Clastogenic effect of fenfluramine in mice bone marrow cells in vivo

Fenfluramine, an amphetamine derivative used in the treatment of obesity, has been evaluated in vivo in the bone marrow cells of Swiss albino mice using two cytogenetic endpoints for assessing its genotoxic and clastogenic potentials. Concentrations of 0.75, 1.5, 3.0, and 5.0 mg/kg b.w. were administered orally for the study of sister chromatid exchange frequencies and chromosome aberrations (CA). SCE frequencies showed a positive dose response; 1.5 mg/kg being the minimum effective concentration. Fen caused a prolongation of cell cycle at all concentrations. Except for the minimum therapeutic dose (0.75 mg), all other doses (1.5, 3.0, and 5.0 mg) showed a significant increase in the percentage of damaged cells over that of the vehicle control. The degree of clastogenicity was directly proportional to the dosage used and inversely related with the duration of treatment. A gradual reduction of the clastogenic potential was observed after 12 and 24 hr of exposure, indicating that the maximum effect occurs at the middle or late synthetic phase of the cell cycle. This study, probably the first detailed screening of the drug for its genotoxicity, shows that Fen is moderately clastogenic and a DNA damaging agent in vivo.     

Impact of nutritional status on peritonitis in CAPD patients.

OBJECTIVE: To determine the impact of nutritional status on peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) in a developing country. METHODS: 56 patients with end-stage renal disease on CAPD were randomly selected for this study. These patients were assessed for nutritional status and peritonitis episodes. Nutritional parameters were assessed by anthropometry, diet, body mass index (BMI), Nutritional Risk Index (NRI), serum albumin level, and Subjective Global Assessment (SGA). Based on SGA, patients were categorized into either group 1 (malnutrition, n = 31) or group 2 (normal nutritional status, n = 25). Peritonitis was considered the primary outcome and was compared between the two groups. RESULTS: Demographic profiles, Kt/V, creatinine clearance, and mean follow-up of the two groups were similar. Number of peritonitis episodes was significantly higher in patients with malnutrition (25/31) compared to patients with normal nutritional status (4/25) (p = 0.001). Mean peritonitis rate per patient per year was also significantly higher in patients with malnutrition (0.99 +/- 1.07) compared to patients with normal nutritional status (0.18 +/- 0.42) (p = 0.007). On univariate analysis, malnutrition based on SGA (p = 0.009), NRI (p = 0.02), serum albumin level (p = 0.005), and calorie intake (p = 0.006) was a significant predictor of peritonitis. On multivariate Cox regression analysis, only SGA (p = 0.001, odds ratio 0.08, 95% confidence interval 0.02-0.36) was found to be a significant predictor of peritonitis. On general linear model, the observed power of prediction of peritonitis was 0.96 based on SGA. On Kaplan-Meier survival analysis, peritonitis-free survival in patients with normal nutrition (42 months) was significantly higher compared to patients with malnutrition (21 months) based on SGA (log rank p = 0.003). CONCLUSION: We conclude that peritonitis rate is high in patients with malnutrition and that malnutrition indices, especially SGA, can predict the peritonitis rate in CAPD patients.     

Plasma cell granuloma of jaw A case report

A 65 year old Punjabi male presented with an exophytic lesion, 3 Cm. in diameter, which was pedunculated, on the attached gingiva. It was situated on the right side, near the motars. On histological examination, it was diagnosed as plasma cell granuloma.     

CD1d deficiency exacerbates inflammatory dermatitis in MRL-lpr/lpr mice

Mechanisms responsible for the development of autoimmune skin disease in humans and animal models with lupus remain poorly understood. In this study, we have investigated the role of CD1d, an antigen-presenting molecule known to activate natural killer T cells, in the development of inflammatory dermatitis in lupus-susceptible MRL-lpr/lpr mice. In particular, we have established MRL-lpr/lpr mice carrying a germ-line deletion of the CD1d genes. We demonstrate that CD1d-deficient MRL-lpr/lpr mice, as compared with wild-type littermates, have more frequent and more severe skin disease, with increased local infiltration with mast cells, lymphocytes and dendritic cells, including Langerhans cells. CD1d-deficient MRL-lpr/lpr mice had increased prevalence of CD4(+) T cells in the spleen and liver and of TCR alpha beta (+)B220(+) cells in lymph nodes. Furthermore, CD1d deficiency was associated with decreased T cell production of type 2 cytokines and increased or unchanged type 1 cytokines. These findings indicate a regulatory role of CD1d in inflammatory dermatitis. Understanding the mechanisms by which CD1d deficiency results in splenic T cell expansion and cytokine alterations, with increased dermal infiltration of dendritic cells and lymphocytes in MRL-lpr/lpr mice, will have implications for the pathogenesis of inflammatory skin diseases.     

Mechanisms by which Candida albicans induces endothelial cell prostaglandin synthesis.

One strategy for improving resistance to opportunistic pathogens is to determine host cellular responses during the invasion process and upregulate those responses that are relevant to host defense mechanisms. Within this context, we have shown previously that invasion of endothelial cells by Candida albicans in vitro causes increased production of prostaglandins. As a prerequisite for modulating endothelial cell prostaglandin production, we now characterize the mechanisms through which this process occurs. Endothelial cell invasion by C. albicans appeared to stimulate the conversion of arachidonic acid into prostaglandins by upregulating the synthesis of endothelial cell cyclooxygenase and increasing the activity of the endothelial cell phospholipase. The enhanced activities of these two enzymes were independent of calphostin C-sensitive protein kinase C and resulted in the increased production and extracellular secretion of prostaglandin I2 (PGI2), PGF2 alpha, and PGE2. The secretion of these prostaglandins had no effect on the amount of endothelial cell injury induced by C. albicans. The role of the increased prostaglandin secretion by endothelial cells is likely related to modulation of the leukocyte response at the candida-leukocyte-endothelial cell interface.     

A human recessive neurosensory nonsyndromic hearing impairment locus is a potential homologue of the murine deafness (dn) locus

A locus for recessive neurosensory nonsyndromic hearing impairmentmaps to chromosome 9q13–q21 in two regionally separateconsanguineous families from India. Each family demonstratesa LOD score greater than 4.5 to this region. D9S15, tightlylinked to the Friedreich's ataxia locus, a region that has beendefined with over 1 Mb of YAC contig information and severalexpressed sequences, is one of the flanking markers. In mice,the deafness (dn) locus maps to mouse chromosome 19 and flankingloci are syntenic to human chromosome 9q11–q21. The dnmouse is a potential model for the hearing impairment foundin both these families.     

The use of computer-assisted diagnosis in cardiac perfusion nuclear medicine studies: A review (part 3)

Computer-assisted diagnosis (CAID) is commonly used to evaluate cardiac nuclear medicine studies such as thallium perfusion scans. Part 1 of this series (Journal of Digital Imaging, 5:209–222, 1992) reviewed the basic theory underlying CAID in nuclear medicine and its use in planar thallium imaging. Part 2 discussed the application of CAID to SPECT perfusion studies (Journal of Digital Imaging, 6:1–15, 1993). This article reviews new variations of CAID programs for SPECT imaging and the application of expert systems and neural networks to CAID of nuclear medicine perfusion studies.     

Dystrophin gene deletions in South Indian Duchenne muscular dystrophy patients

66 unrelated patients from Southern India with Duchenne Muscular Dystrophy (DMD) were studied for intragenic deletion in 18 exons and Pm region of the DMD gene using multiplex PCR. Of these 41 (62.1%) showed intragenic deletions. 78% of the deletions were located at the distal hotspot region (44-55 exons) and 22% of the deletions were located at the proximal region (exon 2-19). Exon 50 is most frequently deleted. Deletions in isolated cases were significantly more compared to familial cases. The lower incidence reported from South India compared to North India, is suggestive of variations in the Southern and Northern population.     

A model for susceptibility artefacts from respiration in functional echo-planar magnetic resonance imaging

Respiration causes variations in the signals acquired during magnetic resonance imaging (MRI) and therefore is a significant source of noise in functional brain imaging. A primary component of respiratory noise may arise from variations of bulk susceptibility or air volume in the chest. Here we investigate the nature of the image artefacts that can be caused by such changes. We develop a simple model which attempts to mimic the effects of variations in susceptibility and volume during respiration. Theoretical calculations, computer simulations and imaging experiments with this model show that small variations in susceptibility within the thorax from alterations in the paramagnetism of cavity gas may lead to a shift of the image on the order of 0.1 pixels as well as a shading of the intensity by +/-1%. These effects are observed to be predominant in the phase-encoding direction. They may lead to the production of spurious activations in functional MRI and are likely to be of more importance at higher field strengths.     

Malignant nasal paraganglioma: a case report and review of the literature

A rare case of malignant nasal paraganglioma is described. A 30 year old female patient presented with a one year history of bilateralnasal obstruction, nasal deformity and recurrent epistaxis. CT scan demonstrated an enhancing mass occupying both nasal cavities, right maxillary antrum and anterior ethmoid sinus. Histopathologic diagnosis was malignant paraganglioma. A total maxillectomy with excision of growth was performed. Post-operative radiotherapy and chemotherapy was given but patient expired before the completion of therapy. Nose being a rare site for paragangliomas, these lesions present a diagnostic challenge to histopathologists and clinicians alike. A review of the four previously described malignant nasal paragangliomas is also presented.