Elevated interleukin-6 in schizophrenia

Interleukin 6 (IL-6) levels have been shown to be increased in a number of autoimmune disorders and have recently been shown to be elevated in the serum of schizophrenic patients. Given the involvement of the CNS in schizophrenia, levels of interleukin-6 in the CSF are also of interest. Thus, we examined levels of both CSF and serum IL-6 concomitantly to determine if these levels were different from control values. In addition, we examined these measures in patients both on and off antipsychotic drugs to determine if any medication or exacerbation effects may account for the difference from controls. CSF IL-6 was measured by ELISA in 61 drug-free male schizophrenic (DSM-IIIR) patients and 25 well-screened healthy male control subjects. Serum IL-6 was measured in 43 of the 61 patients, and in 16 control subjects. Serum IL-6 was significantly higher in the schizophrenic patients compared to control subjects. CSF IL-6 was also higher in the patients, but the difference was not statistically significant. Paired data showed no medication or exacerbation effects on CSF IL-6, but plasma IL-6 significantly decreased in patients that experienced an exacerbation after medication withdrawal. The results indicate that IL-6 levels may be altered in schizophrenia. The relative decrease in exacerbated patients following haloperidol withdrawal may be indicative of a compensatory response of plasma IL-6 levels to relapse.     

Reaction of pial arteries and veins to hypercapnia in hypertensive and normotensive rats

The lumen diameters of the main cortical surface arteries were continuously monitored through a closed cranial window in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). The arterial diameter was significantly smaller in SHR (55 +/- 1 micron) than in WKY (87 +/- 1 micron) during resting conditions as well as during hypercapnic dilatation (87 +/- 2 micron compared to 117 +/- 5 micron). The per cent increase in diameter induced by hypercapnia was larger in SHR (54%) than in WKY (36%), presumably a consequence of the altered vascular wall to lumen ratio. Alpha-adrenoreceptor blockade with yohimbine and phenoxybenzamine had no significant effect on arterial diameter during hypercapnia. The diameters of the largest pial surface veins increased to the same extent in SHR and WKY during hypercapnia (about 10%).     

Pseudomonas aeruginosa forms biofilms in acute infection independent of cell-to-cell signaling

Biofilms are bacterial communities residing within a polysaccharide matrix that are associated with persistence and antibiotic resistance in chronic infections. We show that the opportunistic pathogen Pseudomonas aeruginosa forms biofilms within 8 h of infection in thermally injured mice, demonstrating that biofilms contribute to bacterial colonization in acute infections as well. Using light, electron, and confocal scanning laser microscopy, P. aeruginosa biofilms were visualized within burned tissue surrounding blood vessels and adipose cells. Although quorum sensing (QS), a bacterial signaling mechanism, coordinates differentiation of biofilms in vitro, wild-type and QS-deficient P. aeruginosa strains formed similar biofilms in vivo. Our findings demonstrate that P. aeruginosa forms biofilms on specific host tissues independently of QS.     

Cyclin D1 and t(11;14)-positive B-cell neoplasms resembling marginal zone B-cell lymphoma: a morphological variant of mantle cell lymphoma

We describe 3 unusual B-cell non-Hodgkin's lymphomas in which the entire tumors histologically mimicked marginal zone B-cell lymphoma. All patients were male (mean age, 65 years). Excisional biopsy from lymph node (2 of 3) and parotid gland (1 of 3) showed proliferation of monocytoid B-cells with plasmacytoid features (2 of 3) and conspicuous absence of large lymphoma cells (3 of 3). By immunohistochemistry, cyclin D1 was positive (3 of 3), CD23 was negative (3 of 3), and aberrant expression of CD5/CD43 was present in 1 case. Ki67 labeling was greater than 50% in 1 case and 10% to 25% in the other 2 cases. Evidence of the t(11;14) was detectable in all by molecular techniques. One patient died within 15 months, and the other 2 patients had widely disseminated diseases at the last follow-up (8 months). Based on these features, we believed that the best classification for these lesions is the marginal zone B-cell lymphoma-like mantle cell lymphoma.     

Treating insomnia in Swiss primary care practices: A survey study based on case vignettes

Guidelines recommend cognitive behavioural therapy for insomnia (CBT‐I) as first‐line treatment for chronic insomnia, but it is not clear how many primary care physicians (PCPs) in Switzerland prescribe this treatment. We created a survey that asked PCPs how they would treat chronic insomnia and how much they knew about CBT‐I. The survey included two case vignettes that described patients with chronic insomnia, one with and one without comorbid depression. PCPs also answered general questions about treating chronic insomnia and about CBT‐I and CBT‐I providers. Of the 820 Swiss PCPs we invited, 395 (48%) completed the survey (mean age 54 years; 70% male); 87% of PCPs prescribed sleep hygiene and 65% phytopharmaceuticals for the patient who had only chronic insomnia; 95% prescribed antidepressants for the patient who had comorbid depression. In each case, 20% of PCPs prescribed benzodiazepines or benzodiazepine receptor agonists, 8% prescribed CBT‐I, 68% said they knew little about CBT‐I, and 78% did not know a CBT‐I provider. In the clinical case vignettes, most PCPs treated chronic insomnia with phytopharmaceuticals and sleep hygiene despite their lack of efficacy, but PCPs rarely prescribed CBT‐I, felt they knew little about it, and usually knew no CBT‐I providers. PCPs need more information about the benefits of CBT‐I and local CBT‐I providers and dedicated initiatives to implement CBT‐I in order to reduce the number of patients who are prescribed ineffective or potentially harmful medications.     

Severe pancytopenia after leflunomide in rheumatoid arthritis

Leflunomide is a novel drug recently introduced for treatment of rheumatoid arthritis as a DMARD (disease-modifying antirheumatic drug). So far, leflunomide has not been associated with severe bone marrow toxicity and pancytopenia. We report of a 62-year-old woman with a 14-year history of rheumatoid arthritis with bone marrow toxicity and reversible pancytopenia developing after treatment with leflunomide.     

Centrosome amplification and instability occurs exclusively in aneuploid, but not in diploid colorectal cancer cell lines, and correlates with numerical chromosomal aberrations

Measurement of the nuclear DNA content allows classification of human cancers as either diploid or aneuploid. To gain further insight into mechanisms of aneuploidy, we compared the cytogenetic profile of mismatch-repair-deficient diploid versus mismatch-repair-proficient aneuploid colorectal carcinoma cell lines using comparative genomic hybridization and spectral karyotyping. Aneuploid carcinomas revealed an average of 19 chromosomal imbalances per cell line. Such numerical aberrations were exceedingly scarce in the diploid tumors. This pattern of chromosomal aberrations is consistent with a mechanism involving the impairment of chromosome segregation fidelity during mitotic cell division. In support of this idea, we demonstrate the exclusive occurrence of centrosome amplification and instability in all of the aneuploid tumor cell lines analyzed. All diploid tumors contained centrosomes that were functionally and structurally indistinguishable from those in normal human fibroblasts. Due to the observed differences in centrosomes between these two classes of tumors, we incubated the cells with the microtubule depolymerizing drugs nocodazole and griseofulvin. Our results indicate that the aneuploid tumor cell lines have an increased sensitivity to these reagents and a delay in aster formation and microtubule regrowth. However, microtubule nucleation was initiated from one or two centers in both the diploid and aneuploid cells. These observations support the notion that the integrity of the centrosome plays a central role in the development of aneuploidy. Genes Chromosomes Cancer 27:183-190, 2000. Published 2000 Wiley-Liss, Inc.     

Evaluation of purified antigen fraction in the immunodiagnosis of cystic echinococcosis

Echinococcus granulosus antigen B fraction (AgB) was evaluated for its prognostic value in the serological follow-up of cystic echinococcosis (CE), compared to crude hydatid fluid (HF) as well as soluble somatic Echinococcus multilocularis antigen (Em). The sensitivity and specificity of enzyme-linked immunosorbent assays (ELISA) were compared examining 177 sera from patients with different clinical courses and outcome of CE and with other parasitic infections. AgB-ELISA in comparison to confirmed cystic echinococcosis has 96.4 % sensitivity and 97.2 % specificity, with 93.1 % positive predictive value and 98.6 % negative predictive value. The HF-ELISA was more sensitive than the AgB-ELISA, but its specificity was lower. Our results indicate that AgB-ELISA was more satisfactory for seroconfirmation of acute echinococcosis than HF-ELISA. Moreover, the AgB-ELISA has a potential key role in control measures implemented in patients undergoing surgery. In sera of patients more than 3 months after the treatment, no antibody response to antigen B was detected; however, with conventionally used HF-ELISA, they were still positive. The AgB is recommended for the confirmatory diagnosis. AgB-WB allocated low background with typical “triplet” bands at 8-12-16 kDa.