Local inflammation and devascularization--in vivo mechanisms of the "bystander effect" in VPC-mediated HSV-Tk/GCV gene therapy for human malignant glioma.

Somatic gene therapy with the herpes simplex virus type I thymidine kinase gene/ganciclovir (HSV-Tk/GCV) system and murine retroviral vector producer cells (VPCs) was introduced as a new adjuvant treatment modality to treat tumor bulk and to prevent tumor recurrence in patients harboring malignant glioma. The single-center experience after treatment of 27 patients undergoing tumor resection followed by intracerebral VPC injection for HSV-Tk suicide gene therapy will be presented focused on findings of systematic and close MRI follow-up and a few histological specimens. The data indicate that hemorrhagic necrosis due to endothelial cell transfection mediated vessel necrosis and that local inflammatory immune response occurs frequently after gene therapy. These phenomena seem to be specific because none of the patients of a control group showed any similar features. The prognosis (time to progression, survival) of the patients with "bystander effects" after gene therapy was better, but compared to those patients without bystander effects, they were also privileged by a favorable constellation of prognostic factors. Therefore, the appearance of these neuroradiologic features cannot serve as an indicator for treatment effectiveness and outcome.     

Neonatal treatment with beta-cell stimulatory agents reduces the incidence of diabetes in BB rats

The aim of the study was to investigate whether various beta-cell stimulatory drugs, given neonatally, influence the incidence of diabetes in BB rats. Newborn BB rats were treated twice daily for 6 days and diabetes development was observed during the following 200-day study period. Compared to a diabetes incidence of 63.8% in 163 control BB rats which received saline or were untreated, the percentage of experimental BB rats that developed diabetes was as follows in the different subgroups: arginine-glucose: 47% (n = 73, p < 0.02); glucagon: 37% (n = 93, p < 0.0001); tolbutamide-glucose: 36% (n = 58, p < 0.0005); and theophylline-glucose: 39% (n = 41, p < 0.005). A long-term arginine-glucose treatment was not superior to the shorter neonatal treatment. Histological examination revealed a higher degree of insulitis in diabetic than in non-diabetic animals but no difference according to the kind of treatment was observed. Finally, we found that the diabetes incidence in BB rats was higher in the first litter compared to subsequent litters (p = 0.04). Thus, neonatal treatment with various beta-cell stimulatory agents reduces diabetes incidence in BB rats. The theory behind the study, that the treatment accelerates beta-cell maturation leading to increased immunological tolerance towards beta cells, is discussed.     

Akute Exazerbation einer hereditären Pankreatitis

Ohne Zusammenfassung     

Malaria and pregnancy: placental cytokine expression and its relationship to intrauterine growth retardation

Malaria infections during pregnancy can lead to the delivery of low-birth-weight infants. In this study, cytokine mRNA was measured in placentas from 23 malaria-infected and 21 uninfected primigravid women who had delivered in Mangochi, Malawi, a region with a high rate of transmission of falciparum malaria. Significantly increased expression of interleukin (IL)-1beta, IL-8, and tumor necrosis factor (TNF)-alpha and decreased expression of IL-6 and transforming growth factor-beta1 were found in malaria-infected compared with uninfected placentas. TNF-alpha and IL-8 were produced by maternally derived hemozoin-laden placental macrophages. Increased TNF-alpha expression was associated with increased placental hemozoin concentrations. Increased TNF-alpha or IL-8 expression in the placenta was associated with intrauterine growth retardation but not with preterm delivery. The results suggest that malaria infections induce a potentially harmful proinflammatory response in the placenta.     

Weight control smoking among sedentary women

This study examined characteristics associated with weight control smoking among 281 sedentary women enrolled in a smoking cessation trial. A series of regression models were developed to identify predictors of weight control smoking as measured by the Smoking Situations Questionnaire. Predictor variables included demographic variables, dietary intake, weight gain following previous quit attempts, dietary restraint, self-efficacy for weight management, smoking behavior, exercise behavior, negative affect and psychological constructs relevant to smoking cessation, and exercise adoption. In the final predictor model, anticipation of weight gain in the current quit attempt, higher dietary restraint, younger age, greater Fagerstrom scores, greater number of pounds gained in previous quit attempts, and lower levels of self-efficacy to manage weight in negative affect situations were associated with smoking for weight control. Treatment implications for women who smoke for weight control reasons are discussed.     

The Blau syndrome gene is not a major risk factor for sarcoidosis

BACKGROUND: A genetic predisposition to sarcoidosis has long been postulated, although no specific susceptibility genes are known. Candidate genes for the two granulomatous inflammatory disorders with clinical similarities to sarcoidosis, Blau syndrome and Crohn's disease, have been localized to a 40 centimorgan region spanning the chromosome 16 centromere. PATIENTS AND METHODS: Using a sample of 35 African-American sibling pairs, who both had clinically confirmed sarcoidosis, we tested for genetic linkage between the 16p12-q21 interval (the likely location of the Blau syndrome gene) and sarcoidosis. RESULTS: We found no evidence for linkage to any of the eight markers we tested in the 16p12-q21 interval. Ninety percent of the 16p12-q21 region had a LOD score < -2 for a dominant gene conferring a relative risk of 3 or greater for sarcoidosis. One hundred percent of the region had a LOD score < -2 for a dominant gene with a relative risk of 3.5 or greater or recessive gene with relative risk of 2.5 or greater. Based on simulation results we could not exclude a dominant gene with relative risk < 5 at the 0.05 significance level, nor a recessive gene with relative risk < 3, over the entire 16p12-q21 interval. CONCLUSIONS: While the clinical similarities between Blau Syndrome and sarcoidosis suggest genetic homogeneity between the disorders, we found no evidence for linkage of sarcoidosis to the Blau syndrome locus. Our exclusion results suggest that the Blau Syndrome gene does not have a major effect on sarcoidosis susceptibility.     

A caloric vestibular test with increased positive evidence (author's transl)

The positive evidence of the caloric test increases, when the time-course of the induced heat wave in the petrous bone was eliminated, which differs from man to man. This is possible by changing head position during calorisation, so that a nearly rectangular stimulus results.     

Inverse relationship between task complexity and performance deficit in 5 m water immersion

Previous research on cognitive deficits during shallow water immersion led to inconsistent results: some authors observed deficits at 5 m, but others only at depths well beyond 5 m. The present study evaluates whether this discrepancy could be related to different levels of difficulty. Forty-eight subjects participated in a mental rotation task and in a color-word task, both having multiple levels of difficulty. The two tasks were administered once 5 m below the water’s surface and once on dry land. Compared to land, subjects’ reaction time increased in 5 m depth when task difficulty was low, but it did not increase when task difficulty was high. Thus, performance deficits in 5 m depth were inversely related to task complexity. We interpret this counter-intuitive finding within the framework of a multiple-channel parallel processing model, with channels that are differentially sensitive to immersion. This model correctly predicts performance deficits on simple, but not on complex skills at smaller depths, and deficits on simple as well as complex skills at larger depths, in accordance with the present findings and data from literature.