Transdermal penetration of physostigmine: Effects of oleic acid enhancer

The efficiency of the transdermal penetration of physostigmine through the guinea-pig skin, in a vehicle containing propionic acid, was studied in the course of developing a transdermal physostigmine pad for the potential treatment of Alzheimer's disease patients. In an attempt to improve drug penetration, the addition of various concentrations of oleic acid(0.5–5%) was tested. The study included histological examination of skin biopsies from application site. The addition of 0.5% oleic acid to the vehicle enhanced the permeation of physostigmine and shortened the time needed to reach steady state levels of blood cholinesterase inhibition, without any damage to the skin. Stable values of physostigmine concentration and of cholinesterase inhibition were measured both in blood and in brain up to 72 h. A high correlation was found between physostigmine concentration in the plasma and cholinesterase inhibition in whole blood samples (r = 0.99 for the values measured up to 48 h). A lower correlation was found between physostigmine concentration and cholinesterase inhibition in the brain (r = 0.57). In a vehicle containing up to 1% oleic acid, physostigmine was stable for at least one month. Oleic acid concentrations higher than 1%, while increasing the flux of the drug through the skin, resulted in considerable skin damage. © Wiley-Liss, Inc.     

Intraoperative echocardiographic diagnosis of previously unrecognized cor triatriatum.

Cor triatriatum is a congenital heart defect resulting in abnormal septation of the left atrium by a fibromuscular membrane. Echocardiography has improved the preoperative diagnosis of this rare congenital heart defect. We report a case where transesophageal echocardiography proved useful in the intraoperative diagnosis of a previously undetected cor triatriatum.     

Myocardial contrast echocardiography: Enhancement of perfusion images by color coding

To determine whether real-time color coding enhances the detection of myocardial perfusion through the use of echocardiographic contrast agents, we used a recently developed real-time color system during contrast injection in six open-chest dogs. Small amounts of echocardiographic contrast were injected into the left atrium. Short-axis epicardial images were obtained with a 5-MHz transducer before and after left anterior descending artery ligation. Gray-scale and rainbow-color map images were obtained for each contrast agent. The color map allowed detection of small increment in echo intensity that were not evident with routine gray-scale imaging. Thus, realtime color coding may improve the detection of myocardial perfusion with echocardiographic contrast agents. © 1994 John Wiley & Sons, Inc.     

Induction of spermatogenesis in isolated hypogonadotropic hypogonadism with exogenous human chorionic gonadotropin

A 21-year old male patient with isolated hypogonadotropic hypogonadism (IGD) is described. Basal serum levels of testosterone (0.5 ng/ml), FSH (2.1 mIU/ml) and LH (2.3 mIU/ml) were low and did not respond to administration of clomiphene citrate. The FSH and LH responses to LHRH were normal. Pituitary-thyroid and pituitary-adrenal function as well as GH reserve were also normal. However, prolactin (PRL) response to both TRH and metoclopramide were blunted compared with normal male subjects. The patient was treated with human chorionic gonadotropin (HCG). Within 20 months he developed full testicular maturation with spermatogenesis and full androgenization. Serum testosterone levels rose to 6.5-13.5 ng/ml. Both basal serum PRL levels and the response to TRH and metoclopramide became normal. Spermatogenesis and androgenization proceeded in the absence of FSH. These results suggest further trials of treatment with HCG alone in patients with IGD are warranted.