Self-reported psychosis-like experiences in patients with mood disorders.

BACKGROUND: Self-reported psychosis-like experiences (PEs) may be common in patients with mood disorders, but their clinical correlates are not well known. We investigated their prevalence and relationships with self-reported symptoms of depression, mania, anxiety, borderline (BPD) and schizotypal (SPD) personality disorders among psychiatric patients with mood disorders. METHODS: The Community Assessment of Psychic Experiences (CAPE-42), Mood Disorder Questionnaire (MDQ), McLean Screening Instrument (MSI), The Beck Depressive Inventory (BDI), Overall Anxiety Severity and Impairment Scale (OASIS) and Schizotypal Personality Questionnaire-Brief form (SPQ-B) were filled in by patients with mood disorders (n=282) from specialized care. Correlation coefficients between total scores and individual items of CAPE-42 and BDI, SPQ-B, MSI and MDQ were estimated. Hierarchical multivariate regression analysis was conducted to examine factors influencing the frequency of self-reported PE. RESULTS: PEs are common in patients with mood disorders. The "frequency of positive symptoms" score of CAPE-42 correlated strongly with total score of SPQ-B (rho=0.63; P<0.001) and moderately with total scores of BDI, MDQ, OASIS and MSI (rho varied from 0.37 to 0.56; P<0.001). Individual items of CAPE-42 correlated moderately with specific items of BDI, MDQ, SPQ-B and MSI (rφ varied from 0.2 to 0.5; P<0.001). Symptoms of anxiety, mania or hypomania and BPD were significant predictors of the "frequency of positive symptoms" score of CAPE-42. CONCLUSIONS: Several, state- and trait-related factors may underlie self-reported PEs among mood disorder patients. These include cognitive-perceptual distortions of SPD; distrustfulness, identity disturbance, dissociative and affective symptoms of BPD; and cognitive biases related to depressive or manic symptoms.

Mediating role of borderline personality disorder traits in the effects of childhood maltreatment on suicidal behaviour among mood disorder patients.

BACKGROUND: Substantial evidence supports an association between childhood maltreatment and suicidal behaviour. However, few studies have examined factors mediating this relationship among patients with unipolar or bipolar mood disorders. METHODS: Depressive disorder and bipolar disorder (ICD-10-DCR) patients (n=287) from the Helsinki University Psychiatric Consortium (HUPC) Study were surveyed on self-reported childhood experiences, current depressive symptoms, borderline personality disorder traits, and lifetime suicidal behaviour. Psychiatric records served to complement the information on suicide attempts. We examined by formal mediation analyses whether (1) the effect of childhood maltreatment on suicidal behaviour is mediated through borderline personality disorder traits and (2) the mediation effect differs between lifetime suicidal ideation and lifetime suicide attempts. RESULTS: The impact of childhood maltreatment in multivariate models on either lifetime suicidal ideation or lifetime suicide attempts showed comparable total effects. In formal mediation analyses, borderline personality disorder traits mediated all of the total effect of childhood maltreatment on lifetime suicide attempts, but only one fifth of the total effect on lifetime suicidal ideation. The mediation effect was stronger for lifetime suicide attempts than for lifetime suicidal ideation (P=0.002) and independent of current depressive symptoms. CONCLUSIONS: The mechanisms of the effect of childhood maltreatment on suicidal ideation versus suicide attempts may diverge among psychiatric patients with mood disorders. Borderline personality disorder traits may contribute to these mechanisms, although the influence appears considerably stronger for suicide attempts than for suicidal ideation.

Level of functioning, perceived work ability, and work status among psychiatric patients with major mental disorders.

BACKGROUND: Major mental disorders are highly disabling conditions that result in substantial socioeconomic burden. Subjective and objective measures of functioning or ability to work, their concordance, or risk factors for them may differ between disorders. METHODS: Self-reported level of functioning, perceived work ability, and current work status were evaluated among psychiatric care patients with schizophrenia or schizoaffective disorder (SSA, n=113), bipolar disorder (BD, n=99), or depressive disorder (DD, n=188) within the Helsinki University Psychiatric Consortium Study. Correlates of functional impairment, subjective work disability, and occupational status were investigated using regression analysis. RESULTS: DD patients reported the highest and SSA patients the lowest perceived functional impairment. Depressive symptoms in all diagnostic groups and anxiety in SSA and BD groups were significantly associated with disability. Only 5.3% of SSA patients versus 29.3% or 33.0% of BD or DD patients, respectively, were currently working. About half of all patients reported subjective work disability. Objective work status and perceived disability correlated strongly among BD and DD patients, but not among SSA patients. Work status was associated with number of hospitalizations, and perceived work disability with current depressive symptoms. CONCLUSIONS: Psychiatric care patients commonly end up outside the labour force. However, while among patients with mood disorders objective and subjective indicators of ability to work are largely concordant, among those with schizophrenia or schizoaffective disorder they are commonly contradictory. Among all groups, perceived functional impairment and work disability are coloured by current depressive symptoms, but objective work status reflects illness course, particularly preceding psychiatric hospitalizations.

Anxiety symptoms in a major mood and schizophrenia spectrum disorders.

BACKGROUND: Comorbid anxiety symptoms and disorders are present in many psychiatric disorders, but methodological variations render comparisons of their frequency and intensity difficult. Furthermore, whether risk factors for comorbid anxiety symptoms are similar in patients with mood disorders and schizophrenia spectrum disorders remains unclear. METHODS: The Overall Anxiety Severity and Impairment Scale (OASIS) was used to measure anxiety symptoms in psychiatric care patients with schizophrenia or schizoaffective disorder (SSA, n=113), bipolar disorder (BD, n=99), or depressive disorder (DD, n=188) in the Helsinki University Psychiatric Consortium Study. Bivariate correlations and multivariate linear regression models were used to examine associations of depressive symptoms, neuroticism, early psychological trauma and distress, self-efficacy, symptoms of borderline personality disorder, and attachment style with anxiety symptoms in the three diagnostic groups. RESULTS: Frequent or constant anxiety was reported by 40.2% of SSA, 51.5% of BD, and 55.6% of DD patients; it was described as severe or extreme by 43.8%, 41.4%, and 41.2% of these patients, respectively. SSA patients were significantly less anxious (P=0.010) and less often avoided anxiety-provoking situations (P=0.009) than the other patients. In regression analyses, OASIS was associated with high neuroticism, symptoms of depression and borderline personality disorder and low self-efficacy in all patients, and with early trauma in patients with mood disorders. CONCLUSIONS: Comorbid anxiety symptoms are ubiquitous among psychiatric patients with mood or schizophrenia spectrum disorders, and in almost half of them, reportedly severe. Anxiety symptoms appear to be strongly related to both concurrent depressive symptoms and personality characteristics, regardless of principal diagnosis.

Self-reported symptoms of schizotypal and borderline personality disorder in patients with mood disorders.

BACKGROUND: Distinguishing between symptoms of schizotypal (SPD) and borderline personality disorders (BPD) is often difficult due to their partial overlap and frequent co-occurrence. We investigated correlations in self-reported symptoms of SPD and BPD in questionnaires at the levels of both total scores and individual items, examining overlapping dimensions. METHODS: Two questionnaires, the McLean Screening Instrument (MSI) for BPD and the Schizotypal Personality Questionnaire Brief (SPQ-B) for SPD, were filled in by patients with mood disorders (n=282) from specialized psychiatric care in a study of the Helsinki University Psychiatric Consortium. Correlation coefficients between total scores and individual items of the MSI and SPQ-B were estimated. Multivariate regression analysis (MRA) was conducted to examine the relationships between SPQ-B and MSI. RESULTS: The Spearman's correlation between total scores of the MSI and SPQ-B was strong (rho=0.616, P<0.005). Items of MSI reflecting disrupted relatedness and affective dysregulation correlated moderately (rφ varied between 0.2 and 0.4, P<0.005) with items of SPQ. Items of MSI reflecting behavioural dysregulation correlated only weakly with items of SPQ. In MRA, depressive symptoms, sex and MSI were significant predictors of SPQ-B score, whereas symptoms of anxiety, age and SPQ-B were significant predictors of MSI score. CONCLUSIONS: Items reflecting cognitive-perceptual distortions and affective symptoms of BPD appear to overlap with disorganized and cognitive-perceptual symptoms of SPD. Symptoms of depression may aggravate self-reported features of SPQ-B, and symptoms of anxiety features of MSI. Symptoms of behavioural dysregulation of BPD and interpersonal deficits of SPQ appear to be non-overlapping.

Differences and overlap in self-reported symptoms of bipolar disorder and borderline personality disorder.

BACKGROUND: Differential diagnosis between bipolar disorder (BD) and borderline personality disorder (BPD) is often challenging due to some overlap in symptoms and comorbidity of disorders. We investigated correlations in self-reported symptoms of BD and BPD in screening questionnaires at the levels of both total scores and individual items and explored overlapping dimensions. METHODS: The McLean Screening Instrument (MSI) for BPD and the Mood Disorder Questionnaire (MDQ) for BD were filled in by patients with unipolar and bipolar mood disorders (n=313) from specialized psychiatric care within a pilot study of the Helsinki University Psychiatric Consortium. Pearson's correlation coefficients between total scores and individual items of the MSI and the MDQ were estimated. Relationships between MDQ and MSI were evaluated by exploratory factor analysis (EFA). RESULTS: The correlation between total scores of the MDQ and MSI was moderate (r=0.431, P<0.001). Significant correlations were found between the MSI items of "impulsivity" and "mood instability" and all MDQ items (P<0.01). In the EFA, the MSI "impulsivity" and "mood instability" items had significant cross-loadings (0.348 and 0.298, respectively) with the MDQ factor. The MDQ items of "irritability", "flight of thoughts" and "distractibility" (0.280, 0.210 and 0.386, respectively) cross-loaded on the MSI factor. CONCLUSIONS: The MDQ and MSI items of "affective instability", "impulsivity", "irritability", "flight of thoughts" and "distractibility" appear to overlap in content. The other scale items are more disorder-specific, and thus, may help to distinguish BD and BPD.

Impact of eLearning course on nurses' professional competence in seclusion and restraint practices: 9-month follow-up results of a randomized controlled study (ISRCTN32869544).

eLearning may facilitate continuing vocational education, but data on the long-term effects of an eLearning course are lacking. The aim of this study was to explore the long-term impact of an eLearning course entitled ePsychNurse.Net on psychiatric nurses' professional competence in practicing seclusion and restraint and on their job satisfaction and general self-efficacy at 9-month follow-up. In a randomized controlled study, 12 wards were randomly assigned to the ePsychNurse.Net (intervention) or training as usual (control). Baseline and 9-month follow-up data on nurses' knowledge of coercion-related legislation, physical restraint and seclusion, their attitudes towards physical restraint and seclusion, job satisfaction and general self-efficacy were analysed for 137 completers (those who participated in the 9-month follow-up assessment). No between-group differences were found on any variable, with the exception of a change in attitude to seclusion in favour of the control group. The findings of the long-term effects did not differ from the immediate outcomes (3-month follow-up) and the improved level of knowledge acquired and further consolidation of that knowledge did not take place in the 6-month period after the 3-month ePsychNurse.Net course. The ePsychNurse.Net should be further developed and its future modifications will require additional studies, probably with some new outcome measures.

Attitudes towards different containment measures: a questionnaire survey in Finnish adolescent psychiatry.

Use of containment measures in the treatment of underage patients is controversial, and empirical evidence about which containment methods are preferred is lacking. This study aimed to investigate attitudes of staff towards various containment measures in the field of adolescent psychiatry. The sample comprised 128 Finnish nurses and doctors working in closed wards with 13- to 17-year-old patients. The attitudes were studied using the Attitude to Containment Measures Questionnaire. The three methods with the most approval were as-needed medication, transfer to specialist locked wards and mechanical restraint. The method with the least approval was the net bed. Total approval scores for the various containment measures were very similar among nurses and doctors. The differences appeared in attitudes towards mechanical restraint and constant observation, doctors showing a more critical attitude. Women tended to be more critical than men, but only intramuscular medication and mechanical restraint reached statistical significance. The results emphasize the importance of wide-ranging and in-depth training as well as the difficulty of changing practices in psychiatric wards while attitudes are so strongly pro-containment.

Factors affecting assessment of severity of aggressive incidents: using the Staff Observation Aggression Scale - Revised (SOAS-R) in Japan.

The aim of this study is to investigate factors associated with overall judgements of aggression severity as provided by ward nurses, using the Japanese-language version of the Staff Observation Aggression Scale - Revised (SOAS-R). Nurses who observed 326 aggressive incidents involving psychiatric inpatients at five mental health facilities in Japan provided their assessments of the incident severity both on the established rating scale, the SOAS-R, and on a visual analogue scale (VAS), a one-item scale to indicate overall aggression severity. To evaluate the factors influencing the VAS severity scores, a multiple regression analysis was performed, in which consumer, nurse and ward characteristics were added consecutively, along with SOAS-R severity scores as independent variables. SOAS-R scores explained 17.6% of the VAS severity scores. Independently from the SOAS-R scores, the gender and age of the aggressive consumers (adjusted R(2) = 10.0%), as well as the gender of the nurses who reported the aggression (adjusted R(2) = 4.1%), each explained VAS severity score to a significant degree. Apart from the SOAS-R scores, consumer and nurse characteristics appeared to influence the overall judgements of severity of aggressive incidents, which may be connected to decisions about the use of coercive measures, such as seclusion/restraint or forced medication.

Impact of eLearning course on nurses' professional competence in seclusion and restraint practices: a randomized controlled study (ISRCTN32869544).

Education on the care of aggressive and disturbed patients is fragmentary. eLearning could ensure the quality of such education, but data on its impact on professional competence in psychiatry are lacking. The aim of this study was to explore the impact of ePsychNurse.Net, an eLearning course, on psychiatric nurses' professional competence in seclusion and restraint and on their job satisfaction and general self-efficacy. In a randomized controlled study, 12 wards were randomly assigned to ePsychNurse.Net (intervention) or education as usual (control). Baseline and 3-month follow-up data on nurses' knowledge of coercion-related legislation, physical restraint and seclusion, their attitudes towards physical restraint and seclusion, job satisfaction and general self-efficacy were analysed for 158 completers. Knowledge (primary outcome) of coercion-related legislation improved in the intervention group, while knowledge of physical restraint improved and knowledge of seclusion remained unchanged in both groups. General self-efficacy improved in the intervention group also attitude to seclusion in the control group. In between-group comparison, attitudes to seclusion (one of secondary outcomes) favoured the control group. Although the ePsychNurse.Net demonstrated only slight advantages over conventional learning, it may be worth further development with, e.g. flexible time schedule and individualized content.

Risperidone versus clozapine in treatment-resistant schizophrenia: a randomized pilot study.

1. The atypical antipsychotic risperidone may constitute an alternative to clozapine, the current treatment of choice for refractory schizophrenia. The objectives of this study were to evaluate the effectiveness of risperidone in comparison to clozapine in everyday practice and to assess the feasibility of a pragmatic trial procedure. 2. Patients were randomly assigned to open-label clozapine or risperidone treatment for 10 weeks and treatment outcomes were assessed blindly. Twenty-one patients were recruited and nineteen entered the randomized phase. 3. Five of 10 participants allocated to clozapine and one of nine risperidone participants dropped out before study completion. Five clozapine patients and six risperidone patients achieved clinical improvement, defined as a 20% decrease in the Positive and Negative Symptom Scale (PANSS) total score. No significant differences between the groups were detected in baseline or endpoint positive or negative symptoms, disease severity, or global or social functioning scores. Patients' opinion on the drugs did not differ between groups. 4. The findings of the intention-to-treat analysis of this study corroborates previous findings that risperidone may be equally effective as clozapine, and supports the feasibility and need of a multicenter randomized pragmatic trial with sufficient power to detect differences between treatments.

Will cervicovaginal interleukin-6 combined with fetal fibronectin testing improve the prediction of preterm delivery?

OBJECTIVE: We sought to investigate if determination of cervicovaginal interleukin-6 (IL-6) levels would enhance the positive predictive value of fetal fibronectin (fFN) for preterm birth. METHODS: A prospective cohort study was undertaken of 135 women between 24 and 34 weeks gestation with symptoms of suspected preterm labor. Cervicovaginal secretions were collected for both IL-6 and fFN and measured by immunoassay and ELISA, respectively. Outcome variables included preterm delivery in less than 48 h, within 7 days, and prior to 37 weeks. Statistical analysis was performed with Fisher's exact test, regression for logarithmic transform levels, and multivariate logistic regression. ROC curves were created for IL-6 levels. RESULTS: IL-6 and fFN levels were both elevated in cervicovaginal secretions of women with symptoms of preterm labor. IL-6 values >100 pg/ml resulted in a odds ratio for delivery at <37 weeks of 1.57 (95%CI=0.89-2.75, P=.11), whereas fFN values >50 ng/ml resulted in a preterm delivery risk of 4.58 (95%CI=1.54-13.35, P=.003). Combining IL-6 and fFN results did not improve upon the predictive value of fFN alone for preterm birth [odds ratio 4.00 (95%CI=1.31-12.17, P=.015)]. CONCLUSION: Cervicovaginal IL-6 levels did not provide any additional, independent effect on the prediction of preterm birth beyond that of fFN testing alone.

Adjunctive nefazodone in neuroleptic-treated schizophrenic patients with predominantly negative symptoms: an open prospective pilot study.

A combination of nefazodone with a conventional neuroleptic would lead to a serotonin (5-HT)2 and D2 receptor blockade resembling that of an atypical neuroleptic, with an additional increase of 5-HT (and noradrenaline) turnover. This may be of benefit in some cases of schizophrenia. In this study, eight patients with schizophrenia with predominantly negative and/or depressive symptoms underwent an open prospective 26-week trial with nefazodone, added to conventional neuroleptics. The total Positive and Negative Syndrome Scale (PANSS) and the Montgomery-Asberg Depression Rating Scale (MADRS) scores (the last observations carried forward, LOCF) significantly (P < 0.05) decreased in these eight patients by a mean of 31% and 63%, respectively, mainly within the first 6 weeks. Positive symptoms, observed in three patients and panic attacks in two patients disappeared entirely. The doses of neuroleptics, stable during the first 6 weeks of the trial, subsequently were able to be decreased by 28%. Extrapyramidal symptoms noticeably improved during the phase of stable neuroleptic dose regimen. Of the three patients who discontinued the trial prematurely (after 14 weeks or more), only one evidenced a nefazodone-related adverse event. Adjunctive nefazodone may be a useful treatment option in this patient population, but additional studies are recommended.

Impact of the fetal fibronectin assay on admissions for preterm labor.

OBJECTIVE: The aim of the study was to determine whether use of the fetal fibronectin assay would decrease the number of admissions to labor and delivery for diagnosis and treatment of preterm labor. STUDY DESIGN: A prospective cohort design was used to compare preterm labor admissions during a 12-month period of fetal fibronectin assay use (study) against a baseline period before fetal fibronectin assay was implemented as standard protocol. Patients coming to the physician's office or hospital with signs and symptoms of preterm labor had a sample obtained for fetal fibronectin assay per labeling criteria. Comparisons were made with the Mann-Whitney U test, independent Student t test, chi2 test, and Fisher exact test. P <.05 was considered significant. RESULTS: There was no difference noted in the number of deliveries between the baseline and study years. During the study year 251 of 330 patients evaluated for preterm labor met study criteria and had the fetal fibronectin assay completed. Eight patients did not have fetal fibronectin assay results available because of specimen handling errors, leaving 243 subjects available for study. Compared with the baseline year, the study year had significantly fewer admissions for preterm labor, preterm labor admissions per patient, and prescriptions written for tocolytic agents. In addition, the length of stay per admitted patient was significantly reduced. The study population had no differences in neonatal outcomes from the baseline population in terms of deliveries at <35.0 weeks' gestation, number of admissions to the neonatal intensive care unit, neonatal intensive care unit length of stay, or days of ventilatory support per patient admitted to the neonatal intensive care unit. CONCLUSIONS: Use of the fetal fibronectin assay resulted in significantly reduced preterm labor admissions, length of stay, and prescriptions for tocolytic agents. No negative impact on neonatal outcomes was observed. Reductions in admissions for preterm labor and in charges per admission resulted in approximately $486,000 saved during the study period. A trend toward increased corticosteroid administration (for neonates ultimately admitted to the neonatal intensive care unit) was noted.

Scattering of primary care: doctor switching and utilization of health care by children on fee-for-service Medicaid.

OBJECTIVE: To determine whether children on fee-for-service Medicaid who switch primary care doctors use less health care and are less up to date with preventive care visits than children who do not switch primary care doctors. DESIGN: Retrospective cohort study using Medicaid claims data. SETTING: 51,027 children enrolled on Medicaid in Monroe County, New York. PATIENTS: 14,187 children enrolled continuously on fee-for-service Medicaid between January 1992 and December 1994. MAIN OUTCOME MEASURES: Utilization of primary care, emergency department (ED) services, and specialty care and proportion up to date with preventive care visits according to American Academy of Pediatrics guidelines. RESULTS: During the 2-year study period, 22% of children switched primary care doctors. Compared with children who did not switch primary care doctors, those who switched had more primary care visits (4.7 vs. 3.2 visits/year, P < .01), age-adjusted preventive care visits (1.2 vs. 1.0 visits/year), ED visits (0.72 vs. 0.47 visits/year, P < .01), and specialist visits (0.99 vs. 0.31, P < .01). On multivariate analysis, doctor switching was associated with increased odds of being up to date with preventive care visits (odds ratio [OR] = 1.7; 95% confidence interval [CI] 1.3 to 2.1). However, on multivariate analysis stratified by age, the association was significant only for older children (ages 11 to 14). Altogether, 68% of all children and 44% of infants less than 1 year old made the recommended number of preventive care visits during the study period. CONCLUSIONS: All groups of children received less preventive care than recommended by the American Academy of Pediatrics. Children who switched primary care doctors had higher utilization of health care, including primary care, ED, and specialty care. Contrary to expectations, they were more likely to be up to date with preventive care visits. The heavy utilization of health services by doctor switchers indicates that this subgroup of children on Medicaid may not be at risk for poor access to health care, but additional research is needed to determine whether the quality of care is related to doctor switching.

The relationship between abnormal glucose tolerance and hypertensive disorders of pregnancy in healthy nulliparous women. Calcium for Preeclampsia Prevention (CPEP) Study Group.

OBJECTIVE: The study's aim was to determine whether healthy nulliparous women with abnormal glucose tolerance during pregnancy are at increased risk for development of pregnancy-associated hypertension or preeclampsia. STUDY DESIGN: A series of 4589 healthy nulliparous women from 5 university centers were evaluated prospectively to determine whether calcium supplementation would prevent preeclampsia. Pregnancy-associated hypertension was a diastolic blood pressure > or = 90 mm Hg on 2 occasions 4 hours to 1 week apart. Pregnancy-associated proteinuria was proteinuria > or = 1+ by dipstick testing on 2 occasions 4 hours to 1 week apart, proteinuria > or = 300 mg/24 h, a protein to creatinine ratio of > or = 0.35, or a single dipstick measurement of > or = 2+. Preeclampsia was defined as pregnancy-associated hypertension and pregnancy-associated proteinuria documented within 7 days of each other. Normal glucose tolerance was a plasma glucose level < 140 mg/dL 1 hour after a 50-g oral glucose challenge. Abnormal glucose tolerance was a plasma glucose level > or = 140 mg/dL 1 hour after a 50-g oral glucose challenge followed by a 3-hour 100-g oral glucose tolerance test yielding < 2 abnormal values. Gestational diabetes mellitus was a plasma glucose level > or = 200 mg/dL 1 hour after a 50-g oral glucose challenge in the absence of an oral glucose tolerance test or > or = 2 abnormal plasma glucose values in a 3-hour 100-g oral glucose tolerance test (> or = 105 mg/dL fasting, > or = 190 mg/dL at 1 hour, > or = 165 mg/dL at 2 hours, or > or = 145 mg/dL at 3 hours). For purposes of this study women with preeclampsia were excluded from the category of pregnancy-associated hypertension. RESULTS: Calcium supplementation did not prevent pregnancy-associated hypertension or preeclampsia. Of 3689 women with complete glucose testing data, 227 (6%) had abnormal glucose tolerance and 81 (2%) had gestational diabetes mellitus. Compared with women with normal glucose tolerance, women with abnormal glucose tolerance were significantly older, had greater body mass index, and were more likely to be white non-Hispanic, to smoke, and to have private medical insurance. Among women with gestational diabetes mellitus, after adjustment for clinical center the relative risks of preeclampsia and of all hypertensive disorders were increased (relative risk 1.67, 95% confidence interval 0.92-3.05, and relative risk 1.54, 95% confidence interval 1.28-2.11, respectively). Risk ratios were not substantially reduced after further adjustment for race and body mass index (odds ratios 1.41 and 1.48, respectively). Even within the normal range, multivariate analysis demonstrated that the level of plasma glucose 1 hour after a 50-g oral glucose challenge was an important predictor of preeclampsia. CONCLUSION: Even within the normal range, the level of plasma glucose 1 hour after a 50-g oral glucose challenge was positively correlated with the likelihood of preeclampsia. Women with gestational diabetes mellitus were at increased risk for hypertensive disorders during pregnancy after adjustment for clinical center, race, and body mass index, although the increase was not statistically significant. These findings suggest that insulin resistance may play a role in the pathogenesis of the hypertensive disorders of pregnancy.

Secondary inhibition of 2-ketoglutarate dehydrogenase complex by MPTP.

The parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridine (MPP+) acts through inhibition of complex I of the electron transport chain. Recent evidence suggests that it may also act through inhibition of 2-ketoglutarate dehydrogenase complex (KDHC). We confirmed this observation in isolated rat liver mitochondria but found that this inhibition is prevented by preincubation with the radical quencher, cysteine (Cys). KDHC is also inhibited by the NO generator S-nitroso-N-acetyl-penicillamine (SNAP) and this inhibition is similarly blocked by cysteine. MPP+ may inhibit KDHC secondary through a radical-mediated event rather than through direct interaction with KDHC.

Risk factors associated with preeclampsia in healthy nulliparous women. The Calcium for Preeclampsia Prevention (CPEP) Study Group.

OBJECTIVE: Our goal was to identify risk factors for the development of preeclampsia in nulliparous women enrolled in a multicenter trial comparing calcium supplementation to a placebo. STUDY DESIGN: A total of 4589 women from five centers was studied. Analysis of risk factors for preeclampsia was performed in 4314 who carried the pregnancy to > 20 weeks. Baseline systolic and diastolic blood pressure, demographic characteristics, and findings after randomization were examined for the prediction of preeclampsia. Preeclampsia was defined as hypertension (diastolic blood pressure > or = 90 mm Hg on two occasions 4 hours to 1 week apart) and proteinuria (> or = 300 mg/24 hours, a protein/creatinine ratio > or = 0.35, one dipstick measurement > or = 2+ or two dipstick measurements > or = 1+ at an interval as specified for diastolic blood pressure). RESULTS: Preeclampsia developed in 326 women (7.6%). The first analysis treated each risk factor as a categoric variable in a univariate regression. Maternal age, blood group and Rh factor, alcohol use, previous abortion or miscarriage, private insurance, and calcium supplementation were not statistically significant. Risk factors initially found to be significant were body mass index, systolic blood pressure, diastolic blood pressure, non-white race (African-American and other), clinical center, and smoking. Adjusted odds ratios computed with a logistic regression model revealed that body mass index (odds ratio 3.22 for > or = 35 kg/m2 vs < 19.8 kg/m2), systolic blood pressure (odds ratio 2.66 for > or = 120 vs < 101 mm Hg), diastolic blood pressure (odds ratio 1.72 for > or = 61 mm Hg vs < 60 mm Hg), and clinical center (odds ratio 1.85 for Memphis vs the other clinical centers) were statistically significant predictors of preeclampsia. Results of the final model fit revealed that preeclampsia risk increases significantly (p < 0.0001) with increased body mass index at randomization, as well as with increased systolic and diastolic blood pressure at randomization. Calcium supplementation had no effect on the risks posed by body mass index and blood pressure. Among risk factors developing after randomization, an abnormal results of a glucose screen (plasma glucose > or = 140 mg/dl 1 hour after a 50 gm glucose challenge) was not found to be associated with a significant risk of preeclampsia. CONCLUSION: These risk factors should be of value in counseling women regarding preeclampsia and should aid in understanding the pathophysiologic characteristics of this syndrome.

Vertical transmission of herpes simplex virus acquired after primary outbreak in second trimester of a dichorionic twin gestation.

BACKGROUND: The incidence of genital herpes simplex virus (HSV) has increased in recent years, particularly among women of reproductive age. This places more neonates at risk for severe morbidity and mortality. Treatment recommendations for primary disease in pregnancy are lacking, particularly for those who acquire. HSV remote from term. CASE: A patient at 17 weeks of gestation carrying dichorionic twins developed primary herpes with subsequent vertical transmission of the virus and significant neonatal morbidity. CONCLUSION: Data regarding risks and benefits of treatments such as acyclovir and immunoprophylaxis are lacking at a time when the incidence of HSV infection is on the rise.

Clozapine response in early treatment-resistant schizophrenia.

Eleven consecutive schizophrenic patients with a mean duration of illness of 2.2 (range 0.9-3.8) years and early signs of resistance to conventional neuroleptics were studied prospectively in a 26-week open trial with clozapine (mean dose 192.5 mg at week 8 and 225.0 mg at end-point). Of the ten patients who completed the study, nine improved by 20% or more on total Brief Psychiatric Rating Scale (BPRS) scores; six (good responders) showed more than 30%, and four (fair responders) 21-26% improvement on total Positive and Negative Syndrome Scale (PANSS) scores. The improvement was observed mainly within the first 8 weeks. Duration of illness correlated negatively (P=0.047) with the decrease of positive PANSS scores. The duration of illness of the fair responders was more than twice that of the good responders. Clozapine appears to be a safe and effective treatment alternative for early treatment-resistant schizophrenic patients. These patients seem to respond to relatively low clozapine doses. Early rather than late transfer to clozapine in this population may be of benefit for later clinical outcome.