Hereditary xanthinuria presenting in infancy with nephrolithiasis.
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Biomedical subjects
Publications and source records attributed to D Nelson.
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An orifice equation is derived relating the effective aortic valve area, A, the average aortic valve pressure gradient, dP, the stroke volume, SV, and the heart frequency, FH, through considerations of momentum conservation across the aortic valve. This leads to a formula consistent with Newton's second law of motion. The form of the new equation is A = (7.5 X 10(-5)) SV FH2/Pd, where A, VS, FH and Pd are expressed in cm2, ml, s-1 and mmHg, respectively. Aortic valve areas computed with the new orifice equation are found to correlate with those computed by the Gorlin formula in conditions of resting haemodynamic states at a level of r = 0.86, SE = 0.25 cm2, N = 120. The results suggest that the new formula may be considered as an independent orifice equation having a similar domain of validity as the Gorlin formula. The new equation offers the possibility of deriving additional useful haemodynamic relationships through combination with established cardiological formulas and applying it in a noninvasive Doppler ultrasonic or echocardiographic context.
A rapid sample preparation procedure, which requires no solvent extraction or concentration, for the high performance liquid chromatographic (HPLC) determination of disopyramide is described. The chromatography is performed on a C-18 radial compression mu-Bondapak column and detection by absorbance at 254 nm with a run time of 12 min. The mobile phase is 10 mM sodium acetate (pH 4.5)/acetonitrile (3:1 vol/vol). For the total drug assay, 50 microliter 30% (wt/vol) trichloroacetic acid is added to 500 microliter serum, which causes the precipitation of protein. Following centrifugation, 100 microliter of supernatant is mixed with 25 microliters of internal standard (25 micrograms/ml, ethyl p-aminobenzoate), and 50 microliters of this mixture is injected into the HPLC. Unbound disopyramide is separated from protein-bound drug by filtration with an Amicon Centrifree filter, which removes 99.6% of protein and does not retain disopyramide. To 100 microliters of this filtrate is added 25 microliters of internal standard, and 50 microliters is injected into the HPLC. The assay is linear to at least 20 micrograms/ml. The total drug assay shows an average recovery of 93.0% with an average coefficient of variation (CV) of 3.4%. The unbound drug assay shows an average CV of 4.1%. The percentage of free drug in a sample containing 4.85 g/dl protein varies from 68.0 to 83.5% at concentrations of 2.5-10 micrograms/ml, which illustrates the concentration-dependent nature of the protein binding, and the need to measure the unbound fraction of drug. Of 31 drugs tested for interference, none was found to interfere.
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In 33 patients with end-stage renal disease undergoing chronic dialysis, serum parathyroid hormone (PTH) levels were correlated with serum concentrations and dietary intakes of calcium and phosphate. The average dietary calcium intake (549 +/- 54 mg/24 h) was lower than the recommended dietary allowance. There was a weak correlation between serum PTH and serum calcium concentrations (r = 0.39, p less than 0.03). There was also a significant negative exponential relationship between dietary calcium intake and serum PTH (y = 162e-0.0016x, r = 0.61, p less than 0.002). Likewise, when divided into low calcium (less than 500, 304 +/- 27 mg/24 h) and modest calcium (greater than 500, 809 +/- 56 mg/24 h) intake groups, in the low calcium-intake group, serum PTH (128 +/- 20 pg/ml) was more than 2-fold greater than that in the modest calcium-intake group (53 +/- 8 pg/ml, p less than 0.003). These results suggest that low dietary calcium intake may contribute to the occurrence of secondary hyperparathyroidism in patients with chronic renal failure undergoing chronic dialysis.
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The number of specific [3H]ouabain binding sites in T-lymphocytes was determined and linear Scatchard plots were obtained. The number of sites was 30088 +/- 3039 (mean +/- SD) per lymphocyte in 14 healthy males and 33939 +/- 3185 in 11 males with type 2 diabetes (P less than 0.01). No difference between the dissociation constants were found (Kd = 3.91 and 3.86 mmol/l). The number of binding sites in lymphocytes from 15 healthy males with normal glucose tolerance but with a strong family history of type 2 diabetes did not differ from the controls. In T-lymphocytes a significantly higher number of specific ouabain binding sites was found than in non-T-lymphocytes (P less than 0.01). There was no difference between the dissociation constants. (Kd = 3.69 and 3.97 mmol/l). Intra-lymphocytic sodium was measured in 18 healthy individuals and the mean content was 8.1 +/- 2.3 mmol/kg lymphocytes. A lower content of sodium in T- compared to non-T-lymphocytes was also found (5.9 +/- 0.8 mmol/kg vs 15.5 +/- 0.8 mmol/kg, P less than 0.001). There was no correlation between lymphocytes and erythrocytes concerning [3H]ouabain binding sites or sodium concentration.
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The levels of amino acids in 6 regions of the brain (cortex, hippocampus, striatum, diencephalon, stem and cerebellum) were determined during an ischemic insult of 30 min and after recovery periods of up to 10 h. The results were analyzed in two groups: putative neurotransmitters (GABA, aspartate, glutamate, taurine, glycine and alanine) and non-neurotransmitters. In the neurotransmitter group, it was found that at the end of 30 min ischemia the levels of aspartate and glutamate slightly decreased whereas those of GABA and alanine rose substantially. The amounts of glycine and taurine remained unchanged. In 30 min after the ischemic insult, there were much larger decreases in aspartate and glutamate and increases in GABA and alanine with no change in glycine and taurine. At 2 h recovery the levels of the neurotransmitter amino acids had almost returned to control values and were fully recovered by 10 h after ischemia. It is postulated that glutamate and aspartate are released during ischemia into the extracellular space and subsequently 'washed-out' into the blood during the reperfusion. Release of GABA, if it occurs, is however, compensated by increase in its synthesis and decrease in its degradation under anaerobic conditions, both of which contribute to the rise in its steady-state level. In the non-transmitter category, increases were seen in amino acids present normally in very small concentrations; tyrosine, lysine, leucine and 3 hydrophobic amino acids: valine, methionine and phenylalanine, which were most pronounced at 2 h after ischemia. It is suggested that the rise in the levels of these molecules is the consequence of stimulation of protein breakdown caused by activation of intracellular proteases by calcium and H+ during the ischemic episode. Regional variations in the patterns of changes were small although in the ischemic models used the brainstem seemed to be least affected.
The effects of in vitro anoxia and membrane depolarization by veratridine on the uptake and release of amino acids were investigated in suspensions of synaptosomes isolated from the forebrains of rats. It was observed that GABA, aspartate and glutamate were released from synaptosomes in anaerobic conditions and upon addition of veratridine in a time-dependent manner. The release of the two latter amino acids was faster and more pronounced than that of GABA. The other amino acids were not affected in any systematic way by either condition. Re-introduction of oxygen or addition of tetrodotoxin to veratridine-treated synaptosomes resulted in the re-uptake of GABA, aspartate and glutamate, which was much faster and more complete for GABA than for the acidic amino acids, especially at acid pH values. The amounts of aspartate and glutamate in the incubation mixture remained constant during all the manipulations whereas that of GABA increased by about 30% during anaerobiosis, in agreement with the results obtained during in vivo ischemia. It is postulated that synaptosomes which utilize glutamate and aspartate as neurotransmitters are more damaged by anoxia and depolarization with veratridine than the population which utilizes GABA. These observations may explain reports that those neurons which are thought to receive major glutamatergic input are particularly sensitive to the lack of oxygen.
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Ten members of a white American family, spanning three generations, were studied. Three family members from two different generations were affected with hair loss. Two had alopecia universalis; one had alopecia areata. All subjects were HLA-typed using 131 antiserum samples obtained from multiparous female donors defining 41 HLA-A and HLA-B antigen specificities. Six haplotypes were identified. The affected persons and four other family members shared a common haplotype, HLA-A2,B40. The OKT4 (helper), OKT8 (suppressor-cytotoxic) cells, OKT4-OKT8 (helper-suppressor-cytotoxic) ratios and the percentage of B cells found were comparable for both the 12 control subjects and the family members studied. However, family members showed increased autoantibody formation, decreased T-cell percentages, and concanavalin A-induced suppression of the normal lymphocyte response to mitogens.
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The incidence and severity of cerebral vasospasm and hydrocephalus following induced subarachnoid hemorrhage in an experimental group of animals that subsequently received epsilon-aminocaproic acid was compared to that seen in a control group that received no antifibrinolytic therapy. No augmentation of either vasospasm or hydrocephalus could be attributed to the epsilon-aminocaproic acid in the treated as compared to the control group.
A novel series of N,N-dimethylisotryptamine (isoDMT) derivatives, i.e., derivatives of 1-[2-(dimethylamino)ethyl]indole, was prepared and found to be isosteric with their corresponding N,N-dimethyltryptamine (DMT) counterparts with respect to serotonin receptor (rat fundus) affinity. Whereas the isoDMT derivatives possessed a greater affinity than did their corresponding DMT derivatives, they were relatively ineffective in displacing [3H]-5-HT binding from rat brain (cortex) homogenates. In a drug discrimination paradigm, using rats as subjects, 6-OMe-isoDMT produced effects similar to those of 5-OMe-DMT. Attempts to antagonize the discriminative stimulus effects of the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) using two of the isoDMT derivatives proved unsuccessful.
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