Effects of age on prefrontal subregions and hippocampal volumes in young and middle-aged healthy humans.

There are limited data available regarding the effects of age and sex on discrete prefrontal gray and white matter volumes or posterior and anterior hippocampal volumes in healthy humans. Volumes of the superior frontal gyrus, anterior cingulate gyrus, and orbital frontal lobe were computed manually from contiguous magnetic resonance (MR) images in 83 (39M/44F) healthy humans (age range = 16-40) and segmented into gray and white matter. Volumes of the posterior and anterior hippocampal formation were also computed with reliable separation of the anterior hippocampal formation from the amygdala. There were significant age-by-tissue type interactions for the superior frontal gyrus and orbital frontal lobe such that gray matter within these regions correlated significantly and inversely with age. In contrast, no significant age effects were evident within regional white matter volumes. Analysis of hippocampal volumes indicated that men had larger volumes of the anterior, but not posterior hippocampal formation compared to women even following correction for total brain size. These data highlight age effects within discrete prefrontal cortical gray matter regions in young and middle aged healthy humans and suggest that the white matter comprising these regions may be more resistant to age effects. Furthermore, understanding the potential role of sex and age in mediating prefrontal cortical and hippocampal volumes may have strong relevance for psychiatric disorders such as schizophrenia that have implicated neurodevelopmental abnormalities within frontotemporal circuits in their pathogenesis.

Weight gain in an eating disorders day program.

BACKGROUND: Day treatment programs have increasingly become an important level of care in the medical and psychiatric management of patients with eating disorders, yet there is little in the literature describing the weight gain patterns of patients in these programs. METHODS: Weight gain accomplished by 198 patients admitted to a day program over a 2-year period was studied. Weight gain was analyzed by demographic, diagnostic and program-related variables and was compared for weekdays and weekends. RESULTS: The mean length of stay was 2.6 weeks and patients gained a mean of 2.1 pounds (0.95 kg) in the program. Approximately one-quarter of patients lost weight, one-quarter gained 0 to <2 pounds (0.9 kg), one-quarter gained 2-4 pounds (0.9-1.8 kg), and one-quarter gained more than 4 pounds (1.8 kg). Weight gain was greater in those with a diagnosis of anorexia nervosa or eating disorder not otherwise specified (compared to bulimia nervosa), a longer time in the program, and a lower body mass index on admission. Patients gained more on weekdays, while in the program, than on weekends, when they were home. CONCLUSIONS: The data showed that most patients accomplished modest weight gains during a relatively short stay in an eating disorders day program, demonstrating what can be expected for this level of care in the current healthcare environment.

Olanzapine vs. risperidone in patients with first-episode schizophrenia and a lifetime history of cannabis use disorders: 16-week clinical and substance use outcomes.

The purpose of this study is to compare the efficacy of olanzapine and risperidone for the acute treatment of first-episode schizophrenia patients with cannabis use disorders. This secondary analysis of a previously published study included 49 first-episode patients with a diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder and a co-occurring lifetime diagnosis of cannabis use disorders randomly assigned to treatment with either olanzapine (n=28) or risperidone (n=21) for 16weeks. The olanzapine group did not differ significantly from the risperidone group for initial response rates of positive symptoms, and rates of cannabis use or alcohol use during the study. Positive symptoms and the Scale for Assessment of Negative Symptoms (SANS) global asociality-anhedonia scores improved over time but did not differ between study medications. In both groups, cannabis use during the study was higher in patients who used cannabis within three months of the admission. Thus, our results suggest that olanzapine and risperidone had a similar initial efficacy on psychotic symptoms and substance use in first-episode patients with co-occurring cannabis use disorders. If clinicians are choosing between olanzapine versus risperidone treatment for this population, their decision should be based upon factors other than symptom response and short-term substance misuse.

Palliative medicine consultation impacts DNR designation and length of stay for terminal medical MICU patients.

OBJECTIVE: The purpose of this study was to assess the impact of a palliative medicine consultation on medical intensive care unit (MICU) and hospital length of stay, Do Not Resuscitate (DNR) designation, and location of death for MICU patients who died during hospitalization. METHOD: A comparison of two retrospective cohorts in a 17-bed MICU in a tertiary care university-affiliated hospital was conducted. Patients admitted to the MICU between January 1, 2003 and June 30, 2004 (N = 515) were compared to MICU patients who had had a palliative medicine consultation between January 1, 2005 and June 1, 2009 (N = 693). To control for disease severity, only patients in both cohorts who died during their hospitalization were considered for this study. RESULTS: Palliative medicine consultation reduced time until death during the entire hospitalization (log-rank test, p < 0.01). Time from MICU admission until death was also reduced (log-rank test, p < 0.01), further demonstrating the impact of the palliative care consultation on the duration of dying for hospitalized patients. The intervention group contained a significantly higher percentage of patients with a DNR designation at death than did the control group (86% vs. 68%, χ2 test, p < 0.0001). SIGNIFICANCE OF RESULTS: Palliative medicine consultation is associated with an increased rate of DNR designation and reduced time until death. Patients in the intervention group were also more likely to die outside the MICU as compared to controls in the usual care group.

DRD2 promoter region variation predicts antipsychotic-induced weight gain in first episode schizophrenia.

Many antipsychotic medications carry a substantial liability for weight gain, and one mechanism common to all antipsychotics is binding to the dopamine D2 receptor. We therefore examined the relationship between -141C Ins/Del (rs1799732), a functional promoter region polymorphism in DRD2, and antipsychotic-induced weight gain in 58 first episode schizophrenia patients enrolled in a randomized trial of risperidone versus olanzapine. Carriers of the deletion allele (n=29) were compared with Ins/Ins homozygotes (noncarriers, n=29) in a mixed model encompassing 10 weight measurements over 16 weeks. Deletion allele carriers showed significantly more weight gain after 6 weeks of treatment regardless of assigned medication. Although deletion carriers were prescribed higher doses of olanzapine (but not risperidone), dose did not seem to account for the genotype effects on weight gain. Given earlier evidence that deletion carriers show reduced symptom response to medication, additional study of appropriate treatment options for these patients seems warranted.

Cadmium concentrations in blood and seminal plasma: correlations with sperm number and motility in three male populations (infertility patients, artificial insemination donors, and unselected volunteers).

To investigate a possible common environmental exposure that may partially explain the observed decrease in human semen quality, we correlated seminal plasma and blood cadmium levels with sperm concentration and sperm motility. We studied three separate human populations: group 1, infertility patients (Long Island, NY, USA); group 2, artificial insemination donors (AID) (Rochester, NY, USA); and group 3, general population volunteers (Rochester, NY, USA). Information about confounding factors was collected by questionnaire. Seminal plasma cadmium did not correlate with blood cadmium (Spearman correlation, n = 91, r = -0.092, P = 0.386, NS). Both blood and seminal plasma cadmium were significantly higher among infertility patients than the other subjects studied (for example, median seminal plasma cadmium was 0.282 microg/L in infertility patients versus 0.091 microg/L in AID and 0.092 microg/L in general population volunteers; Kruskal-Wallis test, P < 0.001). The percentage of motile sperm and sperm concentration correlated inversely with seminal plasma cadmium among the infertility patients (r = -0.201, P < 0.036 and r = -0.189, P < 0.05, respectively), but not in the other two groups. Age (among infertility patients) was the only positive confounder correlating with seminal plasma cadmium. To validate our human findings in an animal model, we chronically exposed adolescent male Wistar rats to low-moderate cadmium in drinking water. Though otherwise healthy, the rats exhibited decreases in epididymal sperm count and sperm motility associated with cadmium dose and time of exposure. Our human and rat study results are consistent with the hypothesis that environmental cadmium exposures may contribute significantly to reduced human male sperm concentration and sperm motility.

Long-term outcomes in younger men following permanent prostate brachytherapy.

PURPOSE: We reviewed the long-term outcomes in men undergoing permanent prostate brachytherapy with a focus on those presenting before age 60 years. MATERIALS AND METHODS: Between 1992 and 2005 a total of 2,119 patients with clinical stage T1-T2, N0, M0 prostate cancer treated with permanent prostate brachytherapy were included in this study. Treatment regimens consisted of permanent prostate brachytherapy with or without hormone therapy, permanent prostate brachytherapy with external beam radiotherapy, or all 3 modalities. Biochemical recurrence was defined using the Phoenix definition. Multivariate analysis was performed to determine if age and/or other clinicopathological features were associated with disease progression. The Kaplan-Meier method was used to calculate rates of freedom from progression with the log rank test to compare patients younger than 60 vs 60 years or older. RESULTS: Median followup was 56.1 months. In the study population 237 patients were younger than 60 years at diagnosis (11%). The 5 and 10-year freedom from progression rates were 90.1% and 85.6%, respectively, for the entire population. Multivariate analysis demonstrated that prostate specific antigen (p <0.01), biopsy Gleason score (p <0.0001) and year of treatment (p <0.001) were associated with freedom from progression while age (p = 0.95) and clinical stage (p = 0.11) were not. There was no significant difference in freedom from progression between men younger than 60, or 60 years or older (log rank p = 0.46). In the younger cohort the 10-year freedom from progression for patients presenting with low, intermediate and high risk disease was 91.3%, 80.0% and 70.2% compared to 91.8%, 83.4% and 72.1%, respectively, for men 60 years or older. CONCLUSIONS: Our long-term results confirm favorable outcomes after permanent prostate brachytherapy in men younger than 60 years. Outcomes are impacted by disease related risk factors but not by age or clinical stage. Definitive treatment options for younger men with clinically localized prostate cancer should include permanent prostate brachytherapy.

Lack of an inverse relationship between duration of untreated psychosis and cognitive function in first episode schizophrenia.

This study assessed the relationship between duration of untreated psychosis (DUP) and cognitive measures in order to assess if longer DUP was associated with worse performance. One hundred two patients with first episode schizophrenia or schizoaffective disorder were assessed on cognitive measures of speed of processing, episodic memory, executive function, and visual spatial processing at baseline (when patients were drug naive and after 16 weeks of olanzapine or risperidone treatment), so that a change score could be derived. DUP was defined by the emergence of psychiatric symptoms and the emergence of psychotic symptoms. Data were analyzed correlationally, parametrically (after the group was divided into long and short DUP by median split), and by regression. We found that DUP for psychotic symptoms in this group of patients was long, with a median of 46 weeks. Neither correlational, parametric analyses in which DUP served as a class variable, nor multiple regression indicated that longer DUP was associated with worse cognition at baseline or smaller magnitude of improvement in cognition. Our results suggest that while early intervention may be critical for symptom amelioration by shortening DUP, early intervention for treatment of psychiatric symptoms may have little or no impact on cognitive function. Furthermore, assuming that cognition is a core symptom of schizophrenia, the notion that ongoing psychosis is somehow toxic for a variety of information processing domains appears questionable.

Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents.

CONTEXT: Cardiometabolic effects of second-generation antipsychotic medications are concerning but have not been sufficiently studied in pediatric and adolescent patients naive to antipsychotic medication. OBJECTIVE: To study the association of second-generation antipsychotic medications with body composition and metabolic parameters in patients without prior antipsychotic medication exposure. DESIGN, SETTING, AND PATIENTS: Nonrandomized Second-Generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) cohort study, conducted between December 2001 and September 2007 at semi-urban, tertiary care, academic inpatient and outpatient clinics in Queens, New York, with a catchment area of 4.5-million individuals. Of 505 youth aged 4 to 19 years with 1 week or less of antipsychotic medication exposure, 338 were enrolled (66.9%). Of these patients, 272 had at least 1 postbaseline assessment (80.5%), and 205 patients [corrected] completed the study (60.7%). Patients had mood spectrum (n = 130; 47.8%), schizophrenia spectrum (n = 82; 30.1%), and disruptive or aggressive behavior spectrum (n = 60; 22.1%) disorders. Fifteen patients who refused participation or were nonadherent served as a comparison group. INTERVENTION: Treatment with aripiprazole, olanzapine, quetiapine, or risperidone for 12 weeks. MAIN OUTCOME MEASURES: Weight gain and changes in lipid and metabolic parameters. RESULTS: After a median of 10.8 weeks (interquartile range, 10.5-11.2 weeks) of treatment, weight increased by 8.5 kg (95% confidence interval [CI], 7.4 to 9.7 kg) with olanzapine (n = 45), by 6.1 kg (95% CI, 4.9 to 7.2 kg) with quetiapine (n = 36), by 5.3 kg (95% CI, 4.8 to 5.9 kg) with risperidone (n = 135), and by 4.4 kg (95% CI, 3.7 to 5.2 kg) with aripiprazole (n = 41) compared with the minimal weight change of 0.2 kg (95% CI, -1.0 to 1.4 kg) in the untreated comparison group (n = 15). With olanzapine and quetiapine, respectively, mean levels increased significantly for total cholesterol (15.6 mg/dL [95% CI, 6.9 to 24.3 mg/dL] P < .001 and 9.1 mg/dL [95% CI, 0.4 to 17.7 mg/dL] P = .046), triglycerides (24.3 mg/dL [95% CI, 9.8 to 38.9 mg/dL] P = .002 and 37.0 mg/dL [95% CI, 10.1 to 63.8 mg/dL] P = .01), non-high-density lipoprotein (HDL) cholesterol (16.8 mg/dL [95% CI, 9.3 to 24.3 mg/dL] P < .001 and 9.9 mg/dL [95% CI, 1.4 to 18.4 mg/dL] P = .03), and ratio of triglycerides to HDL cholesterol (0.6 [95% CI, 0.2 to 0.9] P = .002 and (1.2 [95% CI, 0.4 to 2.0] P = .004). With risperidone, triglycerides increased significantly (mean level, 9.7 mg/dL [95% CI, 0.5 to 19.0 mg/dL]; P = .04). Metabolic baseline-to-end-point changes were not significant with aripiprazole or in the untreated comparison group. CONCLUSIONS: First-time second-generation antipsychotic medication use was associated with significant weight gain with each medication. Metabolic changes varied among the 4 antipsychotic medications.

DISC1 is associated with prefrontal cortical gray matter and positive symptoms in schizophrenia.

BACKGROUND: DISC1 is considered a susceptibility gene for schizophrenia and schizoaffective disorder, but little is known regarding the potential mechanisms through which it may confer increased risk. Given that DISC1 plays a role in cerebral cortex development, polymorphisms in this gene may have relevance for neurobiological models of schizophrenia that have implicated cortical deficits in its pathophysiology. METHODS: We investigated whether the DISC1 leu607phe polymorphism was associated with prefrontal gray matter volumes using magnetic resonance imaging in a cohort of patients with schizophrenia (N=19) and healthy volunteers (N=25) and positive and negative symptoms in 200 patients with schizophrenia. RESULTS: Among patients and healthy volunteers, phe carriers (N=11) had significantly less gray matter in the superior frontal gyrus and anterior cingulate gyrus compared to leu/leu homozygotes (N=33). Further, among patients left superior frontal gyrus gray matter volume was significantly negatively correlated with severity of hallucinations. In addition, patients who were phe carriers (N=144) had significantly greater severity of positive symptoms (hallucinations) compared to patients who were leu/leu homozygotes (N=56). DISCUSSION: These findings implicate DISC1 in variation of prefrontal cortical volume and positive symptoms, thus providing a potential mechanism through which DISC1 may confer increased risk for schizophrenia or schizoaffective disorder.

Randomized comparison of olanzapine versus risperidone for the treatment of first-episode schizophrenia: 4-month outcomes.

OBJECTIVE: The authors compared 4-month treatment outcomes for olanzapine versus risperidone in patients with first-episode schizophrenia spectrum disorders. METHOD: One hundred twelve subjects (70% male; mean age=23.3 years [SD = 5.1]) with first-episode schizophrenia (75%), schizophreniform disorder (17%), or schizoaffective disorder (8%) were randomly assigned to treatment with olanzapine (2.5-20 mg/day) or risperidone (1-6 mg/day). RESULTS: Response rates did not significantly differ between olanzapine (43.7%, 95% CI=28.8%-58.6%) and risperidone (54.3%, 95% CI=39.9%-68.7%). Among those responding to treatment, more subjects in the olanzapine group (40.9%, 95% CI=16.8%-65.0%) than in the risperidone group (18.9%, 95% CI=0%-39.2%) had subsequent ratings not meeting response criteria. Negative symptom outcomes and measures of parkinsonism and akathisia did not differ between medications. Extrapyramidal symptom severity scores were 1.4 (95% CI=1.2-1.6) with risperidone and 1.2 (95% CI=1.0-1.4) with olanzapine. Significantly more weight gain occurred with olanzapine than with risperidone: the increase in weight at 4 months relative to baseline weight was 17.3% (95% CI=14.2%-20.5%) with olanzapine and 11.3% (95% CI=8.4%-14.3%) with risperidone. Body mass index at baseline and at 4 months was 24.3 (95% CI=22.8-25.7) versus 28.2 (95% CI=26.7-29.7) with olanzapine and 23.9 (95% CI=22.5-25.3) versus 26.7 (95% CI=25.2-28.2) with risperidone. CONCLUSIONS: Clinical outcomes with risperidone were equal to those with olanzapine, and response may be more stable. Olanzapine may have an advantage for motor side effects. Both medications caused substantial rapid weight gain, but weight gain was greater with olanzapine.

Emotion-based decision-making in healthy subjects: short-term effects of reducing dopamine levels.

INTRODUCTION: Converging evidences from animal and human studies suggest that addiction is associated with dopaminergic dysfunction in brain reward circuits. So far, it is unclear what aspects of addictive behaviors are related to a dopaminergic dysfunction. DISCUSSION: We hypothesize that a decrease in dopaminergic activity impairs emotion-based decision-making. To demonstrate this hypothesis, we investigated the effects of a decrease in dopaminergic activity on the performance of an emotion-based decision-making task, the Iowa gambling task (IGT), in 11 healthy human subjects. MATERIALS AND METHODS: We used a double-blind, placebo-controlled, within-subject design to examine the effect of a mixture containing the branched-chain amino acids (BCAA) valine, isoleucine and leucine on prolactin, IGT performance, perceptual competency and visual aspects of visuospatial working memory, visual attention and working memory, and verbal memory. The expectancy-valence model was used to determine the relative contributions of distinct IGT components (attention to past outcomes, relative weight of wins and losses, and choice strategies) in the decision-making process. OBSERVATIONS AND RESULTS: Compared to placebo, the BCAA mixture increased prolactin levels and impaired IGT performance. BCAA administration interfered with a particular component process of decision-making related to attention to more recent events as compared to more distant events. There were no differences between placebo and BCAA conditions for other aspects of cognition. Our results suggest a direct link between a reduced dopaminergic activity and poor emotion-based decision-making characterized by shortsightedness, and thus difficulties resisting short-term reward, despite long-term negative consequences. These findings have implications for behavioral and pharmacological interventions targeting impaired emotion-based decision-making in addictive disorders.

Early-onset schizophrenia is associated with impaired adolescent development of attentional capacity using the identical pairs continuous performance test.

The authors examined performance on the Continuous Performance Test-Identical Pairs "numbers" task in adolescents with schizophrenia (n=59) and healthy controls (n=55). Adjusting for an estimate of premorbid intelligence and socioeconomic status, patients performed worse than normal controls on all three d' conditions (2-digit, 3-digit, 4-digit). However, there was a significant group-by-age-by-condition interaction (F[4,100]=4.69, p<.01) indicating an interaction between development and disease state. At the simplest level of the task (2-digit) the difference between patients with schizophrenia and controls was evident at all ages; while for the more difficult levels of the task (3-digit, 4-digit), differences between groups gradually increased across the tested age span (10 to 20 years of age). Premorbid social isolation was associated with worse attentional performance in patients, suggesting a relationship and continuity with negative symptoms. These data suggest that attentional differences in adolescents with schizophrenia are better captured by different tasks at different ages. The discrepant findings of attentional impairments reported in the literature for adolescents with schizophrenia could reflect the underlying etiological complexity of the disorder that may have a variable impact on involved brain regions and neurocognitive functioning.

Deficits in memory strategy use are related to verbal memory impairments in adolescents with schizophrenia-spectrum disorders.

OBJECTIVE: To assess the nature of learning and verbal memory deficits in adolescents with schizophrenia-spectrum disorders (SzS) (i.e., schizophrenia, schizoaffective disorder, and schizophreniform disorder). METHOD: Sixty patients with SzS (mean age=16.1 years, S.D. = 2.2) and 60 age- and gender-matched diagnosis-free healthy volunteers were assessed using the California Verbal Learning Test (CVLT). Planned analyses were conducted to assess the following aspects of memory: span of apprehension, verbal learning, short-term and long-term memory, rate of forgetting, interference, and organizational strategies. Adolescents with schizophrenia (Sz) were compared to those with schizoaffective disorder (SzA). Second, patients' test profiles were compared to those of controls. Relationships between initial learning and overall verbal learning with organizational strategy were explored. RESULTS: Neurocognitive profiles did not significantly differ between Sz and SzA participants. Patients performed significantly worse than healthy comparison subjects on measures of span of apprehension, verbal learning, short- and long-term memory, and organizational strategies after adjusting for differences in premorbid intelligence. No group differences were found in rate of forgetting or susceptibility to proactive or retroactive interference. CONCLUSIONS: Adolescents with SzS are characterized by significant verbal memory dysfunction similar to what has been observed in adults with first-episode schizophrenia. Deficits in consistency of learning over several trials, as well as a strong relationship between semantic organizational strategies and reduced learning capacity, implicate dysfunction of the dorsolateral prefrontal cortex as a contributor to verbal memory deficits in adolescents with SzS.

Hematological adverse events in clozapine-treated children and adolescents.

OBJECTIVE: To retrospectively examine rates of hematological adverse events (HAEs) in psychiatrically ill, hospitalized children treated with clozapine. METHOD: Clozapine treatment was administered in an open-label fashion using a flexible titration schedule, and data from weekly complete blood counts was obtained. The rate of neutropenia and agranulocytosis (HAEs) development was determined for 172 eligible patients (mean age at clozapine initiation, 15.03 +/- 2.13 years) with a median observation period of 8 months. RESULTS: Neutropenia (absolute neutrophil count <1,500/mm) developed in 23 (13%) patients and agranulocytosis (absolute neutrophil count <500/mm) in one (0.6%) patient. The cumulative probability of developing an initial HAE at 1 year of clozapine treatment was 16.1% (95% confidence interval 9.7%-22.5%). Eleven (48%) of 24 patients who developed an HAE were successfully rechallenged on clozapine. Eight (5%) of 172 patients from this sample eventually discontinued clozapine because of an HAE (one agranulocytosis, seven neutropenia). CONCLUSIONS: The occurrence of HAEs is a significant risk associated with the administration of clozapine. However, in this sample, few children actually discontinued therapy because of an HAE and the incidence of agranulocytosis does not appear higher than what has been reported in the adult literature.

Comparison of lung area by chest radiograph, with estimation of lung volume by helium dilution during prone and supine positioning in mechanically ventilated preterm infants: a pilot study.

Measurement of lung volume may be useful in determining the degree of lung disease and for optimizing an infant's mechanical ventilator settings. A chest radiograph (CXR) is often used to estimate lung volume, because direct measurement, e.g., functional residual capacity (FRC), is neither practical nor possible in the neonatal intensive care unit. In supinely positioned infants, good correlation was found between lung area determined by CXR and lung volume, e.g., functional residual capacity (FRC). Whether this is true for the prone position is unknown. Since positioning may affect oxygenation and pulmonary function, we studied the relationship between lung area measured from CXR and FRC during both supine and prone positioning in 14 mechanically ventilated preterm infants. Lung area was determined from CXRs using computed radiography and FRCs obtained by helium dilution at end-expiration in both supine and prone positions. Reproducibility of lung area measurements was demonstrated by high correlations between two observers (R2 = 0.92 and 0.99 for supine and prone, respectively). When supine, lung area was 15.4 +/- 3.1 cm2, and FRC was 19.5 +/- 7.3 ml. In prone position, lung area was 16.7 +/- 4.2 cm2, and FRC 23.0 +/- 9.4 ml. There was a moderate to strong positive correlation between lung area and FRC for both positions (supine: r = 0.57, P < 0.03; prone: r = 0.63, P < 0.02). Lung area measured by computed radiography is a reproducible and practical method for estimating lung volume from routine chest X-rays in both supine and prone positions in mechanically ventilated preterm infants.

In vitro fertilization-intracytoplasmic sperm injection split: an insemination method to prevent fertilization failure.

OBJECTIVE: To determine whether the performance of intracytoplasmic sperm injection (ICSI) in cases of unexplained infertility and of borderline semen parameters can prevent fertilization failure. DESIGN: Prospective cohort study. SETTING: Hospital-based assisted reproductive technology program. PATIENT(S): Sixty couples with unexplained infertility (group 1) and 50 couples with borderline semen (group 2). INTERVENTION(S): Conventional IVF and ICSI were performed on sibling oocyte cumulus complexes. MAIN OUTCOME MEASURE(S): Rate of fertilization according to patient diagnosis. RESULT(S): The fertilization rate per oocyte cumulus complex in couples with unexplained infertility (group 1) was significantly higher with ICSI (65.3%) compared with IVF insemination (48.1%). Fertilization rates per OCC in couples with borderline semen (group 2) were not significantly different between ICSI (58.1%) and IVF (56.7%). In group 1, failure of fertilization after IVF insemination occurred in 10 of the 60 couples (16.7%) and in none with ICSI. In group 2, 2 of 50 couples (4.0%) failed fertilization by IVF, and 1 (2.0%) failed with ICSI. No couple in group 2 failed both IVF insemination and ICSI. CONCLUSION(S): In couples with unexplained infertility, a higher fertilization rate was achieved through ICSI compared with conventional IVF. No such benefit could be demonstrated for couples with borderline semen parameters. The use of ICSI rescued 12 of 110 cycles (10.9%) where IVF failed. Adoption of the ICSI-IVF insemination split in cases of unexplained infertility may help eliminate fertilization failures.

Seminal lead concentrations negatively affect outcomes of artificial insemination.

OBJECTIVE: To determine the relationships among seminal lead levels, acrosome status, and artificial insemination cycle fecundity (AI f) in semen donors. DESIGN: Longitudinal analysis of seminal lead levels, sperm function testing, and fecundity. SETTING: University medical center andrology and research laboratories. PATIENT(S): Semen donors (n = 15) participating in a therapeutic donor insemination program. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Seminal plasma lead levels, acrosome sensitivity to progesterone (P) and voltage-gated potassium channel inhibitors (e.g., charybdotoxin [CBTx]), and AI f. RESULT(S): Seminal plasma lead levels and AI f were strongly negatively correlated. Semen donors were divided into three groups by acrosome response to P: normal (CBTx sensitive [Rs] or CBTx resistant [Rr]: responders) and reduced (nonresponders [NR]) (Rs > Rr >> NR). Seminal lead differed among the three groups (NR > Rr > Rs). Comparison of 330 artificial insemination cycles from four Rs, four Rr, and two NR demonstrated that cycle AI f also differed significantly between groups (Rs >Rr >>NR). CONCLUSION(S): Measurements of seminal plasma lead, P-stimulated acrosome loss, and sensitivity to CBTx may provide prognostic information on the fertility status of potential donors as well as male infertility patients. Such evaluations may assist in donor acceptance, or in the case of patients, in selection of the appropriate treatment regimen.

Dysmetabolic Signals in "Metabolically Healthy" Obesity.

BACKGROUND: Obesity is associated with decreased insulin sensitivity, atherogenic dyslipidemia and hypertension, but clinical studies have also identified a "metabolically healthy" obese phenotype. OBJECTIVE: To compare the characteristics of so-called "metabolically healthy" obese (MHO), normal weight subjects (MHNW) and obese with insulin resistance in a nationally representative sample in the United States. DESIGN, SETTING AND PARTICIPANTS: Insulin resistance was defined by a homeostatic model assessment (HOMA) value in the upper tertile for the entire NHANES cohort. "Metabolic health" was defined as the absence of diabetes, insulin resistance, metabolic syndrome, and lipid-lowering therapy. The study evaluated the 314 MHO, 1173 MHNW and 843 insulin-resistant obese from among the 6485 non-diabetic, nno-pregnant adults aged 20-79 years, who participated to the United States National Health and Nutrition Examination Survey, 1999-2004. MAIN OUTCOME MEASURES: Demographic, metabolic, nutrition and physical activity features. RESULTS: MHO and MHNW groups were similar regarding age, and fasting glucose and triglyceride levels. MHO had higher insulin (P<0.0001), insulin resistance as measured with the homeostatic model (p<0.0001), non-HDL cholesterol (P=0.002 in females and P=0.049 in males) and C-reactive protein levels (P<0.0001 in females and P=0.038 in males), and lower high-density lipoprotein cholesterol (HDL) levels (P<0.002). In addition, MHO females had higher low-density lipoprotein (LDL) cholesterol levels (P=0.012) and systolic blood pressure (P=0.02), and lower intake of dietary fiber (P=0.0009) and levels of physical activity (p=0.002). Triglycerides levels were normal in the MHO group. CONCLUSIONS: "Metabolically healthy" obese people have multiple dysmetabolic changes that may signal increased risk for coronary artery disease.

Dysmetabolic signals in "metabolically healthy" obesity.

BACKGROUND: Obesity is associated with decreased insulin sensitivity, atherogenic dyslipidemia and hypertension, but clinical studies have also identified a "metabolically healthy" obese phenotype. OBJECTIVE: To compare the characteristics of so-called "metabolically healthy" obese (MHO), normal weight subjects (MHNW) and obese with insulin resistance in the United States National Health and Nutrition Examination Survey, 1999-2004 (NHANES). DESIGN, SETTING AND PARTICIPANTS: Insulin resistance was defined by a homeostatic model assessment (HOMA) value in the upper tertile for the entire NHANES cohort. "Metabolic health" was defined as the absence of diabetes, insulin resistance, metabolic syndrome, and lipid-lowering therapy. The study evaluated the 314 MHO, 1173 MHNW and 843 insulin-resistant obese from among the 6485 non-diabetic, non-pregnant adults aged 20-79 years. MAIN OUTCOME MEASURES: Demographic, metabolic, nutrition and physical activity features. RESULTS: MHO and MHNW groups were similar regarding age, and fasting glucose and triglyceride levels. MHO had higher insulin (P < 0.0001), insulin resistance as measured with the homeostatic model (P < 0.0001), non-HDL cholesterol (P = 0.002 in females and P = 0.049 in males) and C-reactive protein levels (P < 0.0001 in females and P = 0.038 in males), and lower high-density lipoprotein cholesterol (HDL) levels (P < 0.002). In addition, MHO females had higher low-density lipoprotein (LDL) cholesterol levels (P = 0.012) and systolic blood pressure (P = 0.02), and lower intake of dietary fiber (P = 0.0009) and levels of physical activity (P = 0.002). Triglycerides levels were normal in the MHO group. CONCLUSIONS: "Metabolically healthy" obese people have multiple dysmetabolic changes that may signal increased risk for coronary artery disease.