Efficacy of ziprasidone in dysphoric mania: pooled analysis of two double-blind studies.

BACKGROUND: Dysphoric mania is a common and often difficult to treat subset of bipolar mania that is associated with significant depressive symptoms. OBJECTIVE: This post hoc analysis was designed to evaluate the efficacy of ziprasidone in the treatment of depressive and other symptoms in a cohort of patients with dysphoric mania. METHODS: Pooled data were examined from two similarly designed, 3-week placebo-controlled trials in acute bipolar mania. Patients scoring >/=2 on at least two items of the extracted Hamilton Rating Scale for Depression (HAM-D) met criteria for dysphoric mania and were included in the post hoc analysis. Changes from baseline in symptom scores were evaluated by a mixed-model analysis of covariance. RESULTS: 179 patients with dysphoric mania were included in the post hoc analysis (ziprasidone, n=124; placebo, n=55). Beginning at day 4, HAM-D scores were significantly lower at all visits in patients treated with ziprasidone compared with those treated with placebo (p<0.05). Ziprasidone-treated patients also demonstrated significant improvements on the Mania Rating Scale and all secondary efficacy measures, and had significantly higher response and remission rates compared with placebo. LIMITATIONS: The main limitations are the use of a post hoc analysis and the pooling of two studies with slightly different designs. CONCLUSION: In this analysis, ziprasidone significantly improved both depressive and manic mood symptoms in patients with dysphoric mania, suggesting that it might be a useful treatment option in this patient population. Further prospective controlled trials are needed to confirm these findings.

Differences between adolescents and young adults at presentation to an eating disorders program.

OBJECTIVE: To describe differences between adolescents and adults in clinical presentation of eating disorders. METHODS: Data from the charts of 622 female patients treated for an eating disorder in a division of adolescent medicine between 1980 and 1994 were coded and computerized. General categories included demographic and family factors, weight loss and weight changes, eating-related behaviors, diagnosis and severity, and treatment issues. Differences between the 438 patients who were aged 9-19 years (adolescents) and 184 patients who were aged 20-46 years (adults) were analyzed. RESULTS: Adolescents were more likely than adults (p <.05) to have a diagnosis of "eating disorder not otherwise specified," lower global severity score, greater denial and less desire for help, weight loss > or = 3 lb/month, lower original and maximum weights, and history of fasting and elimination of junk food from their diets. Adults were more likely than adolescents (p <.05) to have >1 year of weight loss, greater total weight loss, history of binge eating and laxative use, history of diuretic and ipecac use, diagnosis of bulimia nervosa, and prior use of psychiatric medications. Adolescents and adults did not differ (p >.05) in parents' occupational level; height, weight, and percent ideal body weight at presentation; original percent ideal body weight; use of diet pills, elimination of meat and use of a low-fat diet; daily calorie intake; prior eating disorder hospitalizations; and hospitalization during the course of treatment. CONCLUSIONS: The findings in this study document and confirm that there are important differences between adolescents and adults that must be taken into account in the evaluation and treatment of patients with eating disorders.

Psychiatric disorders in adolescents exposed to domestic violence and physical abuse.

The relationship between abuse and psychiatric diagnoses was investigated in two groups of physically abused adolescents, 57 living in homes with interparental violence and 32 in homes without such violence, and in 96 nonabused adolescents living in nonviolent homes. Adolescents in the first group were found to be at greater risk for depression, separation anxiety disorder, post-traumatic stress disorder, and oppositional defiant disorder than were those in the second group. Adolescents in the first group also appeared more vulnerable to anxiety and depression.

An examination of bias in volunteer subject selection: findings from an in-depth child abuse study.

Remarkably few reported studies tested the assumption that a research sample can be constructed which is representative of the population of interest. In order to investigate potential volunteer bias in abuse research, we utilized a database assembled for an NIMH funded study investigating the relationship among adolescent physical abuse, suicidal behavior, and psychopathology. Extensive information was available concerning the nonparticipant pool from which this sample was assembled, allowing for a comprehensive assessment of possible sample bias. The volunteer sample of 99 abused families who agreed to participate in our study was compared on a large number of variables with a random sample of 99 abused families who declined to participate. Comparisons of the two groups did not support the hypothesis that the non-participating families represented a more dysfunctional population. The two groups were far more similar to, than disparate from, each other.

A preliminary study of a cartoon measure for children's reactions to chronic trauma.

Preliminary psychometric properties of a new instrument, Angie/Andy Cartoon Trauma Scales (ACTS), are presented. Angie/Andy features a cartoon-based methodology, measuring trauma-related sequelae of prolonged, repeated abuse. A sample of 208 children comprised intrafamilial trauma, extrafamilial trauma, combined trauma, and nontrauma groups. Angie/Andy demonstrated high internal consistency, with coefficient alphas from 0.70 to 0.95. The three trauma groups scored significantly higher than the nontrauma group on all scales (p's < 0.0001). Generally, the most severely traumatized group scored significantly higher than the less severely traumatized groups. The number of types of violence exposures correlated with Angie/Andy scores from 0.55 to 0.74. The frequency and severity of trauma exposure correlated with Angie/Andy scores from 0.44 to 0.56. The Angie/Andy parent version correlated with a standardized parent scale from 0.71 to 0.81. Parent/child agreement was significant. Angie/Andy is a promising tool for clinical assessment of chronic childhood abuse.

Perception of family functioning and depressive symptomatology in individuals with anorexia nervosa or bulimia nervosa.

This study investigated the relationship between the perception of family functioning and depressive symptomatology in individuals with eating disorders (EDs). Subjects were evaluated by diagnostic clinical interview using DSM-III-R criteria for EDs, the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L), and two self-report measures, the Beck Depression Inventory (BDI) and the Family Assessment Device (FAD). A significant association was found between self-reported depressive symptomatology and perceived poor family functioning. Subjects with bulimia nervosa (BN) reported a significantly more dysfunctional family background than subjects with anorexia nervosa (AN). In our sample, the presence of self-reported depressive symptomatology was a more powerful predictive variable for perceived family dysfunction than the diagnosis of affective disorder. Also, the diagnosis of BN was a more consistent predictor of dysfunctional family interaction than the diagnosis of affective disorder. Depressive symptoms and EDs seem to play different roles in the way in which they contribute to dysfunctional family patterns.

Mannose ligand receptor assay as a test to predict fertilization in vitro: a prospective study.

OBJECTIVE: To assess whether mannose receptor assays can predict fertilization outcome in vitro. DESIGN: A prospective, double-blind study of the mannose receptor properties of spermatozoa. SETTING: Assisted human reproduction program at a university hospital. PATIENT(S): Partners of 140 consecutive women undergoing their first in vitro fertilization cycle. INTERVENTION(S): Motile sperm populations were tested for surface receptors for mannose by measuring their ability to bind fluorescein-labeled mannosylated albumin and to undergo a free mannose-induced acrosome reaction as judged by Pisum, sativum agglutinin binding. MAIN OUTCOME MEASURE(S): Mannose receptor assay results were correlated with fertilization outcomes using several statistical tests, including the chi2 test, chi2 for proportions, t-tests, analysis of variance with Student-Newman-Keuls tests and correlational and receiver operating characteristic (ROC) curve analysis. RESULT(S): The fractional increment increase on incubation in the percent of sperm binding mannose ligand over an intact acrosome correlated with fertilization rates in vitro. Threshold values of mannose ligand binding and of mannose-induced acrosome reactions predictive of fertilization rates were identified by ROC curve analysis. Men were thus classified into one of four groups with differing fertilization rates in vitro. CONCLUSION(S): The increment increase in sperm surface mannose ligand binding by acrosome-intact sperm correctly predicts high and low fertilization rates in vitro and identifies cases where conventional insemination can result in failed fertilization.

Course and outcome of chronic fatigue in children and adolescents.

PURPOSE: To describe the epidemiology, symptoms, and psychosocial characteristics of children and adolescents evaluated in a chronic fatigue program and determine the course and outcome of the syndrome in these patients. METHODS: During the summer of 1994, chart review was performed for the 58 patients evaluated between 1990 and 1994 and a telephone follow-up was conducted with 42 of the 58 families. Patients were predominantly female (71%) and white (94%), with 50% between the ages of 7 and 14 years and 50% between the ages of 15 and 21 years (mean age 14.6 years). RESULTS: At time of presentation, 50% of patients had been fatigued for 1 to 6 months and 50% had been fatigued for 7 to 36 months. Sixty percent indicated the fatigue had begun with an acute illness and 60% had a history of allergies. Most commonly reported symptoms were fatigue (100%), headache (74%), sore throat (59%), abdominal pain (48%), fever (36%), and difficulties with concentration and/or memory (33%). Most patients had a worsening of school performance and a decrease in social activities. On follow-up, there was significant improvement in many patients during the summer after the first visit, with continued improvement in most patients during the second and third years. At time of the follow-up telephone call, 43% of families considered their child "cured" and 52% considered their child "improved," whereas only 5% considered their child to be "the same." Statistical analyses demonstrated no demographic or clinical factors that distinguished between those who did or did not participate in the follow-up study, or between those who did or did not do well on follow-up. CONCLUSIONS: These data demonstrate that children and adolescents with chronic fatigue have a syndrome that is similar to that described in adults, but that the syndrome differs in several ways, most specifically, presentation earlier in the course of the illness and a more optimistic outcome.

Adolescent physical abuse: risk for adolescent psychiatric disorders.

OBJECTIVE: The present study examined whether physical abuse functions as an additional risk factor for adolescent psychopathology after other important known risk factors are controlled for. METHOD: The authors recruited 99 adolescents aged 12 to 18 years directly from the New York State Department of Social Services after official documentation of physical abuse. The abused adolescents were compared to 99 nonabused adolescents matched for age, gender, race, and community income. Diagnostic interviews and measures of selected risk factors for psychopathology were administered to the adolescents and their parents and then entered into a multiple logistic regression model testing the added risk contributed by physical abuse to adolescent psychopathology. RESULTS: Physical abuse added significantly to other risk factors in accounting for lifetime diagnoses of major depression, dysthymia, conduct disorder, drug abuse, and cigarette smoking. Physical abuse also contributed significantly to prediction of current adolescent unipolar depressive disorders, disruptive disorders, and cigarette smoking. CONCLUSIONS: Since physically abused adolescents are at greater risk for the development of psychiatric disorders, recognition of adolescent abuse and the provision of psychiatric and substance abuse services may reduce morbidity.

PIP: The association between physical abuse of adolescents and adolescent psychopathology was investigated in a case-control study conducted in Long Island, New York (US). 99 White adolescents 12-18 years of age identified from the New York State Department of Social Services Central Register for Child Abuse in 1989-91 and 99 nonabused adolescents matched for age, gender, race, and community income were enrolled. Diagnostic interviews and measures of selected risk factors for psychopathology were administered to the adolescents and their parents and then entered into a multiple logistic regression model testing the added risk contributed by physical abuse. Physical abuse added significantly to other risk factors in accounting for lifetime diagnoses of major depression, dysthymia, conduct disorder, drug abuse or dependence, and cigarette smoking. Physical abuse also contributed significantly to the prediction of current adolescent unipolar depressive disorders, disruptive disorders, and cigarette smoking. These findings underscore the importance of increased identification of physically abused adolescents so that mental health and substance abuse services can be provided.

Human sperm non-nuclear progesterone receptor expression is a novel marker for fertilization outcome.

In a prospective, blind study, we have examined the relationship among the expression of human sperm surface progesterone receptors, the ability to undergo a mannose-stimulated acrosome reaction and the rate of fertilization in vitro. Individual aliquots of motile spermatozoa were surface-labelled with progesterone and/or mannose-fluoresceinated ligands. Spontaneous acrosome loss and the increase in acrosome reactions following exposure of spermatozoa to mannose ligands were assessed using rhodaminated Pisum sativum agglutinin. Progesterone fluoresceinated ligand binding was observed to occur in two patterns: (i) a uniform distribution of labelling over the acrosome cap (pattern II), and (ii) labelling limited to the equatorial and postacrosomal regions of the human sperm head (pattern III). A conversion of pattern II to pattern III binding was observed and was associated with the acrosome reaction. Pattern III binding was highly correlated with both fertilization potential and the ability to undergo a mannose-stimulated acrosome reaction (P < 0.001). In contrast, normal sperm mannose receptor expression was seen in five men whose abnormal progesterone receptor expression/function and inability to acrosome react after mannose treatment were correlated with their reduced fertility in vitro. In conclusion, surface progesterone receptor aggregation enhances the mannose ligand-stimulated acrosome reaction. Such detection of defective sperm surface progesterone receptor expression/function may be useful in the evaluation and management of male infertility.

Future orientation and life expectations of adolescents and young adults with thalassemia major.

Until recently, Thalassemia Major was considered a fatal disease and patients did not usually live into adulthood. Advances in the medical management of the disease have greatly increased the life expectancy of these patients. The present study aims to evaluate the future orientation and other aspects of psychosocial functioning of thalassemics compared to healthy controls. Thirty patients and 33 healthy subjects of similar age, ethnicity, education, and geographic area were compared on measures of future expectations, perceived social support, life orientation, health locus of control and hopelessness. Results show no significant differences between thalassemics and controls on all measures except for higher levels of internal health locus of control among the patient group. Results and implications of perceptions of thalassemics' future orientation relevant to patient care are discussed.

Induction of the human sperm acrosome reaction with mannose-containing neoglycoprotein ligands.

In the interest of classifying cases of male factor infertility, we have paid particular attention to the sugar ligand binding properties of the human sperm surface and the functional capacity of the acrosome for exocytosis--key parameters for assessing sperm fertilizing ability. Zona recognition and binding involve the interactions of sperm surface mannose receptors (lectins) with mannose ligands on the zona pellucida. Sperm surface mannose lectins can be visualized by their ability to bind a synthetic model zona ligand, fluorescein isothiocyanate (FITC)-conjugated mannosylated bovine serum albumin (BSA) (Man-FITC-BSA). We now report that Man-FITC-BSA biologically also mimics the effects of solubilized authentic human zonae, in that binding of Man-FITC-BSA results in a time-dependent receptor aggregation and the induction of acrosome exocytosis in capacitated sperm populations from fertile donors. In our assay, the addition of mM amounts of mannose monosaccharide to Man-FITC-BSA increases the number of polyvalent mannose ligands bound by individual spermatozoa and increases the rate of the acrosome reactions induced by Man-FITC-BSA, thereby increasing specimen processing efficiency. We conclude that exposure of human spermatozoa to polyvalent mannose ligands + D-mannose monosaccharide offers a new, convenient and readily available system to study sperm capacity for induced acrosome loss.

Use of mannose ligands in IVF screens to mimic zona pellucida-induced acrosome reactions and predict fertilization success.

A predictive test for determining whether motile populations of human spermatozoa will fertilize eggs in vitro has been an elusive goal of clinical research. We have developed an assay for the ability of motile human spermatozoa to bind fluorescein isothiocyanate-labelled mannosylated bovine serum albumin (Man-FITC-BSA) as a test for the presence of sperm surface receptors (lectins) for mannose ligands. Mannosylated ligands are present on the human zona pellucida and are involved in the species-specific binding of human spermatozoa to the zona pellucida. We now demonstrate in prospective blinded analysis that the fractional increase in acrosome loss following a mannose ligand challenge is highly correlated with the rate of fertilization in vitro. Using an incremental increase of acrosome exocytosis of >0.1 as a threshold to predict which specimens will yield normal fertilization, the assay has a sensitivity of 97.8%, a specificity of 83.3%, a positive predictive value of 95.7% and a negative predictive value of 90.7%. These data indicate that testing for a mannose-induced acrosome reaction may be useful in assessment of sperm function prior to in-vitro fertilization in order to assign males to conventional insemination or intracytoplasmic sperm injection protocols.

Complex PTSD in victims exposed to sexual and physical abuse: results from the DSM-IV Field Trial for Posttraumatic Stress Disorder.

Two hundred thirty four participants in the DSM-IV Posttraumatic Stress Disorder (PTSD) Field Trial who reported sexual and/or physical abuse were evaluated. Participants were categorized according to type of abuse (physical, sexual, both), duration of abuse (acute versus chronic), and onset of abuse (early versus late). Separate logistic regression analyses examined the relationship between age of onset, duration, abuse type, and the complex PTSD (CP) lifetime diagnosis for women and men. Sexually abused women, especially those who also experienced physical abuse, had a higher risk of developing CP, although CP symptoms occurred at a high base rate among physically abused women. The theoretical implications and incremental clinical usefulness of targeting CP symptoms with abused populations are discussed.

Are emergency department patients thinking about advance directives?

OBJECTIVES: To assess the percentage of adult patients presenting to an urban ED who have a written advance directive (AD) and to determine whether age, sex, a patient's perception of his or her health status, and having a regular physician are associated with the patient's having an AD. METHODS: This was a cross-sectional patient survey performed at a community teaching hospital ED. Surveys were completed by 511 adult ED patients during representative shifts over a 3-month period. The questions included age, sex, "self-reported" health status, whether the patient had a "regular" physician, a patient-generated list of medical problems, and whether the patient had a written AD. For this study, ADs included health care proxies, living wills, and do-not-attempt-resuscitation (DNAR) orders. RESULTS: Of the patients surveyed, 27% reported having an AD. Males and females were equally likely to have an AD. Factors associated with an increased likelihood of having an AD were older age, having a "regular" physician, and the patient's perception of his or her health status as ill. Most patients who had an AD (82%) discussed it with their families, but only 48% discussed it with their physicians. CONCLUSION: Only 27% of the adult patients presenting to the ED had an AD. Older age, the patient's perception of his or her health status as ill, and having a "regular" physician increased the likelihood of having an AD.

Acrobeads test as a predictor of fertilization in vitro.

PROBLEM: To determine whether the results of the Acrobeads test, which measures the expression of the complement regulator molecule CD46 on the inner acrosomal membrane following the acrosome reaction, accurately identifies semen specimens that will exhibit reduced or failed fertilization following conventional IVF insemination. METHOD: The Acrobeads test was performed on semen specimens from 97 consecutive patients preparing to undergo an IVF cycle utilizing a standardized insemination protocol. Motile sperm populations were examined at 6 h and 24 h post-isolation for sperm-bead agglutination. Results of the Acrobeads test were compared to that of TRITC-PSA staining in matched specimens to directly measure the spontaneous loss of acrosome content. The percentages of TRITC-PSA-negative sperm were determined in freshly isolated motile populations and in duplicate aliquots incubated 18 to 20 h under sperm capacitating conditions. The relationship between the results of both analyses estimating spontaneous acrosome reactions and the rate of fertilization of metaphase II oocytes was examined. RESULTS: The Acrobeads score did not correlate significantly with the rate of fertilization by insemination at 6 h or at 24 h. The negative predictive value of this test was 21.4%. There was no correlation between the Acrobeads score and the percentage of sperm undergoing a spontaneous acrosome reaction as detected by TRITC-PSA labeling. In contrast, the increment increase in the percentage of spontaneous acrosome reactions as quantified by TRITC-PSA staining was correlated with the fertilization rate. CONCLUSIONS: Contrary to previous reports, our prospective, double-blinded study failed to demonstrate that the Acrobeads test can accurately predict fertilization outcome in IVF. Therefore, the routine use of this test to screen patients prior to an IVF cycle in order to select appropriate treatment (i.e., ICSI) cannot be recommended.

Isolation and characterization of the primary structure of testis-specific L-type calcium channel: implications for contraception.

Therapeutic administration of calcium channel-blocking medications has been correlated with reduced mannose receptor expression and iatrogenic human male infertility. In this report, we investigate whether the pharmacological activity of dihydropyridines, which block calcium influx through voltage-dependent calcium channels, contributes to the production of an infertile state. An influx of extracellular calcium is an absolute requirement for the initiation of a progesterone-stimulated acrosome reaction by human spermatozoa. To determine whether dihydropyridines could inhibit progesterone-induced acrosome loss, we have studied a protein expressed in rat and human spermatozoa which is related both antigenically and by cDNA sequence to the alpha 1 subunit of the rat cardiac muscle voltage-dependent calcium channel, which forms the pore of the channel. Using reverse transcription-polymerase chain reaction, we have isolated a 2169 base clone from rat testis mRNA whose sequence was largely identical to that of the alpha 1 subunit of the rat cardiac muscle calcium channel, but had an 84 base change, attributable to splicing and alternate exon usage. This change inserts a peptide cassette encoding an amphipathic membrane-spanning helix that constitutes part of the ionic pore of the skeletal muscle calcium channel regulating the kinetics of activation of the calcium channel and may serve as an intramembrane dihydropyridine binding site. In parallel, human spermatozoa from fertile donors were exposed to nifedipine in vitro. Nifedipine inhibited progesterone-stimulated calcium influx and subsequent acrosome reactions in human spermatozoa at concentrations effective in excitable cells, but required a prolonged time to do so. In contrast, progesterone ligand binding was unaffected by nifedipine treatment. These data demonstrate that human spermatozoa express an L-type calcium channel which is responsive to nifedipine. Assuming sperm calcium transport pathways are highly conserved, the slow kinetics by which the blockade of the human sperm channel was obtained can be correlated with alterations in channel activation and conductance associated with isoform diversity generated by alternate splicing as observed in the rat. These data provide unequivocal evidence for the presence of functional L-type voltage-dependent calcium channels in rat and human spermatozoa. The data also define an altered binding site for calcium entry antagonists in this channel and offer a unique target for the design of new male contraceptive agents.

Follow-up of children with respiratory syncytial virus bronchiolitis in 1986 and 1987: potential effect of ribavirin on long term pulmonary function. The Bronchiolitis Study Group.

BACKGROUND: Hospitalization for respiratory syncytial virus (RSV) bronchiolitis is considered a risk factor for reactive airway disease and/or abnormal pulmonary function tests (PFTs) later in childhood. This study attempted to assess this observation with newer PFTs and to determine whether ribavirin therapy of initial RSV infection may affect the long term outcome. METHODS: Medical records of all infants hospitalized with RSV infection in 1986 and 1987 at six institutions (North Shore University Hospital, Children's Hospital of Buffalo, University Florida-Gainesville, University of Connecticut, Children's Hospital National Medical Center, Denver Children's Hospital) were requested. Patients who could be contacted were recalled in 1993 and 1994 for PFTs and given a pulmonary status questionnaire. RESULTS: One hundred patients were evaluated. Overall PFTs were within normal ranges. There was less "bronchitis" over the interval years in the ribavirin-treated patients (13 of 33) vs. those who did not receive ribavirin (44 of 67, P < 0.01). There was no difference for the diagnosis of reactive airway disease (15 of 33 ribavirin vs. 36 of 67 no ribavirin). Patients who received ribavirin were then matched by age (within 2 weeks) at initial RSV infection and underlying risk factor (bronchopulmonary dysplasia, heart disease). Of the 27 patients matched, the ribavirin patients had longer intensive care unit stays (median (25 to 75% interquartile range): 2 (0 to 7) vs. 0 (0 to 0), P < 0.05). On follow-up evaluation there were no significant differences in PFTs or reactive airway disease between the 2 groups. There was a trend toward lower forced expiratory volume at 1 s and midexpiratory flow rate (25 to 75%) in the ribavirin-treated group, and there were more reported pneumonias on follow-up in the ribavirin patients. CONCLUSION: During our 5- to 6- year follow-up of children, status post bronchiolitis, we noted a good long term prognosis. No long term adverse effects on pulmonary function were detected. Despite being potentially sicker at presentation as assessed by intensive care unit stay, ribavirin recipients were doing equally well at the time of follow-up.

A potential role for cadmium in the etiology of varicocele-associated infertility.

OBJECTIVE: To determine whether mannose ligand receptor and acrosome reaction deficits in sperm from men with varicocele are related to the transition metal content of their semen. DESIGN: Cadmium and zinc in semen and blood plasma were assayed for fertile males, men without varicocele who required intracytoplasmic sperm injection to achieve fertilization, and men evaluated for potential varicocele-associated infertility. The relationship between actin cytoskeletal distributions and acrosome status was determined for fertile donor sperm in the presence and absence of exogenous cadmium. SETTING: University hospital-based molecular biology research laboratory. PATIENT(S): Patients from two university hospital-based IVF-assisted reproductive technology programs and two male urology private practices. INTERVENTION(S): Fertile donor sperm were exposed to exogenous cadmium during capacitating incubations followed by culture at temperatures up to 41 degrees C. MAIN OUTCOME MEASURE(S): Metal ion levels in semen and blood plasma were determined by graphite furnace atomic absorption spectroscopy. Motile sperm were examined for mannose ligand binding and the ability to undergo spontaneous and induced acrosome reactions. Unfixed, Triton-permeabilized sperm were probed with antiactin and antimyosin antibodies. RESULT(S): Cadmium was elevated and zinc was decreased in the seminal plasma of men with varicocele. The content of these metals in semen and blood was not correlated. Cadmium exposure in vitro reduced mannose receptor expression, acrosome exocytosis, and cytoskeletal formation by fertile donor sperm. CONCLUSION(S): Defects in transition metal regulation or excessive cadmium exposure are involved in varicocele-associated infertility.

Jugular venous blood flow velocity waveforms in human fetuses between 20 and 42 weeks of pregnancy.

BACKGROUND: The goal of the study was to measure the blood flow parameters of the fetal internal jugular vein during the second half of normal pregnancy using Doppler ultrasound. METHODS: Jugular blood flow was analyzed in 95 normal singleton fetuses between 20 and 42 weeks gestation. Color and pulsed Doppler ultrasound was used to obtain jugular venous waveforms at the level of the mid-neck. Peak velocities, ratios of velocities, and time-averaged maximum velocities were measured. RESULTS: Jugular venous waveforms in healthy fetuses consist of three phases--the first forward peak occurs during ventricle systole; the second forward peak occurs during early diastole and the third peak occurs during atrial contraction. Forty-eight percent of the fetuses demonstrated absent flow during atrial contraction; 32% of fetuses demonstrated forward flow during atrial contraction and finally 20% of fetuses demonstrated flow reversal during atrial contraction. CONCLUSIONS: The reported jugular venous profile may serve as a foundation for future studies of jugular blood flow in high risk fetuses.