Biomedical subjects
R L Morgan
Publications and source records attributed to R L Morgan.
Skin irritation testing in rabbits complicated by dermal mucormycosis.
Two insecticide formulations were evaluated for skin irritation using albino rabbits (Stauffland-White strain). While the active ingredient alone produced only mild skin irritation, corn grit formulation produced severe skin irritation. Corn grit from three sources (A, B, and C) was similarly evaluated for skin irritation and at 24 hr, all samples produced erythema and edema of both the abraded and nonabraded test sites. Eschar was observed in 72 hr in about half of the rabbits and persisted through termination on the 7th day. Histologic examination of skin specimens revealed that all three corn grit samples produced epidermatitis. In addition, rabbits exposed to corn grit from two sources (A and B), developed moderate focal to severe diffuse suppurative necrotizing folliculitis and dermatitis. Large tubular branching nonseptate hyphae compatible with the Mucorales species were seen in hair follicle micropustules of rabbits treated with corn grit from sources A and B. Mycologic culture techniques applied to corn grit from each source revealed a potential pathogen in the genus Rhizopus isolated from samples from sources A and C but not B. The skin irritation test involved application of test material covered with gauze to both abraded and nonabraded skin. Rubber damming was placed over the gauze and secured with tape. After 24-hr exposure all bandaging and visible test material were removed. Skin irritation was evaluated immediately after removal and then periodically until termination at 7 days.
Recent perspectives on the toxicodynamic basis of cyanide antagonism.
The mechanism of action of nitrite-thiosulfate (Chen et al., 1933a ,b; Hug , 1933) in the antagonism of the lethal effects of cyanide is much more complex than proposed 50 years ago. Some of the recent findings concerning the mechanism of nitrite action have conceptual theoretical and practical significance, as the development of newer cyanide antagonists are dependent on the elucidation of the basic mechanism of antidotal action. There are preliminary evidence which suggest a vasogenic action rather than methemoglobin formation is the primary action of nitrite, as a cyanide antagonist. Various vasogenic compounds have been uncovered and they may play an important role in the future development of a new class of cyanide antagonists. Also recent development in thiol detoxication of cyanide suggest that rhodanese may play a more complex role. The detoxification of cyanide may be viewed from a considerably more complex perspective with the elucidation of recent mechanisms. It also may provide a newer conceptual basis for a more rational development of future compounds to antagonize the lethal effects of cyanide.
Effects of thiosulfate on cyanide pharmacokinetics in dogs.
One method to treat cyanide poisoning involves the administration of a combination of sodium thiosulfate and sodium nitrite. Sodium thiosulfate is believed to exert its antidotal effect by serving as a sulfur donor, thereby increasing the rate of rhodanese catalyzed biotransformation of cyanide to thiocyanate. To gain insight into the mechanism of action of thiosulfate on cyanide toxicity, a pharmacokinetic analysis of cyanide distribution and metabolism with and without sodium thiosulfate was conducted in mongrel dogs. A compartmental model for thiocyanate, the major metabolite of cyanide, was developed from plasma concentrations determined at various times after iv administration of thiocyanate; sodium thiosulfate did not alter thiocyanate-model parameters. The model for thiocyanate was coupled to a model for cyanide, and model based equations were fitted to the blood levels of both cyanide and thiocyanate that were measured after iv administration of cyanide. This kinetic analysis showed that thiosulfate increased the rate of conversion of cyanide to thiocyanate over 30-fold. The mechanism of thiosulfate protection appeared to be due to extremely rapid formation of thiocyanate in the central compartment, which thereby limited the amount of cyanide distribution to sites of toxicity.
In vivo incorporation of a cholesterol-like fluorescent probe into rat brain membranes.
The incorporation of the fluorescent sterol analog, cholesta-5,7,9-trien-3 beta-ol, into rat brain P2 fractions and its feasibility to detect membrane perturbations by polarization analysis were evaluated. This investigation involved the administration (i.c.v.) of the fluorescent compound in sesame oil with subsequent determination of optimal dose and the half-life of this compound within the membrane fraction. The dose giving maximum polarization was found to be 0.65 mumole, and pharmacokinetic analysis revealed that the disappearance of this analog followed a two-compartment open model with an elimination half-life from the membrane fraction of 655 hr. Increasing temperature of the membrane preparation showed an increase in polarization, indicating a consequent decrease in mobility of the molecule, while addition of a fluidizing agent like ethanol caused a decrease in polarization, and thus the expected increase in fluidity.
The changing-criterion design: assessment of running behavior of a handicapped youth.
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Differences in 15-hydroxyprostaglandin dehydrogenase activity in male and female rat kidneys.
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The effect of ethanol tolerance on cholesterol organization and Na+-K+-ATPase activity in rat brain membrane fractions.
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Myasthenia gravis and premature ovarian failure.
Myasthenia gravis is believed to be an autoimmune disorder that results from antibodies directed against acetylcholine receptors. Not infrequently, it is associated with other autoimmune diseases, and, recently, several cases have been reported of coexistent premature ovarian failure. A 25-year-old nullgravida woman with myasthenia gravis became amenorrheic and then had ovarian failure with increased gonadotropin and negligible estrogen levels. Other endocrine functions were normal. An in vitro assay demonstrated the presence, in serum, of an inhibitor of binding to the luteinizing hormone (LH) receptor that suggested the possibility of a similar autoimmune process underlying the myasthenia gravis and premature ovarian failure. This could be the first case in which both disorders occurred with evidence for an LH receptor antagonist.
Fluorometric determination of cyanide in biological fluids with p-benzoquinone.
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Immunization of suckling pigs against enterotoxigenic Escherichia coli-induced diarrheal disease by vaccinating dams with purified K99 or 987P pili: antibody production in response to vaccination.
Pilus-specific antibody levels measured by enzyme-linked immunosorbent assays in serum and colostrum of pregnant swine (dams) were shown to increase after parenteral vaccination with pili. Pilus-specific antibody levels in dams were correlated with protection of their suckling offspring against fatal diarrhea caused by enterotoxigenic Escherichia coli possessing the same pilus as the vaccine.
Antagonism of cyanide intoxication with sodium pyruvate.
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Resolution of thiosulfate interference in cyanide determination.
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Small cell carcinoma: combined approach to treatment.
Fifty-six patients with untreated small cell carcinoma of the bronchus were treated with three courses of chemotherapy (cyclophosphamide, vincristine, and procarbazine and methotrexate) and assessed for response. Thirty-one patients (55.4%) were classified as responders; they were given a course of radiotherapy and were then randomly allocated to continued cyclical chemotherapy or not further chemotherapy until relapse. Non-responders to chemotherapy were treated with radiotherapy or palliatively. The median survival was 10.5 months in responders and 6 months in non-responders (P less than 0.01). The one-year survival in responders was 42%. There was no statistical difference in survival between patients treated with continued chemotherapy and those treated at relapse. Sixty-nine per cent of patients experienced no side effects from chemotherapy. Three indicators of non-response to chemotherapy were identified--exercise tolerance at diagnosis, macroscopic liver metastases, and inappropriate ADH secretion.
Immunization of suckling pigs against enterotoxigenic Escherichia coli-induced diarrheal disease by vaccinating dams with purified 987 or K99 pili: protection correlates with pilus homology of vaccine and challenge.
Pregnant gilts were vaccinated with purified strain 987 pili (987P), strain K99 pili, or a saline-formaldehyde control. Suckling pigs born to vaccinated gilts were allowed to consume colostrum and were then challenged intragastrically with one of three enterotoxigenic Escherichia coli strains: 987 (O9:K103, 987P:NM), 74-5208 (02O:K101, 987P:NM) or 431 (O101:K30, 99:NM). In litters where the dam was vaccinated with the same pilus as that possessed by the challenge organism, the incidence and duration of diarrhea and the degree of intestinal colonization (either duration or extent) were less than those of the other vaccine groups. Surviving pigs in the homologous vaccine groups also had better weight gains than pigs in the other vaccine groups. The experiments extend and confirm previous reports that vaccination of the dam with purified pili confers protection to neonatal suckling pigs against diarrheal disease caused by enterotoxigenic E. coli strains that possess the same pili. Protection did not extend to enterotoxigenic strains possessing different pili.
Results of treating primary tumours of the trachea by irradiation.
Forty-four patients presented with primary tumours of the trachea over a 25-year period. Thirty-nine of them were treated by irradiation. Of these, 24 (61.5%) died as a result of their disease while 30% are either alive and well (4.4-11 years) or have died of intercurrent disease (average four years). Recurrences or metastases when they occurred were in the first two years after diagnosis in all but one patient, who developed local recurrence 3.25 years later. Three patients died of unknown cause (average 5.6 years) after irradiation. Two factors seem to determine the prognosis: the histology and the extent of disease on presentation. Dysphagia without oesophageal involvement carried a grave prognosis.
Combination chemotherapy for small cell carcinoma of the lung.
Sixty-one patients with proven small cell carcinoma of the bronchus were treated by a five-drug pulsed chemotherapy schedule involving cyclophosphamide, vincristine, Adriamycin, methotrexate and prednisolone, given at four-week intervals. The response rate was 60%. All patients also received radiotherapy (4000-5000 rad) to the primary lesion. Survival was identical whether radiotherapy was given first or between the second and third courses of chemotherapy. The survival of responding patients was significantly prolonged as compared both with the non-responders in this series and with a similar group of patients treated only by radiotherapy in this hospital in 1970. The poor results in patients resistant to chemotherapy reflect the fact that 88% of the patients had disseminated disease at the time of diagnosis. The survival of responding patients was not improved over that reported by others as a result of incorporating Adriamycin and prednisolone into the schedule, so there seems no justification for using them in future treatments based on this pattern of chemotherapy. It was possible to identify all responding patients within six weeks of initiating chemotherapy, and a delay of this duration did not affect the efficacy of radiotherapy. Radiotherapy, however, frequently interfered with the subsequent assessment of response to chemotherapy. It therefore seems obligatory to give chemotherapy before radiotherapy in order to determine which patients will benefit from subsequent drug treatment.