[Protracted QT--review and case reports].
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Biomedical subjects
Publications and source records attributed to P Gordon.
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In patients with advanced uterine corpus carcinoma treated with the combination chemotherapy of megestrol, cyclophosphamide, and doxorubicin (MCA) or with this combination and 5-fluorouracil (MCAF), the overall response rate was 22%. There was no significant difference in response rates between the two regimens. There is some indication that survival was longer in ambulatory patients who were treated with MCA, but this combination produced more hematologic toxicity than MCAF. Patients unsuitable for treatment with doxorubicin received megestrol, 1-phenylalanine mustard, and 5-fluorouracil (MLF), which produced objective responses in 2 of 12 patients.
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"An integrated model is proposed to capture economic and demographic interactions in a system of regions. This model links the interregional economic model of Isard (1960) and the interregional demographic model of Rogers (1975) via functions describing consumption and migration patterns. Migration rates are determined jointly with labor force participation rates and unemployment rates."
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The upper limit of the normal bile-duct diameter is significantly smaller by ultrasound than that generally accepted for radiographic techniques. This appears to be due to (a) radiographic magnification, (b) ultrasonic underestimation, (c) a possible choleretic effect of radiographic contrast material, and (d) the fact that different regions are measured with different techniques. The diameter of the common hepatic duct was measured by ultrasound in 30 patients prior to and during intravenous cholangiography, and these measurements were correlated with each other and with the radiographic measurement. In vitro studies were also performed. It was found that the choleretic effect significantly increased duct size in a small percentage of cases. The radiographic magnification was a factor of 1.3, and the ultrasonic diameter was about 1.5-2.0 mm too small. Perhaps the most important cause of the discrepancy was measurement of different regions with different techniques.
In a Canadian population-based case-control study of 480 males and 152 female case-control pairs, the relative risk for development of bladder cancer for ever used versus never used cigarettes was 3.9 for males and 2.4 for females, with a dose-response relationship in both sexes. A reduced risk was associated with the use of filter cigarettes compared to nonfilter cigarettes. After control for cigarette usage, a significant risk was noted for male pipe smokers. For male ex-smokers the risk after 15 years of no smoking was less than one-half that of current male smokers. Bladder cancer risk was found for workers in the chemical, rubber, photographic, petroleum, medical, and food processing industries among males and for workers occupationally exposed to dust or fumes among both sexes. Bladder cancer risk was elevated for males consuming all types of coffee, regular coffee, and instant coffee and for females consuming instant coffee, but no dose-response relationship was found. Risk was found for males consuming water from nonpublic supples but not for females. No risk was observed in males or females consuming nitrate-containing foods, beverages other than coffee, or fiddlehead greens. Hair dye usage in females and phenacetin usage in males and females carried no risk. Divergent findings by area for aspirin suggested that an overall association was not causal. Reevaluation of the data on artificial sweeteners confirmed a significant bladder cancer risk in males and a dose-response relationship. The cumulated population attributable risk for bladder cancer was 90% for males from cigarette smoking, industrial exposure, and exposure to nonpublic water supplies and 29% for females from cigarette smoking, industrial exposure, and instant coffee consumption.
In a series of 56 patients with obstructive jaundice, the presence or absence of calculi in the gallbladder has been correlated with the cause of the obstruction. Seven of 23 patients with obstruction caused by stone had no calculi in the gallbladder. Twelve of 33 patients with obstruction due to tumor also had gallstones. It was concluded that the presence of calculi in the gallbladder is a poor indicator of the cause of obstructive jaundice.
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When cultured human lymphocytes (IM-9) are exposed to 10(-6) M procine insulin for 6 h, washed, and incubated with 125I-insulin, the ability of the cell to bind the labelled hormone is reduced by a mean of 78%. Under these experimental conditions that induce insulin-receptor loss in this cell there is a mean 95% increase in microinvaginations in the plasma membrane revealed by electron microscopy on freez-fractured replicas of the cell. At the same time, horseradish peroxidase uptake, a marker of endocytosis, is increased in the cells incubated with insulin. Coupled with our recent EM autoradiographic evidence that labelled insulin is acutely internalized by this cell, these studies are consistent with the possibility that endocytosis represents a mechanism by which receptor is removed from the cell surface.
A positive association between the use of artificial sweetners, particularly saccharin, and risk of bladder cancer in males has been observed in a case-control study of 480 men and 152 women in three Provinces in Canada. The risk ratio for ever versus never used is 1-6 for males (P=0-009, one-tailed test), and a significant dose-response relationship was obtained for both duration and frequency of use. The population attributable risk for males is estimated at 7%, though for diabetics, who have a similar risk ratio for artificial sweetner use as non-diabetics, the attributable risk is 33%.
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A method for the measurement of immunoglobulin G associated with gel-filtered platelets is described and finding in 70 control subjects and 37 patients with immune thrombocytopenic purpura (ITP) are reported. Control platelet-associated IgG (PAIgG) levels (nanograms IgG per 10(9) platelets) averaged (+/-SD) 1231+/-424; samples studied after 24 and 48 hr remained within the control range. PAIgG values of 19 adult and 12 childhood patients with chronic ITP averaged 4711+/-3025 and 4923+/-3955, respectively, and differed significantly from controls (p less than 0.001). There was an inverse correlation between PAIgG values and the chronic ITP patient's platelet count. Six patients with childhood acute ITP had PAIgG levels ranging from 5588 to 56,250 and appeared to represent a different statistical population from those with chronic ITP. In chronic ITP patients responding to splenectomy, there was an immediate normalization of PAIgG levels; however, a certain percentage of patients studied several months after splenectomy evidenced elevated PAIgG levels in association with normal platelet counts. These data showed that the direct measurement of platelet associated antibody is a useful technique in the diagnosis and follow-up of patients with chronic ITP. Preliminary studies in patients with acute ITP have suggested that this method may be useful in differentiating acute and chronic childhood ITP.
Five-milligram doses of d-, l- and dl-methadone were added to the perfusate of the isolated perfused rat liver and the disposition of each compound was monitored over a period of 120 minutes. There was an initial rapid decline in concentration of each drug in the perfusate, with approximately 70% disappearing in the first 10 minutes of the perfusion. Thereafter, the rate of decline of each compound slowed and the apparent half-life was about 100 minutes. In experiments with d- l- and dl-methadone the mean hepatic extraction from the perfusate at 10 minutes was 72, 66 and 69%, respectively. A comparison of the rate of disappearance of the d- and the l-isomers from the perfusate showed that the concentration of the d-isomer at each sampling time was lower than the concentration of the l-isomer and this concentration ratio ranged between 68 and 79%. A study of the disposition of dl-methadone in the isolated perfused liver indicated that the initial rapid decline of the drug in the perfusate in the first 10 minutes was caused primarily by the uptake of the unchanged drug into the liver. Thereafter, the concentration of methadone in the perfusate and liver declined slowly with time and was paralleled by an increase in the concentration of the primary mono-N-demethylated metabolite, which appeared in the liver, perfusate and bile. Smaller quantities of more polar metabolites, including hydroxylated compounds and conjugates, were also present in the liver and bile. Addition of SKF 525-A retarded the rate of decline of methadone from the perfusate and pretreatment of the rat with phenobarbital increased the rate of biotransformation of methadone in the isolated perfused liver.