McMaster's link with Pakistan.
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Biomedical subjects
Publications and source records attributed to N Edwards.
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The in vivo metabolism of dihydrotachysterol3, an analogue of vitamin D3 and a potent calcemic factor, has been studied in the rat. This in vivo metabolism is compared to the in vitro metabolism of 25-hydroxydihydrotachysterol3 in the perfused rat kidney. Using mass spectrometry and ultraviolet spectroscopy, we have identified seven novel metabolites derived from 25-hydroxydihydrotachysterol3. The seven compounds represent intermediates on two renal pathways (24-oxidation and 26,23-lactone formation) also observed for 25-hydroxyvitamin D3. No evidence was found for the renal synthesis of a 1-hydroxylated metabolite of 25-hydroxydihydrotachysterol3 analogous to the hormone 1,25-dihydroxyvitamin D3. Two of the compounds formed in vitro, 24,25-dihydroxydihydrotachysterol3 and 25-hydroxydihydrotachysterol 26,23-lactone, were also formed in vivo. In vivo studies also revealed the formation of two other unidentified metabolites which are presumed to be formed nonrenally and may be calcemic factors. This work shows that dihydrotachysterol3 metabolism is complex and probably utilizes the same side-chain enzymes as vitamin D3. In addition, our work also confirms that intermediates postulated to lie on pathways to 26,23-lactone in the vitamin D3 series are also formed for the side chain in dihydrotachysterol3.
A number of factors were identified which influence the determination of red blood cell glucose 6-phosphate dehydrogenase (G6PD). White blood cells were effectively removed from whole blood by filtration, resulting in a mean reduction of G6PD activity of greater than 1.0 U/g Hb. Optimal enzyme activity was found using haemolysates with a Hb concentration in the range 0.4-1.2 g/dl. At a constant temperature of 30 degrees C, maximum linear rate of activity was achieved between the 10th and 20th min after initiation of the reaction. As a result of these findings, modifications to standardize the assay system were introduced. The new method exhibits excellent precision (CV less than 2.0%) with normal samples, and 95% reference ranges of 7.00-11.15 U/g Hb for adult females and 7.05-10.75 U/g Hb for adult males.
A new procedure for measuring the outflow facility in conscious rabbits is described. The Langham pneumatic tonometer is applied horizontally against the eye; the intraocular pressure (IOP) is recorded before, during and immediately following 2 min of a pre-determined increased ocular pressure that is maintained at a fixed value by digital pressure applied through the eyelids. An increased volume of aqueous humor outflow resulting from the IOP increase is evaluated from the initial and final IOP values and the pressure volume relation for eyes of living rabbits. Close agreement in values of the outflow facilities in pairs of eyes of individual rabbits and excellent reproducibility of the procedure were found in repeated measurements made over a 24-hr period. The mean values of the IOP and the total outflow facility in 60 eyes of 30 rabbits were 20.5 +/- 0.2 mmHg and 0.17 +/- 0.01 microliter min-1 mmHg-1 respectively. Thirty minutes after an intravenous injection of acetazolamide, the IOP had decreased in both eyes of individual rabbits. This was associated with a decrease in the outflow facility and with a decrease of more than 50% in the rate of aqueous humor formation. One hour after the unilateral application of epinephrine the IOP had decreased in the treated eyes while the outflow facility remained unchanged.
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Neuropsychologic tests of cerebral integrity recorded impairments in visuopractic and learning capacity in patients with Wilson's disease. These psychometric findings point to the presence of a subclinical encephalopathy that is not otherwise revealed upon clinical examination.
Subjects with three different types of hepatic cirrhosis were compared on a battery of neuropsychological tests to determine if cerebral dysfunction varied according to the type of liver disease. It was found that the manifest cognitive impairments varied according to the type and etiology of the liver disease. These findings underscore the sensitivity of neuropsychological tests in the detection of hepatic encephalopathy, particularly in cases where there are no overt clinical signs or symptoms of neurologic disturbance. They also suggest that the nature and severity of the measurable neuropsychological abnormalities may vary within patient populations depending upon the etiology of the individual's liver disease and the specific pathophysiological mechanisms involved in its progression.
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The relationship between serum 25-hydroxyvitamin D (25-OHD) concentrations and sunshine exposure in 61 term, exclusively breast-fed infants younger than 6 months of age was investigated. Sunshine exposure was quantitated using a sunshine and clothing diary, which was verified by infant-adapted ultraviolet dosimetry. By multiple regression techniques, infant serum 25-OHD concentrations were significantly related to UV exposure and maternal serum 25-OHD concentrations. Infant 25-OHD concentrations correlated with sunshine exposure in infants whose mothers had low (less than 35 ng/ml) or high (greater than 35 ng/ml) serum concentrations of 25-OHD (r = 0.70, P less than 0.001 and r = 0.53, P = 0.004, respectively). Estimates were made to determine sunshine exposure conditions necessary to maintain serum 25-OHD concentrations above the lower limit of the normal range (11 ng/ml). A conservative estimate would be 30 minutes per week wearing only a diaper or 2 hours a week fully clothed without a hat.
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