Risk factors for suicide attempts among alcohol dependent patients.

Suicidal behavior is a common and important problem among alcohol dependent patients. The study was designed to examine risk factors for attempting suicide in 499 alcohol dependent patients. Those who had attempted suicide (N = 198) were more likely to be female, report a family history of suicidal behavior, report more childhood trauma, report greater levels of aggressive behavior, began heavy drinking earlier, and were more likely to have received antidepressant medication. Logistic regression analysis showed that gender, family history, and childhood sexual abuse history made significant and independent contributions to the risk of a suicide attempt. Thus, developmental, personality, family history, social, and comorbidity risk factors may differentiate alcohol dependent patients who have attempted suicide from those who have not.     

Simultaneous M-mode echoesophagram and manometry in the sheep esophagus

We report the simultaneous measurement of esophageal wall layer thickness and intraluminal pressure in the sheep esophagus using a miniature suction device incorporating a high-frequency ultrasound transducer and a manometry system. Transnasal placement of the device into the distal esophagus of a conscious sheep allowed observation of 133 swallowing events during three trials, each lasting from 45 to 60 minutes. In a fourth trial, 11 sequential dry and 23 sequential wet swallows were compared. Maximum manometric pressure, esophageal wall layer thickness, and duration of contraction were measured. All swallowing events produced simultaneous increases in intraluminal pressure and esophageal wall thickness. Mean maximal pressures were lower for dry swallows (18 ± 2.1 mm Hg) than wet swallows (22 ± 3.0 mm Hg) (p < .01). Thickness of the inner (circular) muscle layer increased above baseline by 124% for dry swallows and 161% for wet swallows (p < .01). We conclude that thickening of the esophageal inner (circular) muscle layer may be important in the generation of intraluminal esophageal pressure in the sheep esophagus. (Gastrointest Endosc 1995;41:582-6.)     

Graded Pneumatic Dilation using Rigiflex Achalasia Dilators in Patients with Primary Esophageal Achalasia

Pneumatic dilation is the initial therapy for primary esophageal achalasia. Recently, polyethylene balloon (Rigiflex) dilators have been used with varying success and complication rate. We performed a total of 47 dilations in 29 consecutive patients with achalasia using the Rigiflex dilators. The 3.0-cm balloon was always used first. If there was no symptomatic response, a 3.5-cm balloon was used after 4–8 wk. If there was still no symptomatic response after 4-8 wk, a 4.0-cm dilator was used. Eighteen (62%) patients were successfully dilated with a 3.0-cm balloon only. Of 11 patients not responding to a 3.0-cm balloon, five were dilated successfully with a 3.5-cm balloon. Of six patients not responding to a 3.5-cm balloon, four were successfully dilated with a 4.0-cm balloon dilator. Two patients eventually required surgery. The overall success with Rigiflex balloon dilator was achieved in 27 of 29 (93%) patients. There were no complications. We conclude that pneumatic dilation for esophageal achalasia performed in a graded fashion starting with Rigiflex 3.0-cm balloon dilator has a high success rate without complications in patients with achalasia.     

Characterization of drug metabolism enzymes in estrogen-induced kidney tumors in male Syrian hamsters

In an attempt to characterize metabolism enzymes of the estrogen-induced kidney tumor in male Syrian hamsters, the activities of enzymes involved in drug and glutathione metabolism were determined in tumor tissue. Kidney tumors were induced in male Syrian hamsters by treatment with estradiol for 8 months. Cytochrome P-450 and cytochrome b5 concentrations in tumors were below detectable levels. However, when cytochrome P-450-mediated oxidation was analyzed by product formation assays, the oxidation of E-diethylstilbestrol to diethylstilbestrol-4',4"-quinone by tumor microsomes was 10-20% of the rate found in control microsomes. In kidney tissue surrounding estrogen-induced tumors, cytochrome P-450 and b5 contents were 50-60% less than those in untreated kidney. Activities of reducing enzymes of drug metabolism (cytochrome P-450, cytochrome b5 and NADH:cytochrome c reductases), glutathione metabolism enzymes (glutathione peroxidase, glutathione transferase, glutathione reductase, and gamma-glutamyl transpeptidase), and free radical scavenging enzymes (superoxide dismutase, catalase, and quinone reductase) in tumor were significantly lower than in untreated kidney tissue. The activities of these enzymes in renal tumor surrounding tissue were between those observed in tumor and control kidney. Glucose-6-phosphate dehydrogenase activity was increased by 50% in surrounding tissue and 430% in tumor compared to values in untreated controls. The decreased enzyme activity levels in hormone-exposed tissue surrounding tumors likely represented an adaptation of this tissue to the neoplastic environment induced by chronic estrogen treatment.     

Specificity of plasma HVA response to dexamethasone in psychotic depression

Earlier reports have suggested that dexamethasone significantly increases levels of plasma homovanillic acid (HVA) in normal subjects, but that this effect may be altered in some depressed patients. To investigate the specificity of such alterations, we administered dexamethasone (1 mg p.o. at 11 p.m.) to 33 normal subjects, 27 depressed patients (8 with psychotic features), and 16 schizophrenic patients. Plasma for assay of cortisol and HVA was obtained at 4 p.m. before and on the day following dexamethasone administration. Dexamethasone induced significant increases in plasma HVA in the normal subjects and in the schizophrenic patients, but not in the depressed patients. Indeed, psychotically depressed patients tended to show a dexamethasone-associated decrease in plasma levels of HVA. In contrast to cortisol "suppression" or "nonsuppression," dexamethasone-induced changes in plasma levels of HVA (i.e., increases or decreases) sensitively and specifically discriminated between patients with affective and nonaffective psychoses.     

Effects of halothane on arrhythmias induced by myocardial ischaemia

The effect of halothane on arrhythmias induced by ischaemia was investigated in rats, isolated perfused rat hearts, and pigs. Responses to the occlusion of the left anterior descending coronary artery were determined in groups (n = 9) of chronically prepared rats treated with no halothane, 0.5, or 1.0 per cent halothane immediately after occlusion; in isolated rat hearts (n = 10) treated with no halothane, 0.5, 1.0, 2.0, or 4.0 per cent halothane for 15 min before and after occlusion; and 20–25 kg pigs (n = 11) anaesthetised with halothane or pentobarbital. The ECG, arrhythmias, blood pressure (BP), heart rate (HR) and extent of infarction were determined in each model. In pigs, left ventricular pressure, dp/dt_max and cardiac output were also measured. In chronically prepared rats, halothane anaesthesia started after occlusion was antiarrhythmic and decreased the incidence of ventricular fibrillation and resulting mortality. In isolated rat hearts, 0.5 or 1.0 per cent halothane had little effect on occlusion-induced arrhythmias. The highest concentration of halothane increased the incidence of ventricular fibrillation both before and after occlusion. Halothane decreased developed ventricular pressure in a dose-dependent manner. In acutely prepared pigs, halothane pre-treatment had no appreciable effect upon occlusion-induced arrhythmias when compared with pentobarbital anaesthesia. Thus, halothane is antiarrhythmic when treatment is initiated after occlusion in the rat but this action is not seen in isolated hearts or intact pigs. The antiarrhythmic action of halothane is, therefore, species and model dependent.     

Neurotoxicity and dermatotoxicity of cyanomorpholinyl adriamycin

Summary The highly lipophilic cyanomorpholinyl adriamycin (CMA) is the most potent antineoplastic anthracycline yet described. CNS distribution and toxicity were examined after i.v. administration of CMA to mice. At doses 0.1 mg/kg, a neurotoxic syndrome including ataxia, hypokinesia, and tremors appeared. At doses of 0.05 mg/kg, which have been reported to be antineoplastic, no neurotoxicity was observed. On histopathologic examination, no changes were observed in the brain, spinal cord, or dorsal root ganglia. Unlike adriamycin (ADR), which rapidly appears in the nuclei of several tissues, CMA showed no fluorescence, suggesting a different cellular microcompartmentalization. The i.d. injection of CMA disclosed a 200-fold increase in toxicity compared with that of adriamycin. In comparisons of CMA and ADR, neurotoxicity and cardiotoxicity occurred equally only at higher doses; however, the dermatotoxicity and antineoplastic activity of CMA were increased several hundred-fold.     

Mortality in patients with successful initial response to highly active antiretroviral therapy is still higher than in non-HIV-infected individuals

Mortality in HIV-infected patients has decreased dramatically since the introduction of highly active antiretroviral therapy (HAART). We analyzed progression to death in a population of 3678 antiretroviral treatment-naive patients from the ATHENA national observational cohort from 24 weeks after the start of HAART. Mortality was compared with that in the general population in the Netherlands matched by age and gender. Only log-transformed CD4 cell count (hazard ratio [HR] = 0.50, 95% confidence interval [CI]: 0.40 to 0.61 per unit increase) and plasma viral load (HR = 0.30, 95% CI: 0.15 to 0.60, HIV RNA level <100,000 vs. > or = 100,000 copies/mL) measured at 24 weeks and infection via intravenous drug use (IDU) (HR = 0.16, 95% CI: 0.10 to 0.26, non-IDU vs. IDU) were significantly associated with progression to death. For non-IDU patients with 600 x 10 CD4 cells/L and an HIV RNA level <100,000 copies/mL at 24 weeks, mortality was predicted to be 5.3 (95% CI: 3.5 to 8.4) and 10.4 (95% CI: 6.4 to 17.4) times higher than in the general population for 25-year-old men and women, respectively, and 1.15 (95% CI: 1.08 to 1.25) and 1.29 (95% CI: 1.16 to 1.50) times higher for 65-year-old men and women, respectively. Hence, mortality in HIV-infected patients with a good initial response to HAART is still higher than in the general population.