Effect of imipramine treatment on heart rate variability measures.

Recently, heart rate (HR) variability has received considerable attention, and a decreased HR variability has been linked to a significant risk of cardiovascular illness. We have previously reported such a decreased variability in panic disorder patients. In this study, we report on HR variability in 12 depressed and 6 panic disorder patients at baseline and 1 and 3 weeks of treatment with imipramine as measured by the standard deviation, mean consecutive difference and the standard deviation of the mean consecutive difference of the R-R intervals in supine, supine deep breathing and standing postures. In all subjects, imipramine (mean dose: 70 mg/day) produced a significant decrease in heart rate variability at week 3 as measured by the above variables. This decrease in HR variability during imipramine treatment is probably due to its anticholinergic effects.     

Surgery in tropical pancreatitis: analysis of risk factors.

Over a 7-year period, 91 patients with tropical pancreatitis underwent operation for intractable pain. Univariate and multivariate analyses were performed to identify factors correlating with mortality, major complications, poor pain relief and associated malignancy. Patients with benign disease (group 1, n = 72) had longer survival than those with superimposed malignancy (group 2, n = 19). Pain relief was better in group 1 (59 patients compared with none, P less than 0.01). Age above 40 years, short duration of symptoms, mass lesions on ultrasonography and main pancreatic duct obstruction on endoscopic retrograde pancreatography were associated with a high risk of cancer. After reoperation major complications (four of ten) or death (three of ten) occurred more commonly than after primary procedures (seven of 81, P = 0.019 and five of 81, P less than 0.05, respectively). Poor pain relief in group 1 patients was more common after incomplete clearance of main duct stones (four of 13 versus three of 53, P less than 0.01) and after short length ductotomy (three of eight versus four of 58, P less than 0.01). Tropical pancreatitis has a high association with pancreatic adenocarcinoma. Wide ductotomy, stone clearance and drainage gave good symptomatic results in patients with benign disease. Overall results were poor in patients with cancer.     

Interferon-induced depressive illness in hep C patients responds to SSRI antidepressant treatments

This paper examines the role of selective serotonin reuptake inhibitors (SSRIs) in the treatment of hepatitis-C virus (HCV) patients who have developed interferon-α induced depression. A 2-year data analysis of HCV psychiatric liaison clinic has been undertaken. The diagnosis, treatment, and progress of those patients who were treated with interferon-α (INF-α) are reported. 53 of the 78 patients enrolled at the HCV Clinic and treated with INF-α were referred for psychiatric consultation. Six patients developed major depressive illness following INF therapy. They were all treated with SSRIs and they made full recovery. This is a significant observation and is concordant with other studies. Its biochemical ramifications are presented. It is concluded that INF-induced depression is fully reversible. A hypothesis is proposed that SSRIs modulate the neuro-protective neurotoxic ratio by possibly inhibiting the indole-2,3-dioxygenase induction of the kynurenine pathway.     

Evaluation of active and passive transport processes in corneas extracted from preserved rabbit eyes

In vitro transcorneal permeability studies are an important screening tool in drug development. The objective of this research is to examine the feasibility of using corneas isolated from preserved rabbit eyes as a model for permeability evaluation. Eyes from male New Zealand White rabbits were used immediately or were stored overnight in phosphate-buffered saline (PBS) or Hanks balanced salt solution (HBSS) over wet ice. Integrity of isolated corneas was evaluated by measuring the TEER and by determining the permeability of paracellular and transcellular markers. Active transport was assessed by measuring transcorneal permeability of selected amino acids. Esterase activity was estimated using p-nitrophenyl assay. In all cases, corneas from freshly enucleated eyes were compared to those isolated from the day-old preserved eyes. Transcellular and paracellular passive diffusion was not affected by the storage medium and observed to be similar in the fresh and preserved eye models. However, amino acid transporters demonstrated lower functional activity in corneas excised from eyes preserved in PBS. Moreover, preserved eyes displayed almost 1.5-fold lower esterase activity in the corneal tissue. Thus, corneas isolated from day-old eyes, preserved in HBSS, closely mimics freshly excised rabbit corneas in terms of both active and passive transport characteristics but possesses slightly reduced enzymatic activity. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1921–1930, 2010     

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.     

Transglottic carcinoma with intracranial metastases

A sixty year old patient underwent radical Radiotherapy for a transglottic laryngeal carcinoma and the primary site was free of disease 6 weeks later. The initial work up showed a clear roentgenogram of the chest and the vertebral architecture was normal. The patient had neurological symptoms few months later and a diagnostic CT Scan of brain showed intracranial metastases. Locally he was disease free as in the chest. After a palliative course of radiotherapy of the brain, the patient expired. The probable route of spread was discussed.     

Dermal toxicity of Fusarium toxins in combinations

T 2 toxin (T 2), diacetoxyscirpenol (DAS), fusarenon X (FX) and butenolide (Bd) at concentrations of 0.2, 0.3, 5 and 10 g/site, respectively, were applied individually and in combinations on shaved skin of guinea pigs. Erythema and induration were observed on skin patches treated with the toxins. Increase in the thickness of stratum malpighii was the major histological change observed. Mild to moderate degeneration of fibrocytes and cellular infiltration were found in the corium of skin treated with FX, Bd, DAS and T 2. The order of toxicity of individual toxins was T 2 > DAS > FX > Bd. Combinations of T 2 + FX and T 2 + Bd resulted in antagonism, while DAS + FX and DAS + Bd caused synergism.