Sharon Worcester

MIAMI BEACH — Intraumbilical vein injection with oxytocin following cord clamp was effective for preventing placental retention and reducing postpartum blood loss in a randomized, placebo-controlled, double-blind study presented at the annual meeting of the Society for Maternal-Fetal Medicine.

The study is the first to suggest that oxytocin might be beneficial in preventing complications in the third stage of labor, though not its duration, said Dr. Labib M. Ghulmiyyah of the University of Cincinnatti.

A total of 79 women with uncomplicated singleton pregnancies were randomized to 30 mL of saline or 20 IU of oxytocin in 30 mL of saline. The mean time to placental delivery did not differ significantly between the two groups, but significantly more women in the saline group than in the oxytocin group had a retained placenta after 15 minutes (5 vs. 0 women).

The groups had similar mean hemoglobin levels prior to delivery, but those who received saline had significantly lower mean postpartum hemoglobin levels (used as a measure of blood loss) than did those in the oxytocin group.

MIAMI BEACH — Intraumbilical vein injection with oxytocin following cord clamp was effective for preventing placental retention and reducing postpartum blood loss in a randomized, placebo-controlled, double-blind study presented at the annual meeting of the Society for Maternal-Fetal Medicine.

The study is the first to suggest that oxytocin might be beneficial in preventing complications in the third stage of labor, though not its duration, said Dr. Labib M. Ghulmiyyah of the University of Cincinnatti.

A total of 79 women with uncomplicated singleton pregnancies were randomized to 30 mL of saline or 20 IU of oxytocin in 30 mL of saline. The mean time to placental delivery did not differ significantly between the two groups, but significantly more women in the saline group than in the oxytocin group had a retained placenta after 15 minutes (5 vs. 0 women).

The groups had similar mean hemoglobin levels prior to delivery, but those who received saline had significantly lower mean postpartum hemoglobin levels (used as a measure of blood loss) than did those in the oxytocin group.

MIAMI BEACH — Intraumbilical vein injection with oxytocin following cord clamp was effective for preventing placental retention and reducing postpartum blood loss in a randomized, placebo-controlled, double-blind study presented at the annual meeting of the Society for Maternal-Fetal Medicine.

The study is the first to suggest that oxytocin might be beneficial in preventing complications in the third stage of labor, though not its duration, said Dr. Labib M. Ghulmiyyah of the University of Cincinnatti.

A total of 79 women with uncomplicated singleton pregnancies were randomized to 30 mL of saline or 20 IU of oxytocin in 30 mL of saline. The mean time to placental delivery did not differ significantly between the two groups, but significantly more women in the saline group than in the oxytocin group had a retained placenta after 15 minutes (5 vs. 0 women).

The groups had similar mean hemoglobin levels prior to delivery, but those who received saline had significantly lower mean postpartum hemoglobin levels (used as a measure of blood loss) than did those in the oxytocin group.

MIAMI BEACH — Studies increasingly suggest that adolescent girls are particularly vulnerable to many of the risk factors for major depression, and that depression in this population manifests in several unique ways.

For example, depressed girls are more likely than are depressed boys to have poor body image, to feel disappointed in themselves, to feel like a failure, and to have difficulty concentrating, Dr. Nada Stotland said at the annual meeting of the American Society for Adolescent Psychiatry.

Girls tend to have more inwardly directed symptoms, she explained at the meeting, which was cosponsored by the University of Texas at Dallas. And they experience unique consequences of depression. A recent study suggests that depressed girls are at double the risk of nondepressed girls of becoming involved in abusive relationships, said Dr. Stotland of Rush Medical College, Chicago.

Another study showed that 3 years after being diagnosed with depression, girls had decreased self worth, poorer body image, and increased feelings of vulnerability, compared with prior to their depression. Depressive symptoms, along with dietary restrictions, weight control behaviors, and feeling that one's parents are overweight, also appear to be a risk factor for obesity, Dr. Stotland noted.

Race also appears to play an important role in depression in girls; white girls with depression in adolescence were shown in one study to be more likely than African American girls to improve in early adulthood. And in a study of Hawaiian youth, 38% of girls in the study had a psychiatric disorder. Chinese girls in one study commonly reported anxiety, with 48% saying they had anxiety that interfered with enjoyment, 40% saying their anxiety interfered with relaxation, and 27% saying it interfered with sleep.

Ethnic differences also are apparent in the effects of body image on depression, with white girls being the most likely to feel pressure to be model-thin.

As for gender differences in depression, a study from Spain suggests cognitive styles may be to blame. Girls were shown to be less likely than boys to think positively, and when faced with a problem, they were less likely to consider the problem to be solvable. Girls also were more likely to think negatively of themselves.

Other factors shown recently to be particularly associated with depression in girls include:

▸ Maternal depression. A recent large study confirms much of what was already suspected: that maternal depression has a significant impact on adolescent depression risk. Other studies have suggested girls are particularly vulnerable to these effects.

▸ Sexual orientation. Parental discrimination was shown to be “an enormous risk factor” for depression in homosexual adolescents.

▸ High-risk behaviors. There has been some controversy regarding whether high-risk behaviors such as drug use and promiscuity come before or after depression, but findings from a very large study suggest that such behaviors are predictive of depression, particularly in girls.

▸ Parental marital problems. Divorce and marital distress in parents was linked in a longitudinal study in Norway to an increased risk of depression in adolescent children, and the effects were more lasting in girls.

▸ Stress. While stress can be difficult to define, at least one study shows that girls experience more stress than do boys, and that they experience more depression as a result of stress.

▸ Maternal relationship. In a recent study 65% of girls, compared with 34% of boys, who felt their mothers didn't care about them reported depression.

▸ Hormones. Depressive symptoms may change with the menstrual cycle, as may blood levels of certain medications. Premenstrual symptoms and oral contraceptive use should be considered when evaluating girls with depression.

Depressed girls are at double the risk of becoming involved in abusive relationships. DR. STOTLAND

MIAMI BEACH — Studies increasingly suggest that adolescent girls are particularly vulnerable to many of the risk factors for major depression, and that depression in this population manifests in several unique ways.

For example, depressed girls are more likely than are depressed boys to have poor body image, to feel disappointed in themselves, to feel like a failure, and to have difficulty concentrating, Dr. Nada Stotland said at the annual meeting of the American Society for Adolescent Psychiatry.

Girls tend to have more inwardly directed symptoms, she explained at the meeting, which was cosponsored by the University of Texas at Dallas. And they experience unique consequences of depression. A recent study suggests that depressed girls are at double the risk of nondepressed girls of becoming involved in abusive relationships, said Dr. Stotland of Rush Medical College, Chicago.

Another study showed that 3 years after being diagnosed with depression, girls had decreased self worth, poorer body image, and increased feelings of vulnerability, compared with prior to their depression. Depressive symptoms, along with dietary restrictions, weight control behaviors, and feeling that one's parents are overweight, also appear to be a risk factor for obesity, Dr. Stotland noted.

Race also appears to play an important role in depression in girls; white girls with depression in adolescence were shown in one study to be more likely than African American girls to improve in early adulthood. And in a study of Hawaiian youth, 38% of girls in the study had a psychiatric disorder. Chinese girls in one study commonly reported anxiety, with 48% saying they had anxiety that interfered with enjoyment, 40% saying their anxiety interfered with relaxation, and 27% saying it interfered with sleep.

Ethnic differences also are apparent in the effects of body image on depression, with white girls being the most likely to feel pressure to be model-thin.

As for gender differences in depression, a study from Spain suggests cognitive styles may be to blame. Girls were shown to be less likely than boys to think positively, and when faced with a problem, they were less likely to consider the problem to be solvable. Girls also were more likely to think negatively of themselves.

Other factors shown recently to be particularly associated with depression in girls include:

▸ Maternal depression. A recent large study confirms much of what was already suspected: that maternal depression has a significant impact on adolescent depression risk. Other studies have suggested girls are particularly vulnerable to these effects.

▸ Sexual orientation. Parental discrimination was shown to be “an enormous risk factor” for depression in homosexual adolescents.

▸ High-risk behaviors. There has been some controversy regarding whether high-risk behaviors such as drug use and promiscuity come before or after depression, but findings from a very large study suggest that such behaviors are predictive of depression, particularly in girls.

▸ Parental marital problems. Divorce and marital distress in parents was linked in a longitudinal study in Norway to an increased risk of depression in adolescent children, and the effects were more lasting in girls.

▸ Stress. While stress can be difficult to define, at least one study shows that girls experience more stress than do boys, and that they experience more depression as a result of stress.

▸ Maternal relationship. In a recent study 65% of girls, compared with 34% of boys, who felt their mothers didn't care about them reported depression.

▸ Hormones. Depressive symptoms may change with the menstrual cycle, as may blood levels of certain medications. Premenstrual symptoms and oral contraceptive use should be considered when evaluating girls with depression.

Depressed girls are at double the risk of becoming involved in abusive relationships. DR. STOTLAND

MIAMI BEACH — Studies increasingly suggest that adolescent girls are particularly vulnerable to many of the risk factors for major depression, and that depression in this population manifests in several unique ways.

For example, depressed girls are more likely than are depressed boys to have poor body image, to feel disappointed in themselves, to feel like a failure, and to have difficulty concentrating, Dr. Nada Stotland said at the annual meeting of the American Society for Adolescent Psychiatry.

Girls tend to have more inwardly directed symptoms, she explained at the meeting, which was cosponsored by the University of Texas at Dallas. And they experience unique consequences of depression. A recent study suggests that depressed girls are at double the risk of nondepressed girls of becoming involved in abusive relationships, said Dr. Stotland of Rush Medical College, Chicago.

Another study showed that 3 years after being diagnosed with depression, girls had decreased self worth, poorer body image, and increased feelings of vulnerability, compared with prior to their depression. Depressive symptoms, along with dietary restrictions, weight control behaviors, and feeling that one's parents are overweight, also appear to be a risk factor for obesity, Dr. Stotland noted.

Race also appears to play an important role in depression in girls; white girls with depression in adolescence were shown in one study to be more likely than African American girls to improve in early adulthood. And in a study of Hawaiian youth, 38% of girls in the study had a psychiatric disorder. Chinese girls in one study commonly reported anxiety, with 48% saying they had anxiety that interfered with enjoyment, 40% saying their anxiety interfered with relaxation, and 27% saying it interfered with sleep.

Ethnic differences also are apparent in the effects of body image on depression, with white girls being the most likely to feel pressure to be model-thin.

As for gender differences in depression, a study from Spain suggests cognitive styles may be to blame. Girls were shown to be less likely than boys to think positively, and when faced with a problem, they were less likely to consider the problem to be solvable. Girls also were more likely to think negatively of themselves.

Other factors shown recently to be particularly associated with depression in girls include:

▸ Maternal depression. A recent large study confirms much of what was already suspected: that maternal depression has a significant impact on adolescent depression risk. Other studies have suggested girls are particularly vulnerable to these effects.

▸ Sexual orientation. Parental discrimination was shown to be “an enormous risk factor” for depression in homosexual adolescents.

▸ High-risk behaviors. There has been some controversy regarding whether high-risk behaviors such as drug use and promiscuity come before or after depression, but findings from a very large study suggest that such behaviors are predictive of depression, particularly in girls.

▸ Parental marital problems. Divorce and marital distress in parents was linked in a longitudinal study in Norway to an increased risk of depression in adolescent children, and the effects were more lasting in girls.

▸ Stress. While stress can be difficult to define, at least one study shows that girls experience more stress than do boys, and that they experience more depression as a result of stress.

▸ Maternal relationship. In a recent study 65% of girls, compared with 34% of boys, who felt their mothers didn't care about them reported depression.

▸ Hormones. Depressive symptoms may change with the menstrual cycle, as may blood levels of certain medications. Premenstrual symptoms and oral contraceptive use should be considered when evaluating girls with depression.

Depressed girls are at double the risk of becoming involved in abusive relationships. DR. STOTLAND

MIAMI BEACH – Pathologic defenses against shame often lie at the heart of adolescent psychopathology. That's why helping patients understand and accept shame as a universal experience can promote healing, Dr. Alan Wofsey said at the annual meeting of the American Society for Adolescent Psychiatry.

“Some of humanity's most baffling and destructive behaviors are well understood as responses to shame and humiliation,” said Dr. Wofsey, citing excerpts from Adolf Hitler's “Mein Kampf” and the gothic rock singer Marilyn Manson's autobiography “The Long Hard Road Out of Hell.” These works offer examples of how the shame and humiliation of adolescence can lead to pathology and even to a “commitment to evil,” as he considers to be the case with these two authors, he said at the meeting, which was cosponsored by the University of Texas at Dallas.

Shame as the root of adolescent psychopathology is a concept that many therapists suspect, but haven't quite formulated. Most therapists who treat adolescents have an intuitive sense of the impact of adolescent shame, he explained, but a deeper understanding of its role can enable the therapist to maintain his or her bearings even when confronted with the most difficult adolescent, as well as to provide a healing presence for the adolescent, said Dr. Wofsey, a psychiatrist in private practice in Wynnewood, Pa., and chief of psychiatry at Lankenau Hospital there.

“Any clinician who can convey a clear understanding of the dynamics of shame and humiliation quickly gains the attention and interest of the patient, because whatever the issues, feeling understood is crucial for these adolescents,” he said, explaining that adolescents still have a “healthy dose of magical thinking” and are impressed with therapists who can seem to read their minds in this way.

Affect theory provides a context for understanding shame, and a tool that illustrates healthy and pathologic responses to shame is the Compass of Shame, developed by Dr. Donald Nathanson (“Shame and Pride: Affect, Sex, and the Birth of the Self,” [New York: W.W. Norton & Co., 1992]), said Dr. Wofsey, also of the University of Pennsylvania, Philadelphia.

The compass illustrates four basic ways that individuals respond to shame, and explains the healthy and pathologic poles for each.

The first defensive style is labeled “Attack Self.” This mechanism seeks to relieve shame via solace and support, Dr. Wofsey said. The healthy pole might involve poking good-natured fun at oneself to appear humble and appealing. The pathologic pole might involve self-demeaning talk, self-hatred, self-mutilation, or even suicide, all of which convey a sense of control that is preferable to being a passive victim of humiliation.

“Attack Other” is another defensive style, which at its healthy pole involves alleviation of humiliation by defending oneself, and its pathologic pole can involve sarcasm, bullying, or even assault, racism, or genocide.

“Shame Avoidance,” also known as grandiosity, can be applied healthfully by bettering oneself through hard work, or it can be applied pathologically through a “workaholic” perfectionism often seen in eating disorders, for example.

The fourth alternative on the compass is “Withdrawal,” which at its healthiest involves “beating a strategic retreat to understand where one went wrong and to regroup,” Dr. Wofsey said. At its pathologic pole lies a “running and hiding” mechanism for fleeing challenges in most areas of life.

These concepts can be used to help youth reframe how they think about feelings and to recognize how many social, psychological, and political problems result from unhealthy defenses against shame. They also can be used to teach them that feelings are powerful tools for living.

Explaining the dynamics of shame to youth is one instance of providing an owner's manual for the affect system, he said.

Shame is a damper to the emotional system, often existing in precarious balance with affect of interest and excitement. If these are high, shame tends to be low and vice versa, he explained, adding that in the healthy adolescent, shame does not limit the interest and excitement of learning or the joy of self-expression.

Keeping affect at the center of the treatment approach is the key to successful outcomes, because nothing reaches the conscious mind without stimulating affect, and nothing reaches memory without generating an emotional response.

Providing a healing presence by understanding the role of shame and its defenses is an important aspect in treating an adolescent. One can inspire hope by validating these experiences, thus mobilizing and maintaining a compelling therapeutic alliance, he said.

Specific principles for managing adolescent patients include addressing the shame defenses that directly endanger the patient or others, providing empathy and validation for coping with narcissistic rage, improving the social bonds that lessen the shame of isolation, teaching healthier methods of affect management, and replacing toxic shame scripts with healthier “damage-repair” and “commitment scripts,” Dr. Wofsey said.

A failure to validate an adolescent's feelings of shame can be one of the main reasons why therapy doesn't work in certain cases, he suggested.

“When we acknowledge the common human propensity toward shame with which we all struggle, growth becomes possible,” he said.

Neurobiologic Basis for The Power of Shame

Dr. Wofsey's premise about the role of shame in adolescent psychopathology is bolstered by neurobiologic findings in this population.

For example, research has shown that the frontal lobes lack adult status until the mid-20s, and this, combined with the fact that the limbic system is in full force during adolescence, means teens have “industrial-strength affects and drive–without the cognitive horsepower to harness them,” he explained.

Also of interest is that serotonin levels drop in adolescence–a factor with major implications for early adolescence. Studies of cerebral spinal fluid, brain imaging scans, and brain autopsy results in suicide completers show that low serotonin is associated with a lower threshold to acting on both suicidal and aggressive impulses.

Lower serotonin levels also have also been shown to make one more prone to moodiness, anxiety, panic, minor and major depression, obsessive compulsive disorder, social phobia, and a number of impulse disorders and addictions.

Furthermore, primate studies suggest that serotonin levels correlate with self-esteem and dominance/submission patterns.

Shame and humiliation have been acknowledged by mainstream psychiatry as predisposing factors in major depression and generalized anxiety. The fact that selective serotonin reuptake inhibitors have been shown to improve self-esteem in anxious and depressed patients lends further credence to the role of shame in adolescent psychopathology, Dr. Wofsey said.

“Perhaps this is another way of saying that humiliation can lower serotonin levels and make one more prone to a witch's brew of psychopathology. This neurobiologic substrate may provide some underpinnings for my contention that many adolescents are wrestling with shame-related, self-esteem-related problems, and that serotonin dysfunction may be behind that,” he added.

Adding to the adolescent conundrum is the fact that melatonin in adolescence spikes late at night and lingers into the morning.

The result is a “sleep-deprived cadre of teenage zombies in our high schools,” he said.

MIAMI BEACH – Pathologic defenses against shame often lie at the heart of adolescent psychopathology. That's why helping patients understand and accept shame as a universal experience can promote healing, Dr. Alan Wofsey said at the annual meeting of the American Society for Adolescent Psychiatry.

“Some of humanity's most baffling and destructive behaviors are well understood as responses to shame and humiliation,” said Dr. Wofsey, citing excerpts from Adolf Hitler's “Mein Kampf” and the gothic rock singer Marilyn Manson's autobiography “The Long Hard Road Out of Hell.” These works offer examples of how the shame and humiliation of adolescence can lead to pathology and even to a “commitment to evil,” as he considers to be the case with these two authors, he said at the meeting, which was cosponsored by the University of Texas at Dallas.

Shame as the root of adolescent psychopathology is a concept that many therapists suspect, but haven't quite formulated. Most therapists who treat adolescents have an intuitive sense of the impact of adolescent shame, he explained, but a deeper understanding of its role can enable the therapist to maintain his or her bearings even when confronted with the most difficult adolescent, as well as to provide a healing presence for the adolescent, said Dr. Wofsey, a psychiatrist in private practice in Wynnewood, Pa., and chief of psychiatry at Lankenau Hospital there.

“Any clinician who can convey a clear understanding of the dynamics of shame and humiliation quickly gains the attention and interest of the patient, because whatever the issues, feeling understood is crucial for these adolescents,” he said, explaining that adolescents still have a “healthy dose of magical thinking” and are impressed with therapists who can seem to read their minds in this way.

Affect theory provides a context for understanding shame, and a tool that illustrates healthy and pathologic responses to shame is the Compass of Shame, developed by Dr. Donald Nathanson (“Shame and Pride: Affect, Sex, and the Birth of the Self,” [New York: W.W. Norton & Co., 1992]), said Dr. Wofsey, also of the University of Pennsylvania, Philadelphia.

The compass illustrates four basic ways that individuals respond to shame, and explains the healthy and pathologic poles for each.

The first defensive style is labeled “Attack Self.” This mechanism seeks to relieve shame via solace and support, Dr. Wofsey said. The healthy pole might involve poking good-natured fun at oneself to appear humble and appealing. The pathologic pole might involve self-demeaning talk, self-hatred, self-mutilation, or even suicide, all of which convey a sense of control that is preferable to being a passive victim of humiliation.

“Attack Other” is another defensive style, which at its healthy pole involves alleviation of humiliation by defending oneself, and its pathologic pole can involve sarcasm, bullying, or even assault, racism, or genocide.

“Shame Avoidance,” also known as grandiosity, can be applied healthfully by bettering oneself through hard work, or it can be applied pathologically through a “workaholic” perfectionism often seen in eating disorders, for example.

The fourth alternative on the compass is “Withdrawal,” which at its healthiest involves “beating a strategic retreat to understand where one went wrong and to regroup,” Dr. Wofsey said. At its pathologic pole lies a “running and hiding” mechanism for fleeing challenges in most areas of life.

These concepts can be used to help youth reframe how they think about feelings and to recognize how many social, psychological, and political problems result from unhealthy defenses against shame. They also can be used to teach them that feelings are powerful tools for living.

Explaining the dynamics of shame to youth is one instance of providing an owner's manual for the affect system, he said.

Shame is a damper to the emotional system, often existing in precarious balance with affect of interest and excitement. If these are high, shame tends to be low and vice versa, he explained, adding that in the healthy adolescent, shame does not limit the interest and excitement of learning or the joy of self-expression.

Keeping affect at the center of the treatment approach is the key to successful outcomes, because nothing reaches the conscious mind without stimulating affect, and nothing reaches memory without generating an emotional response.

Providing a healing presence by understanding the role of shame and its defenses is an important aspect in treating an adolescent. One can inspire hope by validating these experiences, thus mobilizing and maintaining a compelling therapeutic alliance, he said.

Specific principles for managing adolescent patients include addressing the shame defenses that directly endanger the patient or others, providing empathy and validation for coping with narcissistic rage, improving the social bonds that lessen the shame of isolation, teaching healthier methods of affect management, and replacing toxic shame scripts with healthier “damage-repair” and “commitment scripts,” Dr. Wofsey said.

A failure to validate an adolescent's feelings of shame can be one of the main reasons why therapy doesn't work in certain cases, he suggested.

“When we acknowledge the common human propensity toward shame with which we all struggle, growth becomes possible,” he said.

Neurobiologic Basis for The Power of Shame

Dr. Wofsey's premise about the role of shame in adolescent psychopathology is bolstered by neurobiologic findings in this population.

For example, research has shown that the frontal lobes lack adult status until the mid-20s, and this, combined with the fact that the limbic system is in full force during adolescence, means teens have “industrial-strength affects and drive–without the cognitive horsepower to harness them,” he explained.

Also of interest is that serotonin levels drop in adolescence–a factor with major implications for early adolescence. Studies of cerebral spinal fluid, brain imaging scans, and brain autopsy results in suicide completers show that low serotonin is associated with a lower threshold to acting on both suicidal and aggressive impulses.

Lower serotonin levels also have also been shown to make one more prone to moodiness, anxiety, panic, minor and major depression, obsessive compulsive disorder, social phobia, and a number of impulse disorders and addictions.

Furthermore, primate studies suggest that serotonin levels correlate with self-esteem and dominance/submission patterns.

Shame and humiliation have been acknowledged by mainstream psychiatry as predisposing factors in major depression and generalized anxiety. The fact that selective serotonin reuptake inhibitors have been shown to improve self-esteem in anxious and depressed patients lends further credence to the role of shame in adolescent psychopathology, Dr. Wofsey said.

“Perhaps this is another way of saying that humiliation can lower serotonin levels and make one more prone to a witch's brew of psychopathology. This neurobiologic substrate may provide some underpinnings for my contention that many adolescents are wrestling with shame-related, self-esteem-related problems, and that serotonin dysfunction may be behind that,” he added.

Adding to the adolescent conundrum is the fact that melatonin in adolescence spikes late at night and lingers into the morning.

The result is a “sleep-deprived cadre of teenage zombies in our high schools,” he said.

MIAMI BEACH – Pathologic defenses against shame often lie at the heart of adolescent psychopathology. That's why helping patients understand and accept shame as a universal experience can promote healing, Dr. Alan Wofsey said at the annual meeting of the American Society for Adolescent Psychiatry.

“Some of humanity's most baffling and destructive behaviors are well understood as responses to shame and humiliation,” said Dr. Wofsey, citing excerpts from Adolf Hitler's “Mein Kampf” and the gothic rock singer Marilyn Manson's autobiography “The Long Hard Road Out of Hell.” These works offer examples of how the shame and humiliation of adolescence can lead to pathology and even to a “commitment to evil,” as he considers to be the case with these two authors, he said at the meeting, which was cosponsored by the University of Texas at Dallas.

Shame as the root of adolescent psychopathology is a concept that many therapists suspect, but haven't quite formulated. Most therapists who treat adolescents have an intuitive sense of the impact of adolescent shame, he explained, but a deeper understanding of its role can enable the therapist to maintain his or her bearings even when confronted with the most difficult adolescent, as well as to provide a healing presence for the adolescent, said Dr. Wofsey, a psychiatrist in private practice in Wynnewood, Pa., and chief of psychiatry at Lankenau Hospital there.

“Any clinician who can convey a clear understanding of the dynamics of shame and humiliation quickly gains the attention and interest of the patient, because whatever the issues, feeling understood is crucial for these adolescents,” he said, explaining that adolescents still have a “healthy dose of magical thinking” and are impressed with therapists who can seem to read their minds in this way.

Affect theory provides a context for understanding shame, and a tool that illustrates healthy and pathologic responses to shame is the Compass of Shame, developed by Dr. Donald Nathanson (“Shame and Pride: Affect, Sex, and the Birth of the Self,” [New York: W.W. Norton & Co., 1992]), said Dr. Wofsey, also of the University of Pennsylvania, Philadelphia.

The compass illustrates four basic ways that individuals respond to shame, and explains the healthy and pathologic poles for each.

The first defensive style is labeled “Attack Self.” This mechanism seeks to relieve shame via solace and support, Dr. Wofsey said. The healthy pole might involve poking good-natured fun at oneself to appear humble and appealing. The pathologic pole might involve self-demeaning talk, self-hatred, self-mutilation, or even suicide, all of which convey a sense of control that is preferable to being a passive victim of humiliation.

“Attack Other” is another defensive style, which at its healthy pole involves alleviation of humiliation by defending oneself, and its pathologic pole can involve sarcasm, bullying, or even assault, racism, or genocide.

“Shame Avoidance,” also known as grandiosity, can be applied healthfully by bettering oneself through hard work, or it can be applied pathologically through a “workaholic” perfectionism often seen in eating disorders, for example.

The fourth alternative on the compass is “Withdrawal,” which at its healthiest involves “beating a strategic retreat to understand where one went wrong and to regroup,” Dr. Wofsey said. At its pathologic pole lies a “running and hiding” mechanism for fleeing challenges in most areas of life.

These concepts can be used to help youth reframe how they think about feelings and to recognize how many social, psychological, and political problems result from unhealthy defenses against shame. They also can be used to teach them that feelings are powerful tools for living.

Explaining the dynamics of shame to youth is one instance of providing an owner's manual for the affect system, he said.

Shame is a damper to the emotional system, often existing in precarious balance with affect of interest and excitement. If these are high, shame tends to be low and vice versa, he explained, adding that in the healthy adolescent, shame does not limit the interest and excitement of learning or the joy of self-expression.

Keeping affect at the center of the treatment approach is the key to successful outcomes, because nothing reaches the conscious mind without stimulating affect, and nothing reaches memory without generating an emotional response.

Providing a healing presence by understanding the role of shame and its defenses is an important aspect in treating an adolescent. One can inspire hope by validating these experiences, thus mobilizing and maintaining a compelling therapeutic alliance, he said.

Specific principles for managing adolescent patients include addressing the shame defenses that directly endanger the patient or others, providing empathy and validation for coping with narcissistic rage, improving the social bonds that lessen the shame of isolation, teaching healthier methods of affect management, and replacing toxic shame scripts with healthier “damage-repair” and “commitment scripts,” Dr. Wofsey said.

A failure to validate an adolescent's feelings of shame can be one of the main reasons why therapy doesn't work in certain cases, he suggested.

“When we acknowledge the common human propensity toward shame with which we all struggle, growth becomes possible,” he said.

Neurobiologic Basis for The Power of Shame

Dr. Wofsey's premise about the role of shame in adolescent psychopathology is bolstered by neurobiologic findings in this population.

For example, research has shown that the frontal lobes lack adult status until the mid-20s, and this, combined with the fact that the limbic system is in full force during adolescence, means teens have “industrial-strength affects and drive–without the cognitive horsepower to harness them,” he explained.

Also of interest is that serotonin levels drop in adolescence–a factor with major implications for early adolescence. Studies of cerebral spinal fluid, brain imaging scans, and brain autopsy results in suicide completers show that low serotonin is associated with a lower threshold to acting on both suicidal and aggressive impulses.

Lower serotonin levels also have also been shown to make one more prone to moodiness, anxiety, panic, minor and major depression, obsessive compulsive disorder, social phobia, and a number of impulse disorders and addictions.

Furthermore, primate studies suggest that serotonin levels correlate with self-esteem and dominance/submission patterns.

Shame and humiliation have been acknowledged by mainstream psychiatry as predisposing factors in major depression and generalized anxiety. The fact that selective serotonin reuptake inhibitors have been shown to improve self-esteem in anxious and depressed patients lends further credence to the role of shame in adolescent psychopathology, Dr. Wofsey said.

“Perhaps this is another way of saying that humiliation can lower serotonin levels and make one more prone to a witch's brew of psychopathology. This neurobiologic substrate may provide some underpinnings for my contention that many adolescents are wrestling with shame-related, self-esteem-related problems, and that serotonin dysfunction may be behind that,” he added.

Adding to the adolescent conundrum is the fact that melatonin in adolescence spikes late at night and lingers into the morning.

The result is a “sleep-deprived cadre of teenage zombies in our high schools,” he said.

MIAMI BEACH – Studies increasingly suggest that adolescent girls are particularly vulnerable to many of the risk factors for major depression, and that depression in this population manifests in several unique ways.

For example, depressed girls are more likely than are depressed boys to have poor body image, to feel disappointed in themselves, to feel like a failure, and to have difficulty concentrating, Dr. Nada Stotland said at the annual meeting of the American Society for Adolescent Psychiatry.

Girls tend to have more inwardly directed symptoms, she explained at the meeting, which was cosponsored by the University of Texas at Dallas.

And they experience unique consequences of depression. A recent study suggests that depressed girls are at double the risk of nondepressed girls of becoming involved in abusive relationships, said Dr. Stotland of Rush Medical College, Chicago.

Another study showed that 3 years after being diagnosed with depression, girls had decreased self worth, poorer body image, and increased feelings of vulnerability, compared with prior to their depression. Depressive symptoms, along with dietary restrictions, weight control behaviors, and feeling that one's parents are overweight, also appear to be a risk factor for obesity.

Race also appears to play an important role in depression in girls; white girls with depression in adolescence were shown in one study to be more likely than African American girls to improve in early adulthood. And in a study of Hawaiian youth, 38% of girls in the study had a psychiatric disorder. Most of those had anxiety disorders, but crossover between depression and anxiety is significant, Dr. Stotland said.

Chinese girls in one study commonly reported anxiety; 48% said they had anxiety that interfered with enjoyment, 40% saying their anxiety interfered with relaxation, and 27% saying it interfered with sleep. About one-third of girls reported depressive symptoms, with 16% saying they sometimes feel that life is not worth living, and 9% reporting a suicide attempt.

Ethnic differences also are apparent in the effects of body image on depression, with white girls being the most likely to feel pressure to be model thin.

As for gender differences in depression, a study from Spain suggests cognitive styles may be to blame. Girls were shown to be less likely than boys to think positively, and when faced with a problem, they were less likely to consider the problem to be solvable.

Other factors shown recently to be associated with depression in girls include:

▸ Maternal depression. A recent large study confirms much of what was already suspected: that maternal depression has a significant impact on adolescent depression risk. Other studies have suggested girls are particularly vulnerable to these effects. Adult psychiatrists should take more care in addressing this risk in the children of the depressed mothers they treat, she said.

▸ Sexual orientation. Parental discrimination was shown to be “an enormous risk factor” for depression in homosexual teens.

▸ High-risk behaviors. There has been some controversy regarding whether high-risk behaviors such as drug use and promiscuity come before or after depression, but findings from a very large study suggest that such behaviors are predictive of depression, particularly in girls.

▸ Parental marital problems. Divorce and marital distress in parents was linked in a longitudinal study in Norway to increased risk of depression in adolescents, and the effects were more lasting in girls than in boys.

▸ Stress. While stress can be difficult to define, at least one study shows that girls experience more stress than do boys, and that they experience more depression as a result of stress.

▸ Hormones. Depressive symptoms may change cyclically with the menstrual cycle. Premenstrual symptoms and oral contraceptive use should be considered when evaluating girls with depression.

MIAMI BEACH – Studies increasingly suggest that adolescent girls are particularly vulnerable to many of the risk factors for major depression, and that depression in this population manifests in several unique ways.

For example, depressed girls are more likely than are depressed boys to have poor body image, to feel disappointed in themselves, to feel like a failure, and to have difficulty concentrating, Dr. Nada Stotland said at the annual meeting of the American Society for Adolescent Psychiatry.

Girls tend to have more inwardly directed symptoms, she explained at the meeting, which was cosponsored by the University of Texas at Dallas.

And they experience unique consequences of depression. A recent study suggests that depressed girls are at double the risk of nondepressed girls of becoming involved in abusive relationships, said Dr. Stotland of Rush Medical College, Chicago.

Another study showed that 3 years after being diagnosed with depression, girls had decreased self worth, poorer body image, and increased feelings of vulnerability, compared with prior to their depression. Depressive symptoms, along with dietary restrictions, weight control behaviors, and feeling that one's parents are overweight, also appear to be a risk factor for obesity.

Race also appears to play an important role in depression in girls; white girls with depression in adolescence were shown in one study to be more likely than African American girls to improve in early adulthood. And in a study of Hawaiian youth, 38% of girls in the study had a psychiatric disorder. Most of those had anxiety disorders, but crossover between depression and anxiety is significant, Dr. Stotland said.

Chinese girls in one study commonly reported anxiety; 48% said they had anxiety that interfered with enjoyment, 40% saying their anxiety interfered with relaxation, and 27% saying it interfered with sleep. About one-third of girls reported depressive symptoms, with 16% saying they sometimes feel that life is not worth living, and 9% reporting a suicide attempt.

Ethnic differences also are apparent in the effects of body image on depression, with white girls being the most likely to feel pressure to be model thin.

As for gender differences in depression, a study from Spain suggests cognitive styles may be to blame. Girls were shown to be less likely than boys to think positively, and when faced with a problem, they were less likely to consider the problem to be solvable.

Other factors shown recently to be associated with depression in girls include:

▸ Maternal depression. A recent large study confirms much of what was already suspected: that maternal depression has a significant impact on adolescent depression risk. Other studies have suggested girls are particularly vulnerable to these effects. Adult psychiatrists should take more care in addressing this risk in the children of the depressed mothers they treat, she said.

▸ Sexual orientation. Parental discrimination was shown to be “an enormous risk factor” for depression in homosexual teens.

▸ High-risk behaviors. There has been some controversy regarding whether high-risk behaviors such as drug use and promiscuity come before or after depression, but findings from a very large study suggest that such behaviors are predictive of depression, particularly in girls.

▸ Parental marital problems. Divorce and marital distress in parents was linked in a longitudinal study in Norway to increased risk of depression in adolescents, and the effects were more lasting in girls than in boys.

▸ Stress. While stress can be difficult to define, at least one study shows that girls experience more stress than do boys, and that they experience more depression as a result of stress.

▸ Hormones. Depressive symptoms may change cyclically with the menstrual cycle. Premenstrual symptoms and oral contraceptive use should be considered when evaluating girls with depression.

MIAMI BEACH – Studies increasingly suggest that adolescent girls are particularly vulnerable to many of the risk factors for major depression, and that depression in this population manifests in several unique ways.

For example, depressed girls are more likely than are depressed boys to have poor body image, to feel disappointed in themselves, to feel like a failure, and to have difficulty concentrating, Dr. Nada Stotland said at the annual meeting of the American Society for Adolescent Psychiatry.

Girls tend to have more inwardly directed symptoms, she explained at the meeting, which was cosponsored by the University of Texas at Dallas.

And they experience unique consequences of depression. A recent study suggests that depressed girls are at double the risk of nondepressed girls of becoming involved in abusive relationships, said Dr. Stotland of Rush Medical College, Chicago.

Another study showed that 3 years after being diagnosed with depression, girls had decreased self worth, poorer body image, and increased feelings of vulnerability, compared with prior to their depression. Depressive symptoms, along with dietary restrictions, weight control behaviors, and feeling that one's parents are overweight, also appear to be a risk factor for obesity.

Race also appears to play an important role in depression in girls; white girls with depression in adolescence were shown in one study to be more likely than African American girls to improve in early adulthood. And in a study of Hawaiian youth, 38% of girls in the study had a psychiatric disorder. Most of those had anxiety disorders, but crossover between depression and anxiety is significant, Dr. Stotland said.

Chinese girls in one study commonly reported anxiety; 48% said they had anxiety that interfered with enjoyment, 40% saying their anxiety interfered with relaxation, and 27% saying it interfered with sleep. About one-third of girls reported depressive symptoms, with 16% saying they sometimes feel that life is not worth living, and 9% reporting a suicide attempt.

Ethnic differences also are apparent in the effects of body image on depression, with white girls being the most likely to feel pressure to be model thin.

As for gender differences in depression, a study from Spain suggests cognitive styles may be to blame. Girls were shown to be less likely than boys to think positively, and when faced with a problem, they were less likely to consider the problem to be solvable.

Other factors shown recently to be associated with depression in girls include:

▸ Maternal depression. A recent large study confirms much of what was already suspected: that maternal depression has a significant impact on adolescent depression risk. Other studies have suggested girls are particularly vulnerable to these effects. Adult psychiatrists should take more care in addressing this risk in the children of the depressed mothers they treat, she said.

▸ Sexual orientation. Parental discrimination was shown to be “an enormous risk factor” for depression in homosexual teens.

▸ High-risk behaviors. There has been some controversy regarding whether high-risk behaviors such as drug use and promiscuity come before or after depression, but findings from a very large study suggest that such behaviors are predictive of depression, particularly in girls.

▸ Parental marital problems. Divorce and marital distress in parents was linked in a longitudinal study in Norway to increased risk of depression in adolescents, and the effects were more lasting in girls than in boys.

▸ Stress. While stress can be difficult to define, at least one study shows that girls experience more stress than do boys, and that they experience more depression as a result of stress.

▸ Hormones. Depressive symptoms may change cyclically with the menstrual cycle. Premenstrual symptoms and oral contraceptive use should be considered when evaluating girls with depression.

MIAMI BEACH — Continuous subcutaneous insulin lispro infusion appears to be superior to multiple daily insulin lispro injections for the treatment of pregnant women with type 1 diabetes, Dr. Giorgio Mello reported at the annual meeting of the Society for Maternal-Fetal Medicine.

In a randomized controlled study of 71 pregnant women with type 1 diabetes and 142 matched, nondiabetic, pregnant controls, continuous subcutaneous insulin infusions (CSII) were found to mimic more closely than multiple daily injections (given as a premeal bolus) the normal postprandial glucose excursion pattern.

The CSII approach also was associated with fetal fat mass growth patterns similar to those seen in normal pregnancies, said Dr. Mello of the University of Florence, Italy.

The postprandial glucose excursions were calculated as areas under the curves at 0–1, 1–2, 2–4, and 0–4 hours in the three-meal postprandial area. Patients in both treatment groups had similar average daily glucose levels throughout gestation. But at 16−, 26−, and 36-week evaluations, those in the CSII group had 24-hour glycemic profiles similar to the normal group; those in the multiple daily injections group had a significantly longer time period in the three-meal postprandial areas.

Furthermore, fetuses in the CSII group, but not in the multiple daily injection group, had growth patterns similar to those of controls, as measured by ultrasound scans performed every 2 weeks between 25 and 38 weeks' gestation. Those in the multiple daily injections group had significantly higher abdominal and midthigh fat deposition during that period, Dr. Mello noted.

MIAMI BEACH — Continuous subcutaneous insulin lispro infusion appears to be superior to multiple daily insulin lispro injections for the treatment of pregnant women with type 1 diabetes, Dr. Giorgio Mello reported at the annual meeting of the Society for Maternal-Fetal Medicine.

In a randomized controlled study of 71 pregnant women with type 1 diabetes and 142 matched, nondiabetic, pregnant controls, continuous subcutaneous insulin infusions (CSII) were found to mimic more closely than multiple daily injections (given as a premeal bolus) the normal postprandial glucose excursion pattern.

The CSII approach also was associated with fetal fat mass growth patterns similar to those seen in normal pregnancies, said Dr. Mello of the University of Florence, Italy.

The postprandial glucose excursions were calculated as areas under the curves at 0–1, 1–2, 2–4, and 0–4 hours in the three-meal postprandial area. Patients in both treatment groups had similar average daily glucose levels throughout gestation. But at 16−, 26−, and 36-week evaluations, those in the CSII group had 24-hour glycemic profiles similar to the normal group; those in the multiple daily injections group had a significantly longer time period in the three-meal postprandial areas.

Furthermore, fetuses in the CSII group, but not in the multiple daily injection group, had growth patterns similar to those of controls, as measured by ultrasound scans performed every 2 weeks between 25 and 38 weeks' gestation. Those in the multiple daily injections group had significantly higher abdominal and midthigh fat deposition during that period, Dr. Mello noted.

MIAMI BEACH — Continuous subcutaneous insulin lispro infusion appears to be superior to multiple daily insulin lispro injections for the treatment of pregnant women with type 1 diabetes, Dr. Giorgio Mello reported at the annual meeting of the Society for Maternal-Fetal Medicine.

In a randomized controlled study of 71 pregnant women with type 1 diabetes and 142 matched, nondiabetic, pregnant controls, continuous subcutaneous insulin infusions (CSII) were found to mimic more closely than multiple daily injections (given as a premeal bolus) the normal postprandial glucose excursion pattern.

The CSII approach also was associated with fetal fat mass growth patterns similar to those seen in normal pregnancies, said Dr. Mello of the University of Florence, Italy.

The postprandial glucose excursions were calculated as areas under the curves at 0–1, 1–2, 2–4, and 0–4 hours in the three-meal postprandial area. Patients in both treatment groups had similar average daily glucose levels throughout gestation. But at 16−, 26−, and 36-week evaluations, those in the CSII group had 24-hour glycemic profiles similar to the normal group; those in the multiple daily injections group had a significantly longer time period in the three-meal postprandial areas.

Furthermore, fetuses in the CSII group, but not in the multiple daily injection group, had growth patterns similar to those of controls, as measured by ultrasound scans performed every 2 weeks between 25 and 38 weeks' gestation. Those in the multiple daily injections group had significantly higher abdominal and midthigh fat deposition during that period, Dr. Mello noted.

MIAMI BEACH — Serum levels of soluble endoglin and soluble fms-like tyrosine kinase 1 are increased months before onset of clinical disease in patients with preeclampsia, Dr. Richard Levine said at the annual meeting of the Society for Maternal-Fetal Medicine.

The findings suggest that a circulating antiangiogenic state is important in the pathogenesis of this maternal syndrome, said Dr. Levine of the National Institute of Child Health and Human Development, Bethesda, Md.

“We believe that soluble endoglin [a cell surface receptor for the proangiogenic protein transforming growth factor-β and soluble fms-like tyrosine kinase 1 [an antiangiogenic factor that binds placental growth factor and vascular endothelial growth factor] act in concert to produce the maternal syndrome of preeclampsia,” he said.

A nested case-control study of the Calcium for Preeclampsia Prevention (CPEP) trial cohort of healthy nulliparas showed that compared with serum samples from gestational age-matched controls, the levels of these factors were significantly higher beginning 9–11 weeks before preterm preeclampsia. After preeclampsia onset, soluble endoglin (sEng) levels were almost fivefold higher (46 vs. 10 ng/mL) and soluble fms-like tyrosine kinase 1 (sFlt1) levels were nearly threefold higher (6,356 vs. 2,316 pg/mL). Placental growth factor (PlGF) levels were approximately fourfold lower (144 vs. 546 pg/mL), Dr. Levine said.

The findings were based on an analysis of 867 serum samples obtained from 120 controls; 120 patients with term preeclampsia; 72 patients with preterm preeclampsia; 9 patients with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome; and 8 patients with eclampsia. In patients with term preeclampsia, sEng was increased beginning at 12–14 weeks, free PlGF decreased beginning at 9–11 weeks, and sFlt1 increased less than 5 weeks before preeclampsia onset. Alterations in angiogenic factors were more pronounced in early preeclampsia patients and in patients with preeclampsia plus a small-for-gestational age fetus, HELLP syndrome, or eclampsia, he noted.

Laboratory studies have suggested independent roles for both sEng and sFlt1 in the development of preeclampsia. The present study was designed to test the hypothesis that in preeclampsia, excess soluble endoglin is released from the placenta into the circulation and that it may then synergize with sFlt1, which binds PlGF and vascular endothelial growth factor to cause endothelial dysfunction, he explained. Women in this analysis with high levels of either sEng or sFlt1—but not both—had small elevations in preeclampsia risk.

MIAMI BEACH — Serum levels of soluble endoglin and soluble fms-like tyrosine kinase 1 are increased months before onset of clinical disease in patients with preeclampsia, Dr. Richard Levine said at the annual meeting of the Society for Maternal-Fetal Medicine.

The findings suggest that a circulating antiangiogenic state is important in the pathogenesis of this maternal syndrome, said Dr. Levine of the National Institute of Child Health and Human Development, Bethesda, Md.

“We believe that soluble endoglin [a cell surface receptor for the proangiogenic protein transforming growth factor-β and soluble fms-like tyrosine kinase 1 [an antiangiogenic factor that binds placental growth factor and vascular endothelial growth factor] act in concert to produce the maternal syndrome of preeclampsia,” he said.

A nested case-control study of the Calcium for Preeclampsia Prevention (CPEP) trial cohort of healthy nulliparas showed that compared with serum samples from gestational age-matched controls, the levels of these factors were significantly higher beginning 9–11 weeks before preterm preeclampsia. After preeclampsia onset, soluble endoglin (sEng) levels were almost fivefold higher (46 vs. 10 ng/mL) and soluble fms-like tyrosine kinase 1 (sFlt1) levels were nearly threefold higher (6,356 vs. 2,316 pg/mL). Placental growth factor (PlGF) levels were approximately fourfold lower (144 vs. 546 pg/mL), Dr. Levine said.

The findings were based on an analysis of 867 serum samples obtained from 120 controls; 120 patients with term preeclampsia; 72 patients with preterm preeclampsia; 9 patients with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome; and 8 patients with eclampsia. In patients with term preeclampsia, sEng was increased beginning at 12–14 weeks, free PlGF decreased beginning at 9–11 weeks, and sFlt1 increased less than 5 weeks before preeclampsia onset. Alterations in angiogenic factors were more pronounced in early preeclampsia patients and in patients with preeclampsia plus a small-for-gestational age fetus, HELLP syndrome, or eclampsia, he noted.

Laboratory studies have suggested independent roles for both sEng and sFlt1 in the development of preeclampsia. The present study was designed to test the hypothesis that in preeclampsia, excess soluble endoglin is released from the placenta into the circulation and that it may then synergize with sFlt1, which binds PlGF and vascular endothelial growth factor to cause endothelial dysfunction, he explained. Women in this analysis with high levels of either sEng or sFlt1—but not both—had small elevations in preeclampsia risk.

MIAMI BEACH — Serum levels of soluble endoglin and soluble fms-like tyrosine kinase 1 are increased months before onset of clinical disease in patients with preeclampsia, Dr. Richard Levine said at the annual meeting of the Society for Maternal-Fetal Medicine.

The findings suggest that a circulating antiangiogenic state is important in the pathogenesis of this maternal syndrome, said Dr. Levine of the National Institute of Child Health and Human Development, Bethesda, Md.

“We believe that soluble endoglin [a cell surface receptor for the proangiogenic protein transforming growth factor-β and soluble fms-like tyrosine kinase 1 [an antiangiogenic factor that binds placental growth factor and vascular endothelial growth factor] act in concert to produce the maternal syndrome of preeclampsia,” he said.

A nested case-control study of the Calcium for Preeclampsia Prevention (CPEP) trial cohort of healthy nulliparas showed that compared with serum samples from gestational age-matched controls, the levels of these factors were significantly higher beginning 9–11 weeks before preterm preeclampsia. After preeclampsia onset, soluble endoglin (sEng) levels were almost fivefold higher (46 vs. 10 ng/mL) and soluble fms-like tyrosine kinase 1 (sFlt1) levels were nearly threefold higher (6,356 vs. 2,316 pg/mL). Placental growth factor (PlGF) levels were approximately fourfold lower (144 vs. 546 pg/mL), Dr. Levine said.

The findings were based on an analysis of 867 serum samples obtained from 120 controls; 120 patients with term preeclampsia; 72 patients with preterm preeclampsia; 9 patients with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome; and 8 patients with eclampsia. In patients with term preeclampsia, sEng was increased beginning at 12–14 weeks, free PlGF decreased beginning at 9–11 weeks, and sFlt1 increased less than 5 weeks before preeclampsia onset. Alterations in angiogenic factors were more pronounced in early preeclampsia patients and in patients with preeclampsia plus a small-for-gestational age fetus, HELLP syndrome, or eclampsia, he noted.

Laboratory studies have suggested independent roles for both sEng and sFlt1 in the development of preeclampsia. The present study was designed to test the hypothesis that in preeclampsia, excess soluble endoglin is released from the placenta into the circulation and that it may then synergize with sFlt1, which binds PlGF and vascular endothelial growth factor to cause endothelial dysfunction, he explained. Women in this analysis with high levels of either sEng or sFlt1—but not both—had small elevations in preeclampsia risk.

MIAMI BEACH — Unexplained vaginal bleeding and fetal exposure to oral pathogens have been linked individually with spontaneous preterm birth, and new data suggest the presence of both is associated with greater risk than either alone.

Of 660 pregnancies analyzed, 229 (35%) demonstrated fetal exposure to oral pathogens. Pregnancies that demonstrated such exposure were more likely to be in white women, women who had symptomatic bacterial vaginosis, and women who experienced vaginal bleeding, which was the most significant variable associated with oral pathogen exposure (adjusted risk ratio 1.6).

A total of 51 women (8%) in this planned secondary analysis of the Oral Conditions and Pregnancy Study—a prospective observational study of oral health and pregnancy outcomes—delivered before 35 weeks' gestation, Dr. Kim Boggess reported at the annual meeting of the Society for Maternal-Fetal Medicine.

When women with vaginal bleeding were stratified according to whether fetal exposure to oral pathogens occurred, preterm birthrates were significantly higher in those with both factors. Preterm birth occurred in 30% of those with both factors, compared with 8% in those with only vaginal bleeding, 9% of those with only oral pathogen exposure, and 6% of those with neither.

After adjustment for age, race, prior preterm birth, prior elective or spontaneous abortion, bacterial vaginosis, and enrollment weight, the differences remained. The adjusted hazard ratio for spontaneous preterm birth, compared with those with neither risk factor, was 6.4 for those with both factors, 1.9 for those with only vaginal bleeding, and 2.0 for those with only exposure to oral pathogens, said Dr. Boggess of the University of North Carolina at Chapel Hill.

Fetal exposure to oral pathogens was considered to have occurred if umbilical cord serum at delivery demonstrated an immunoglobulin M-positive (IgM-positive) response to at least one of five oral pathogens, she explained.

“Our findings show that antepartum vaginal bleeding is associated with fetal exposure to oral pathogens, and that the combination of fetal exposure to oral pathogens and vaginal bleeding provides the highest risk for premature birth at less than 35 weeks,” Dr. Boggess said.

“We think that vaginal bleeding may in fact be an effect measure modifier of fetal exposure to oral pathogens.”

Unexplained vaginal bleeding may be one of the mechanisms of fetal exposure to oral pathogens during pregnancy, but further study is needed to determine whether vaginal bleeding is the cause or the effect of fetal exposure to oral pathogens, she said.

The findings also suggest that clinical determination of periodontal disease is a poor marker for fetal exposure to oral pathogens, she noted.

MIAMI BEACH — Unexplained vaginal bleeding and fetal exposure to oral pathogens have been linked individually with spontaneous preterm birth, and new data suggest the presence of both is associated with greater risk than either alone.

Of 660 pregnancies analyzed, 229 (35%) demonstrated fetal exposure to oral pathogens. Pregnancies that demonstrated such exposure were more likely to be in white women, women who had symptomatic bacterial vaginosis, and women who experienced vaginal bleeding, which was the most significant variable associated with oral pathogen exposure (adjusted risk ratio 1.6).

A total of 51 women (8%) in this planned secondary analysis of the Oral Conditions and Pregnancy Study—a prospective observational study of oral health and pregnancy outcomes—delivered before 35 weeks' gestation, Dr. Kim Boggess reported at the annual meeting of the Society for Maternal-Fetal Medicine.

When women with vaginal bleeding were stratified according to whether fetal exposure to oral pathogens occurred, preterm birthrates were significantly higher in those with both factors. Preterm birth occurred in 30% of those with both factors, compared with 8% in those with only vaginal bleeding, 9% of those with only oral pathogen exposure, and 6% of those with neither.

After adjustment for age, race, prior preterm birth, prior elective or spontaneous abortion, bacterial vaginosis, and enrollment weight, the differences remained. The adjusted hazard ratio for spontaneous preterm birth, compared with those with neither risk factor, was 6.4 for those with both factors, 1.9 for those with only vaginal bleeding, and 2.0 for those with only exposure to oral pathogens, said Dr. Boggess of the University of North Carolina at Chapel Hill.

Fetal exposure to oral pathogens was considered to have occurred if umbilical cord serum at delivery demonstrated an immunoglobulin M-positive (IgM-positive) response to at least one of five oral pathogens, she explained.

“Our findings show that antepartum vaginal bleeding is associated with fetal exposure to oral pathogens, and that the combination of fetal exposure to oral pathogens and vaginal bleeding provides the highest risk for premature birth at less than 35 weeks,” Dr. Boggess said.

“We think that vaginal bleeding may in fact be an effect measure modifier of fetal exposure to oral pathogens.”

Unexplained vaginal bleeding may be one of the mechanisms of fetal exposure to oral pathogens during pregnancy, but further study is needed to determine whether vaginal bleeding is the cause or the effect of fetal exposure to oral pathogens, she said.

The findings also suggest that clinical determination of periodontal disease is a poor marker for fetal exposure to oral pathogens, she noted.

MIAMI BEACH — Unexplained vaginal bleeding and fetal exposure to oral pathogens have been linked individually with spontaneous preterm birth, and new data suggest the presence of both is associated with greater risk than either alone.

Of 660 pregnancies analyzed, 229 (35%) demonstrated fetal exposure to oral pathogens. Pregnancies that demonstrated such exposure were more likely to be in white women, women who had symptomatic bacterial vaginosis, and women who experienced vaginal bleeding, which was the most significant variable associated with oral pathogen exposure (adjusted risk ratio 1.6).

A total of 51 women (8%) in this planned secondary analysis of the Oral Conditions and Pregnancy Study—a prospective observational study of oral health and pregnancy outcomes—delivered before 35 weeks' gestation, Dr. Kim Boggess reported at the annual meeting of the Society for Maternal-Fetal Medicine.

When women with vaginal bleeding were stratified according to whether fetal exposure to oral pathogens occurred, preterm birthrates were significantly higher in those with both factors. Preterm birth occurred in 30% of those with both factors, compared with 8% in those with only vaginal bleeding, 9% of those with only oral pathogen exposure, and 6% of those with neither.

After adjustment for age, race, prior preterm birth, prior elective or spontaneous abortion, bacterial vaginosis, and enrollment weight, the differences remained. The adjusted hazard ratio for spontaneous preterm birth, compared with those with neither risk factor, was 6.4 for those with both factors, 1.9 for those with only vaginal bleeding, and 2.0 for those with only exposure to oral pathogens, said Dr. Boggess of the University of North Carolina at Chapel Hill.

Fetal exposure to oral pathogens was considered to have occurred if umbilical cord serum at delivery demonstrated an immunoglobulin M-positive (IgM-positive) response to at least one of five oral pathogens, she explained.

“Our findings show that antepartum vaginal bleeding is associated with fetal exposure to oral pathogens, and that the combination of fetal exposure to oral pathogens and vaginal bleeding provides the highest risk for premature birth at less than 35 weeks,” Dr. Boggess said.

“We think that vaginal bleeding may in fact be an effect measure modifier of fetal exposure to oral pathogens.”

Unexplained vaginal bleeding may be one of the mechanisms of fetal exposure to oral pathogens during pregnancy, but further study is needed to determine whether vaginal bleeding is the cause or the effect of fetal exposure to oral pathogens, she said.

The findings also suggest that clinical determination of periodontal disease is a poor marker for fetal exposure to oral pathogens, she noted.

MIAMI BEACH — Fetoscopic endoluminal tracheal occlusion, or FETO, results in “impressive” relative increases in lung volume in cases of severe congenital diaphragmatic hernia, Dr. Jacques C. Jani reported at the annual meeting of the Society for Maternal-Fetal Medicine.

In eight fetuses with the condition who underwent FETO, and who were followed by regular magnetic resonance imaging beginning at 24–26 weeks' gestation, the mean relative increase in lung volume from first MRI to near birth was 110%, compared with 22% in eight fetuses managed expectantly, said Dr. Jani of the University Hospital Gasthuisberg, Leuven, Belgium.

The mean maximal increase in lung volume in the FETO patients was observed 4 weeks after treatment. The volume decreased by 23%, compared with the posttreatment maximum, following balloon removal, which typically occurred at 34 weeks' gestation, but volume remained higher than in those managed expectantly.

The fetuses in the FETO group all had severe congenital diaphragmatic hernia (CDH), which by definition involves liver herniation into the chest cavity. The eight who did not undergo FETO were managed expectantly either because the cases were less severe (six cases) or because FETO was denied (two cases).

Further evaluation of the fetal liver in those managed expectantly showed that liver herniation, present in half of the cases, was associated with lower increases in lung volume; the increase was only 9% if the liver was herniated, compared with 35% when the liver was down, Dr. Jani noted.

The findings show that liver position is an important factor for predicting lung volume gains in fetuses with CDH, and that in severe CDH, FETO is effective for increasing lung volume. These effects persist after in utero balloon removal, he said.

MIAMI BEACH — Fetoscopic endoluminal tracheal occlusion, or FETO, results in “impressive” relative increases in lung volume in cases of severe congenital diaphragmatic hernia, Dr. Jacques C. Jani reported at the annual meeting of the Society for Maternal-Fetal Medicine.

In eight fetuses with the condition who underwent FETO, and who were followed by regular magnetic resonance imaging beginning at 24–26 weeks' gestation, the mean relative increase in lung volume from first MRI to near birth was 110%, compared with 22% in eight fetuses managed expectantly, said Dr. Jani of the University Hospital Gasthuisberg, Leuven, Belgium.

The mean maximal increase in lung volume in the FETO patients was observed 4 weeks after treatment. The volume decreased by 23%, compared with the posttreatment maximum, following balloon removal, which typically occurred at 34 weeks' gestation, but volume remained higher than in those managed expectantly.

The fetuses in the FETO group all had severe congenital diaphragmatic hernia (CDH), which by definition involves liver herniation into the chest cavity. The eight who did not undergo FETO were managed expectantly either because the cases were less severe (six cases) or because FETO was denied (two cases).

Further evaluation of the fetal liver in those managed expectantly showed that liver herniation, present in half of the cases, was associated with lower increases in lung volume; the increase was only 9% if the liver was herniated, compared with 35% when the liver was down, Dr. Jani noted.

The findings show that liver position is an important factor for predicting lung volume gains in fetuses with CDH, and that in severe CDH, FETO is effective for increasing lung volume. These effects persist after in utero balloon removal, he said.

MIAMI BEACH — Fetoscopic endoluminal tracheal occlusion, or FETO, results in “impressive” relative increases in lung volume in cases of severe congenital diaphragmatic hernia, Dr. Jacques C. Jani reported at the annual meeting of the Society for Maternal-Fetal Medicine.

In eight fetuses with the condition who underwent FETO, and who were followed by regular magnetic resonance imaging beginning at 24–26 weeks' gestation, the mean relative increase in lung volume from first MRI to near birth was 110%, compared with 22% in eight fetuses managed expectantly, said Dr. Jani of the University Hospital Gasthuisberg, Leuven, Belgium.

The mean maximal increase in lung volume in the FETO patients was observed 4 weeks after treatment. The volume decreased by 23%, compared with the posttreatment maximum, following balloon removal, which typically occurred at 34 weeks' gestation, but volume remained higher than in those managed expectantly.

The fetuses in the FETO group all had severe congenital diaphragmatic hernia (CDH), which by definition involves liver herniation into the chest cavity. The eight who did not undergo FETO were managed expectantly either because the cases were less severe (six cases) or because FETO was denied (two cases).

Further evaluation of the fetal liver in those managed expectantly showed that liver herniation, present in half of the cases, was associated with lower increases in lung volume; the increase was only 9% if the liver was herniated, compared with 35% when the liver was down, Dr. Jani noted.

The findings show that liver position is an important factor for predicting lung volume gains in fetuses with CDH, and that in severe CDH, FETO is effective for increasing lung volume. These effects persist after in utero balloon removal, he said.

KISSIMMEE, FLA. — Mild stroke symptoms should not preclude thrombolytic therapy in eligible patients, Dr. Nicole R. Gonzales said at the 31st International Stroke Conference.

Patients with mild acute ischemic stroke are often excluded from thrombolytic therapy despite presenting within the 3-hour window for recombinant tissue plasminogen activator (r-TPA) treatment, because it is assumed they will do well without the therapy.

However, in a large prospective study, administration of r-TPA to patients with mild stroke improved their chances of an excellent outcome and appeared to reduce the risk of death, said Dr. Gonzales of the University of Texas, Houston.

Of 885 patients presenting with acute ischemic stroke over a 14-month period, 238 had a National Institutes of Health Stroke Scale (NIHSS) score of between 1 and 7, indicating minimal symptoms (103 patients) or mild symptoms (135 patients).

Overall, 41 patients were treated with r-TPA. Of 46 who arrived within the 3-hour treatment window, 72% were excluded due to mild symptoms.

Outcome at discharge was excellent in 59% of all stroke patients who were treated, regardless of the severity of the stroke, compared with 44% of those not treated.

Of those with minimal stroke symptoms according to the NIHSS score, 90% of those treated had an excellent outcome. The differences were statistically significant, compared with only 58% of those not treated.

Nearly 50% of those with mild symptoms according to the NIHSS score who were treated, compared with 32% who were not treated, also had an excellent outcome, however the numbers in this group were too small to show statistical significance.

None of the treated patients with minor or mild symptoms died, while two in the untreated group died, although these numbers were also too small to show statistical significance.

“The findings argue strongly against exclusion of patients from thrombolytic therapy based on minimal or mild symptoms,” Dr. Gonzales said.

The conference was sponsored by the American Stroke Association.

KISSIMMEE, FLA. — Mild stroke symptoms should not preclude thrombolytic therapy in eligible patients, Dr. Nicole R. Gonzales said at the 31st International Stroke Conference.

Patients with mild acute ischemic stroke are often excluded from thrombolytic therapy despite presenting within the 3-hour window for recombinant tissue plasminogen activator (r-TPA) treatment, because it is assumed they will do well without the therapy.

However, in a large prospective study, administration of r-TPA to patients with mild stroke improved their chances of an excellent outcome and appeared to reduce the risk of death, said Dr. Gonzales of the University of Texas, Houston.

Of 885 patients presenting with acute ischemic stroke over a 14-month period, 238 had a National Institutes of Health Stroke Scale (NIHSS) score of between 1 and 7, indicating minimal symptoms (103 patients) or mild symptoms (135 patients).

Overall, 41 patients were treated with r-TPA. Of 46 who arrived within the 3-hour treatment window, 72% were excluded due to mild symptoms.

Outcome at discharge was excellent in 59% of all stroke patients who were treated, regardless of the severity of the stroke, compared with 44% of those not treated.

Of those with minimal stroke symptoms according to the NIHSS score, 90% of those treated had an excellent outcome. The differences were statistically significant, compared with only 58% of those not treated.

Nearly 50% of those with mild symptoms according to the NIHSS score who were treated, compared with 32% who were not treated, also had an excellent outcome, however the numbers in this group were too small to show statistical significance.

None of the treated patients with minor or mild symptoms died, while two in the untreated group died, although these numbers were also too small to show statistical significance.

“The findings argue strongly against exclusion of patients from thrombolytic therapy based on minimal or mild symptoms,” Dr. Gonzales said.

The conference was sponsored by the American Stroke Association.

KISSIMMEE, FLA. — Mild stroke symptoms should not preclude thrombolytic therapy in eligible patients, Dr. Nicole R. Gonzales said at the 31st International Stroke Conference.

Patients with mild acute ischemic stroke are often excluded from thrombolytic therapy despite presenting within the 3-hour window for recombinant tissue plasminogen activator (r-TPA) treatment, because it is assumed they will do well without the therapy.

However, in a large prospective study, administration of r-TPA to patients with mild stroke improved their chances of an excellent outcome and appeared to reduce the risk of death, said Dr. Gonzales of the University of Texas, Houston.

Of 885 patients presenting with acute ischemic stroke over a 14-month period, 238 had a National Institutes of Health Stroke Scale (NIHSS) score of between 1 and 7, indicating minimal symptoms (103 patients) or mild symptoms (135 patients).

Overall, 41 patients were treated with r-TPA. Of 46 who arrived within the 3-hour treatment window, 72% were excluded due to mild symptoms.

Outcome at discharge was excellent in 59% of all stroke patients who were treated, regardless of the severity of the stroke, compared with 44% of those not treated.

Of those with minimal stroke symptoms according to the NIHSS score, 90% of those treated had an excellent outcome. The differences were statistically significant, compared with only 58% of those not treated.

Nearly 50% of those with mild symptoms according to the NIHSS score who were treated, compared with 32% who were not treated, also had an excellent outcome, however the numbers in this group were too small to show statistical significance.

None of the treated patients with minor or mild symptoms died, while two in the untreated group died, although these numbers were also too small to show statistical significance.

“The findings argue strongly against exclusion of patients from thrombolytic therapy based on minimal or mild symptoms,” Dr. Gonzales said.

The conference was sponsored by the American Stroke Association.

KISSIMMEE, FLA. — The administration of microbubbles bolsters the combined thrombolytic effects of ultrasound-enhanced systemic thrombolysis and tissue plasminogen activator and improves outcomes in patients with atherothrombotic stroke, Dr. Marta Rubiera reported at the 31st International Stroke Conference.

In a study of 155 consecutive patients with stroke attributable to middle cerebral artery (MCA) occlusion, patients were allocated to one of three groups. One group received intravenous tissue plasminogen activator (TPA) treatment plus continuous 2-hour, 2-MHz-pulsed-wave transcranial Doppler ultrasound and three intravenous doses of galactose-based microbubbles given at 2, 20, and 40 minutes after TPA bolus. The remaining patients received TPA and ultrasound without microbubble administration or TPA with placebo monitoring.

The 2-hour complete recanalization rate was significantly higher in the microbubble group, compared with the ultrasound and control groups (42% vs. 40% and 24%, respectively), said Dr. Rubiera of the Hospital Vall d'Hebron, Barcelona.

The differences were significant only for those with atherothrombotic stroke, compared with cardioembolic and “undetermined” or “other” types of strokes (which comprised 24%, 49%, 23%, and 4% of stroke types in the study, respectively). In the 37 patients with atherothrombotic stroke, micro-bubbles increased the success rate of 2-hour recanalization 1.5-fold over TPA plus ultrasound (39% vs. 26%), and nearly twofold over TPA alone (39% vs. 21%).

Furthermore, at 3-month follow-up atherothrombotic stroke was significantly associated with a poor outcome in the ultrasound and control groups, but not in the microbubble group, as determined by modified Rankin Scale score, Dr. Rubiera noted.

Patients in the study had a median National Institutes of Health Stroke Scale (NIHSS) score of 16. On transcranial Doppler ultrasound, 76% of the 155 patients had occlusion of the proximal MCA, and 24% had occlusion of the distal MCA. Of those 37 patients with atherothrombotic stroke, 96% had occlusion of both the MCA and internal carotid artery (ICA) occlusion. Patients in all stroke subtype categories were similar with regard to baseline NIHSS, clot locations, and time to treatment.

Ultrasound used for monitoring has been shown to safely enhance thrombolysis by accelerating the transport and penetration of TPA into the clot, according to Dr. Rubiera and her associates.

Microbubbles, small air- or gas-filled microspheres approved for use in Europe and Japan as a contrast agent for ultrasound, appear to disrupt blood clots via cavitation. In a recently published article on the effects of microbubbles on clot lysis during ultrasound monitoring, Dr. Rubiera and her colleagues explained that by acting as cavitation nuclei, microbubbles lower the amount of energy needed for cavitation, and that high-acoustic-pressure ultrasound induces nonlinear oscillations of microbubbles. This process leads to continuous absorption of energy, which eventually causes the bubbles to explode, releasing the absorbed energy, they noted.

“Thus ultrasound-mediated microbubble destruction may further accelerate the clot-dissolving effect of ultrasound,” they wrote (Stroke 2006;37:425–9).

The expanded data presented at the conference, which was sponsored by the American Stroke Association, provide further evidence that microbubble administration during continuous ultrasound monitoring and systemic thrombolysis improves recanalization and outcomes in patients with tandem ICA and MCA occlusion, Dr. Rubiera concluded.

KISSIMMEE, FLA. — The administration of microbubbles bolsters the combined thrombolytic effects of ultrasound-enhanced systemic thrombolysis and tissue plasminogen activator and improves outcomes in patients with atherothrombotic stroke, Dr. Marta Rubiera reported at the 31st International Stroke Conference.

In a study of 155 consecutive patients with stroke attributable to middle cerebral artery (MCA) occlusion, patients were allocated to one of three groups. One group received intravenous tissue plasminogen activator (TPA) treatment plus continuous 2-hour, 2-MHz-pulsed-wave transcranial Doppler ultrasound and three intravenous doses of galactose-based microbubbles given at 2, 20, and 40 minutes after TPA bolus. The remaining patients received TPA and ultrasound without microbubble administration or TPA with placebo monitoring.

The 2-hour complete recanalization rate was significantly higher in the microbubble group, compared with the ultrasound and control groups (42% vs. 40% and 24%, respectively), said Dr. Rubiera of the Hospital Vall d'Hebron, Barcelona.

The differences were significant only for those with atherothrombotic stroke, compared with cardioembolic and “undetermined” or “other” types of strokes (which comprised 24%, 49%, 23%, and 4% of stroke types in the study, respectively). In the 37 patients with atherothrombotic stroke, micro-bubbles increased the success rate of 2-hour recanalization 1.5-fold over TPA plus ultrasound (39% vs. 26%), and nearly twofold over TPA alone (39% vs. 21%).

Furthermore, at 3-month follow-up atherothrombotic stroke was significantly associated with a poor outcome in the ultrasound and control groups, but not in the microbubble group, as determined by modified Rankin Scale score, Dr. Rubiera noted.

Patients in the study had a median National Institutes of Health Stroke Scale (NIHSS) score of 16. On transcranial Doppler ultrasound, 76% of the 155 patients had occlusion of the proximal MCA, and 24% had occlusion of the distal MCA. Of those 37 patients with atherothrombotic stroke, 96% had occlusion of both the MCA and internal carotid artery (ICA) occlusion. Patients in all stroke subtype categories were similar with regard to baseline NIHSS, clot locations, and time to treatment.

Ultrasound used for monitoring has been shown to safely enhance thrombolysis by accelerating the transport and penetration of TPA into the clot, according to Dr. Rubiera and her associates.

Microbubbles, small air- or gas-filled microspheres approved for use in Europe and Japan as a contrast agent for ultrasound, appear to disrupt blood clots via cavitation. In a recently published article on the effects of microbubbles on clot lysis during ultrasound monitoring, Dr. Rubiera and her colleagues explained that by acting as cavitation nuclei, microbubbles lower the amount of energy needed for cavitation, and that high-acoustic-pressure ultrasound induces nonlinear oscillations of microbubbles. This process leads to continuous absorption of energy, which eventually causes the bubbles to explode, releasing the absorbed energy, they noted.

“Thus ultrasound-mediated microbubble destruction may further accelerate the clot-dissolving effect of ultrasound,” they wrote (Stroke 2006;37:425–9).

The expanded data presented at the conference, which was sponsored by the American Stroke Association, provide further evidence that microbubble administration during continuous ultrasound monitoring and systemic thrombolysis improves recanalization and outcomes in patients with tandem ICA and MCA occlusion, Dr. Rubiera concluded.

KISSIMMEE, FLA. — The administration of microbubbles bolsters the combined thrombolytic effects of ultrasound-enhanced systemic thrombolysis and tissue plasminogen activator and improves outcomes in patients with atherothrombotic stroke, Dr. Marta Rubiera reported at the 31st International Stroke Conference.

In a study of 155 consecutive patients with stroke attributable to middle cerebral artery (MCA) occlusion, patients were allocated to one of three groups. One group received intravenous tissue plasminogen activator (TPA) treatment plus continuous 2-hour, 2-MHz-pulsed-wave transcranial Doppler ultrasound and three intravenous doses of galactose-based microbubbles given at 2, 20, and 40 minutes after TPA bolus. The remaining patients received TPA and ultrasound without microbubble administration or TPA with placebo monitoring.

The 2-hour complete recanalization rate was significantly higher in the microbubble group, compared with the ultrasound and control groups (42% vs. 40% and 24%, respectively), said Dr. Rubiera of the Hospital Vall d'Hebron, Barcelona.

The differences were significant only for those with atherothrombotic stroke, compared with cardioembolic and “undetermined” or “other” types of strokes (which comprised 24%, 49%, 23%, and 4% of stroke types in the study, respectively). In the 37 patients with atherothrombotic stroke, micro-bubbles increased the success rate of 2-hour recanalization 1.5-fold over TPA plus ultrasound (39% vs. 26%), and nearly twofold over TPA alone (39% vs. 21%).

Furthermore, at 3-month follow-up atherothrombotic stroke was significantly associated with a poor outcome in the ultrasound and control groups, but not in the microbubble group, as determined by modified Rankin Scale score, Dr. Rubiera noted.

Patients in the study had a median National Institutes of Health Stroke Scale (NIHSS) score of 16. On transcranial Doppler ultrasound, 76% of the 155 patients had occlusion of the proximal MCA, and 24% had occlusion of the distal MCA. Of those 37 patients with atherothrombotic stroke, 96% had occlusion of both the MCA and internal carotid artery (ICA) occlusion. Patients in all stroke subtype categories were similar with regard to baseline NIHSS, clot locations, and time to treatment.

Ultrasound used for monitoring has been shown to safely enhance thrombolysis by accelerating the transport and penetration of TPA into the clot, according to Dr. Rubiera and her associates.

Microbubbles, small air- or gas-filled microspheres approved for use in Europe and Japan as a contrast agent for ultrasound, appear to disrupt blood clots via cavitation. In a recently published article on the effects of microbubbles on clot lysis during ultrasound monitoring, Dr. Rubiera and her colleagues explained that by acting as cavitation nuclei, microbubbles lower the amount of energy needed for cavitation, and that high-acoustic-pressure ultrasound induces nonlinear oscillations of microbubbles. This process leads to continuous absorption of energy, which eventually causes the bubbles to explode, releasing the absorbed energy, they noted.

“Thus ultrasound-mediated microbubble destruction may further accelerate the clot-dissolving effect of ultrasound,” they wrote (Stroke 2006;37:425–9).

The expanded data presented at the conference, which was sponsored by the American Stroke Association, provide further evidence that microbubble administration during continuous ultrasound monitoring and systemic thrombolysis improves recanalization and outcomes in patients with tandem ICA and MCA occlusion, Dr. Rubiera concluded.