Biomedical subjects
J Scott
Publications and source records attributed to J Scott.
5-Thiopyridoxine in rheumatoid arthritis: clinical and experimental studies.
Twelve patients with rheumatoid arthritis who had failed to respond to or developed side effects preventing further use of penicillamine were given 5-thiopyridoxine (5-TP). These patients were compared with 48 patients with similar indications randomly assigned to placebo or penicillamine. Both 5-TP and penicillamine were superior to placebo, and the effectiveness of the two active drugs was similar. Both produced a gradual amelioration of symptoms and signs of the disease accompanied by reduction in erythrocyte sedimentation rate, rheumatoid factor titer, and immunoglobulins. Nine patients on 5-TP were able to continue treatment with good control of the disease for at least 18 months. Toxic effects included rashes, proteinuria, loss of taste, and mouth ulcers. Patients who had developed a particular side effect with penicillamine did not necessarily do the same with 5-TP. This is the second mercaptan compound which has suppressive effects on the clinical and laboratory features of rheumatoid arthritis. Because of their similarities, 5-TP and penicillamine were studied in various experimental systems in an attempt to find some common biochemical or pharmacologic action. Among the properties studied were the effects on copper, vitamin B6 metabolism, dermal collagen, and mixed disulfide formation. Results with animal models of inflammation were also examined. The only common action was enhancement of the secondary lesions of adjuvant arthritis.
Radio-isotope scanning in the painful shoulder.
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Benign recurrent intrahepatic cholestasis: studies of bilirubin kinetics, bile acids, and cholangiography.
Three patients with benign recurrent intrahepatic cholestasis are described. They had had between five and 16 attacks of cholestasis. Between attacks the liver function tests, including serum bile acids, were normal. Serial serum bilirubin and bile acid estimations during the cholestasis in one patient revealed a consistent discrepancy between the serum bilirubin and bile acid concentrations during three consecutive attacks. In the other two patients the serum concentrations of bile acids and bilirubin varied in parallel. Analysis of the individual serum bile acids did not reveal high concentrations of any 'toxic' bile acid. In one patient, plasma bromsulphthalein (BSP) curves were obtained during both remission and cholestatic periods. The 45 minute retention was slightly increased (10.8%) during remission. During the cholestasis, the 45 minute retention (25%) and the fractional extraction coefficient (Ke=0.069 min-1) were markedly abnormal. The hepatic clearance of unconjugated radiobilirubin was normal at all times in this patient, although during cholestasis, conjugated bilirubin reflexed from the liver to the plasma and was then cleared slowly with a half life of approximately 12 hours. Treatment with corticosteroids, cholestyramine, and phenobarbitone was unsatisfactory.
Bile duct carcinoma: a late complication of congenital hepatic fibrosis. Case report and review of literature.
Bile duct carcinoma is reported in a 50-year old man as a rare late presentation of congenital hepatic fibrosis (CHF). A survey of the world literature suggests that carcinoma occurs with increased frequency in congenital biliary dilatation. It appears to be a particular risk in patients with prolonged survival but is rare in CHF, where portal hypertension and renal insufficiency make the long-term prognosis poor. In this patient the absence of both gastroesophageal varices and renal disease may have permitted longevity with development of carcinoma. The finding of carcinoma arising in the bile ducts distal to the basic lesion of CHF suggests that active carcinogens may be present in the bile in CHF. The tumor in this patient was unusual in producing mucinous biliary obstruction and terminal hypercalcemia.
Legionnaires' disease: facts and fancies.
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Qualitative and quantitative observations on the histology of human labial salivary glands obtained post mortem.
Ostensibly non-diseased labial salivary glands from 70 necropsies evenly divided by sex and age between 18-90 years were examined histologically. In each case minor pathological changes in the parenchyma were subjectively graded and a morphometric investigation was made of the proportional volumes of component tissues in the glands. A wide variation was found in the histology throughout the series. Acinar atrophy and ductal dilatation and hyperplasia were frequent, tending to increase with age and affecting females earlier than males. As age increased there was a progressive reduction in proportional acinar volume with corresponding increases in the proportions of ducts and fibrous tissue. A quarter of the series contained foci of lymphorecticular cells mostly in lobules affected by parenchymal atrophy, dilatation and hyperplasia. Occasionally lymphoreticular foci were present in otherwise unaltered parenchyma suggesting, therefore, that such foci may not develop exclusively in rheumatoid diseases, as these conditions had been excluded from the present series.
Management of sickle cell disease in pregnant patients.
Data from a total of 74 pregnancies in 42 patients with sickling disorders seen at Johns Hopkins Hospital are compared with similar data from other centers. Although risks are still higher than those for women without sickle cell disease, they have diminished significantly from those reported earlier. Prophylactic transfusion therapy may decrease these risks further, but benefits of transfusion are unproved at present. Patients with sickling disorders should receive meticulous individualized treatment until further data are made available.
Trial and measure.
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Tolbutamide pharmacogenetics and the UGDP controversy.
We analyzed the relationship between the pharmacogenetics of tolbutamide metabolism and the controversial University Group Diabetes Program (UGDP) study. Before the institution of that study, the extent of genetic control over the variation in the rate of tolbutamide metabolism was unknown, and all subjects included in the tolbutamide treatment group were given 1,500 mg/day of tolbutamide in a fixed dosage. We addressed the hypothesis that high accrued blood levels of tolbutamide in genetically predisposed slow inactivators might have contributed to the toxic effects reported by the UGDP study. This proposal is based on recent findings from population, twin, and family studies that tolbutamide metabolism is under monogenic control, with nearly one fourth of the population classified as slow inactivators.
Nursing care study. Multiple handicap: stimulating Stanley - one small step at a time.
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Genetic control of tolbutamide metabolism in humans.
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Extractive acylation of ethylenethiourea from water.
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The proportional volume of mucous acinar cells in normal human submandibular salivary glands.
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Myocardial subcellular fractionation studies on cardiomyopathic Syrian hamsters.
Myocardial homogenates from control animals and from hamsters with hereditary cardiomyopathy were subjected to analytical subcellular fractionation and enzymic microanalysis. Animals without ventricular hypertrophy or overt heart failure were used in this study. The principal subcellular organelles were characterised by density gradient centrifugation. Apart from evidence of enhanced lysosomal and peroxisomal fragility, probably secondary to the intracellular oedema, the intracellular organelles investigated in this study were unaffected by the myopathic process. Highly significant increases in 5'-nucleotidase activity, a marker for the sarcolemma, and an increased equilibrium density of this organelle were found in the myopathic tissue. Ultrastructural studies revealed patchy myocytolysis associated with lysosomes and with more extensive invaginations of the sarcolemma. It is suggested that a primary defect in membrane composition, leading to increased cation permeability, is the underlying abnormality in the myopathic hamster.
Analgesic and anti-inflammatory properties of indoprofen.
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Treatment of rheumatoid arthritis with a single daily dose of benoxaprofen.
A single daily dose of 600 mg of henoxaprofen has been shown to be more effective than a previously reported dosage regime in patients with rheumatoid arthritis. Increased total daily dosage was not associated with a greater incidence of side-effects. The drug worked slowly reaching a plateau after eight days of treatment. It was usually well tolerated especially by the gastro-intestinal tract.
Effect of rabbit anti-human thymocyte globulin on lymphocyte subpopulations and functions following allotransplantation in the rhesus monkey.
The survival time of skin allografts from RhLA-nonidentical, unrelated donors was increased from a mean of 7.69 days in controls (n = 20) to a mean of 32.53 days in rhesus monkeys (n = 21) receiving a total dose of 250 mg of rabbit anti-human thymocyte globulin (RATG) per kg. Immunological monitoring studies were performed on the peripheral blood of mononuclear cells in control and treated monkeys. After administration of RATG, the percentage of E rosette-forming cells (E-RFC) was greater than 90% depressed, and the percentage of EAC rosette-forming cells was increased 5-fold in the circulation. Significant numbers of RATG-coated cells were detected only during the first week after RATG treatment. The percentage of E-RFC recovered to pretreatment levels within 3 to 4 weeks after RATG treatment, although the absolute E-RFC count remained depressed for 2 to 3 months. In addition, the in vitro proliferative responsiveness to polyclonal mitogens and to allogeneic lymphocytes remained greater than 80% depressed for 2 to 3 months after RATG treatment. The incidence of post-transplant-specific antidonor lymphocyte-mediated cytotoxicity (LMC) was similar in controls (85%) and RATG-treated monkeys (81%), and the appearance of LMC was correlated (r = 0.711) with partial recovery of absolute ERFC counts in the treated group. The appearance and peak of LMC were delayed (P less than 0.001) in RATG-treated monkeys, but preceded and correlated with rejection. Prior to rejection, the serum of RATG-treated monkeys inhibited LMC. Antibody-dependent cellular cytotoxicity appeared after rejection in the majority of recipients in both groups. The appearance and peak of antibody-dependent cell-mediated cytotoxicity (ADCC) were delayed (P less than than 0.001) in RATG-treated monkeys, but did not exhibit a significant correlation with the time of rejection.