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PubMedDate not supplied

Chromatin decondensation of human sperm in vitro and its relation to fertilization rate after ICSI.

The inability of sperm chromatin to decondense has been implicated in the failure of fertilization, This study was undertaken to identify the relationship between sperm chromatin decondensation in vitro after incubation with follicular fluid at various points in time and fertilization or pregnancy rates after intracytoplasmic sperm injection. Moreover, an attempt was made to determine whether this test could be used as a predictive test for the outcome of ICSI. Thirty-two infertile couples undergoing ICSI therapy were included in this prospective study. One milliter of semen from each sample was mixed with 1 mL of follicular fluid obtained from ICSI patients at the time of oocyte retrieval and incubated for 24 h. Many smears were made directly after semen liquefaction at the following time intervals: 30, 60, and 120 min and 24 h. Chromatin decondensation was evaluated with acridine orange staining. The mean percentage of uncondensed chromatin of spermatozoa in the native semen samples was 25 +/- 18.3%, which increased within 24 h to 91 +/- 9.5%. On the other hand, the fertilization and ongoing pregnancy rates were 64 +/- 21.7% and 20%, respectively. However, no correlations were found between chromatin decondensation at various point of time (30, 60, and 120 min and 24 h) and fertilization rate. No correlation was shown between the chromatin decondensation and sperm counts in the ejaculate. morphology, or the percentage of condensed chromatin. In light of this study, chromatin decondensation in vitro cannot be recommended for predicting the fertilization potential of spermatozoa and pregnancy rates in the ICSI program. Further research is necessary, especially in cases where ICSI is being considered as a therapeutic option.

Adult↗
PubMed2000

The Preterm Prediction Study: sequential cervical length and fetal fibronectin testing for the prediction of spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVES: This study was undertaken to further elucidate the pathogenesis of preterm birth by means of traditional risk factors and new markers for preterm birth derived from the Preterm Prediction Study. STUDY DESIGN: A total of 3076 women (2929 with singleton gestations and 147 with twin pregnancies) were categorized according to the presence of risk factors including black race, low body mass index, the presence of bacterial vaginosis, and previous preterm birth. At 24 and 28 weeks' gestation cervical length was measured and categorized as short (</=25 mm) or normal (>25 mm). Vaginal and cervical fetal fibronectin concentrations were measured at 24, 26, 28, and 30 weeks' gestation and results were categorized as positive (>/=50 ng/mL) or negative (<50 ng/mL). RESULTS: At 24 to 26 weeks' gestation women with each of the risk factors were more likely to have positive fibronectin test results or to have a short cervix. Among women with negative fetal fibronectin results at 24 to 26 weeks' gestation those with a short cervix were more likely to have positive fetal fibronectin results at 28 to 30 weeks' gestation, and among those with normal cervical length those women who had positive fetal fibronectin results were more likely to have a short cervix at later evaluation. Most women who had positive fetal fibronectin results at 24 to 26 weeks' gestation had negative results at 28 to 30 weeks' gestation, whereas most but not all women who had a short cervix at 24 to 26 weeks' gestation still had a short cervix at 28 to 30 weeks' gestation. In each period women with both a positive fetal fibronectin result and a short cervix were at substantially increased risk of spontaneous preterm birth; women with either marker alone had intermediate and approximately equal risks of spontaneous preterm birth, and women without either marker had a low risk of spontaneous preterm birth. CONCLUSION: Regardless of other risk factors, a short cervix predicts a subsequent positive fetal fibronectin result, and a positive fetal fibronectin result predicts subsequent cervical shortening. These data do not support a single sequence of events leading to spontaneous preterm birth.

Biomarkers↗
PubMed1986

Predictive value of electrophysiologic testing in the treatment of drug-refractory ventricular arrhythmias with amiodarone.

The value of serial electrophysiologic testing in predicting the outcome of patients receiving amiodarone is controversial. Thirty-six patients with drug-refractory sustained ventricular tachyarrhythmias underwent serial electrophysiologic drug testing. All patients had inducible sustained ventricular tachyarrhythmias off any antiarrhythmic medication. After an oral amiodarone loading regimen there was no change in inducibility in 23 patients (group I), whereas ventricular tachycardia was made more difficult to induce in 5 patients, i.e. sustained ventricular tachycardia was only inducible using a basic drive which was 40 bpm faster than during control (group II). In the remaining 8 patients, induction of ventricular tachycardia was suppressed (group III). During follow-up of 11 +/- 12.3 months, 6 patients in group I had a recurrence of ventricular tachycardia and 2 died suddenly, whereas the course of groups II and III patients was uneventful (P less than 0.03, Breslow; P less than 0.01, Mantel-Cox). The predictive accuracy of the response to serial electrophysiologic testing during amiodarone therapy was 64%, the sensitivity was 46% and the specificity 100%. Thus, serial electrophysiologic drug testing is useful in determining prognosis and predicts the long-term response to amiodarone therapy in patients with ventricular tachyarrhythmias using a graded stimulation protocol.

Amiodarone↗
PubMed1999

No support for HLA-DQ encoded susceptibility in rheumatoid arthritis.

OBJECTIVE: To test predictions based on data from immunogenetic and peptide-binding studies of collagen-induced arthritis in mice, in which it has been suggested that susceptibility to rheumatoid arthritis (RA) might be determined by the interaction between susceptibility alleles at the HLA-DQ locus and protective alleles at the HLA-DRB1 locus (including susceptibility effects for HLA-DQ7 and DQ8). METHODS: Predictions based on these models were tested in 166 healthy controls and 167 patients with RA, all of whom were typed for HLA-DRB1 and HLA-DQ alleles. RESULTS: In this population, HLA-DQ7 did not encode an increased risk for RA. This lack of susceptibility effect of HLA-DQ7 could not be attributed to competing HLA-DQ susceptibility alleles, protective HLA-DRB1 alleles, or the absence of DQA1*0301. CONCLUSION: These observations do not support the DR/DQ hypothesis in its present form.

Alleles↗
PubMed1995

Characterization of autoantibodies against the platelet glycoprotein antigens IIb/IIIa in childhood idiopathic thrombocytopenia purpura.

The majority of children with idiopathic thrombocytopenia (ITP) have an acute self-limiting course and no diagnostic test has been identified which will predict the course of thrombocytopenia and detect those with the chronic autoimmune form. The detection of autoantibodies directed against the platelet glycoprotein complex IIB/IIIa, may identify patients with chronic ITP. Serum anti-GP IIb/IIIa antibodies were assessed by the indirect MAIPA assay in 54 children with immune thrompocytopenia at initial presentation along with an additional 7 children previously diagnosed with chronic ITP, to determine if there was a difference in antibody positivity between acute and chronic ITP patients, and whether the identification of antibodies could be used as a predictive test at diagnosis. There was no significant difference in the percentage of antibodies detected in children classified with acute ITP (27/40-68%) compared to children with chronic ITP (13/21-62%, P > 0.05). Patients with acute ITP had significantly lower mean platelet counts at diagnosis compared to the chronic ITP group (16,225/mm3 vs 32,250/mm3, P < 0.05), though there was no significant difference in the bleeding manifestations between the acute and chronic ITP groups. Serum anti-GP IIb/IIIa antibodies are detected in a high percentage of children with ITP and autoantibodies appear to be involved in the pathogenesis of both acute and chronic ITP. The detection of anti-GP IIb/IIIa antibodies at diagnosis, however, does not appear to be a useful prognostic test in childhood ITP.

Adolescent↗
PubMed1995

Prenatal diagnostic testing for familial dysautonomia using linked genetic markers.

Familial dysautonomia (FD), a recessively inherited disease, has been mapped to chromosome 9q31. Highly polymorphic dinucleotide repeat markers flanking the genetic locus and at the same genetic location have been identified. We describe the prenatal diagnosis of FD using linkage and linkage disequilibrium analyses with these markers. Twelve families were analysed for informativeness and of these, seven went on to have prenatal testing (a total of eight fetuses tested). All of these fetuses were predicted to be heterozygous unaffected (FD carriers). Seven fetuses have come to term and are normal. In the absence of a recombinant proband, a panel of three proximal and three distal markers is sufficient to provide informative flanking markers and an 87-96 per cent likelihood of a highly predictive test. In an additional family at 1:4 risk for FD, no DNA was available from the propositus. This family was analysed using linkage disequilibrium to the #18 allele of the tightly linked marker D9S58 in conjunction with linkage analysis using data from two unaffected children. Prenatal diagnosis in this family indicated an affected fetus.

Base Sequence↗
PubMed1995

A consensus prediction of the secondary structure for the 6-phospho-beta-D-galactosidase superfamily.

Two separate unrefined models for the secondary structure of two subfamilies of the 6-phospho-beta-D-galactosidase superfamily were independently constructed by examining patterns of variation and conservation within homologous protein sequences, assigning surface, interior, parsing, and active site residues to positions in the alignment, and identifying periodicities in these. A consensus model for the secondary structure of the entire superfamily was then built. The prediction tests the limits of an unrefined prediction made using this approach in a large protein with substantial functional and sequence divergence within the family. The protein belongs to the (alpha-beta class), with the core beta strands aligned parallel. The supersecondary structural elements that are readily identified in this model is a parallel beta sheet built by strands C, D, and E, with helices 2 and 3 connecting strands (C+D) and (D+E), respectively, and an analogous beta-alpha unit (strand G and helix 7) toward the end of the sequence. The resemblance of the supersecondary model to the tertiary structure formed by 8-fold alpha-beta barrel proteins is almost certainly not coincidental.

Amino Acid Sequence↗
PubMed2000

Diagnosis and management of normal-pressure hydrocephalus.

The syndrome of normal-pressure hydrocephalus (NPH) remains a diagnostic and therapeutic challenge, especially as many patients do not display the classical clinical and neuroimaging patterns of NPH, thus questioning the usefulness of a shunt. Gait impairment remains the cardinal symptom, while mental deterioration may be subtle and even unrecognized. NPH is rarely the cause of severe dementia, and substantial improvement in NPH-related mental deterioration is limited to 30-40% of shunted patients. Many ancillary investigations have been described that can increase the probability of selecting the appropriate candidates for a shunt. The reliability and reproducibility of these tests are limited. Unfortunately, the best predictive tests are technically complex and are used only in a few specialized centers. The best management is still to adhere to strict clinical and magnetic resonance imaging criteria and to rely on a positive - but not negative - CSF tap test and the occurrence of B-waves during at least 50% of the continuous intracranial pressure recording time, when this procedure is available.

Humans↗
PubMed1990

A comparison of serum mucoprotein with serum alpha 1 acid glycoprotein, haptoglobin, and alpha 1 antitrypsin assays in monitoring inflammatory bowel disease.

Serum mucoprotein level is a monitor for inflammatory bowel disease activity although its method of measurement is laborious. An easier assay of alpha 1 acid glycoprotein is described. The ability of the two proteins to differentiate active from non-active cases was evaluated and the results compared with acute inflammatory reactants such as alpha 1 antitrypsin and haptoglobin. Amongst 79 patients with inflammatory bowel disease linear discriminant analysis was used to segregate overlapping ranges for patients with and without active disease and thus enabling the evaluation of sensitivity and specificity of each test. Predictive values of 78.6% for mucoprotein and 76.7% for alpha 1 acid glycoprotein were achieved and were due to the fact that there is a very strong linear correlation between these two proteins (r = 0.83, p less than 0.01). Furthermore the mucoprotein fraction is predominantly comprised of alpha 1 acid glycoprotein by as much as 91.5%. alpha 1 antitrypsin and haptoglobin showed poor predictive values. Pairing up all the proteins each with mucoprotein improved the sensitivity, specificity, and predictive value slightly. As a single test alpha 1 acid glycoprotein gave highest specificity, proved easy to assay and was automatable. It was therefore recommended as a substitute for serum mucoprotein in routine assays and as an effective monitor and predictor of inflammatory bowel disease.

Colitis, Ulcerative↗
PubMed1994

Ethical issues in prenatal testing.

Many ethical concerns raised by prenatal testing are based on the use and effects of genetic information in nonclinical contexts. Correct or incorrect beliefs about social uses of genetic information may limit the voluntariness of informed consent to prenatal testing. A qualitative study of persons predictively tested for Huntington's disease illustrates how the social context, in this case the family history of being at risk, affects the interpretation of the genetic information and alters relationships. This constitutes a risk of genetic testing. Prenatal testing also requires ethical analysis based on careful understanding of how social attitudes and nonclinical uses affect voluntariness and potential harm and benefits of testing. Investigators conducting research on prenatal tests share the responsibility to evaluate social attitudes toward at-risk persons, nonclinical uses of genetic information, and the social benefits and harm of such uses.

Ethics, Medical↗
PubMed2004

Measuring quality of life in multiple sclerosis patients with urinary disorders using the Qualiveen questionnaire.

OBJECTIVES: To assess the impact of urinary disorders on multiple sclerosis (MS) patients' health-related quality of life and to examine the cross-sectional construct validity of Qualiveen, a questionnaire originally developed for spinal cord injury patients with urinary disorders, in patients with MS. DESIGN: Cohort study. SETTING: Neurourodynamic units in 3 French university hospitals. PARTICIPANTS: Patients with MS (N=197). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We tested predictions about the relationships among clinical features, the French version of the Multiple Sclerosis Quality of Life questionnaire (SEP-59), the Expanded Disability Status Scale (EDSS), and the 4 domains of the 30-item Qualiveen. RESULTS: Cross-sectional correlations among the 4 Qualiveen domains and type (range, .36-.54), number of symptoms (range, .23-.50), and severity of incontinence (.39-.68) were generally moderate to strong. The SEP-59 bowel and bladder function domain showed moderate to strong relationships with the Qualiveen (range, .39-.59). Relationships with other SEP-59 domains were generally weak (range, .22-.35), and with the EDSS they were very weak. Predictions proved generally accurate (weighted kappa=.61). CONCLUSIONS: Our data supported the Qualiveen's validity as a discriminative instrument for use with patients with MS. Further studies should explore the Qualiveen's longitudinal validity and responsiveness.

Activities of Daily Living↗
PubMed2005

Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test.

Selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed antidepressant class today and exert their antidepressant-like effects by increasing synaptic concentrations of serotonin (5-HT). The rat forced swim test (FST) is the most widely used animal test predictive of antidepressant action. Procedural modifications recently introduced by our laboratory have enabled SSRI-induced behavioral responses to be measured in the modified FST. The use of this model to understand the pharmacological and physiological mechanisms underlying the role of 5-HT in the behavioral effects of antidepressant drugs is reviewed. Although all antidepressants reduced behavioral immobility, those antidepressants that increase serotonergic neurotransmission predominantly increase swimming behavior whereas those that increase catacholaminergic neurotransmission increase climbing behavior. The 5-HT(1A), 5-HT(1B/1D) and 5-HT(2C) receptors are the 5-HT receptors most important to the therapeutic effects of SSRIs, based on extensive evaluation of agonists and antagonists of individual 5-HT receptor subtypes. Studies involving chronic administration have shown that the effects of antidepressants are augmented following chronic treatment. Other studies have demonstrated strain differences in the response to serotonergic compounds. Finally, a physiological model of performance in the rat FST has been proposed involving the regulation of 5-HT transmission by corticotropin releasing factor (CRF).

Animals↗
PubMed1995

Approximating the isometric force-calcium relation of intact frog muscle using skinned fibers.

In previous papers we used estimates of the composition of frog muscle and calculations involving the likely fixed charge density in myofibrils to propose bathing solutions for skinned fibers, which best mimic the normal intracellular milieu of intact muscle fibers. We tested predictions of this calculation using measurements of the potential across the boundary of skinned frog muscle fibers bathed in this solution. The average potential was -3.1 mV, close to that predicted from a simple Donnan equilibrium. The contribution of ATP hydrolysis to a diffusion potential was probably small because addition of 1 mM vanadate to the solution decreased the fiber actomyosin ATPase rate (measured by high-performance liquid chromatography) by at least 73% but had little effect on the measured potential. Using these solutions, we obtained force-pCa curves from mechanically skinned fibers at three different temperatures, allowing the solution pH to change with temperature in the same fashion as the intracellular pH of intact fibers varies with temperature. The bath concentration of Ca2+ required for half-maximal activation of isometric force was 1.45 microM (22 degrees C, pH 7.18), 2.58 microM (16 degrees C, pH 7.25), and 3.36 microM (5 degrees C, pH 7.59). The [Ca2+] at the threshold of activation at 16 degrees C was approximately 1 microM, in good agreement with estimates of threshold [Ca2+] in intact frog muscle fibers.

Adenosine Triphosphatases↗
PubMedDate not supplied

Cognitive correlates of anxious and depressive symptomatology: an examination of the Helplessness/Hopelessness model.

Expectancies about future life events were assessed in anxious and depressed patients to test predictions of the Helplessness/Hopelessness model of anxiety and depression (Alloy, Kelly, Mineka, & Clements, 1990). In addition to expectancies for future events, patients from affective and anxiety treatment clinics completed anxiety and depression symptom ratings and positive and negative affects scales. Findings revealed partial support for the model. Negative outcome and helplessness expectancies were related specifically to depression. Cognitions regarding future positive events were interrelated and associated with symptom measures more strongly than were cognitions regarding negative events. Additionally, positive affects was more strongly related to depression than to anxiety symptom ratings. Implications and limitations of these findings are discussed.

Adult↗
PubMed2004

Cognitive processes in stereotype formation: the role of correct contingency learning for biased group judgments.

Three studies investigated contingency learning and stereotype formation in a scenario about group membership and behavior with a confounding context factor. The studies tested predictions from theoretical accounts of biased group judgments in terms of simplistic reasoning, parallel distributed memory, and pseudocontingencies. Study 1 revealed a positive correlation between erroneous stereotype formation and learning of the true contingencies with the confounding factor. Study 2 showed that a focus manipulation during encoding moderated the correlation between stereotype formation and contingency learning but not the strength of the erroneous stereotype. Study 3 used a quasiexperimental comparison between participants with biased versus unbiased group judgments and extended the findings of a positive relation between stereotype formation and contingency learning. The results support an explanation of biased group judgments by pseudocontingencies; that is, unwarranted inferences from accurately perceived bivariate correlations in complex environments.

Adult↗
PubMed2005

Competition between antecedent and between subsequent stimuli in causal judgments.

In the analysis of stimulus competition in causal judgment, 4 variables have been frequently confounded with respect to the conditions necessary for stimuli to compete: causal status of the competing stimuli (causes vs. effects), temporal order of the competing stimuli (antecedent vs. subsequent) relative to the noncompeting stimulus, directionality of training (predictive vs. diagnostic), and directionality of testing (predictive vs. diagnostic). In a factorial study using an overshadowing preparation, the authors isolated the role of each of these variables and their interactions. The results indicate that competition may be obtained in all conditions. Although some of the results are compatible with various theories of learning, the observation of stimulus competition in all conditions calls for a less restrictive reformulation of current learning theories that allows similar processing of antecedent and subsequent events, as well as of causes and effects.

Choice Behavior↗
PubMed1997

Development and validation of a geriatrics knowledge test for primary care residents.

This study reports the development and preliminary validation of an instrument to measure geriatrics knowledge of primary care residents. A 23-item test was developed using questions selected from the American Geriatrics Society's Geriatrics Review Syllabus. Ninety-six internal medicine and family practice residents, 14 geriatrics fellows, and 11 geriatrics faculty members participated in the study. Findings support the reliability (Cronbach's alpha = 0.66) and validity (content and "known groups") of this short test. Predictive validity and sensitivity of the test to changes in knowledge will have to be further explored as residents progress through their training.

Adult↗
PubMedDate not supplied

Effect of off-pump coronary artery bypass grafting on risk-adjusted and cumulative sum failure outcomes after coronary artery surgery.

BACKGROUND AND AIM: We have shown that cumulative sum (CUSUM) failure analysis may be more sensitive than standard statistical methods in detecting a cluster of adverse patient outcomes after cardiac surgical procedures. We therefore applied CUSUM, as well as standard statistical techniques, to analyze a surgeon's experience with off-pump coronary artery bypass grafting (OPCAB) and on-pump procedures to determine whether the two techniques have similar or different outcomes. METHODS: In 320 patients undergoing nonemergent, first time coronary artery bypass grafting, preoperative patient characteristics, rates of mortality and major complications, and ICU and hospital lengths of stay were compared between the on-pump and OPCAB cohorts using Fisher's exact tests and Wilcoxon two sample tests. Predicted mortality and length of stay were determined using previously validated models of the Cardiac Care Network of Ontario. Observed versus expected ratios of both variables were calculated for the two types of procedures. Furthermore, CUSUM curves were constructed for the on-pump and OPCAB cohorts. A multivariable analysis of the predictors of hospital length of stay was also performed to determine whether the type of coronary artery bypass procedure had an independent impact on this variable. RESULTS: The predicted mortality risk and predicted hospital length of stay were almost identical in the 208 on-pump patients (2.2 +/- 3.9%; 8.2 +/- 2.5 days) and the 112 OPCAB patients (2.0 +/- 2.2%; 7.8 +/- 2.1 days). The incidence of hospital mortality and postoperative stroke were 2.9% and 2.4% in on-pump patients versus zero in OPCAB patients (p = 0.09 and 0.17, respectively). Mechanical ventilation for greater than 48 hours was significantly less common in OPCAB (1.8%) than in on-pump patients (7.7%, p = 0.04). The rate of 10 major complications was 14.9% in on-pump versus 8.0% in OPCAB patients (p = 0.08). OPCAB patients experienced a hospital length of stay that was a median of 1.0 day shorter than on-pump patients (p = 0.01). The observed versus expected ratio for length of stay was 0.78 in OPCAB patients versus 0.95 in on-pump patients. On CUSUM analysis, the failure curve in OPCAB patients was negative and was flatter than that of on-pump patients throughout the duration of the study. Furthermore, OPCAB was an independent predictor of a reduced hospital length of stay on multivariable analysis. CONCLUSIONS: OPCAB was associated with better outcomes than on-pump coronary artery bypass despite a similar predicted risk. This robust finding was documented on sensitive CUSUM analysis, using standard statistical techniques and on a multivariable analysis of the independent predictors of hospital length of stay.

Aged↗