Polygenic liability for schizophrenia and childhood adversity influences daily-life emotion dysregulation and psychosis proneness.

OBJECTIVE: To test whether polygenic risk score for schizophrenia (PRS-S) interacts with childhood adversity and daily-life stressors to influence momentary mental state domains (negative affect, positive affect, and subtle psychosis expression) and stress-sensitivity measures. METHODS: The data were retrieved from a general population twin cohort including 593 adolescents and young adults. Childhood adversity was assessed using the Childhood Trauma Questionnaire. Daily-life stressors and momentary mental state domains were measured using ecological momentary assessment. PRS-S was trained on the latest Psychiatric Genetics Consortium schizophrenia meta-analysis. The analyses were conducted using multilevel mixed-effects tobit regression models. RESULTS: Both childhood adversity and daily-life stressors were associated with increased negative affect, decreased positive affect, and increased subtle psychosis expression, while PRS-S was only associated with increased positive affect. No gene-environment correlation was detected. There is novel evidence for interaction effects between PRS-S and childhood adversity to influence momentary mental states [negative affect (b = 0.07, P = 0.013), positive affect (b = -0.05, P = 0.043), and subtle psychosis expression (b = 0.11, P = 0.007)] and stress-sensitivity measures. CONCLUSION: Exposure to childhood adversities, particularly in individuals with high PRS-S, is pleiotropically associated with emotion dysregulation and psychosis proneness.

Clinical guidelines for the practice of peripheral nerve blocks in the adult.

These guidelines, made by BARA, are, like the "Safety First Guidelines" of the SARB, clinical recomendations for a good and safe practice when performing peripheral nerve blocks (PNB). These recommendations were made according to the most recent literature and experts opinion and are therefore prone to changes due to evolution of literature. The guidelines deal with "Informed Consent", preoperative visit, monitoring, equipment and the PNB procedure itself regardless of using ultrasound or neurostimultion or both. Advise is given when combining a PNB with general anesthesia and when a catheter technique is used.

Is sensitivity to daily stress predictive of onset or persistence of psychopathology?

PURPOSE: The aim of the current study was to replicate findings in adults indicating that higher sensitivity to stressful events is predictive of both onset and persistence of psychopathological symptoms in a sample of adolescents and young adults. In addition, we tested the hypothesis that sensitivity to mild stressors in particular is predictive of the developmental course of psychopathology. METHODS: We analyzed experience sampling and questionnaire data collected at baseline and one-year follow-up of 445 adolescent and young adult twins and non-twin siblings (age range: 15-34). Linear multilevel regression was used for the replication analyses. To test if affective sensitivity to mild stressors in particular was associated with follow-up symptoms, we used a categorical approach adding variables on affective sensitivity to mild, moderate and severe daily stressors to the model. RESULTS: Linear analyses showed that emotional stress reactivity was not associated with onset (ß=.02; P=.56) or persistence (ß=-.01; P=.78) of symptoms. There was a significant effect of baseline symptom score (ß=.53; P<.001) and average negative affect (NA: ß=.19; P<.001) on follow-up symptoms. Using the categorical approach, we found that affective sensitivity to mild (ß=.25; P<.001), but not moderate (ß=-.03; P=.65) or severe (ß=-.06; P=.42), stressors was associated with symptom persistence one year later. DISCUSSION: We were unable to replicate previous findings relating stress sensitivity linearly to symptom onset or persistence in a younger sample. Whereas sensitivity to more severe stressors may reflect adaptive coping, high sensitivity to the mildest of daily stressors may indicate an increased risk for psychopathology.

Knowledge acquisition, accessibility, and use in person perception and stereotyping: simulation with a recurrent connectionist network.

Connectionist models contrast in many ways with the symbolic models that have traditionally been applied within social psychology. In this article the authors apply an autoassociative connectionist model originally developed by J. L. McClelland and D. E. Rumelhart (1986) to reproduce several well-replicated and theoretically important phenomena related to person perception and stereotyping. These phenomena are exemplar-based inference, group-based stereotyping, the simultaneous application of several stereotypes to generate emergent characteristics, and the effects of recency and frequency of prior exposures on accessibility (the probability of a representation's use). Though many of these phenomena are explained by current theories in social psychology, the simulation contributes to parsimony and theoretical integration by showing that a single, very simple mechanism can generate them all. The model also predicts a new phenomenon--rapid recovery of accessibility after it has declined to zero.

Prostaglandin F2 alpha for interrupting pregnancy, managing intrauterine death and molar pregnancy and inducing labor.

Serial intramuscular injections of 250 microgram of 15 (S), 15-methyl-prostaglandin F2 alpha were given to 105 women every 1-3 hours in an attempt to induce second-trimester abortion (N = 80) or labor (N = 25), the latter because of late intrauterine death or anencephaly. The treatment was highly successful; the cumulative expulsion rates at 12 and 24 hours were 69% and 95%, respectively. There were no serious complications, and significant alterations in the mother's vital signs were uncommon. Gastrointestinal side effects are tolerable if the woman is properly premedicated and maintained on the antiemetic, antidiarrheic and analgesic treatments.

PIP: Serial intramuscular injections of 250 mcg of 15(S,15-methyl-prostaglandin F2alpha were given to 105 women every 1-3 hours in an attempt to induce second trimester abortion (N=80) or labor (N=25). Patients were divided into 5 groups: those with missed abortions; those with pregnancy terminations; those with molar pregnancy; those with intrauterine death; and those where labor was induced with a live anencephalic fetus. The treatment was highly successful; the cumulative expulsion rates at 12 and 24 hours were 69% and 95% respectively. There were no serious complications, and significant alterations in the mother's vital signs were uncommon. Gastrointestinal side effects are tolerable if the woman is properly premedicated and maintained on the antiemetic, antidiarrheic, and analgesic treatments.

Vaginal cytologic evaluation as a practical link between hormone blood levels and tumor hormone dependency in exclusive medroxyprogesterone treatment of recurrent or metastatic endometrial adenocarcinoma.

In one hundred patients treated by means of one gram medroxyprogesterone a week for disseminated or recurrent endometrial adenocarcinoma, vaginal cytohormonal evaluation seemed to be an important predictive factor of hormone dependency and tumoral responsiveness to progestational therapy. Almost all 51 patients, representing the responsive group, revealed an evident drop of the Karyopyknotic Index and a complete shift to the left of the Maturation Index. Both cytohormonal and tumoral response to medroxyprogesterone seemed directly related to estrogen-progestogen interaction on a cellular level. The striking LH response in the responsive group has previously not been integrated in this mechanism of action.

[Six-monthly administration of medroxyprogesterone acetate (MPA) (author's transl)]. / Administration semestrielle d'acétate de medroxyprogestérone (MPA).

For more than six years the authors have studied the acceptability and the effectiveness of Medroxyprogesterone Acetate (450 mg) as a long acting contraceptive (six months). With a Pearl index of 0.85, the method was considered as effective whereas its acceptability was adversely influenced by the bleeding irregularities that take place during the first year of use. A good patient-doctor relationship could lessen this influence.

PIP: 105 patients were treated in a small family planning clinic in Luxembourg with 450 mg of medroxyprogesteroneo cetate every 6 months as a contraceptive measure; 228 patients were similarly treated in a large university hospital in Brussels, Belgium. Socioeconomic characteristics of the 2 groups of patients were different, while results from treatment were very similar. Major side effects were constituted by menstruation disorders and changes in body weight. After the first year of use 27.6% of patients abandoned the method in Luxembourg, and 61.8% in Brussels; most patients recurred to another method. The difference in the percentage of termination of the method between the 2 localities can be explained by the fact that in Luxembourg the clinic is manned essentially by one person who gives his patients attentive and personal guidance, while in Brussels the amount of work is divided among several doctors with a rotating schedule, and consequently the quality of the physician-patient relation is not as good as it would be in other circumstances.

Prostaglandins for the management of anencephalic pregnancy.

In 17 women carrying an anencephalic fetus (3 or them dead) an attempt was made to terminate the pregnancy with either intravaginal suppositories containing 20 mg prostaglandin E2 each or serial intramuscular injections of 250 microgram of 15(S)-15-methyl-prostaglandin F2 alpha. The duration of pregnancy ranged from 18 to 39 weeks (mean: 28.5 weeks). Fifteen women expelled the complete uterine contents after a period ranging from 4:15 to 39:10 h:min (mean: 15:11 h:min) following the initiation of treatment. There were two failures, and in both of these cases labor started spontaneously after cessation of the prostaglandin treatment. No serious complications occurred. The PG treatment induced no changes in routine laboratory values and significant alterations in the mother's vital signs were uncommon. Even though intravaginal prostaglandin E2 and intramuscular 15-methyl-prostaglandin F2 alpha often produced gastro-intestinal side effects, there can be no doubt as to the unique utility of these compounds for the management of anencephalic pregnancies, whatever the duration of gestation and vital status of the fetus.

Management of second-trimester missed abortion with intramuscular 15-methyl-prostaglandin F2 alpha.

Midtrimester missed abortion was successfully managed by serial intramuscular injections of 15(S)-15-methyl-prostaglandin F2alpha (PGF2alpha) in 255 patients, the cumulative abortion rates after 24 and 36 hours being 97.6 and 99.6%, respectively. The mean 1st-dose-to-expulsion interval was significantly shorter in the paras, but the period after fetal death was not significant in this respect. In 60% of the cases, abortion was complete. No serious complications occurred. 2/3 of the patients developed gastrointestinal side effects. These side effects were not improved by standardized antiemetic and antidiarrheal treatment, but they were strongly reduced by priming the cervix with extraamniotic PGE2 gel before the PGF2alpha analog was administered.

Termination of pregnancy by intramuscular administration of 15 (S)-15-methyl-prostaglandin in F2 alpha.

The use of 15 (S)-15-methyl-prostaglandin F2 alpha for second-trimester termination of pregnancy, induction of labor in the presence of a dead or severely malformed fetus, and the management of molar pregnancy was investigated in 212 women. The dosage regime was 250 microgram of the prostaglandin analogue every 1 to 3 hours. Cumulative expulsion rates amounted to 94 and 97% after 24 to 36 hours, respectively. Gastrointestinal side effects occurred in 48% of the patients, and both the number and intensity of the episodes were significantly reduced by antiemetic and antidiarrheal drugs. No serious complications occurred.

Vaginal prostaglandin E2 for interruption of pregnancy and management of intrauterine death.

Vaginal suppositories containing 20 mg prostaglanding E2, administered at 2-5h intervals, are very effective in interrupting second-trimester pregnancy and in inducing labor in case of death in utero. However, side effects are common and make the treatment unpleasant to most patients. Premedication with an maintenance of a potent anti-emetic (e.g. haloperidol) and an anti-diarrheic (e.g. loperamide) considerably reduce the frequency and severity of these side effects.

PIP: This study assesses the efficacy, safety and acceptability of PGE2 (prostaglandin) vaginal suppositories for terminating pregnancies. The subjects were divided into 4 groups: 1) A (missed abortion, n=29); 2) B (termination of pregnancy, n=9); 3) C (molar pregnancy, n=3); and 4) D (late intrauterine death, n=12). 22 obstetricians (20 with no previous experience with PGE2) participated in this multicentre trial. 1 gm vaginal suppository containing 20 mg PGE2 was inserted into the posterior fornix of the 53 patients every 2-5 hours until the uterine contents were expelled. Satisfactory overall results were obtained in 52 women. Total cumulative expulsion rates were 40/53 (75%) after 12 hours, 51/53 (96%) after 24 hours, and 52/53 (98%) after 36 hours. Group B required a greater total dose of PGE2 and a longer 1st dose-expulsion interval than pregnancies complicated by fetal death (Groups A and D). Systemic absorption plays a role in the abortifacient efficacy of vaginally administered PGE2. This is why adequate myometrial stimulation has similar side effects as those seen during intravenous infusion of the compound. The severity and frequency of side effects experienced by the patients in this series can be reduced by means of premedication with a potent anti-emetic (haloperidol) and an anti-diarrheic (loperamide).

Assessment of a two dose scheme of PGE2 gel for preinduction cervical softening.

A single dose technique of endocervically administered 0.5 mg PGE2 triacetin gel has been reliably effective for preinduction cervical softening. This study examined the value of a 2 times 0.25 mg dosing scheme over a 12 hour period and compared it with the single dose method. It was concluded that there was no advantage in the two dose scheme and given the potential for contamination or inadvertent rupture of the membranes with more frequent dosing, the single application remains the procedure of choice.

Preinduction cervical softening with endocervical PGE2 gel. A multi-center trial.

In a prospective, randomized trial, a single dose of PGE2 gel, 0.5 mg (2.5 ml), was given to 416 low Bishop Score patients 12 h prior to indicated oxytocin induction and compared with 404 non-gel controls. Successful initial induction was achieved in 83% of the treated and 58% of the non-treated subjects. In addition the induction-delivery interval was shortened (median times 9.0 h vs. 11.3 h) and fewer cesarean sections were performed (16% vs. 21%) in the PGE2 gel series. The endocervical administration of PGE2 was well tolerated and, provided care is taken to avoid excess extra-amniotic placement, systemic PGE2 effects are minimal.

Subcutaneous hemangiosarcomas in a rhesus macaque (Macaca mulatta).

Hemangiosarcoma is a malignant tumor of vascular endothelial cell origin. The occurrence of hemangiosarcoma in nonhuman primates has been rarely documented. An adult male rhesus monkey was reported having a firm subcutaneous swelling, approximately 4.5 cm in diameter, on the ventral midline of the abdomen. Fine-needle aspiration, microbial culture, biopsy, radiographs, exploratory laparotomy, histopathology, immunohistochemistry, hematology, and serology were performed. A second subcutaneous mass approximately 4.5 x 4.0 x 2.7 cm developed on the ventral midline several weeks later. A fine-needle aspirate of the first mass consisted of numerous erythrocytes with few polymorphonuclear cells and lymphocytes. Histopathology showed foci of spindle-shaped cells surrounding the vascular spaces. Many spindle-shaped cells had prominent nucleoli, and mitotic figures could occasionally be seen. Immunohistochemical staining of the masses for Factor VIII-related antigen, an endothelial cell and tumor marker, yielded positive results. Both masses were consistent with hemangiosarcoma.

Endocervical prostaglandin E2 gel for preinduction cervical softening.

A single, endocervical application of a new commercial preparation of prostaglandin E2 (PGE2) gel, 0.5 mg of PGE2 in 2.5 ml (3 g), was evaluated for preinduction cervical softening. Safety and efficacy were assessed in a comparison with a 2.0 mg PGE2 vaginal tablet and placebo in normal nulliparous women at term, with low Bishop scores. Treatment was administered in randomized, double blind fashion. Overall success, defined as a progression in Bishop score of at least 3 points within 12 hours, was achieved in 22/40 (55%) of the gel group, 15/41 (37%) in the tablet treated women, and 8/40 (20%) in those receiving placebo. Of interest was the observation that of women with very unfavorable induction features (Bishop score 0-2), the cervical gel treatment resulted in a 6/8 (75%) success rate compared with 2/13 (15%) success for the vaginal tablet and 0/17 (0%) for placebo. In as much as a very low incidence of side effects accompanied this treatment scheme, expanded multi-center testing is recommended.

Oxytetracycline-induced nephrotoxicosis in dogs after intravenous administration for experimental bone labeling.

Tetracyclines have been used as in vivo indicators of new bone formation because they form complexes with mineral at bone-forming surfaces. Four of 12 dogs in a bone-labeling study developed clinical signs of renal disease (vomiting, diarrhea, dehydration, and azotemia) within 1 to 2 days of receiving oxytetracycline at a bone-labeling dose of 25 mg/kg of body weight, once daily for 2 consecutive days. To delineate the relationship between oxytetracycline administration and renal damage, six dogs were given the bone-labeling dose intravenously and were subsequently evaluated by determination of clinical signs, serum biochemical analysis, urinalysis, and histologic examination (experiment 1). Drug administration was modified in the five dogs remaining in the bone-labeling orthopedic study. These dogs received the oxytetracycline dose as a slow intravenous infusion diluted with 250 ml of lactated Ringer's solution (experiment 2). All six dogs of experiment 1 developed persistent isosthenuria within 2 days of receiving the bone-labeling dose of oxytetracycline. Clinical illness (three of six dogs) was associated with azotemia, creatinemia, and hyperphosphatemia. All dogs had multifocal, mild to moderate flattening of renal tubular epithelium, characteristic of nephrosis. None of the dogs of experiment 2 developed any clinical indications of renal disease, and the only biochemical abnormality was isosthenuria in two of the five dogs. Thus the development of clinical signs and biochemical abnormalities associated with the intravenous administration of oxytetracycline was obviated by the slow administration of a dilution of the calculated bone-labeling dose of the antibiotic.

The effect of endocervical PGE2-gel (Prepidil) gel on plasma levels of 13,14-dihydro-15-keto-PGE2 (PGEM) in women at term.

Term pregnant patients undergoing preinduction cervical softening were randomized to receive no treatment (controls) or 0.5 mg PGE2-triacetin gel (Prepidil gel) endocervically. Plasma samples containing PGEM collected 4 hrs post-treatment and converted to the stable bicyclo degradation product (bicyclo-PGEM) were assayed by RIA. Positive clinical effect (responders) during 12 hrs after treatment (Bishop score increase greater than or equal to 3, in labor or delivered) were assessed. All evaluations were blind. In nonresponders (n = 35), the means of the bicyclo-PGEM variables (mean, maximum, area under the curve) were all about 18% higher in gel-treated patients (n = 6) than controls (n.s.). In responders (n = 38), the variables were all about 80% higher in gel-treated women (n = 32) than controls (p less than .01). In controls (n = 35), the responders (n = 6) had 50% higher levels than nonresponders (n.s.). In the gel-treated women (n V 38), responders (n = 32) had about 140% higher levels than nonresponders (less than .01). The results suggest that both exogenous and endogenous bicyclo-PGEM were measured. Differences in pairwise comparisons suggest that there may be substantially less exogenous bicyclo-PGEM in the gel nonresponders than in gel responders or substantially more endogenous bicyclo-PGEM in gel responders than in control-responders.