IFN-gamma production of adult rat astrocytes triggered by TNF-alpha

IFN-gamma plays an important role in modulating inflammatory responses within the CNS. The cell type responsible for IFN-gamma production within the CNS is less well defined. We examined the production and regulation of IFN-gamma by adult rat astrocytes. IFN-gamma was hardly detectable in cultured astrocytes, while addition of TNF-alpha dose-dependently induced IFN-gamma production by astrocytes. No IFN-gamma production by astrocytes could be induced by LPS, IL-10 or TGF-beta 1. TNF-alpha-induced IFN-gamma production by astrocytes was inhibited by treatment of astrocytes with TGF-beta 1, but not IL-10. TNF-alpha induced IFN-gamma production by astrocytes was confirmed by using immunocytochemical staining. The data suggest that astrocyte-derived IFN-gamma induced by TNF-alpha may participate in local immune reactions of the brain in an autocrine and paracrine fashion.     

Venlafaxine and nefazodone, two pharmacologically distinct antidepressants

Venlafaxine, a phenylethylamine, and nefazodone, a phenylpiperazine compound, are the newest antidepressants to receive approval of the Food and Drug Administration and to be marketed in the United States. Both strongly inhibit serotonin (5-HT) reuptake; venlafaxine also inhibits norepinephrine reuptake, and nefazodone also exhibits 5-HT2-receptor antagonism. Venlafaxine inhibits the cytochrome P-450 2D6 isozyme to a lesser extent than the selective serotonin reuptake inhibitors (SSRIs) and is 27% protein bound. Structurally, the drugs are unrelated to SSRIs and have some clinically important differences in side effect profiles. Nausea, headache, somnolence, and dry mouth are the most frequently reported side effects with both. Sustained hypertension was reported by a limited number of venlafaxine-treated patients.     

Family background characteristics and relationship satisfaction in a native community in Canada

Using data collected from a Native Canadian community by Embree (1993), we examine the influence of personal and family background characteristics on satisfaction with spousal relationships, both legal marriages and cohabitations. Of special interest are the quality of relationships with parents while growing up, alcohol abuse by the parent(s), and the experience of sexual abuse during childhood. Personal traits such as age, sex, and gender role attitudes and the respondent's own drinking behavior are also considered. Path analytic techniques model both the direct effects of independent variables on relationship satisfaction as well as the role of personal consumption of alcohol as an intervening variable in level of satisfaction with a relationship. The results of the analysis indicate that personal consumption of alcohol and the experience of sexual abuse during childhood are the best direct predictors of level of satisfaction with the current relationship, with higher alcohol consumption and experience of sexual abuse related to lower satisfaction. Age also has a significant direct, though smaller, positive influence on relationship satisfaction. Sexual abuse and the respondent's sex are also linked to level of satisfaction through personal alcohol consumption. With personal alcohol use, both the respondent's sex and the experience of sexual abuse during childhood have a significant effect, with males and those sexually abused as children reporting higher levels of alcohol consumption. The socialization explanation of the intergenerational consequences of parental behavior argues that parental role models are primary to the future family formation behavior of children. Consistent with this hypothesis, the findings concerning sexual abuse, in particular, as a predictor of both personal alcohol use and relationship satisfaction seem to underscore the importance of antecedent family characteristics in influencing later adjustment to adult roles and responsibilities.     

Internet listservers in radiology

Anorexia nervosa (AN) and bulimia nervosa (BN) are currently classified as eating disorders. Both disorders are the product of a complex interaction between psychological and physiological processes and both show considerable comorbidity with other psychiatric disorders. Physiological and endocrine abnormalities, including primary or secondary amenorrhea and menstrual dysfunction, are common and for the most part a function of the severity of weight loss, malnutrition and/or abnormal eating habits. Therefore, assessment needs to include several steps: (1) Clinical evaluation to ascertain the diagnosis, including weight and height measurements; (2) Determination of co-existing psychiatric illnesses; and (3) Physical examination and evaluation of the physiological and endocrine status. Eating disorders interfere with reproductive function. In view of the fact that dieting has reached epidemic proportions among the young female population, and given the high association between eating disorders and endocrine abnormalities as well as menstrual disturbances, all women participating in research studies should be screened for the presence of eating disorders, disordered eating, and excessive exercise.     

Coronal microleakage in conservatively restored endodontic access preparations

The results of 122 hepatic resections in 112 patients with hepatocellular carcinoma are described. The type of liver resection performed was selected according to the patient's liver function. Forty-nine patients underwent anatomic resections, including 1 trisegmentectomy, 5 lobectomies, 11 segmentectomies, and 32 subsegmentectomies; the remaining 63 patients had nonanatomic resections. The 1-, 2-, and 3-year survivals after liver resection for all patients, taking into account one operative and one hospital death (0.9% each), were 92.4%, 85.0%, and 78.9%, and disease-free survivals at 1, 2, and 3 years were 68.6%, 46.2%, and 32.6%, respectively. Twenty-one repeat hepatic resections (17.2% of the total of 122 resections) were performed with no hospital mortality. Cumulative survival from the time of repeat hepatectomy in these 21 patients was 84.2% and 56.3% at 1 and 2 years, respectively. Among the factors that may affect survival or disease-free survival, the absence of vascular invasion (p < 0.05) and intrahepatic metastases (p < 0.01) were significantly related to the disease-free survival time. A good outcome was obtained after liver resection in 112 patients with hepatocellular carcinoma through appropriate choice of the type of resection, careful follow-up, and a vigorous surgical approach for recurrence.     

In vitro dissociation of antifungal efficacy and toxicity for amphotericin B-loaded poly(ethylene oxide)-block-poly(beta benzyl L aspartate) micelles

Amphotericin B (AmB) is a membrane-active drug used frequently for the treatment of systemic fungal diseases. Limitations for the use of AmB include poor water solubility and potential for serious systemic toxicities. Recently, it has been demonstrated that the aggregation state of AmB is a determinant factor for toxicity. To increase its therapeutic index, AmB has been solubilized in micelles based on poly(ethylene oxide)-block-poly(beta-benzyl-l-aspartate) (PEO-block-PBLA), using a dialysis method of drug loading. The aggregation state of AmB has been investigated by electronic absorption spectroscopy. AmB loaded in PEO-block-PBLA micelles is non-hemolytic for concentrations up to 15 microgram/ml. AmB as Fungizone(R) initiates hemolysis at 1.0 microgram/ml. The onset of hemolysis correlates with the respective critical aggregation concentrations (CACs) of AmB. The antifungal activity of the AmB-loaded PEO-block-PBLA micelles is four to eight times higher than Fungizone(R) in terms of minimal inhibitory concentrations (MICs). PEO-block-PBLA has no antifungal activity for concentrations up to 200 microgram/ml. The basis for the increase in antifungal activity of AmB-loaded PEO-block-PBLA micelles is unclear, but may be related to a stabilizing effect of the polymeric micelles against auto-oxidation of the AmB heptaene moiety or alternatively, an enhancement in membrane perturbation of fungal cells.     

Reduced expression of retinoblastoma gene product (pRB) and high expression of p53 are associated with poor prognosis in ovarian cancer

Paraffin sections (n = 168, 27 benign, 16 low malignant potential [LMP] and 125 malignant tumours) from epithelial ovarian tumours were evaluated immunohistochemically for expression of retinoblastoma gene product (pRB) and p53 protein, and the relationship among pRB, p53 and cyclin-dependent kinase inhibitor 2 (CDKN2) gene product p16INK4A (p16) was analysed, following our previous study of p16. Forty-one percent of the benign, 50% of the LMP and most (71%) of the malignant tumours showed high pRB expression. High expression of pRB (>50% pRB-positive cells) significantly correlated with non-mucinous histological subtypes. Reduced pRB expression, substage and residual disease were significant predictors for poor prognosis in stage I patients. All the benign and most of the LMP (81%) tumours were in either the p53-negative or low p53-positive category, but nearly half of the malignant tumours had high p53 expression. High p53 accumulation was found in non-mucinous, high grade and late stage tumours. For well-differentiated carcinomas, high p53 expression was a predictor of poor prognosis. However, even though high p53 expression was not associated with histological subtype, stage or the presence of residual disease, high p53 expression was not an independent predictor when all clinical parameters were combined. For all ovarian cancers, a close correlation was found between high p53 and high p16 expression. The relationship between the expression of pRB and p16 depended on tumour stage. In stage I tumours, high pRB was associated with low p16 reactivity. On the other hand, most advanced tumours showed both high pRB and high p16 reactivity.     

Risk factors for the development of NIDDM in Yonchon County, Korea

OBJECTIVE: To determine the risk factors for the development of NIDDM in Yonchon County of Korea. RESEARCH DESIGN AND METHODS: We studied 1,193 Korean nondiabetic subjects at baseline who participated in a 2-year follow-up study on diabetes in Yonchon County. A 75-g oral glucose tolerance test was performed 2 years after the baseline examination. Age, sex, and anthropometric and metabolic characteristics at baseline were analyzed simultaneously as potential predictors of conversion to NIDDM. We also designed a nested case-control study to determine the role of hyperinsulinemia and/or hyperproinsulinemia in the conversion to NIDDM in patients with newly developed diabetes and control subjects matched for age, sex, BMI, and waist-to-hip-ratio. RESULTS: At 2 years, 67 subjects developed diabetes, as defined by World Health Organization criteria. The age-adjusted incidence was significantly higher in men (6.4%) than in women (3.0%), and the incidence increased as age increased in both sexes. Multiple logistic regression analysis revealed age, male sex, and fasting and 2-h glucose levels to be significant risk factors for the development of NIDDM, whereas waist-to-hip ratio and BMI were not. In a nested case-control study, baseline proinsulin but not insulin levels were significantly higher in subjects who progressed to NIDDM than in those who did not. CONCLUSIONS: In the Korean population, beta-cell dysfunction, as measured by high proinsulin levels, seems to be associated with subsequent development of NIDDM, whereas regional and general obesity and fasting insulin levels, which may be a surrogate for insulin resistance, were not.     

Repair of ventricular septal defect in the first two years of life using profound hypothermia-circulatory arrest techniques

Ventricular septal defect repair had been performed in 57 infants ages 21 days to 21 months and under 10 kg in weight using profound hypothermia-circulatory arrest technics. Severe congestive heart failure was the indication for operation in all but two infants under 6 months of age, and in those under 3 months there was usually an associated moderate or large sized atrial septal defect or patent ductus arteriosus or a coarctation. In infants over 6 months controlled heart failure was accompanied by failure to thrive and often recurrent respiratory infections. The main indication for surgery in three infants was repeated severe respiratory infections and in 7 infants, ages 10-15 months, an elevation of pulmonary vascular resistance of 6 units M2 or more. There were two hospital deaths among the 49 infants without coarctation (ages 6 and 20 months) and two among the 8 with coarctation. Postoperative respiratory and other complications were uncommon. On late review there was no significant residual VSD amongst the 11 recatheterized patients. Psychometric studies in 19 children who had reached the age of three to four years gave no evidence of cerebral damage due to the circulatory arrest period. In view of these results palliative pulmonary artery banding is no longer performed for VSD in infancy unless there is a Swiss cheese septum or an associated severe coarctation.