An open pilot study of nefazodone in depression with anger attacks: relationship between clinical response and receptor binding

Nefazodone has been widely used as an antidepressant, but it has not been tested for depression with anger attacks. In an open study, we administered nefazodone (maximum 600 mg/day) for 12 weeks to 16 outpatients who had major depression with anger attacks. Assessment instruments comprised the Structured Clinical Interview for DSM-IV (SCID), Anger Attacks Questionnaire (AAQ), 17-item Hamilton Rating Scale for Depression (HAM-D-17), Clinician Global Impression Scale (CGI), Symptom Questionnaire (SQ), Modified Overt Aggression Scale (MOAS), and MOAS-Self-Rated. Three subjects underwent positron emission tomography (PET) with [¹⁸F]-setoperone for 5-HT2 binding potential (BP) and [¹¹C]-SCH-23,390 for D1 BP, both at baseline and after 6 weeks of treatment. Eight subjects underwent PET with [¹⁸F]-setoperone and with [¹¹C]-SCH-23,390 at baseline only. In an examination of whether D1 and 5HT2 (data available in six subjects) receptor BP predicted treatment response, we found significant decreases in the HAM-D-17, CGI-S, weighted MOAS, MOAS verbal scale, OAS Self-Rated verbal, SQ Depression and Anger/Hostility scales after nefazodone; 50% responded to nefazodone (defined as ≥50% decrease in HAM-D-17 score), and 44% reported disappearance of anger attacks. A statistically significant percentage decrease in 5HT2 BP was observed for the right mesial frontal and left parietal regions after 6 weeks of treatment. No significant change was observed in D1 BP in any region. Although CGI-I scores correlated significantly with D1 BP in the left thalamic region, the correlation was not significant after Bonferroni correction. The effectiveness of nefazodone for depression with anger attacks may be related to widespread changes in 5HT2 receptor BP.     

The effect of laser refractive surgery on the on-field performance of professional baseball players.

BACKGROUND: The aim of this study was to determine the effect of laser refractive surgery on the offensive performance of professional baseball players. METHODS: Extensive search of the public media was conducted to determine which major league baseball players had undergone laser refractive surgery and when the procedure was performed. Baseball performance data were then used to determine presurgery and postsurgery baseball performance averages. A total of 17 position players were identified; however, 5 of these players were not considered in the analysis owing to insufficient playing experience either before or after the laser procedure. RESULTS: No statistically significant or practically significant difference was found between the presurgery and postsurgery means on either on-base percentage (P = 0.31), batting average (P = 0.39), slugging percentage (P = 0.66) or on-base plus slugging (OPS; P = 0.997) of major league baseball players. CONCLUSIONS: These preliminary findings suggest that professional baseball players should not expect a laser refractive surgical procedure to significantly improve their offensive baseball performance, despite the elimination of glasses or contact lens wear.     

Lack of rapid initiating, promoting or sequential syncarcinogenic effects of di(2-ethylhexyl)phthalate in rat liver carcinogenesis

The effect of prolonged dietary administration of the peroxisomeproliferating plasticizer di(2-ethylhexy1)phthalate (DEHP wasstudied on liver carcinogenesis initiated by N-2- fltuorenylmxhmide(FAA) and with that of the neoplasm-promoter phenobarbital (PB).Also, DEHP was studied as an initiator by giving it in placeof FAA before PB. Male rats were fed FAA for 7 weeks to inducebepatocellular altered foci, and were subsequently given nochemical, 12 000 p.p.m. DEHP or 500 p.p.m. PB for 24 weeks inthe diet. In the rats fed DEHP, substantial hepatomegaly andperoxisome proliferation were induced. No evidence of indudionof hepatacellular altered foci or hepatic neoplasms was foundeither when DEHP was given alone for 24 weeks or for 7 weeksfollowed by PB. Also, DEHP fed for 24 weeks had no promotingeffect on liver altered foci that were induced by FAA and producedlittle or no enhancement of the occurrence of FAA-induced liverneoplasms. In contrast, PB exerted a marked enhancing effecton foci and substantially increased the incidence and multiplicityof liver neoplasms. Thus, the findings demonstrate that DEHPdid not have either a rapid initiating activity, a significantsequential syncarcinogenic activity, or a promoting effect onliver carcinogenesis under conditions in which numerous agentswith such activities have been identified.     

Management of bacterial peritonitis and exit‐site infections in continuous ambulatory peritoneal dialysis*

SUMMARY: Peritonitis and exit‐site infections remain the most important limitations to the delivery of continuous ambulatory peritoneal dialysis (CAPD). Contamination of the peritoneum, from endogenous or exogenous sources, is responsible for most peritonitis episodes. Patients usually present with a cloudy bag, although other causes should be distinguished. Clinical suspicion of peritonitis should be followed rapidly by microbiological examination and empirical treatment. Microbiological confirmation allows for subsequent treatment based on sensitivities. Other interventions such as catheter removal may be appropriate in some patients. Exit‐site infections should also be identified and treated early. Peritonitis may be further prevented by adequate exit‐site care, hygienic methods, and techniques to minimise early contamination of the exit site. Mupirocin may also have a role in preventing infections caused by Staphylococcus aureus.     

Pre-operative assessment of anal fistulas using endoanal ultrasound

Objective To study the accuracy of endoanal ultrasound in pre‐operative assessment of cryptoglandular anal fistulas, with respect to the site of the internal opening, type and depth of the fistula tract. Patients and methods A consecutive series of 151 patients with anal sepsis underwent pre‐operative endoanal ultrasound assessment of a suspected anal fistula. Hydrogen peroxide was used to define the tract when there was doubt as to the course of the fistula. All patients subsequently had surgical exploration under anaesthesia, irrespective of findings at sonography. The site of the internal opening, depth and type of fistula were recorded at surgery, and concordance with the ultrasound was assessed. Results One hundred and forty‐five patients were subsequently shown to have a fistula at surgical exploration. Type of fistula: Two thirds were transsphincteric (63%) and one third were inter sphincteric (32%), with a few submucosal, and supra sphincteric fistulas. Ultrasound correctly predicted surgical findings in 82% of patients (124/151). Concordance was highest for transsphincteric fistulas (87%). Internal opening: Accuracy of predicting the site of the internal opening was 93% (140/151). The commonest site for the internal opening was the midline posteriorly (49%), followed by the midline anteriorly (25%), the rest lay laterally. Fistula depth: Ultrasound and surgical assessment of the depth of fistulas was concordant in 120 of 145 patients (83%). Conclusions Endoanal ultrasound has a high accuracy of predicting the site of internal opening of an anal fistula. Endoanal ultrasound is able to assess the type and depth of a fistula. This information is useful for pre‐operative planning of fistula treatment.     

Immature Megakaryocytes in the Mouse: Morphology and quantitation by acetylcholinesterase staining

Three types of immature megakaryocytes, detected by their morphological properties, have been characterized in bone marrow of normal C57BL/6 mice. Morphological classification of these cells was carried out by determining (1) presence and relative amount of acetylcholinesterase, (2) cell size, (3) nuclear/cytoplasm ratio, and (4) nuclear shape. The immature megakaryocytes were classified as: (A) cells distinguished by a round nucleus (10.6 +/- 1.1 mu diameter; mean +/- SEM), which had the highest nucleus / cytoplasm ratio and lowest content of acetylcholinesterase; (B) cells with an indented nucleus (13.0 +/- 1.9 mu diameter), which had increased acetylcholinesterase content and reduced nucleus/cytoplasm ratio compared to the round-nucleus cell type; and (C) lobed-nucleus cells (14.5 +/- 2.9 mu diameter), which showed further increase in acetylcholinesterase content and reduction in nucleus/cytoplasm ratio. Increased numbers of immature megakaryocytes were detected, indicating that a proportion of these cells are undetected using conventional staining techniques. Based on the observed alterations in size, acetylcholinesterase content, and nuclear complexity, it was concluded that these cells constitute part of a progressive maturation sequence intermediate between the progenitor cell (CFU-Mk) and mature easily recognizable megakaryocytes.     

Type II pneumocytes modulate surfactant production in response to cigarette smoke constituents: Restoration by vitamins A and E

This study was to evaluate the effects of cigarette smoke constituents upon type II pneumocyte surfactant production in vitro, and how vitamins A and E may alter the response. Freshly isolated type II pneumocytes from Sprague–Dawley rats were incubated 20 h in medium with fetal bovine serum that was or was not treated with cigarette smoke. The number of adherent cells was inversely related to the dose of smoke or benzo(a)pyrene. Despite the decreased number of treated cells, the total amount of surfactant per culture well was unchanged, whereas surfactant production per cell was significantly increased (P < 0.05). Vitamin A concentration was significantly (P < 0.05) lower in the smoke-treated serum compared with untreated serum. When vitamin A or E was added to the cigarette smoke-treated serum, cell adherence and surfactant production returned to control values. In conclusion, cigarette smoke constituents or benzo(a)pyrene alone decreased the number of adherent type II pneumocytes, but did not alter surfactant amounts because of an increased production of surfactant per cell. Type II pneumocytes seem to adjust surfactant production dependent upon the number of type II pneumocytes to produce it and vitamin A or E enhance cell attachment in the presence of the smoke toxins.