Application of paired-ion high-pressure liquid column chromatography to the analysis of L-3,4-dihydroxyphenylalanine metabolites.
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Biomedical subjects
Publications and source records attributed to J Mitchell.
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The analgesic efficacy of fendosal, a new nonsteroidal anti-inflammatory agent structurally related to salicylic acid, was compared with that of aspirin and placebo in 100 patients with postpartum uterine pain in a single oral dose, parallel, stratified, randomized, double-blind design. With 650 mg aspirin and with 200 or 400 mg fendosal, but not with 100 mg, analgesic effects, as measured subjectively by mean pain intensity scores, began within 1 hr and had similar time-effect patterns for the first 4 or 5 hr. Thereafter with the 2 higher doses of fendosal analgesia contimued to increase, reaching a peak at 6 hr (p less than 0.05) and persisting beyond 7 hr (p less than 0.01), whereas there was no aspirin analgesia after the fifth hour. With 100 mg fendosal time of onset tended to be delayed 2 hr or more, and duration was short. The most effective treatment (largest mean 7-hr sum of pain intensity difference [SPID] scores) was 400 mg fendosal (p less than 0.01); 200 mg fendosal was rated second (p less than 0.01), 650 mg aspirin, third (p less than 0.05), 100 mg fendosal, fourth, and placebo, fifth. There was no significant side effects. These results demonstrate the efficacy of single doses of fendosal as well as the dose-dependent magnitude and time course of effects on postpartum uterine pain.
Guinea-pig inferior mesenteric ganglia (IMG)/hypogastric nerve preparations were incubated in tissue culture media containing ethylene glycol-bis-(beta-aminoethyl ether)N,N'tetra-acetic acid (EGTA) or colchicine and examined either by fluorescence microscopy or by transmission electron microscopy. Two millimolar EGTA inhibited the accumulation of noradrenaline (NA) fluophore proximal to a crush, but did not produce an increase in the fluorescent intensity of, or the number of dense-cored vesicles (DCVs) within the neuronal perikarya. Calcium ions, but not magnesium ions, were able to block this effect of EGTA. Preparations incubated in the presence of colchicine (2.5 microgram/ml) showed a reduction in the amount of fluorescent material accumulating proximal to a crush, but an increase in both the fluorescent intensity and the number of DCVs within the neuronal perikarya. The suggestion that calcium ions are required for the synthesis of some part of the NA-containing vesicle rather than for their loading onto the axoplasmic transport mechanism is discussed.
A suspension of kaolin was injected into the cisterna magna of 44 rats at 2 weeks of age. Animals killed at intervals from 5--19 weeks of age showed varying degrees of hydrocephalus. Light microscopy, scanning and transmission electron microscopy revealed stretching and flattening of the ependymal cells but no significant loss of cilia. Histological evidence of periventricular tissue damage in these chronically hydrocephalic animals was only present when the ventricular dilatation was extensive. A quantitative assessment was made of the ependymal and subependymal cell reactions around the lateral ventricles of the hydrocephalic animals. Although the ependymal cells were clearly stretched around the ventricles, there was no apparent proliferation of these cells. An increase in the total number of subependymal cells was observed in hydrocephalic animals when compared with a series of 39 aged-matched controls. The greatest proliferation was in the dorsal and lateral walls of the ventricles which were the regions most severely stretched by the ventricular dilatation. There is evidence that subependymal cells differentiate into astrocytes and microglia so that proliferation of these cells may be interpreted as a response to continuing and progressive brain damage in chronic hydrocephalus. Such progressive tissue damage could adversely affect the developing brain.
To investigate the effects of physical conditioning and deconditioning on the coronary vasculature, eight dogs were exercised by treadmill running. Five dogs were deconditioned by confinement in cages following the conditioning period. A technique was developed and validated for measuring circumflex coronary artery diameter from magnified projections of standardized coronary angiograms. Myocardial capillary density, perimeter, and basement membrane thickness were determined from electron microscopy of serial ventricular septal biopsy samples. Physical conditioning caused a small but statistically significant increase in cross-sectional area of the circumflex artery. Although physical conditioning caused no statistically significant changes in the myocardial capillaries, trends were apparent for increases in density and perimeter of myocardial capillaries and a decrease in basement membrane thickness. Physical deconditioning caused statistically significant reductions in cross-sectional area of the circumflex artery and in myocardial capillary density but little change in perimeter or basement membrane thickness of myocardial capillaries. The results suggest that physical conditioning may be associated with an improvement in coronary vascular capacity which may regress rapidly with deconditioning.
The erythropoietin responsive cells (ERC) in suspension cultures (ERCSC) of fetal mouse liver and the cells producing erythroid colonies in 2-day plasma clot cultures (CFU-E) sediment at similar rates. However, the sedimented fractions containing the majority of nucleated cells show minimal sensivitity to erythropoietin (Ep) and these cells sediment at a slower rate than the ERCSC. The studies suggest that in short-term suspension cultures of fetal mouse liver, Ep acts on morphologically unrecognizable cells to increase the number of hemoglobin-synthesizing cells rather than by increasing the quantity of hemoglobin synthesized per cell. This effect is similar to the principal in vivo action of Ep.
Medicaid requires that physicians who accept Medicaid reimbursement for treating a patient agree to accept its payment as payment in full. Policy instruments under Medicaid's control are both levels of reimbursement and various administrative burdens imposed on physicians by the program. A model depicting the physician's participation decision is developed, and predictions from the comparative statics analysis are discussed. Data came from a 1975--76 survey of fee-for-service physicians. The results indicate that high fee schedules and low administrative burdens are ways to stimulate physician involvement with Medicaid patients. Results on the Medicaid policy instruments and other explanatory variables on the whole lend support to the model of physician behavior proposed earlier in the paper.
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One hundred and five patients with acute bronchitis were treated with co-trimoxazole, and amoxycillin, in a single-blind trial. The present study confirms that co-trimoxazole and amoxycillin are effective, and well tolerated agents, both suitable for the management of acute bronchitis.
The analgesic efficacy of oral naproxen and its sodium salt was compared with that of aspirin and codeine in two separate trials involving 140 and 90 patients, respectively, with postpartum uterine pain in a single-dose, parallel, stratified, randomized, placebo-controlled, double-blind design. With 300 or 600 mg naproxen and with 275 mg naproxen sodium, significant analgesia, measured subjectively by pain intensity differences (PID), was prolonged at least 7 or 8 hr; onset tended to be delayed 2 hr or more. With 650 mg aspirin analgesia began within 1 hr and continued until the fifth hour, while with 60 mg codeine responses were indistinguishable from placebo responses throughout the 8-hr time course. Although time-effect patterns with naproxen sodium and aspirin were different, summed analgesic effects (SPID) showed equal efficacy and superiority over placebo (p less than 0.005). With each of the 2 doses of naproxen, SPID separation from placebo was comparable to that above (p less than 0.02 and 0.005, respectively), but analgesic dose response, though measurable, was not significant. Side effects were not significant with any of the treatments. It appears that naproxen and naproxen sodium are analgesics with efficacy equal to aspirin and may prove to be rational substitutes for currently available analgesics in some painful states in which longer pain relief would be desireable.
Precipitin tests by two different methods, double-diffusion (DD) and counterimmunoelectrophoresis (CIE), and measurements of total and specific IgE against Aspergillus fumigatus were made in 50 patients with chronic allergic bronchopulmonary aspergillosis and in three control groups--atopics with a positive immediate prick test to A. fumigatus but no evidence of allergic aspergillosis, atopics with a negative prick test to A. fumigatus, and non-atopics. Precipitins were found in 84% and 78% of the patients with aspergillosis by the DD and CIE methods respectively. Precipitins were also found in 6 out of 27 (22%) patients with a positive prick test to A. fumigatus but no evidence of aspergillosis and in 1 of 24 patients with a negative prick test to A. fumigatus. The means of specific and total IgE values were significantly higher in the group of patients with aspergillosis than in the three other groups of patients. The increase in specific but not total IgE showed a statistically significant correlation with positive precipitin tests in the patients with aspergillosis. Total IgE but not specific IgE values were significantly higher (0-02 less than P less than 0-05) in patients who had had a transient radiographic shadow in the previous three months. Positive precipitin tests were also significantly correlated with the number of transient shadows in the past and with the interval of time since the last transient shadow.
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Sodium diethyldithiocarbamate, D-penicillamine, and triethylene-tetramine were administered to rats by im injection in dosages equivalent to 0.6 times their respective LD50 values in order to compare their relative effectiveness in prevention of death caused by exposure for 15 min to inhalation of nickel carbonyl (1.4 or 4.2 mg Ni (CO)4/liter of air). When the three drugs were administered to groups of rats at 10 min before or after the exposure to nickel carbonyl, sodium diethyldithiocarbamate was the most effective antidote. In contrast, then the drugs were administered at 6 hr after exposure to nickel carbonyl, D-penicillamine was the most effective antidote. Based upon the combined results of 4 sets of experiments, sodium diethyldithiocarbamate and D-penicillamine were significantly more effective than triethylenetetramine. The authors recommend that sodium diethyldithio-carbamate should remain the chelating agent of choice for therapy of nickel carbonyl poisoning. If sodium diethyldithiocarbamate is not available or if its use is contraindicated, D-penicillamine might be considered as an alternative chelating agent.
beta-Thalassemia is a major public health problem in Algeria. During a survey, a family including two cases of betaO-thalassemia was studied. The family study indicated that two of the affected siblings had homozygous beta-thalassemia; there were also both normal and heterozygous siblings, and both parents had beta-thalassemia trait. In the two cases of betaO-thalassemia there was no hemoglobin A in the peripheral blood, and no beta-globin chain synthesis in whole cell incubations. Hybridization of purified complementary DNA specific for alpha- and beta-globin messenger RNAs demonstrated less than 1% mRNAbeta relative to mRNAalpha in circulating reticulocytes, and for one case in total RNA from bone marrow. There is no apparent beta-globin gene deletion as determined by hybridization in globin cDNAbeta sequence excess. Therefore the Algerian cases studied are similar in molecular pathology to some Southern Italian and Asian cases described previously, and differ from other Italian and Chinese betaO-thalassemias, in which hybridizable mRNAbeta has been demonstrated, and from deltabetaO-thalassemia, which is caused by a gene deletion.
In one southern Italian and one Pakistani patient with homozygous beta0 thalassaemia in which no detectable beta-globin synthesis occurs and no beta-globin messenger RNA is found, the gene for beta globin has been shown to be present using complementary DNA. This demonstrates that for these patients the imbalance in chain synthesis is not attributable to a gene deletion.
Aspirin and codeine, standard reference analgesics, are frequently used as positive controls in clinical trials of new oral analgesics. In randomized parallel double-blind studies, single doses of aspirin and codeine were compared with placebo in episiotomy pain (99 patients) and in postpartum uterine pain (130 patients), common models in analgesic trials. With aspirin, 600 and 1,200 mg, in episiotomy pain, analgesia as measured by pain intensity difference (PID) scores began within 1 hr, peaked at the second hour (p less than 0.01), and continued to the fifth hour (p less than 0.01). In uterine pain, responses with aspirin, 650 mg, were observed to be equally good. With codeine, 60 mg, in episiotomy pain measurable analgesia was present by the second hour and was significant at the fourth hour (p less than 0.05); in uterine pain, responses were indistinguishable from placebo throughout an 8-hr time-course. Codeine seemed ineffective and therefore umacceptable as a positive control in uterine pain. These data imply that the two postpartum pain models are qualitatively different: episiotomy pain seems sensitive to both aspirin and codeine, while uterine pain appears sensitive to aspirin but not to codeine.