Histopathologic changes seen in esophagectomy specimens from the high-risk region of Linxian, China: potential clues to an etiologic exposure?

Esophageal cancer is one of the most fatal cancers worldwide and is characterized by great variation in rates among different populations. Linxian, a county in Henan Province, located in north-central China, has one of the highest rates of esophageal squamous cell carcinoma in the world. Most squamous cell carcinomas in low-risk populations are attributable to alcohol and tobacco consumption, but the causative agents in high-risk populations are less clear. The prevention and treatment of esophageal cancer in high-risk regions, such as Linxian, are limited by our inability to identify these agent(s). During a preliminary histological review, the authors noticed characteristic findings in the arteries, nerves, and lymph nodes of esophagectomy specimens from Linxian and wondered whether these findings might offer clues to the cause of squamous cell carcinoma (eg, polycyclic aromatic hydrocarbon exposure) in the Linxian population. The purpose of this study was to report these previously undescribed histopathologic changes and to compare their presence and severity with those found in esophageal squamous cell carcinomas and adenocarcinomas from a lower-risk population in the United States. Forty esophagectomies were reviewed, including 13 squamous cell carcinomas from Linxian and 21 squamous cell carcinomas and six adenocarcinomas from the United States. The presence and severity of arteriosclerosis and myxoid degeneration of nerves and the presence of anthracosis in periesophageal lymph nodes were recorded. The prevalence and severity of these findings in the three groups of esophagectomies were compared. The esophageal squamous cell carcinomas from Linxian, China, had a higher prevalence of arteriosclerotic vessels, nerves with myxoid degeneration, and anthracotic lymph nodes than the squamous cell carcinomas from the United States (Wilcoxon test, P < .04 for all comparisons). There were also significant differences in the prevalence of arteriosclerotic vessels and anthracotic lymph nodes between the esophageal squamous cell carcinomas from Linxian and the adenocarcinomas from the United States. Arteriosclerosis and the myxoid degeneration were significantly more severe in the esophageal squamous cell carcinomas from Linxian than in the esophageal squamous cell carcinomas or adenocarcinomas from the United States (Mantel trend test, P < .006 for all comparisons). Arteriosclerotic vessels, nerves with myxoid degeneration, and anthracotic lymph nodes can be seen in association with esophageal squamous cell carcinomas from the high-risk region of Linxian, China. These changes appear to be more prevalent and severe than those seen in association with esophageal squamous cell carcinomas or adenocarcinomas from a low-risk population in the United States. These characteristic changes may be causatively significant and may represent histological evidence of high-level environmental exposure to polycyclic aromatic hydrocarbons.     

Biosynthesis of the ansamycin antibiotic rifamycin: deductions from the molecular analysis of the rif biosynthetic gene cluster of Amycolatopsis mediterranei S699

Depression is a common disorder which causes intense personal suffering and socio-occupational dysfunction. It also imposes a heavy economic burden on society. It has been shown that between 29% and 46% of depressed patients fail to respond adequately to antidepressant medication. Treatment-resistant depression may contribute to the morbidity and mortality associated with affective illness. When treatment resistance is suspected, the patient's history should be reevaluated particularly regarding diagnostic subtypes and comorbidity. An assessment of treatment adequacy in terms of dose, duration and compliance should also be made. Treatment strategies for treatment-resistant depression should be systematic and empirically grounded because of the risk of increased resistance and loss of time in case of a random trial-and-error approach, and the inherent risks in certain novel strategies. A stepped care approach to treatment-resistant depression involves optimization of the current drug under trial, augmentation with drugs such as lithium and triiodothyronine, and switching to other somatic therapies such as electroconvulsive therapy and monoamine inhibitors. Only if these strategies fail, should novel treatments such as the use of venlafaxine, antidepressant combinations and augmentation with sleep deprivation be considered. Experimental strategies such as the use of antiglucocorticoids and sex hormones, which carry considerable risk, should be restricted to research settings. Somatotherapy should be combined in all cases with depression-specific psychotherapy. Psychosurgery should be considered only in truly intractable cases. Rational and energetic treatment can adequately help a large majority of patients with treatment-resistant depression.     

Transient kinetics and thermodynamics of anthroylouabain binding to Na/K-ATPase

In this study the antiarrhythmic and the proarrhythmic activities of almokalant, a selective class III antiarrhythmic agent, were compared. The antiarrhythmic effect of the drug was tested in pentobarbital-anaesthetised rabbits. Arrhythmia was evoked by occluding and releasing the left circumflex coronary artery. Almokalant in a dose of 250 nmol/kg i.v., significantly decreased the incidence of reperfusion induced ventricular fibrillation (21% vs. 75% in the control group) and increased the proportion of surviving animals during reperfusion (86% vs. 42%). The proarrhythmic effect of almokalant was examined during alpha1-adrenoceptor stimulation in chloralose-anaesthetised rabbits. Almokalant (75 nmol/kg per min) triggered torsade de pointes arrhythmias in 8 animals out of 11. The dose of almokalant (mean+/-S.E.M.) required to produce this effect was 1181+/-519 nmol/kg. It is concluded that, although almokalant is an effective antiarrhythmic agent against ischaemia-reperfusion induced arrhythmias, it has marked proarrhythmic activity during alpha1-adrenoceptor stimulation.     

Percutaneous gastrostomy with T-fastener gastropexy: results of 316 consecutive procedures

PURPOSE: To assess the rates of technical success and complications associated with radiologic gastrostomy or gastrojejunostomy performed with T-fastener gastropexy. MATERIALS AND METHODS: In 316 consecutive patients, radiologic gastrostomy or gastrojejunostomy with T-fastener gastropexy was performed over a 10-year period. Results of the procedures were reviewed. Results of follow-up were available for all patients. RESULTS: Of 316 procedures, 314 were successful (technical success rate, 99.4%). Six (1.9%) major complications occurred; 50% occurred in patients with peritoneal involvement from ovarian carcinoma. Ten (3.2%) minor complications occurred. Four minor complications occurred in patients with ovarian cancer and ascites. The 30-day mortality rate was 3.8% (12 patients) with one procedure-related death (0.3%). CONCLUSION: A T-fastener gastropexy may have a protective role in prevention of leakage of gastric contents into the peritoneum in patients with ascites. Ascites need no longer be considered a contraindication for radiologic gastrostomy. A gastropexy enables routine use of larger gastrostomy tubes and ready replacement of a displaced tube even before the development of a mature tract.     

PORE EVOLUTION AND SOLVENT TRANSPORT DURING DRYING OF GELLED SOL-GEL COATINGS: PREDICTING 'SPR1NGBACK'*

This paper reports predictions of drying phenomena in deformable porous gel coatings (i.e. a porous solid elastic network filled with air or solvent). Initially, a gelled coating is saturated with solvent, but as it dries, liquid-vapor menisci begin to recede into larger pores and the gel becomes a partially-saturated porous medium. The tensile capillary pressure in the liquid causes a compressive deformation on the solid skeleton and a consequent reduction in thickness and pore-size of the coating. A theory coupling the large deformation of the solid skeleton to capillary pressure in the interstitial liquid is used to predict the course of drying of dip-coated porous gel coatings. The theory predicts a 'springback' effect in late stages of drying as the effects of capillary pressure diminish, which matches with experimental observations.