The effect of a nutritional model of chronic liver injury on the hepatic glucuronidation of morphine in rats

Abstract— The effect of a choline-deficient diet on the hepatic glucuronidation of morphine was investigated using a rat perfused liver system. Rats fed a choline-deficient diet developed a fatty liver with minimal necrosis. Despite the morphological changes, neither hepatic extraction ratio (0·51 ± 0·02 incontrol; 0·45 ± 0·04 in the choline-deficient rats) nor intrinsic clearance (0·85 ± 0·05 in control; 0·77 ± 0·09 in choline-deficient rats) were affected by this injury model. This finding suggests that glucuronidation is relatively resistant to this chronic liver injury.     

The Conduction System Findings in Sudden Cardiac Death

Conduction System in Sudden Death. This is a brief review of the findings in the conduction system in cases of sudden death victims who were living "normal" active lives. Twenty–two representative samples from more than 100 cases of sudden cardiac death, especially in young and asymptomatic individuals, revealed a plethora of findings that varied from normal to congenital and acquired changes, in most cases either at the gross or microscopic level, especially in the conduction system to a varying degree. Despite these changes, the individuals were living normal, symptom–free lives and were not clinically diagnosed to have lethal cardiac problems. This suggests that these individuals might have experienced lethal arrhythmias in the past, which might have been "silent" in nature. Innovative new methodologies must be developed to detect the silent lethal arrhythmic focus that may lead to sudden cardiac death.     

Implantable Cardioverter Defibrillators in Patients with Valvular Cardiomyopathy

Sudden Death Prevention in Valvular Cardiomyopathy. Background: Implantable cardioverter‐defibrillators (ICDs) are beneficial for preventing sudden cardiac death (SCD) in patients with previous SCD or left ventricular dysfunction. Objective: The objective was to investigate the outcomes of ICD implantation in patients who have surgery for valvular cardiomyopathy (VCM). Methods: We identified patients with VCM who had ICD implantation after valve surgery. Age‐ and sex‐matched patients who received an ICD for ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) served as controls. Patients with VCM who had valve surgery but did not receive an ICD served as an additional control group. We compared mortality and appropriate ICD discharges between the study group and control groups. Results: Mean (SD) age (31 patients with VCM with ICD, 30 with ICM, 26 with DCM, and 62 patients with VCM without ICD) was 60 (15) years, 73% were men. Ejection fraction at ICD implantation was 34%, 26%, and 23% for the VCM with ICD, ICM, and DCM groups, respectively (P = 0.03). After a median follow‐up of 4.1 years, survival was not significantly different among ICD groups (P = 0.06). The annual appropriate shock rate was 5%, 10%, and 4% for the VCM with ICD, ICM, and DCM groups, respectively (P = 0.71). Compared to VCM without ICD, patients with VCM and ICD had comparable survival (P = 0.82) despite a reduced LVEF following valve surgery. Conclusion: Patients with VCM who undergo ICD implantation for SCD prevention have similar appropriate ICD discharge rates and mortality as do those with ICM and DCM. These data are hypothesis generating and deserve confirmation with large‐scale prospective studies. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1326‐1332, December 2012)     

Predictive Factors in Recurrent Spontaneous Aborters—A Multicenter Study

PROBLEM : Compare data from several centers relating to success rates in recurrent spontaneous miscarriage and assess the significance of indicators of subsequent pregnancy loss. METHOD : Data from 777 couples with unexplained recurrent spontaneous abortion from independent studies at seven centers were analyzed using logistic regression analysis. The following covariates were considered: age of patient, number of previous spontaneous abortions, length of previous abortions history, sub-fertility index (defined as the product of the number of spontaneous abortions and the abortion history), whether a patient was a primary or secondary aborter, and whether a patient had received leukocyte immunotherapy. RESULTS : There was a highly significant difference between the seven centers in success rates in the subsequent pregnancy and a highly significant association between success rate and each of the following covariates: the number of previous abortions, the length of the previous abortion history and the sub-fertility index. In particular, for each increase of 10 units in the value of the sub-fertility index, up to a value of 30, the odds in favor of a successful pregnancy decreased by a factor of 0.6, i.e., 40%. There was, however, little evidence of an association between the success rate in the subsequent pregnancy and age, parity, or immunization with cells from the husband. CONCLUSIONS : The sub-fertility index may be a useful measure of likelihood of success in a subsequent pregnancy.     

The effect of thalidomide on arachidonic acid metabolism in human polymorphonuclear leukocytes and platelets

The effect of thalidomide on the metabolism of arachidonic acid by purified washed human platelets and polymorphonuclear leukocytes was examined. The drug was found to be without effect under the conditions used. The action of thalidomide cannot therefore be attributed to a direct inhibition of prostaglandin or leukotriene biosynthesis.     

DESIGN AND SYNTHESIS OF POTENT IN VIVO ANTAGONISTS OF OXYTOCIN

We have previously shown that the substitution of 8-ornithine and 2-O-methyltyrosine alone and in combination in [1-deaminopenicillamine] oxytocin (dPOT) brought about enhancements in antagonistic potencies to responses to oxytocin in vivo. To explore the effects of these subtitutions in analogs of dPOT containing larger alkyl substitutents on the β carbon at position 1 and on the tyrosine residue at position two, the following six analogs were synthesized: [1-(β-mercapto-β, β-diethylpropionic acid), 8-ornithine] vasotocin (1, dEt₂OVT); [1-β-mercapto-β, β-cyclopentamethylenepropionic acid), 8-ornithine] vasotocin [2, d(CH₂)₅OVT); [1-β-mercapto-β, β-diethylpropionic acid), 2-O-methyltyrosine, 8-ornithine]vasotocin [3, dEt₂ Tyr(Me)OVT]; [1-(β-mercapto-β, β-diethylpropionic acid), 2-O-ethyltyrosine, 8-ornithine] vasotocin [4, dEt₂ Tyr(Et)OVT]; [1-β-mercapto-β', β-cyclopentamethylenepropionic acid), 2-O-methyltyrosine, 8-ornithine] vasotocin [5, d(CH₂)₅ Tyr(Me)OVT]; [1-β-mercapto-β, β-cyclopentamethylenepropionic acid), 2-O-methyltyrosine, 8-ornithine] vasotocin [6, d(CH₂)₅ Tyr(Et)OVT]. The required protected intermediates were synthesized by a combination of solid-phase synthesis and by individual 8 + 1 couplings in solution. All six analogs antagonize the actions of oxytocin on the rat uterus in the absence of Mg²⁺, in the presence of 0.5 mM Mg²⁺ and in situ. They also antagonize milk ejection responses to oxytocin, and the vasopressor responses to arginine vasopressin, and all have very low antidiuretic activities. With pA₂ values of 7.35 ± 0.08 and 7.37 ± 0.17, respectively, compounds 3 and 5 are the two most potent in vivo antagonists of oxytocin reported to date.     

AN OPTICAL CLASSIFICATION OF KERATOCONUS A PRELIMINARY REPORT*

The paper describes a procedure utilizing a modified biomicroscope and corneal toposcope for the objective determination of the physical parameters of the corneal cone (horizontal cone width and sagittal depth) and the development of a classification of the condition based on comparative ratios of the obtained data. The paper initially describes some existing classifications based on: (a) photo-keratoscopic findings: (b) correlation of the disease stage to visual acuity; (c) observable corneal changes associated with the disease severity; and (d) sequential studies utilizing an electron microscope. The paper then describes the research plan with emphasis on the specific instrumentation utilized and the types of data obtained. A discussion is presented of Lindstedt's device as altered by Stenström, and a procedure noted for the approximate alignment of the target on the corneal apex. By virtue of the methods described, it is felt that the practitioner will have the means to detect more accurately and chart the course of the keratonic condition.