Leukocyte activation and cytokine production during experimental human endotoxemia

Background: At present, it is unclear whether in experimental endotoxemia, the pro-inflammatory response observed in healthy volunteers is followed by an anti-inflammatory response, as observed in patients with sepsis. We studied the evolution of a number of inflammatory parameters during a prolonged period (24 h) after infusion of endotoxin in healthy subjects. Methods: Six healthy male subjects received an infusion of endotoxin (4 ng/kg body weight). Blood was drawn before, and at various intervals up to and including 24 h after, endotoxin infusion. Circulating cytokine levels, leukocyte activation surface markers, plasma lactoferrin, and neopterin levels were measured, and clinical signs and symptoms were noted during a 24-h period. Monocyte and neutrophil activation after endotoxin infusion is investigated in relation to the inflammatory response. The extent of neutrophil and monocyte activation was correlated to clinical markers and blood levels of inflammatory mediators and cytokines. Results: Tumor necrosis factor-alpha appeared 30 min after infusion in the circulation, peaking (5665+/-1910 pg/ml) at 2 h. Interleukin-10 appeared 60 min after infusion, peaking (427+/-348 pg/ml) at 3 h. The expression of leukocyte activation markers increased significantly after infusion. Expression of HLA-DR on monocytes decreased significantly after 3 h (P=0.03). There was a correlation between the TNF-alpha:IL-10 ratio and the CD11b:HLA-DR ratio (P=0.03). Conclusions: During experimental human endotoxemia, an initial pro-inflammatory response is successfully compensated by an anti-inflammatory response, leading to homeostasis. This is in contrast to what happens in septic patients with compensatory anti-inflammatory response syndrome. The inflammatory balance, expressed as the cytokine pro:anti-inflammatory ratio, is reflected at a cellular level.     

Gallstone Obstructive Ileus 3 Years Post-cholecystectomy to a Patient with an Old Ileoileal Anastomosis

The present case is one of gallstone obstructive ileus due to gallstones 3 yr after laparoscopic cholecystectomy. It is interesting because of the sex of the patient, the fact that ileus occurred 3 yr after cholecystectomy and that the localization of the obstruction was an old side-to-side ileoileal anastomosis due to a diverticulectomy following intussusception of Meckels'' diverticulum at the age of 3.     

Deaths from nasopharyngeal cancer among waiters and waitresses in Chinese restaurants

Objective: Previous studies have shown that waiters have a high risk of developing cancers of the buccal cavity and pharynx, but nasopharyngeal cancer (NPC) has not been specifically studied. This study was carried out to investigate whether waiters/waitresses in Chinese restaurants have an increased risk of dying from NPC. Methods: A mortality odds ratio study was used to estimate the relative risk of dying from NPC for waiters/waitresses working in Chinese restaurants in Hong Kong during the period 1986–1995, using the general population as the external comparison group and deceased kitchen workers as an internal comparison group. Cases were deaths from NPC and the controls were deaths from the selected sets of reference causes. Results: Seventeen deaths from NPC were identified among 415 deceased waiters and four NPC deaths occurred among 140 deceased waitresses. The adjusted mortality odds ratio (aMOR) for NPC was increased among waiters, being 3.02 (95% CI 1.82–5.00) and 2.61 (95% CI 1.02–6.69) in the external and internal comparisons, respectively. For waitresses, the aMOR was 4.58 (95% CI 1.63–12.86) in the external comparison. Analysis by duration of union membership suggested a dose–response relationship. Conclusions: An increased risk of dying from NPC was observed among waiters/waitresses and could not be fully explained by bias or confounding factors. Possible risk factors related to poor indoor air quality in the service areas of Chinese restaurants in Hong Kong should be further investigated.     

A multicenter, open-label study to assess the safety and efficacy of ciclopirox topical suspension 0.77% in the treatment of diaper dermatitis due to Candida albicans

Ciclopirox is a broad-spectrum antifungal, antibacterial, and anti-inflammatory agent. This open-label study investigated the safety and efficacy of ciclopirox topical suspension 0.77% in the treatment of diaper dermatitis due to Candida albicans (C. albicans). Forty-four male and female subjects aged 6 to 29 months were included in the study. Study medication was applied topically to the affected diaper area twice daily for 1 week. Subjects were clinically evaluated at baseline and days 3, 7, and 14 (7 days post-treatment). Safety and efficacy variables included adverse events, mycological culture studies, KOH tests, Severity Scores, and Global Evaluation of Clinical Response. All adverse events were mild to moderate and considered not related to the study medication. Treatment provided statistically significant improvement (P < .05) for both the rate of mycological cure and reduction of Severity Score at each time point compared with baseline. Ciclopirox was safe and effective in the treatment of diaper dermatitis due to C. albicans.     

Decreased levels of p26-Bcl-2, but not p30 phosphorylated Bcl-2, precede TGFbeta1-induced apoptosis in colorectal adenoma cells

Bcl-2 expression is confined to the base of the colonic crypt, whereas transforming growth factor beta (TGFbeta) is expressed in the upper crypt, as are the apoptotic death promoters, Bak and Bax. In colonic adenoma cells, TGFbeta induces a growth arrest. In some adenoma cell lines, this is accompanied by apoptosis and in others it is not. In this study, we used two human colonic adenoma cell lines: RG/C2, in which TGFbeta induces a G1 arrest without apoptosis, and BH/C1, in which TGFbeta induces both a G1 arrest and apoptosis. TGFbeta does not induce apoptosis in RG/C2 cells even if hydrocortisone and insulin are removed from the culture medium. In BH/C1 cells, TGFbeta induces apoptosis in the presence of insulin and hydrocortisone. Apoptosis induced by TGFbeta is preceded by a reduction in p26-Bcl-2 protein levels. There was no change in the levels of the p30 phosphorylated form of Bcl-2 or in levels of the proapoptotic proteins Bax or Bak. RG/C2 cells did not show decreased Bcl-2 levels in response to TGFbeta- induced growth inhibition. Therefore, TGFbeta regulates Bcl-2 expression in colonic adenoma cells which undergo apoptosis in response to TGFbeta, but not in those which are growth inhibited, but resistant to TGFbeta-induced apoptosis. TGFbeta may play an important role in the colonic epithelium, not only in the inhibition of cell proliferation, but also in the regulation of apoptosis.