Education of medicinal chemists in Departments of Medicinal Chemistry (U.S.A.)

We have evaluated three-week-old compression lesions of the rat spinal cord using two-dimensional and three-dimensional morphometry, reconstruction, and visualization techniques. We offer a new computer assisted method to determine the number and density of macrophages within the spinal lesion using the macrophage specific monoclonal label ED1. We also provide quantitative information on pathological cyst formation and cavitation. This technique does not require: (1) subjective identification of the cell type, (2) human interaction with the data during the phase of quantification, and (3) can be applied to any sampling paradigm based on immunocytochemical labeling. Using novel algorithms based on solutions to 'correspondence' and 'branching' problems inherent in cross-sectional histological data, we provide three-dimensional reconstructions and visualizations of the macrophagic lesions and cysts imbedded within it. Our three-dimensional surface reconstructions can be interrogated to determine volumes and surface areas of structures within the data set. Using these methods we have learned that macrophage numbers approach the maximum density possible for such isodiametric cells (approximately 12 microm diameter) in the central lesion ranging from 4000-7000 cells per mm2 of lesion. At the time point studied, macrophage numbers would have peaked following the initial insult, and would not be expected to decline for several months. While the density of macrophages is highest in the region of most tissue damage, we show that the central regions of cavitated and cystic spinal parenchyma is not. We discuss how this density of cells may effect the secondary pathological responses of the spinal cord to injury.     

Subcutaneous compared with intravenous epoetin in patients receiving hemodialysis. Department of Veterans Affairs Cooperative Study Group on Erythropoietin in Hemodialysis Patients

BACKGROUND: Several studies have suggested that if recombinant human erythropoietin (epoetin) is administered subcutaneously rather than intravenously, a lower dose may be sufficient to maintain the hematocrit at a given level. METHODS: In a randomized, unblinded trial conducted at 24 hemodialysis units at Veterans Affairs medical centers, we assigned 208 patients who were receiving long-term hemodialysis and epoetin therapy to treatment with either subcutaneous or intravenous epoetin. The dose was initially reduced until the hematocrit was below 30 percent and then was gradually increased to a level that would maintain the hematocrit in the range of 30 to 33 percent for 26 weeks. We compared the average doses in the 26-week maintenance phase and the discomfort associated with the two routes of administration. RESULTS: For the 107 patients treated by the subcutaneous route, the average weekly dose of epoetin during the maintenance phase was 32 percent less than that for the 101 patients treated by the intravenous route (mean [+/-SD], 95.1+/-75.0 vs. 140.3+/-88.5 U per kilogram of body weight per week; P<0.001). Only one patient in the subcutaneous-therapy group withdrew from the study because of pain at the injection site, and 86 percent rated the pain associated with subcutaneous administration as ranging from absent to mild. CONCLUSIONS: In patients receiving hemodialysis, subcutaneous administration of epoetin can maintain the hematocrit in a desired target range, with an average weekly dose of epoetin that is lower than with intravenous administration.     

Stability of plasma-polymerized allylamine films with sterilization by autoclaving

BACKGROUND: Survey data on the prevalence of use of oral snuff (toombak) and cigarette consumption according to various demographic factors are needed in the Sudan. METHODS: A house to house cross-sectional survey of a random population sample of 4,535 households was performed. Of the 23,367 household members identified, 21,648 (92.6%) eligible individuals were questioned about tobacco use. RESULTS: Among children and adolescents (4-17 years) prevalence of tobacco use was quite low (2%, range 1-2%), but there was an abrupt increase up to 25% in late adolescence. Among the adult population aged 18 years and older the prevalences of toombak use (34%) and cigarette smoking (12%) among males were significantly higher than among females (2.5 and 0.9%, respectively). The prevalence of toombak use among the male population aged 18 years and older was significantly higher in the rural than in the urban areas (35% vs 24%), while cigarette smoking had a higher prevalence in urban areas (18% vs 12%). The highest rates of toombak use were found in rural areas among the male population ages 30 years and older (mean 46.6%, range 45-47%). CONCLUSIONS: In view of the high prevalence of tobacco use, especially of toombak, among the population surveyed, there is an urgent need to educate the public on the health consequences of these habits.     

Design of hypoxia-targeting radiopharmaceuticals: selective uptake of copper-64 complexes in hypoxic cells in vitro

A freehand technique of patellar resurfacing using anatomic references was prospectively evaluated. This technique utilizes an osteotomy beginning at the inferior pole of the patella just posterior to the insertion of the patellar tendon and is carried proximally posterior to the insertion of the quadriceps tendon. Evaluation of 55 total knee arthroplasties in 41 patients showed an average restored patellar thickness within 0.1 mm. The overall patellar thickness was restored to within 1 mm of its preoperative thickness in 50 (91%) of 55 knees. Patellar tilt was equal to or less than 4 degrees in 42 (89%) of 47 arthroplasties evaluated radiographically. The patellar thickness averaged 17.9 mm, well above the critical value of 15 mm reported in the literature.     

Lepidopterism: two cases of systemic reactions to the cocoon of a common moth, Chelepteryx collesi

Lepidopterism is a general term for the ill-effects to humans from contact with moths and butterflies. We describe two cases of systemic reactions after contact with the cocoon of the Australian species Chelepteryx collesi, or white-stemmed gum moth--irritant and toxic effects in one and a systemic allergic reaction in the other. Early removal of urticating hairs from the skin in such cases may be advisable.     

Vestibular-evoked electromyographic responses in soleus: a comparison between click and galvanic stimulation

The aim of this study was to demonstrate, if possible, vestibulospinal reflex responses in soleus using a stimulus known to be capable of exciting vestibular afferents, namely 100-dB (NHL) clicks. We were able to show short-latency electromyographic (EMG) responses after clicks in five of eight normal subjects, and then we compared these responses with those after transmastoid galvanic stimulation (12 normal subjects). Stimulation of the side towards which the head was rotated (i.e. the side facing backwards) with either clicks or the cathode (anode applied to the opposite side) gave an initial excitatory response in soleus, while click or cathodal stimulation of the opposite side (i.e. the side facing forwards) gave an initial inhibitory response. Onset latencies and modulation with changes in postural task were identical for both click- and galvanic-evoked responses. In addition, there was a significant correlation between the amplitudes of the responses in soleus after click and galvanic stimulation (R2=0.72). These similarities suggest that the earliest reflex responses in soleus after clicks and galvanic stimulation may be mediated by a common central pathway. In contrast, there was no correlation between the amplitudes of responses evoked by 100-dB clicks in soleus and those evoked by the same stimulus in the sternocleidomastoid. We conclude that vestibular activation by clicks can evoke reflex responses in lower-limb muscles and these responses have similar characteristics to the earliest responses evoked by galvanic vestibular stimulation.