in the way, either push it aside or cut through it,” Dr. Marx said.

Despite concerns about informed consent and the ethics of delivering a nonviable or impaired fetus, physicians who perform a perimortem C-section for the correct indication probably aren't in legal danger, Dr. Gonik said. “No physician in the U.S. has ever been found liable in one of these cases. They typically do not go to court or get the physician or hospital in trouble because they were attempting to save the baby.”

However, he strongly cautioned, “Never perform this in anticipation of the mother arresting. If the patient is unstable and you proceed, you could push her into needing resuscitation.”

RIVIERA MAYA, MEXICO — A perimortem cesarean delivery should be performed within 5 minutes of maternal cardiac arrest to maximize survival chances for both the fetus and its mother, presenters said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“I've done it a dozen times in 28 years, and it's probably the most frightening thing you will ever encounter,” said Dr. John Marx, chair of emergency medicine at the Carolinas Medical Center, Charlotte, N.C. “It is the fastest, hardest decision making you will ever do.”

Only about 300 cases of perimortem cesarean section have been reported in the literature, and many of these were confounded by inadequate reporting of time from maternal injury, drawing into question whether the fetus had any chance of survival.

A 2005 review identified 38 cases since 1986 in which the procedure was appropriately documented, and supported it for two reasons: to save the life of a viable fetus and/or to maximize maternal response to resuscitation (AJOG 2005;192:1916–21).

The indication for maternal salvage is a rather new thought, said Dr. Bernard Gonik, the Fann S. Srer Chair of Perinatal Medicine at Wayne State University, Detroit. “There are data indicating that the procedure can dramatically improve maternal cardiac output by emptying the uterus so that it's not pressing on the vena cava and inhibiting return. This can improve cardiac output by 25%.”

The pregnant uterus consumes a large amount of maternal blood, causing gravid women to become anoxic much more quickly during a crisis. “That's another reason to add C-section to your resuscitation efforts,” Dr. Gonik said.

The 2005 review included resuscitation information for 22 women; 12 of them showed profoundly increased response after the procedure. Of 20 potentially salvageable mothers, 13 were discharged from the hospital in good condition.

Time is the most critical factor when a pregnant woman with a gestationally viable fetus arrests, both physicians said. “The earlier you deliver, the more likely you are to have a neurologically intact baby,” Dr. Gonik said, noting that the review indicated that 98% of babies born within 5 minutes of maternal arrest were neurologically intact.

Dr. Marx agreed. “If you get the fetus out within 5 minutes you have a good chance not only for it to survive but to have good neurologic outcome. If you wait 15 minutes, the chance of survival and good neurologic outcome is dim. I'm not sure which is worse from a legal perspective: to wind up with a baby who will never, ever be OK, or to wind up with a dead fetus.”

Difficult decisions abound in this kind of situation, both men said. The patient will not be physically or mentally able to give informed consent, and very often, no kin are available to help in that regard. Opinions differ on the importance of accurately assessing gestational age, which is best done via ultrasound. Dr. Marx advised against performing the procedure to try and save a fetus of less than 24 weeks. But some audience members commented that fetal age is irrelevant, since the primary indication should be to maximize maternal outcome.

A similar discussion arose around fetal heart rate: Whereas a good rate is a deciding factor for some physicians, others proceed with the delivery regardless of the rate, in the hopes of saving the mother's life.

“My counterpoint would be this,” Dr. Marx said. “Turning the mother onto her left side 50 to 30 degrees should help considerably in maximizing maternal response [by decreasing pressure on the inferior vena cava]. Secondly, if we think the fetus has no chance of survival, we may end up doing a thoracotomy on the mother, cross-clamping to eliminate any blood lost to the uterus. We want to be very, very cautious about delivering a fetus that is only semi-viable. That's the conundrum.”

The procedure demands a team effort by the most experienced people available. “You call obstetrics, you call surgery, and you call people who have expert ultrasound capabilities if you don't have them,” Dr. Marx said. “And this is not a procedure for a third-year medical student. You want the most competent person in the room, whether it's the obstetrician or the emergency physician.”

The delivery is a midline crash vertical incision “from stem to stern” through all tissue levels of the anterior uterus. “If the placenta is in the way, either push it aside or cut through it,” Dr. Marx said.

Despite concerns about informed consent and the ethics of delivering a nonviable or impaired fetus, physicians who perform a perimortem C-section for the correct indication probably aren't in legal danger, Dr. Gonik said. “No physician in the U.S. has ever been found liable in one of these cases. They typically do not go to court or get the physician or hospital in trouble because they were attempting to save the baby.”

However, he strongly cautioned, “Never perform this in anticipation of the mother arresting. If the patient is unstable and you proceed, you could push her into needing resuscitation.”

RIVIERA MAYA, MEXICO — A perimortem cesarean delivery should be performed within 5 minutes of maternal cardiac arrest to maximize survival chances for both the fetus and its mother, presenters said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“I've done it a dozen times in 28 years, and it's probably the most frightening thing you will ever encounter,” said Dr. John Marx, chair of emergency medicine at the Carolinas Medical Center, Charlotte, N.C. “It is the fastest, hardest decision making you will ever do.”

Only about 300 cases of perimortem cesarean section have been reported in the literature, and many of these were confounded by inadequate reporting of time from maternal injury, drawing into question whether the fetus had any chance of survival.

A 2005 review identified 38 cases since 1986 in which the procedure was appropriately documented, and supported it for two reasons: to save the life of a viable fetus and/or to maximize maternal response to resuscitation (AJOG 2005;192:1916–21).

The indication for maternal salvage is a rather new thought, said Dr. Bernard Gonik, the Fann S. Srer Chair of Perinatal Medicine at Wayne State University, Detroit. “There are data indicating that the procedure can dramatically improve maternal cardiac output by emptying the uterus so that it's not pressing on the vena cava and inhibiting return. This can improve cardiac output by 25%.”

The pregnant uterus consumes a large amount of maternal blood, causing gravid women to become anoxic much more quickly during a crisis. “That's another reason to add C-section to your resuscitation efforts,” Dr. Gonik said.

The 2005 review included resuscitation information for 22 women; 12 of them showed profoundly increased response after the procedure. Of 20 potentially salvageable mothers, 13 were discharged from the hospital in good condition.

Time is the most critical factor when a pregnant woman with a gestationally viable fetus arrests, both physicians said. “The earlier you deliver, the more likely you are to have a neurologically intact baby,” Dr. Gonik said, noting that the review indicated that 98% of babies born within 5 minutes of maternal arrest were neurologically intact.

Dr. Marx agreed. “If you get the fetus out within 5 minutes you have a good chance not only for it to survive but to have good neurologic outcome. If you wait 15 minutes, the chance of survival and good neurologic outcome is dim. I'm not sure which is worse from a legal perspective: to wind up with a baby who will never, ever be OK, or to wind up with a dead fetus.”

Difficult decisions abound in this kind of situation, both men said. The patient will not be physically or mentally able to give informed consent, and very often, no kin are available to help in that regard. Opinions differ on the importance of accurately assessing gestational age, which is best done via ultrasound. Dr. Marx advised against performing the procedure to try and save a fetus of less than 24 weeks. But some audience members commented that fetal age is irrelevant, since the primary indication should be to maximize maternal outcome.

A similar discussion arose around fetal heart rate: Whereas a good rate is a deciding factor for some physicians, others proceed with the delivery regardless of the rate, in the hopes of saving the mother's life.

“My counterpoint would be this,” Dr. Marx said. “Turning the mother onto her left side 50 to 30 degrees should help considerably in maximizing maternal response [by decreasing pressure on the inferior vena cava]. Secondly, if we think the fetus has no chance of survival, we may end up doing a thoracotomy on the mother, cross-clamping to eliminate any blood lost to the uterus. We want to be very, very cautious about delivering a fetus that is only semi-viable. That's the conundrum.”

The procedure demands a team effort by the most experienced people available. “You call obstetrics, you call surgery, and you call people who have expert ultrasound capabilities if you don't have them,” Dr. Marx said. “And this is not a procedure for a third-year medical student. You want the most competent person in the room, whether it's the obstetrician or the emergency physician.”

The delivery is a midline crash vertical incision “from stem to stern” through all tissue levels of the anterior uterus. “If the placenta is in the way, either push it aside or cut through it,” Dr. Marx said.

Despite concerns about informed consent and the ethics of delivering a nonviable or impaired fetus, physicians who perform a perimortem C-section for the correct indication probably aren't in legal danger, Dr. Gonik said. “No physician in the U.S. has ever been found liable in one of these cases. They typically do not go to court or get the physician or hospital in trouble because they were attempting to save the baby.”

However, he strongly cautioned, “Never perform this in anticipation of the mother arresting. If the patient is unstable and you proceed, you could push her into needing resuscitation.”

RIVIERA MAYA, MEXICO — Prenatal exposure to intrauterine infection is emerging as a possible cause of many cases of cerebral palsy previously classified as idiopathic, Dr. Errol Norwitz said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“Recent data suggest that it is the fetus's inflammatory response which causes problems both in terms of preterm labor and neuronal injury,” said Dr. Norwitz, director of maternal-fetal medicine at Yale-New Haven Hospital, Conn. “Even in the absence of a positive amniotic fluid culture in women with chorioamnionitis, we see proinflammatory cytokines, prostaglandins, and other markers of infection.”

Animal studies have demonstrated direct brain injury from such infections. Fetal rabbits exposed to intrauterine Escherichia coli infections develop white matter injuries, while fetal rhesus monkeys demonstrated brain injuries associated with chronic group B streptococcus intrauterine infections.

In human fetuses, epidemiologic evidence points to a similar association, with infection and brain injury leading to cerebral palsy, Dr. Norwitz said. “In normal- and low-birth-weight infants, we see an association between periventricular leukomalacia and both group B strep sepsis and histologic chorioamnionitis.”

The premature labor associated with intrauterine infection may be triggered by the fetus's inflammatory response, so as to escape the contaminated intrauterine environment. “What we are suggesting here is that the infectious agent gets into the baby by the ascending route or, rarely, across the placenta, and the baby's inflammatory response leads independently to preterm birth,” Dr. Norwitz said. “It's a protective mechanism, because if the baby didn't do this, it would probably die in utero due to overwhelming sepsis.”

The exact mechanism of neuronal damage remains unknown, he said. “There appears to be a fetal vasculitis with activation of leukocytes. This causes a huge surge in proinflammatory cytokines, with an imbalance between the proinflammatory and the anti-inflammatory cytokines. Some of the activated cells appear to cross the blood-brain barrier and cause damage to the brain.” In fact, he said, some studies have shown that elevated proinflammatory cytokines are common in the brains of patients with cerebral palsy and periventricular leukomalacia. A 1997 study found tumor necrosis factor-α, interleukin-1 β, or interleukin-6 in 88% of cases with the lesions, but only 18% of cases without them (Am. J. Obstet. Gynecol. 1997;177:406–11). Another study of neonatal brains with and without the lesions concluded that an immune-mediated inflammatory process might play a role in the development of such lesions, with TNF-α perhaps playing the major role (Neurology 2001;56:1278–84).

Interestingly, higher levels have also been noted in the serum and amniotic fluid of neonates who later developed cerebral palsy (Ann. Neuro. 1999;44:665–75; Am. J. Obstet. Gynecol. 1997;117:19–26).

Given these findings, questions arise about a possible protective effect of immediate cesarean delivery in mothers with intrauterine infection, Dr. Norwitz said. “Right now, intrauterine infection is an absolute indication for delivery, but in some cases, it can take 18–36 hours to get these babies delivered. Are these kids, sitting in this infected environment for all that time, at increased risk? Once we make the diagnosis, should we be getting that baby out immediately by cesarean? Currently there is no indication for this, but I wouldn't be surprised if this changes in 5–10 years, as our understanding of this area develops.”

Estimates are that only 10% of cerebral palsy cases are due to an identifiable intrapartum event, he said. But this statistic and the evolving understanding of the possible role of infection don't ease the difficulty of defending such cases in court, cautioned John Scully, a defendant's lawyer from Dallas. The conference was sponsored by Boston University.

RIVIERA MAYA, MEXICO — Prenatal exposure to intrauterine infection is emerging as a possible cause of many cases of cerebral palsy previously classified as idiopathic, Dr. Errol Norwitz said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“Recent data suggest that it is the fetus's inflammatory response which causes problems both in terms of preterm labor and neuronal injury,” said Dr. Norwitz, director of maternal-fetal medicine at Yale-New Haven Hospital, Conn. “Even in the absence of a positive amniotic fluid culture in women with chorioamnionitis, we see proinflammatory cytokines, prostaglandins, and other markers of infection.”

Animal studies have demonstrated direct brain injury from such infections. Fetal rabbits exposed to intrauterine Escherichia coli infections develop white matter injuries, while fetal rhesus monkeys demonstrated brain injuries associated with chronic group B streptococcus intrauterine infections.

In human fetuses, epidemiologic evidence points to a similar association, with infection and brain injury leading to cerebral palsy, Dr. Norwitz said. “In normal- and low-birth-weight infants, we see an association between periventricular leukomalacia and both group B strep sepsis and histologic chorioamnionitis.”

The premature labor associated with intrauterine infection may be triggered by the fetus's inflammatory response, so as to escape the contaminated intrauterine environment. “What we are suggesting here is that the infectious agent gets into the baby by the ascending route or, rarely, across the placenta, and the baby's inflammatory response leads independently to preterm birth,” Dr. Norwitz said. “It's a protective mechanism, because if the baby didn't do this, it would probably die in utero due to overwhelming sepsis.”

The exact mechanism of neuronal damage remains unknown, he said. “There appears to be a fetal vasculitis with activation of leukocytes. This causes a huge surge in proinflammatory cytokines, with an imbalance between the proinflammatory and the anti-inflammatory cytokines. Some of the activated cells appear to cross the blood-brain barrier and cause damage to the brain.” In fact, he said, some studies have shown that elevated proinflammatory cytokines are common in the brains of patients with cerebral palsy and periventricular leukomalacia. A 1997 study found tumor necrosis factor-α, interleukin-1 β, or interleukin-6 in 88% of cases with the lesions, but only 18% of cases without them (Am. J. Obstet. Gynecol. 1997;177:406–11). Another study of neonatal brains with and without the lesions concluded that an immune-mediated inflammatory process might play a role in the development of such lesions, with TNF-α perhaps playing the major role (Neurology 2001;56:1278–84).

Interestingly, higher levels have also been noted in the serum and amniotic fluid of neonates who later developed cerebral palsy (Ann. Neuro. 1999;44:665–75; Am. J. Obstet. Gynecol. 1997;117:19–26).

Given these findings, questions arise about a possible protective effect of immediate cesarean delivery in mothers with intrauterine infection, Dr. Norwitz said. “Right now, intrauterine infection is an absolute indication for delivery, but in some cases, it can take 18–36 hours to get these babies delivered. Are these kids, sitting in this infected environment for all that time, at increased risk? Once we make the diagnosis, should we be getting that baby out immediately by cesarean? Currently there is no indication for this, but I wouldn't be surprised if this changes in 5–10 years, as our understanding of this area develops.”

Estimates are that only 10% of cerebral palsy cases are due to an identifiable intrapartum event, he said. But this statistic and the evolving understanding of the possible role of infection don't ease the difficulty of defending such cases in court, cautioned John Scully, a defendant's lawyer from Dallas. The conference was sponsored by Boston University.

RIVIERA MAYA, MEXICO — Prenatal exposure to intrauterine infection is emerging as a possible cause of many cases of cerebral palsy previously classified as idiopathic, Dr. Errol Norwitz said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“Recent data suggest that it is the fetus's inflammatory response which causes problems both in terms of preterm labor and neuronal injury,” said Dr. Norwitz, director of maternal-fetal medicine at Yale-New Haven Hospital, Conn. “Even in the absence of a positive amniotic fluid culture in women with chorioamnionitis, we see proinflammatory cytokines, prostaglandins, and other markers of infection.”

Animal studies have demonstrated direct brain injury from such infections. Fetal rabbits exposed to intrauterine Escherichia coli infections develop white matter injuries, while fetal rhesus monkeys demonstrated brain injuries associated with chronic group B streptococcus intrauterine infections.

In human fetuses, epidemiologic evidence points to a similar association, with infection and brain injury leading to cerebral palsy, Dr. Norwitz said. “In normal- and low-birth-weight infants, we see an association between periventricular leukomalacia and both group B strep sepsis and histologic chorioamnionitis.”

The premature labor associated with intrauterine infection may be triggered by the fetus's inflammatory response, so as to escape the contaminated intrauterine environment. “What we are suggesting here is that the infectious agent gets into the baby by the ascending route or, rarely, across the placenta, and the baby's inflammatory response leads independently to preterm birth,” Dr. Norwitz said. “It's a protective mechanism, because if the baby didn't do this, it would probably die in utero due to overwhelming sepsis.”

The exact mechanism of neuronal damage remains unknown, he said. “There appears to be a fetal vasculitis with activation of leukocytes. This causes a huge surge in proinflammatory cytokines, with an imbalance between the proinflammatory and the anti-inflammatory cytokines. Some of the activated cells appear to cross the blood-brain barrier and cause damage to the brain.” In fact, he said, some studies have shown that elevated proinflammatory cytokines are common in the brains of patients with cerebral palsy and periventricular leukomalacia. A 1997 study found tumor necrosis factor-α, interleukin-1 β, or interleukin-6 in 88% of cases with the lesions, but only 18% of cases without them (Am. J. Obstet. Gynecol. 1997;177:406–11). Another study of neonatal brains with and without the lesions concluded that an immune-mediated inflammatory process might play a role in the development of such lesions, with TNF-α perhaps playing the major role (Neurology 2001;56:1278–84).

Interestingly, higher levels have also been noted in the serum and amniotic fluid of neonates who later developed cerebral palsy (Ann. Neuro. 1999;44:665–75; Am. J. Obstet. Gynecol. 1997;117:19–26).

Given these findings, questions arise about a possible protective effect of immediate cesarean delivery in mothers with intrauterine infection, Dr. Norwitz said. “Right now, intrauterine infection is an absolute indication for delivery, but in some cases, it can take 18–36 hours to get these babies delivered. Are these kids, sitting in this infected environment for all that time, at increased risk? Once we make the diagnosis, should we be getting that baby out immediately by cesarean? Currently there is no indication for this, but I wouldn't be surprised if this changes in 5–10 years, as our understanding of this area develops.”

Estimates are that only 10% of cerebral palsy cases are due to an identifiable intrapartum event, he said. But this statistic and the evolving understanding of the possible role of infection don't ease the difficulty of defending such cases in court, cautioned John Scully, a defendant's lawyer from Dallas. The conference was sponsored by Boston University.

SAN ANTONIO — Monthly denosumab may prove to suppress bone turnover when patients with cancer metastatic to bone do not respond adequately to bisphosphonate therapy, Dr. Allan Lipton said at the Sixth International Meeting on Cancer-Induced Bone Disease.

The drug is a fully human monoclonal antibody to RANK ligand, inhibiting the differentiation and proliferation of osteoclasts, and thus reducing bone turnover. It also is being investigated for the treatment of postmenopausal osteoporosis.

Dr. Lipton presented the interim results of a phase II study in patients in whom zoledronic acid or pamidronate failed to adequately suppress urinary markers of bone turnover.

Adequate suppression is important in these patients not only because it helps prevent fractures, but because it delays tumor progression and improves survival.

The interim analysis included 49 patients who have finished the 25-week trial. Eventually the study will enroll 135 patients.

Of initial patients, 40% had metastatic breast cancer, 40% had metastatic prostate cancer, 10% had multiple myeloma, and the rest had other solid tumors. Most (80%) had been on zoledronic acid; the rest had been on pamidronate. All patients still had urinary N-telopeptide (NTx) levels of more than 50 nmol/mmol creatinine.

Overall, more patients on denosumab than on bisphosphonates experienced a decrease in their urinary NTx levels to less than 50 nmol/mmol creatinine (76% vs. 38%). The difference was still significant when the groups were divided according to baseline NTx levels.

Among those who started with a level of 51–100 nmol/mmol creatinine, 87% of those on denosumab achieved the target compared with 50% of those taking bisphosphonates.

Among those with baseline levels of more than 100 nmol/mmol creatinine, two-thirds of the denosumab group achieved the goal compared with 25% of the bisphosphonate group.

Those who received denosumab every 4 weeks had the longest duration of adequate suppression (a mean of 140 days), followed by patients taking the drug every 12 weeks. Bisphosphonate-treated patients maintained adequate suppression for a mean of 30 days.

The meeting was sponsored by the Cancer and Bone Society. The study was sponsored by Amgen Inc. Dr. Lipton, of the Penn State Milton S. Hershey Medical Center, Hershey, Pa., is a consultant for the company.

SAN ANTONIO — Monthly denosumab may prove to suppress bone turnover when patients with cancer metastatic to bone do not respond adequately to bisphosphonate therapy, Dr. Allan Lipton said at the Sixth International Meeting on Cancer-Induced Bone Disease.

The drug is a fully human monoclonal antibody to RANK ligand, inhibiting the differentiation and proliferation of osteoclasts, and thus reducing bone turnover. It also is being investigated for the treatment of postmenopausal osteoporosis.

Dr. Lipton presented the interim results of a phase II study in patients in whom zoledronic acid or pamidronate failed to adequately suppress urinary markers of bone turnover.

Adequate suppression is important in these patients not only because it helps prevent fractures, but because it delays tumor progression and improves survival.

The interim analysis included 49 patients who have finished the 25-week trial. Eventually the study will enroll 135 patients.

Of initial patients, 40% had metastatic breast cancer, 40% had metastatic prostate cancer, 10% had multiple myeloma, and the rest had other solid tumors. Most (80%) had been on zoledronic acid; the rest had been on pamidronate. All patients still had urinary N-telopeptide (NTx) levels of more than 50 nmol/mmol creatinine.

Overall, more patients on denosumab than on bisphosphonates experienced a decrease in their urinary NTx levels to less than 50 nmol/mmol creatinine (76% vs. 38%). The difference was still significant when the groups were divided according to baseline NTx levels.

Among those who started with a level of 51–100 nmol/mmol creatinine, 87% of those on denosumab achieved the target compared with 50% of those taking bisphosphonates.

Among those with baseline levels of more than 100 nmol/mmol creatinine, two-thirds of the denosumab group achieved the goal compared with 25% of the bisphosphonate group.

Those who received denosumab every 4 weeks had the longest duration of adequate suppression (a mean of 140 days), followed by patients taking the drug every 12 weeks. Bisphosphonate-treated patients maintained adequate suppression for a mean of 30 days.

The meeting was sponsored by the Cancer and Bone Society. The study was sponsored by Amgen Inc. Dr. Lipton, of the Penn State Milton S. Hershey Medical Center, Hershey, Pa., is a consultant for the company.

SAN ANTONIO — Monthly denosumab may prove to suppress bone turnover when patients with cancer metastatic to bone do not respond adequately to bisphosphonate therapy, Dr. Allan Lipton said at the Sixth International Meeting on Cancer-Induced Bone Disease.

The drug is a fully human monoclonal antibody to RANK ligand, inhibiting the differentiation and proliferation of osteoclasts, and thus reducing bone turnover. It also is being investigated for the treatment of postmenopausal osteoporosis.

Dr. Lipton presented the interim results of a phase II study in patients in whom zoledronic acid or pamidronate failed to adequately suppress urinary markers of bone turnover.

Adequate suppression is important in these patients not only because it helps prevent fractures, but because it delays tumor progression and improves survival.

The interim analysis included 49 patients who have finished the 25-week trial. Eventually the study will enroll 135 patients.

Of initial patients, 40% had metastatic breast cancer, 40% had metastatic prostate cancer, 10% had multiple myeloma, and the rest had other solid tumors. Most (80%) had been on zoledronic acid; the rest had been on pamidronate. All patients still had urinary N-telopeptide (NTx) levels of more than 50 nmol/mmol creatinine.

Overall, more patients on denosumab than on bisphosphonates experienced a decrease in their urinary NTx levels to less than 50 nmol/mmol creatinine (76% vs. 38%). The difference was still significant when the groups were divided according to baseline NTx levels.

Among those who started with a level of 51–100 nmol/mmol creatinine, 87% of those on denosumab achieved the target compared with 50% of those taking bisphosphonates.

Among those with baseline levels of more than 100 nmol/mmol creatinine, two-thirds of the denosumab group achieved the goal compared with 25% of the bisphosphonate group.

Those who received denosumab every 4 weeks had the longest duration of adequate suppression (a mean of 140 days), followed by patients taking the drug every 12 weeks. Bisphosphonate-treated patients maintained adequate suppression for a mean of 30 days.

The meeting was sponsored by the Cancer and Bone Society. The study was sponsored by Amgen Inc. Dr. Lipton, of the Penn State Milton S. Hershey Medical Center, Hershey, Pa., is a consultant for the company.

RIVIERA MAYA, MEXICO — Routine induction of labor at 41 weeks is safe for women with low-risk singleton pregnancies and may decrease the risk of postterm pregnancy complications for both mother and baby, Dr. Errol Norwitz said at a meeting on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“This would affect 30% of low-risk deliveries and 10%–15% of all deliveries, so this is a big management shift,” said Dr. Norwitz, director of maternal-fetal medicine at Yale-New Haven Hospital, Conn. “It would definitely affect your practice.”

But such a change would be both cost effective and safer for mother and baby, he asserted. Recent data suggest that routine induction of labor in these women is safer than previously thought, with little or no impact on cesarean delivery rates, and that the risks of postterm birth are greater than previously thought.

Stillbirth is the greatest risk for the postterm fetus, with a fourfold increase at 43 weeks and a sevenfold increase by 44 weeks, compared with 40 weeks. Newer studies have identified other problems as well, including fetal macrosomia, meconium staining, “fetal distress,” and uteroplacental insufficiency. Neonatal encephalopathy is also a risk, with a 13-fold increase at 42 weeks, compared with 38 weeks.

But the mother is also at risk, Dr. Norwitz said. “This is an underappreciated problem. Shoulder dystocia is much more common, as is severe perineal injury, with third- and fourth-degree tears. There is also an increased risk of postpartum hemorrhage.”

In 1997, the American College of Obstetricians and Gynecologists recommended induction of labor after 43 weeks for low-risk pregnancies, but the current guidelines, issued in 2004, don't offer specific recommendations. This omission is possibly the result of concerns that labor induction is associated with an increase in the incidence of cesarean deliveries—an association that may never be conclusively proved or disproved, Dr. Norwitz said. “It would take a randomized controlled trial of 150,000 post-term pregnancies to really answer this question, and I don't think we're going to get that. We have to appreciate that the literature in this area is limited.”

The best source of data is a 2000 Cochrane Database review, which included 26 trials of various size and quality (Cochrane Database Syst. Rev. 2000;2:CD000170). Those of highest quality, Dr. Norwitz said, were two randomized controlled trials of 108 (1992) and 440 (1994) pregnancies, and a Canadian trial of almost 3,500 conducted in 1992. Both 1992 trials showed a significant decrease in cesarean rates among pregnancies induced at 41 weeks, while the 1984 study showed no significant difference in cesarean rates between the two groups. The review also concluded that routine induction of labor after 41 weeks appeared to reduce perinatal mortality.

“It appears that in multiparous women and nulliparas with a favorable cervical exam, routine induction at 41 weeks doesn't carry an increased risk of a C-section,” Dr. Norwitz said. “But in nullips with an unfavorable cervical exam, we might see the rate increase slightly. For these women, we must weigh the risk of preventing postterm complications to mom and baby with the risks of a cesarean delivery.”

Dr. Norwitz offered an algorithm for managing post-term, low-risk, singleton pregnancies:

About 50% of all pregnancies reach the 40th week. At this time, discuss the option of induction and check the cervix, but do not institute fetal surveillance. About half of the group will deliver spontaneously within the next week. For the remaining patients, offer either induction of labor or expectant management at 41 weeks.

For the women who elect continued expectant management, discuss the risks of continuing the pregnancy beyond 41 weeks and document the discussion. Institute some method of fetal surveillance to assess the baby's condition. “No single test has ever been shown to be better than another, with the exception of Doppler velocimetry alone—that has not been shown to be adequately sensitive” Dr. Norwitz said. “Most of us do twice weekly fetal testing, and one of those assessments should include an estimation of amniotic fluid volume.”

Most of these women will give birth by 42 weeks, leaving only 3%–4% of pregnancies to continue into the 43rd week. At this time, induction of labor should routinely be recommended because the increased risk of stillbirth is significant, he said.

Most women who choose induction at 41 weeks will deliver successfully, but some inductions will fail. Those women can be admitted for rupture of membranes and oxytocin, or sent home and brought back for a repeat induction in 2–3 days if the fetal testing is reassuring, Dr. Norwitz said.

RIVIERA MAYA, MEXICO — Routine induction of labor at 41 weeks is safe for women with low-risk singleton pregnancies and may decrease the risk of postterm pregnancy complications for both mother and baby, Dr. Errol Norwitz said at a meeting on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“This would affect 30% of low-risk deliveries and 10%–15% of all deliveries, so this is a big management shift,” said Dr. Norwitz, director of maternal-fetal medicine at Yale-New Haven Hospital, Conn. “It would definitely affect your practice.”

But such a change would be both cost effective and safer for mother and baby, he asserted. Recent data suggest that routine induction of labor in these women is safer than previously thought, with little or no impact on cesarean delivery rates, and that the risks of postterm birth are greater than previously thought.

Stillbirth is the greatest risk for the postterm fetus, with a fourfold increase at 43 weeks and a sevenfold increase by 44 weeks, compared with 40 weeks. Newer studies have identified other problems as well, including fetal macrosomia, meconium staining, “fetal distress,” and uteroplacental insufficiency. Neonatal encephalopathy is also a risk, with a 13-fold increase at 42 weeks, compared with 38 weeks.

But the mother is also at risk, Dr. Norwitz said. “This is an underappreciated problem. Shoulder dystocia is much more common, as is severe perineal injury, with third- and fourth-degree tears. There is also an increased risk of postpartum hemorrhage.”

In 1997, the American College of Obstetricians and Gynecologists recommended induction of labor after 43 weeks for low-risk pregnancies, but the current guidelines, issued in 2004, don't offer specific recommendations. This omission is possibly the result of concerns that labor induction is associated with an increase in the incidence of cesarean deliveries—an association that may never be conclusively proved or disproved, Dr. Norwitz said. “It would take a randomized controlled trial of 150,000 post-term pregnancies to really answer this question, and I don't think we're going to get that. We have to appreciate that the literature in this area is limited.”

The best source of data is a 2000 Cochrane Database review, which included 26 trials of various size and quality (Cochrane Database Syst. Rev. 2000;2:CD000170). Those of highest quality, Dr. Norwitz said, were two randomized controlled trials of 108 (1992) and 440 (1994) pregnancies, and a Canadian trial of almost 3,500 conducted in 1992. Both 1992 trials showed a significant decrease in cesarean rates among pregnancies induced at 41 weeks, while the 1984 study showed no significant difference in cesarean rates between the two groups. The review also concluded that routine induction of labor after 41 weeks appeared to reduce perinatal mortality.

“It appears that in multiparous women and nulliparas with a favorable cervical exam, routine induction at 41 weeks doesn't carry an increased risk of a C-section,” Dr. Norwitz said. “But in nullips with an unfavorable cervical exam, we might see the rate increase slightly. For these women, we must weigh the risk of preventing postterm complications to mom and baby with the risks of a cesarean delivery.”

Dr. Norwitz offered an algorithm for managing post-term, low-risk, singleton pregnancies:

About 50% of all pregnancies reach the 40th week. At this time, discuss the option of induction and check the cervix, but do not institute fetal surveillance. About half of the group will deliver spontaneously within the next week. For the remaining patients, offer either induction of labor or expectant management at 41 weeks.

For the women who elect continued expectant management, discuss the risks of continuing the pregnancy beyond 41 weeks and document the discussion. Institute some method of fetal surveillance to assess the baby's condition. “No single test has ever been shown to be better than another, with the exception of Doppler velocimetry alone—that has not been shown to be adequately sensitive” Dr. Norwitz said. “Most of us do twice weekly fetal testing, and one of those assessments should include an estimation of amniotic fluid volume.”

Most of these women will give birth by 42 weeks, leaving only 3%–4% of pregnancies to continue into the 43rd week. At this time, induction of labor should routinely be recommended because the increased risk of stillbirth is significant, he said.

Most women who choose induction at 41 weeks will deliver successfully, but some inductions will fail. Those women can be admitted for rupture of membranes and oxytocin, or sent home and brought back for a repeat induction in 2–3 days if the fetal testing is reassuring, Dr. Norwitz said.

RIVIERA MAYA, MEXICO — Routine induction of labor at 41 weeks is safe for women with low-risk singleton pregnancies and may decrease the risk of postterm pregnancy complications for both mother and baby, Dr. Errol Norwitz said at a meeting on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

“This would affect 30% of low-risk deliveries and 10%–15% of all deliveries, so this is a big management shift,” said Dr. Norwitz, director of maternal-fetal medicine at Yale-New Haven Hospital, Conn. “It would definitely affect your practice.”

But such a change would be both cost effective and safer for mother and baby, he asserted. Recent data suggest that routine induction of labor in these women is safer than previously thought, with little or no impact on cesarean delivery rates, and that the risks of postterm birth are greater than previously thought.

Stillbirth is the greatest risk for the postterm fetus, with a fourfold increase at 43 weeks and a sevenfold increase by 44 weeks, compared with 40 weeks. Newer studies have identified other problems as well, including fetal macrosomia, meconium staining, “fetal distress,” and uteroplacental insufficiency. Neonatal encephalopathy is also a risk, with a 13-fold increase at 42 weeks, compared with 38 weeks.

But the mother is also at risk, Dr. Norwitz said. “This is an underappreciated problem. Shoulder dystocia is much more common, as is severe perineal injury, with third- and fourth-degree tears. There is also an increased risk of postpartum hemorrhage.”

In 1997, the American College of Obstetricians and Gynecologists recommended induction of labor after 43 weeks for low-risk pregnancies, but the current guidelines, issued in 2004, don't offer specific recommendations. This omission is possibly the result of concerns that labor induction is associated with an increase in the incidence of cesarean deliveries—an association that may never be conclusively proved or disproved, Dr. Norwitz said. “It would take a randomized controlled trial of 150,000 post-term pregnancies to really answer this question, and I don't think we're going to get that. We have to appreciate that the literature in this area is limited.”

The best source of data is a 2000 Cochrane Database review, which included 26 trials of various size and quality (Cochrane Database Syst. Rev. 2000;2:CD000170). Those of highest quality, Dr. Norwitz said, were two randomized controlled trials of 108 (1992) and 440 (1994) pregnancies, and a Canadian trial of almost 3,500 conducted in 1992. Both 1992 trials showed a significant decrease in cesarean rates among pregnancies induced at 41 weeks, while the 1984 study showed no significant difference in cesarean rates between the two groups. The review also concluded that routine induction of labor after 41 weeks appeared to reduce perinatal mortality.

“It appears that in multiparous women and nulliparas with a favorable cervical exam, routine induction at 41 weeks doesn't carry an increased risk of a C-section,” Dr. Norwitz said. “But in nullips with an unfavorable cervical exam, we might see the rate increase slightly. For these women, we must weigh the risk of preventing postterm complications to mom and baby with the risks of a cesarean delivery.”

Dr. Norwitz offered an algorithm for managing post-term, low-risk, singleton pregnancies:

About 50% of all pregnancies reach the 40th week. At this time, discuss the option of induction and check the cervix, but do not institute fetal surveillance. About half of the group will deliver spontaneously within the next week. For the remaining patients, offer either induction of labor or expectant management at 41 weeks.

For the women who elect continued expectant management, discuss the risks of continuing the pregnancy beyond 41 weeks and document the discussion. Institute some method of fetal surveillance to assess the baby's condition. “No single test has ever been shown to be better than another, with the exception of Doppler velocimetry alone—that has not been shown to be adequately sensitive” Dr. Norwitz said. “Most of us do twice weekly fetal testing, and one of those assessments should include an estimation of amniotic fluid volume.”

Most of these women will give birth by 42 weeks, leaving only 3%–4% of pregnancies to continue into the 43rd week. At this time, induction of labor should routinely be recommended because the increased risk of stillbirth is significant, he said.

Most women who choose induction at 41 weeks will deliver successfully, but some inductions will fail. Those women can be admitted for rupture of membranes and oxytocin, or sent home and brought back for a repeat induction in 2–3 days if the fetal testing is reassuring, Dr. Norwitz said.

Hemispherectomy or cortical resection may cure catastrophic epilepsy even in a child with generalized seizures, with MRI rather than EEG identifying surgical candidates, according to Dr. Elaine Wyllie, director of the child neurology center at the Cleveland Clinic Children's Hospital.

Candidates for the surgery are children in whom the epileptogenic focus is a unilateral brain lesion that probably occurred prenatally, perinatally, or during infancy. “These extensive congenital or early-acquired unilateral brain lesions may produce generalized—or even contralateral—maximum epileptiform discharge patterns on EEG,” she said in an interview. “Despite these EEG findings, you can still get favorable surgical results in some cases, if you have a clear unilateral brain lesion on MRI with side-appropriate semiology.” Children with this clinical picture are typically turned away from surgery.

In the 1990s, she said, a team from the University of California, Los Angeles, began to report surgical cures of infantile spasms and hypsarrhythmia—that is, seizure types with diffuse EEG patterns (Epilepsia 1993;34:764–71). Other centers, including the Cleveland Clinic, soon were replicating the results. “When a lesion occurs this early, it's actually interacting with the time-locked processes of brain development: the formation of the cortex, the migration of neurons, the increase in synaptogenesis, and myelination,” Dr. Wyllie said. “And when the lesion interacts with this dynamic process, you get the development of epilepsy that looks different—electrically and clinically—from what you see when a fixed electrical brain system acquires a lesion.” In fact, she said, the healthier side of the brain can sometimes express more pronounced epileptiform discharges than does the injured side.

Although the EEG findings—considered in isolation—may suggest that the child has generalized seizures, the seizure semiology, motor deficits, and MRI all point to a focal source. This seeming contradiction makes hemispherectomy a difficult decision for both physician and parent.

At a recent meeting of the Child Neurology Society, Dr. Wyllie reported some preliminary findings from a retrospective study of 50 such children, all of whom underwent functional hemispherectomy or cortical resection at the Cleveland Clinic in 1999–2004. All had ictal or interictal epileptiform discharges that were either generalized or maximum contralateral to the surgical site, and early brain lesions that were unilateral or very strongly asymmetrical. Even though all of the children had an obvious focus for their seizures, their generalized EEG patterns had eliminated some of these patients as surgical candidates at other centers they had visited.

One of her first such patients, a 12-year-old, was a prime example, Dr. Wyllie said. His seizures began when he was 1 month old, and by the time he was 5 months old, he had developed a right hemiparesis with no fine finger movement. By 9 years of age, he had developed medically refractory epilepsy, with daily right arm tonic seizures. His MRI showed a middle cerebral artery infarct, which probably occurred between 34 weeks' gestation and birth, with left-sided gliosis and cortical and subcortical encephalomalacia, all of which corresponded with his seizure semiology and neurologic exam. But his ictal and interictal EEGs showed generalized discharges, mainly in the right hemisphere. “We had to ignore these features on EEG and go with what we saw on the MRI, the exam, and the seizure type,” she said. “He had a left functional hemispherectomy in 1999, and has been off all medications since 2001. He hasn't had any seizures since, has graduated from high school, and is now learning a trade.”

Many of the other 49 patients with focal lesions and diffuse EEGS had a similarly good outcome, she said. Her preliminary results, based on each patient's last follow-up, showed that 72% had become seizure free since their surgery. Major improvements—resolution of catastrophic epilepsy with some remaining seizures—occurred in several of the other patients, with only 6 of the original 50 experiencing little or no improvement. The three wound infections resolved with antibiotics and cranioplasty, one hydrocephalus that required a shunt, and one late expanding cyst that required fenestration. The next step is to further define the best surgical candidates, she said. Her current work-up includes the following considerations:

▸ Imaging must identify an extensive brain lesion that probably occurred pre- or perinatally or during infancy.

▸ The lesion must be capable of epileptogenesis.

▸ The lesion must be unilateral or strongly asymmetric.

▸ Seizures must be medically refractory.

▸ Hemispherectomy candidates must have side-appropriate motor deficit that will not be worsened by surgery.

▸ A video EEG can be helpful in confirming seizures.

Encephalomalacia from a perinatal infarction is shown on MRI (left); perioperative interictal EEG in the same patient shows generalized slow spike-wave complexes (right). Photos courtesy Dr. Elaine Wyllie

Hemispherectomy or cortical resection may cure catastrophic epilepsy even in a child with generalized seizures, with MRI rather than EEG identifying surgical candidates, according to Dr. Elaine Wyllie, director of the child neurology center at the Cleveland Clinic Children's Hospital.

Candidates for the surgery are children in whom the epileptogenic focus is a unilateral brain lesion that probably occurred prenatally, perinatally, or during infancy. “These extensive congenital or early-acquired unilateral brain lesions may produce generalized—or even contralateral—maximum epileptiform discharge patterns on EEG,” she said in an interview. “Despite these EEG findings, you can still get favorable surgical results in some cases, if you have a clear unilateral brain lesion on MRI with side-appropriate semiology.” Children with this clinical picture are typically turned away from surgery.

In the 1990s, she said, a team from the University of California, Los Angeles, began to report surgical cures of infantile spasms and hypsarrhythmia—that is, seizure types with diffuse EEG patterns (Epilepsia 1993;34:764–71). Other centers, including the Cleveland Clinic, soon were replicating the results. “When a lesion occurs this early, it's actually interacting with the time-locked processes of brain development: the formation of the cortex, the migration of neurons, the increase in synaptogenesis, and myelination,” Dr. Wyllie said. “And when the lesion interacts with this dynamic process, you get the development of epilepsy that looks different—electrically and clinically—from what you see when a fixed electrical brain system acquires a lesion.” In fact, she said, the healthier side of the brain can sometimes express more pronounced epileptiform discharges than does the injured side.

Although the EEG findings—considered in isolation—may suggest that the child has generalized seizures, the seizure semiology, motor deficits, and MRI all point to a focal source. This seeming contradiction makes hemispherectomy a difficult decision for both physician and parent.

At a recent meeting of the Child Neurology Society, Dr. Wyllie reported some preliminary findings from a retrospective study of 50 such children, all of whom underwent functional hemispherectomy or cortical resection at the Cleveland Clinic in 1999–2004. All had ictal or interictal epileptiform discharges that were either generalized or maximum contralateral to the surgical site, and early brain lesions that were unilateral or very strongly asymmetrical. Even though all of the children had an obvious focus for their seizures, their generalized EEG patterns had eliminated some of these patients as surgical candidates at other centers they had visited.

One of her first such patients, a 12-year-old, was a prime example, Dr. Wyllie said. His seizures began when he was 1 month old, and by the time he was 5 months old, he had developed a right hemiparesis with no fine finger movement. By 9 years of age, he had developed medically refractory epilepsy, with daily right arm tonic seizures. His MRI showed a middle cerebral artery infarct, which probably occurred between 34 weeks' gestation and birth, with left-sided gliosis and cortical and subcortical encephalomalacia, all of which corresponded with his seizure semiology and neurologic exam. But his ictal and interictal EEGs showed generalized discharges, mainly in the right hemisphere. “We had to ignore these features on EEG and go with what we saw on the MRI, the exam, and the seizure type,” she said. “He had a left functional hemispherectomy in 1999, and has been off all medications since 2001. He hasn't had any seizures since, has graduated from high school, and is now learning a trade.”

Many of the other 49 patients with focal lesions and diffuse EEGS had a similarly good outcome, she said. Her preliminary results, based on each patient's last follow-up, showed that 72% had become seizure free since their surgery. Major improvements—resolution of catastrophic epilepsy with some remaining seizures—occurred in several of the other patients, with only 6 of the original 50 experiencing little or no improvement. The three wound infections resolved with antibiotics and cranioplasty, one hydrocephalus that required a shunt, and one late expanding cyst that required fenestration. The next step is to further define the best surgical candidates, she said. Her current work-up includes the following considerations:

▸ Imaging must identify an extensive brain lesion that probably occurred pre- or perinatally or during infancy.

▸ The lesion must be capable of epileptogenesis.

▸ The lesion must be unilateral or strongly asymmetric.

▸ Seizures must be medically refractory.

▸ Hemispherectomy candidates must have side-appropriate motor deficit that will not be worsened by surgery.

▸ A video EEG can be helpful in confirming seizures.

Encephalomalacia from a perinatal infarction is shown on MRI (left); perioperative interictal EEG in the same patient shows generalized slow spike-wave complexes (right). Photos courtesy Dr. Elaine Wyllie

Hemispherectomy or cortical resection may cure catastrophic epilepsy even in a child with generalized seizures, with MRI rather than EEG identifying surgical candidates, according to Dr. Elaine Wyllie, director of the child neurology center at the Cleveland Clinic Children's Hospital.

Candidates for the surgery are children in whom the epileptogenic focus is a unilateral brain lesion that probably occurred prenatally, perinatally, or during infancy. “These extensive congenital or early-acquired unilateral brain lesions may produce generalized—or even contralateral—maximum epileptiform discharge patterns on EEG,” she said in an interview. “Despite these EEG findings, you can still get favorable surgical results in some cases, if you have a clear unilateral brain lesion on MRI with side-appropriate semiology.” Children with this clinical picture are typically turned away from surgery.

In the 1990s, she said, a team from the University of California, Los Angeles, began to report surgical cures of infantile spasms and hypsarrhythmia—that is, seizure types with diffuse EEG patterns (Epilepsia 1993;34:764–71). Other centers, including the Cleveland Clinic, soon were replicating the results. “When a lesion occurs this early, it's actually interacting with the time-locked processes of brain development: the formation of the cortex, the migration of neurons, the increase in synaptogenesis, and myelination,” Dr. Wyllie said. “And when the lesion interacts with this dynamic process, you get the development of epilepsy that looks different—electrically and clinically—from what you see when a fixed electrical brain system acquires a lesion.” In fact, she said, the healthier side of the brain can sometimes express more pronounced epileptiform discharges than does the injured side.

Although the EEG findings—considered in isolation—may suggest that the child has generalized seizures, the seizure semiology, motor deficits, and MRI all point to a focal source. This seeming contradiction makes hemispherectomy a difficult decision for both physician and parent.

At a recent meeting of the Child Neurology Society, Dr. Wyllie reported some preliminary findings from a retrospective study of 50 such children, all of whom underwent functional hemispherectomy or cortical resection at the Cleveland Clinic in 1999–2004. All had ictal or interictal epileptiform discharges that were either generalized or maximum contralateral to the surgical site, and early brain lesions that were unilateral or very strongly asymmetrical. Even though all of the children had an obvious focus for their seizures, their generalized EEG patterns had eliminated some of these patients as surgical candidates at other centers they had visited.

One of her first such patients, a 12-year-old, was a prime example, Dr. Wyllie said. His seizures began when he was 1 month old, and by the time he was 5 months old, he had developed a right hemiparesis with no fine finger movement. By 9 years of age, he had developed medically refractory epilepsy, with daily right arm tonic seizures. His MRI showed a middle cerebral artery infarct, which probably occurred between 34 weeks' gestation and birth, with left-sided gliosis and cortical and subcortical encephalomalacia, all of which corresponded with his seizure semiology and neurologic exam. But his ictal and interictal EEGs showed generalized discharges, mainly in the right hemisphere. “We had to ignore these features on EEG and go with what we saw on the MRI, the exam, and the seizure type,” she said. “He had a left functional hemispherectomy in 1999, and has been off all medications since 2001. He hasn't had any seizures since, has graduated from high school, and is now learning a trade.”

Many of the other 49 patients with focal lesions and diffuse EEGS had a similarly good outcome, she said. Her preliminary results, based on each patient's last follow-up, showed that 72% had become seizure free since their surgery. Major improvements—resolution of catastrophic epilepsy with some remaining seizures—occurred in several of the other patients, with only 6 of the original 50 experiencing little or no improvement. The three wound infections resolved with antibiotics and cranioplasty, one hydrocephalus that required a shunt, and one late expanding cyst that required fenestration. The next step is to further define the best surgical candidates, she said. Her current work-up includes the following considerations:

▸ Imaging must identify an extensive brain lesion that probably occurred pre- or perinatally or during infancy.

▸ The lesion must be capable of epileptogenesis.

▸ The lesion must be unilateral or strongly asymmetric.

▸ Seizures must be medically refractory.

▸ Hemispherectomy candidates must have side-appropriate motor deficit that will not be worsened by surgery.

▸ A video EEG can be helpful in confirming seizures.

Encephalomalacia from a perinatal infarction is shown on MRI (left); perioperative interictal EEG in the same patient shows generalized slow spike-wave complexes (right). Photos courtesy Dr. Elaine Wyllie

SAN ANTONIO — Monthly ibandronate appears to prevent, and perhaps even reverse, bone loss in women who are taking anastrozole for estrogen receptor-positive breast cancers, Dr. J.E. Lester reported in a poster at the Sixth International Meeting on Cancer-Induced Bone Disease.

While she said that further follow-up is required, her randomized placebo-controlled trial showed that after 1 year, women taking the bisphosphonate showed a significant increase in bone mineral density (BMD) at both the hip and spine, while those taking the placebo experienced a significant decrease at both sites.

Dr. Lester, of the Cancer Research Centre of Weston Park Hospital, Sheffield, England, examined ibandronate's effects in 131 postmenopausal women with estrogen receptor-positive breast cancers. The women were grouped according to baseline BMD: 68 had normal BMD (mean age 63 years), 50 were osteopenic (mean age 67 years), and 13 were osteoporotic (mean age 71 years).

All patients were taking calcium and vitamin D supplements in addition to anastrozole. Those with normal BMD continued on the supplements. Osteopenic patients were randomized to either 150 mg oral ibandronate every 28 days (25 patients) or placebo (25 patients). All osteoporotic women received the same monthly ibandronate treatment.

Ibandronate significantly increased BMD at the hip and spine in both treated groups. At 1 year, osteopenic women had a mean increase of 2.8% at the lumbar spine and 1.4% at the hip. After 1 year, five of the previously osteopenic women were found to have normal BMD.

Women in the placebo group had a decrease of BMD at both sites (mean −2.6% at the lumbar spine and −2.3% at the hip).

During the blinded period, two osteopenic patients lost more than 10% of their BMD at either the spine or hip. They were withdrawn and unblinded; both had been taking the placebo and both were offered open-label ibandronate.

Among the osteoporotic women, the mean increase in BMD was 2.6% at the lumbar spine and 2.6% at the hip. Seven previously osteoporotic patients were found to be osteopenic at 1-year follow-up.

Of the 68 women with initially normal BMD untreated with ibandronate, 20 were followed for 2 years. Follow-up scans showed a mean BMD decrease of −4% at the lumbar spine and −3% at the hip. Despite these changes, however, none of the women developed osteoporosis.

ELSEVIER GLOBAL MEDICAL NEWS

SAN ANTONIO — Monthly ibandronate appears to prevent, and perhaps even reverse, bone loss in women who are taking anastrozole for estrogen receptor-positive breast cancers, Dr. J.E. Lester reported in a poster at the Sixth International Meeting on Cancer-Induced Bone Disease.

While she said that further follow-up is required, her randomized placebo-controlled trial showed that after 1 year, women taking the bisphosphonate showed a significant increase in bone mineral density (BMD) at both the hip and spine, while those taking the placebo experienced a significant decrease at both sites.

Dr. Lester, of the Cancer Research Centre of Weston Park Hospital, Sheffield, England, examined ibandronate's effects in 131 postmenopausal women with estrogen receptor-positive breast cancers. The women were grouped according to baseline BMD: 68 had normal BMD (mean age 63 years), 50 were osteopenic (mean age 67 years), and 13 were osteoporotic (mean age 71 years).

All patients were taking calcium and vitamin D supplements in addition to anastrozole. Those with normal BMD continued on the supplements. Osteopenic patients were randomized to either 150 mg oral ibandronate every 28 days (25 patients) or placebo (25 patients). All osteoporotic women received the same monthly ibandronate treatment.

Ibandronate significantly increased BMD at the hip and spine in both treated groups. At 1 year, osteopenic women had a mean increase of 2.8% at the lumbar spine and 1.4% at the hip. After 1 year, five of the previously osteopenic women were found to have normal BMD.

Women in the placebo group had a decrease of BMD at both sites (mean −2.6% at the lumbar spine and −2.3% at the hip).

During the blinded period, two osteopenic patients lost more than 10% of their BMD at either the spine or hip. They were withdrawn and unblinded; both had been taking the placebo and both were offered open-label ibandronate.

Among the osteoporotic women, the mean increase in BMD was 2.6% at the lumbar spine and 2.6% at the hip. Seven previously osteoporotic patients were found to be osteopenic at 1-year follow-up.

Of the 68 women with initially normal BMD untreated with ibandronate, 20 were followed for 2 years. Follow-up scans showed a mean BMD decrease of −4% at the lumbar spine and −3% at the hip. Despite these changes, however, none of the women developed osteoporosis.

ELSEVIER GLOBAL MEDICAL NEWS

SAN ANTONIO — Monthly ibandronate appears to prevent, and perhaps even reverse, bone loss in women who are taking anastrozole for estrogen receptor-positive breast cancers, Dr. J.E. Lester reported in a poster at the Sixth International Meeting on Cancer-Induced Bone Disease.

While she said that further follow-up is required, her randomized placebo-controlled trial showed that after 1 year, women taking the bisphosphonate showed a significant increase in bone mineral density (BMD) at both the hip and spine, while those taking the placebo experienced a significant decrease at both sites.

Dr. Lester, of the Cancer Research Centre of Weston Park Hospital, Sheffield, England, examined ibandronate's effects in 131 postmenopausal women with estrogen receptor-positive breast cancers. The women were grouped according to baseline BMD: 68 had normal BMD (mean age 63 years), 50 were osteopenic (mean age 67 years), and 13 were osteoporotic (mean age 71 years).

All patients were taking calcium and vitamin D supplements in addition to anastrozole. Those with normal BMD continued on the supplements. Osteopenic patients were randomized to either 150 mg oral ibandronate every 28 days (25 patients) or placebo (25 patients). All osteoporotic women received the same monthly ibandronate treatment.

Ibandronate significantly increased BMD at the hip and spine in both treated groups. At 1 year, osteopenic women had a mean increase of 2.8% at the lumbar spine and 1.4% at the hip. After 1 year, five of the previously osteopenic women were found to have normal BMD.

Women in the placebo group had a decrease of BMD at both sites (mean −2.6% at the lumbar spine and −2.3% at the hip).

During the blinded period, two osteopenic patients lost more than 10% of their BMD at either the spine or hip. They were withdrawn and unblinded; both had been taking the placebo and both were offered open-label ibandronate.

Among the osteoporotic women, the mean increase in BMD was 2.6% at the lumbar spine and 2.6% at the hip. Seven previously osteoporotic patients were found to be osteopenic at 1-year follow-up.

Of the 68 women with initially normal BMD untreated with ibandronate, 20 were followed for 2 years. Follow-up scans showed a mean BMD decrease of −4% at the lumbar spine and −3% at the hip. Despite these changes, however, none of the women developed osteoporosis.

ELSEVIER GLOBAL MEDICAL NEWS

BARCELONA — Meropenem appears to rapidly and significantly decrease serum levels of valproic acid and should be used with caution in patients who are taking the anticonvulsant, Dr. Celeste Dias reported in a poster at the annual congress of the European Society of Intensive Care Medicine.

“We strongly recommend that VPA [valproic acid] serum levels be closely monitored in these patients,” said Dr. Dias of Hospital S. Joao, Oporto, Portugal.

“In high-risk patients, electroencephalographic monitoring should be considered.”

Dr. Dias presented a case review of 12 patients aged 12–78 years who were admitted to the hospital's neurological critical care unit.

Upon admission, all were taking VPA, either for a chronic seizure disorder or for prevention of seizures resulting from an acute brain disorder or injury.

During their stay in the neurological unit, all the patients began meropenem for nosocomial infections with gram-negative bacteria.

Routine serum VPA levels showed a significant and almost immediate drop in anticonvulsant levels after meropenem was initiated.

Within 60 hours, VPA levels had decreased to 20 mg/L or less in all 12 patients.

By day 6, three patients had no measurable levels of VPA during at least one blood draw.

“These decreases happened despite the fact that we actually increased VPA dosing to the maximum dose,” Dr. Dias commented.

Patients were monitored with EEG and none developed acute seizures despite the drop in VPA levels.

However, Dr. Dias noted, four of the patients were also taking other anticonvulsants, including phenytoin, carbamazepine, and topiramate.

There are several possible mechanisms for this drug interaction, she said, including the inhibition of plasma protein binding and suppression of enterohepatic recirculation.

“Meropenem seems to inhibit the hydrolytic enzyme involved in the hydrolysis of VPA-glucuronide to VPA, which results in a decrease in plasma concentration of the active drug,” Dr. Dias commented.

BARCELONA — Meropenem appears to rapidly and significantly decrease serum levels of valproic acid and should be used with caution in patients who are taking the anticonvulsant, Dr. Celeste Dias reported in a poster at the annual congress of the European Society of Intensive Care Medicine.

“We strongly recommend that VPA [valproic acid] serum levels be closely monitored in these patients,” said Dr. Dias of Hospital S. Joao, Oporto, Portugal.

“In high-risk patients, electroencephalographic monitoring should be considered.”

Dr. Dias presented a case review of 12 patients aged 12–78 years who were admitted to the hospital's neurological critical care unit.

Upon admission, all were taking VPA, either for a chronic seizure disorder or for prevention of seizures resulting from an acute brain disorder or injury.

During their stay in the neurological unit, all the patients began meropenem for nosocomial infections with gram-negative bacteria.

Routine serum VPA levels showed a significant and almost immediate drop in anticonvulsant levels after meropenem was initiated.

Within 60 hours, VPA levels had decreased to 20 mg/L or less in all 12 patients.

By day 6, three patients had no measurable levels of VPA during at least one blood draw.

“These decreases happened despite the fact that we actually increased VPA dosing to the maximum dose,” Dr. Dias commented.

Patients were monitored with EEG and none developed acute seizures despite the drop in VPA levels.

However, Dr. Dias noted, four of the patients were also taking other anticonvulsants, including phenytoin, carbamazepine, and topiramate.

There are several possible mechanisms for this drug interaction, she said, including the inhibition of plasma protein binding and suppression of enterohepatic recirculation.

“Meropenem seems to inhibit the hydrolytic enzyme involved in the hydrolysis of VPA-glucuronide to VPA, which results in a decrease in plasma concentration of the active drug,” Dr. Dias commented.

BARCELONA — Meropenem appears to rapidly and significantly decrease serum levels of valproic acid and should be used with caution in patients who are taking the anticonvulsant, Dr. Celeste Dias reported in a poster at the annual congress of the European Society of Intensive Care Medicine.

“We strongly recommend that VPA [valproic acid] serum levels be closely monitored in these patients,” said Dr. Dias of Hospital S. Joao, Oporto, Portugal.

“In high-risk patients, electroencephalographic monitoring should be considered.”

Dr. Dias presented a case review of 12 patients aged 12–78 years who were admitted to the hospital's neurological critical care unit.

Upon admission, all were taking VPA, either for a chronic seizure disorder or for prevention of seizures resulting from an acute brain disorder or injury.

During their stay in the neurological unit, all the patients began meropenem for nosocomial infections with gram-negative bacteria.

Routine serum VPA levels showed a significant and almost immediate drop in anticonvulsant levels after meropenem was initiated.

Within 60 hours, VPA levels had decreased to 20 mg/L or less in all 12 patients.

By day 6, three patients had no measurable levels of VPA during at least one blood draw.

“These decreases happened despite the fact that we actually increased VPA dosing to the maximum dose,” Dr. Dias commented.

Patients were monitored with EEG and none developed acute seizures despite the drop in VPA levels.

However, Dr. Dias noted, four of the patients were also taking other anticonvulsants, including phenytoin, carbamazepine, and topiramate.

There are several possible mechanisms for this drug interaction, she said, including the inhibition of plasma protein binding and suppression of enterohepatic recirculation.

“Meropenem seems to inhibit the hydrolytic enzyme involved in the hydrolysis of VPA-glucuronide to VPA, which results in a decrease in plasma concentration of the active drug,” Dr. Dias commented.