Neurotoxicology of spinal agents.
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Biomedical subjects
Publications and source records attributed to D W Coombs.
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This study was designed to test the hypothesis that administration of clinical doses of cimetidine could affect the metabolic degradation of enflurane to inorganic fluoride via inhibition of the mixed function oxidase enzyme (MFOE) system. In Part 1 of the study 38 female patients undergoing gynaecologic surgery received, double blind, either cimetidine, 300 mg PO the night prior to surgery and 300 mg IV 30 minutes prior to anaesthesia induction or a placebo. In Part 2, 24 patients received either cimetidine as in Part 1, but with continued administration for 24 hours into the postoperative period, or a placebo. Anaesthesia in all cases was with enflurane in oxygen, via a closed circuit. In both Parts 1 and 2 of the study there were no statistically significant differences between the two groups in serum fluoride levels at baseline, four hours or 24 hours postoperatively, or in the total urinary fluoride excretion during the first or second postoperative days. The authors speculate that this is due either to separate interactions of cimetidine and enflurane with the MFOE system or to the relatively low rate of enflurane metabolism.
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Alcoholism and alcohol-related problems in Latin America constitute a serious problem that may be increasing despite variations by ethnicity, country, and other variables. Ethnographic studies since 1940 suggest that heavy, convivial drinking among adult males for recreational reasons is common and has been for some time. Epidemiological surveys and ethnographic research since 1960 suggest that social changes accompanying urbanization and modernization are introducing escapist/utilitarian motives for drinking that interact with traditional recreational motives to cause increasing alcohol use and alcoholism. A resource table on use patterns in Latin America is provided.
The use of hydromorphone and clonidine, delivered intrathecally by an implanted infusion pump, is described in a patient with intractable cancer pain. The patient was a 48-year-old woman with uterine cervical cancer-related pain that was poorly responsive to conventional oral narcotics. Hydromorphone was used because of the patient's history of morphine intolerance. When progressive intrathecal hydromorphone dosages were required, intrathecal clonidine (an alpha 2 adrenergic agonist) was infused concomitantly. Intrathecal hydromorphone and clonidine successfully controlled this patient's pain without the necessity to resort to destructive neurosurgery.
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Factors that help determine physicians' practice locations and specialties were listed by 396 students and 103 medical school faculty members at the University of Alabama School of Medicine. The students preferred practice locations similar in size to their hometowns. Their specialty choices were closely related to both practice location preferences and hometown sizes. However, there was a tendency among the students to prefer a small city (20,000 to 100,000 population) practice location irrespective of their hometown sizes or specialty choices. Factors such as spouse's preference, proximity of relatives, and financial incentives were not related to the students' practice location preferences. Faculty members reported they believed that medical education biases students toward urban and nonprimary care practice, and one-third of them said that they were role models for the students' specialty choices. However, the students said faculty members had little influence on their specialty choices while acknowledging the importance of clinical experiences. In general, Alabama medical students are similar to medical students elsewhere with respect to determinants of practice location preference.
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Preliminary reports of continuous intraspinal morphine analgesia have been enthusiastic regarding the resultant cancer pain control. Reports of continuous intraspinal infusion have not documented the duration of useful analgesia, need for concomitant analgesic therapies, or complication rates. Thus, the overall outcomes and complications of six chronic intrathecal and eight epidural morphine infusions were analyzed in the first 14 cancer pain patients implanted with continuous intraspinal morphine infusion reservoirs at this clinic. A five-point scale was used to assess the analgesic therapy required to maintain pain control during three consecutive intervals of intraspinal morphine infusion (zero to two months, two to six months, after six months). Comparison with pre-implant narcotic requirements revealed equal or reduced narcotic use for up to six months of therapy, with a definite trend toward escalation of intraspinal narcotics, systemic analgesia, and adjunctive procedures after two months. This occurred most likely due to narcotic tolerance and disease progression. Failure of pain control was the rule with continuous intraspinal morphine after six months. Three patients ultimately required neurolytic blocks. No clear difference was found in pain control requirements between epidural and intrathecal morphine infusion. No infection or respiratory depression occurred as a direct result of the intraspinal morphine implanted system.
After toxicity studies in dogs, a preliminary feasibility trial of the continuous intracranial infusion of a muscarinic agonist was begun in four patients with biopsy-documented Alzheimer's disease. During the last 8 months, a totally implantable infusion system has been used to deliver bethanechol chloride into the cerebrospinal fluid of these patients at doses of 0.05 to 0.7 mg/day. Complications have been few and resolved spontaneously or were easily reversible. The subjective response to this treatment has been encouraging, with reports of improved cognitive and social function during drug infusion and a return to base line function with single-blind saline placebo infusions. Obviously, further evaluation will be necessary to demonstrate the efficacy of this treatment, and a double-blind placebo-controlled crossover trial is now being done. However, we think the preliminary results are encouraging and warrant the consideration of this approach as a potential treatment in patients with Alzheimer's disease.
Since the 1960s, there has been a massive effort to reduce suicide mortality in the United States through prevention centers which invite suicidal persons to phone for supportive services. In spite of virtually total lack of evidence concerning the efficacy of these services, they proliferated until, by 1973, nearly every metropolitan area in the United States had at least one. Suicide rates increased slightly throughout this time. We studied 1968 through 1973, the years of greatest growth of suicide prevention facilities, comparing suicide rates in counties that added these centers with counties that did not do so. An association of centers with the reduction of suicides in young white females emerged. This finding was replicated on a different set of counties for a different time span. The results are discussed in light of the fact that this group constitutes the major clients of these centers.
The effect of morphine sulfate concentration on flow rate in an implantable pump was studied. Solutions containing morphine sulfate 5 mg/3 ml, 10 mg/3 ml, 20 mg/3 ml, and 200 mg/3 ml were prepared from morphine sulfate powder; a solution containing morphine sulfate 20 mg/3 ml with bupivacaine hydrochloride 0.125% was also prepared. Sterile water was used for preparing the morphine solutions and as the control solution. A model 400 Infusaid pump was filled with 50 ml of the drug solution, placed in a water bath at 37 degrees C, and allowed to equilibrate for three hours. Samples of each concentration of morphine solution and control solution were then collected in an analytical graduate over 20-hour periods. Between each collection period, the pump was flushed twice with sterile water. Five samples of each morphine solution and control solution were collected. The osmolality of one sample of each solution was determined to assess drug concentration indirectly; morphine sulfate concentrations were not actually measured. Actual solution volumes collected during the 20-hour collection periods were corrected to 24 hours to allow comparison with the pump's preset daily flow rate. Collection volumes and calculated daily flow rates decreased with increasing morphine sulfate concentrations and solution osmolalities; a significant positive correlation between osmolality and assumed drug concentration was found. The flow rate of the solution containing morphine 200 mg/3 ml was approximately equal to the pump's stated flow rate; flow rates for all other solutions were higher than the stated flow rate.(ABSTRACT TRUNCATED AT 250 WORDS)