Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In three groups (n = 12 each) of male controls (22--43 years), patients with recurring calcium urolithiasis (21--36 years) and hyperparathyroidism (HPT; 17--71 years) proven by surgery renal cyclic adenosine monophosphate (RcAMP), fractional tubular phosphate reabsorption and serum parathyroid hormone (PTH) were measured during endogenous creatinine clearance. RcAMP (muMol/g creatinine) was: controls 1.48 +/- SEM 0.27; stone formers 2.037 +/- 0.343 (not significantly different); HPT 6.234 +/- 0.454 (p less than 0.001). There is no overlap between HPT and controls. Phosphate reabsorption is least in HPT (0.84 +/- 0.015), higher in controls (0.924 +/- 0.004) and stone formers (0.941 +/- 0.007). All differences are statistically significant. Under the conditions selected (moderate hydration of individuals) Serum PHT (pg-equiv/ml) is lowest in stome formers (less than 100--339), higher in controls (less than 100--933) and HPT (400--1150). there is no overlap in PHT between the former and the latter group but a marked one between controls and HPT. For clinical purposes the resulting diagnostic uncertainty in a given patient can be overcome by additional determinations of RcAMP and ionised serum calcium: when referring to serum PTH HPT patients fall outside, RCU patients within 2 standard deviations of either parameter in control subjects. This procedure presently appears superior to those proposed in the past (urinary cAMP etc.) but requires confirmation in larger patient populations. Moreover, since HPT prevails in middle and upper age decades, their RcAMP values and those of RCU patients should be related to a range seen in closely age- and sex-matched controls.
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PMID:[Evaluation of renal cyclic adenosine monophosphate, serum parathyroid hormone and phosphate reabsorption in recurrent calcium urolithiasis, healthy controls and hyperparathyroidism (author's transl)]. 21 Mar 11

The disposition and safety of the antiviral drug acyclovir were studied in 14 subjects with advanced malignancies. Acyclovir was administered by a 1-hr intravenous infusion at doses of 0.5, 1.0, 2.5, and 5.0 mg/kg. At the end of infusion, mean peak plasma levels (+/- SEM), determined by radioimmunoassay, were 6.4 +/- 0.7, 12.1 +/- 2.3, 14.9 +/- 2.7, and 33.7 +/- 7.1 microM. The plasma concentration-time profiles could be described by a biexponential equation. The half-life of acyclovir in the slow disposition phase ranged from 2.2 to 5 hr and the drug was detected in the plasma for at least 18 hr after infusion. The total body clearance ranged from 117 to 396 ml/min/1.73 m2. A proportionality between area under the curve and dose suggests that acyclovir exhibits dose-independent kinetics in the dose range studied. There was wide variation in cumulative urinary excretion of unchanged drug, ranging from 30 to 69% of the dose. From renal clearances of acyclovir, which were higher than creatinine clearances, it appears that both glomerular filtration and tubular secretion contribute to its renal excretion. Analysis of the urine by reverse-phase high-performance liquid chromatography revealed the presence of the metabolite 9-carboxymethoxymethylguanine. There was no indication of toxicity either clinically or from laboratory findings in any of the study subjects. This study demonstrates that in addition to selectivity and low toxicity, the kinetic profile and metabolic disposition of acyclovir make it an attractive candidate for therapy in a variety of herpes infections.
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PMID:Acyclovir kinetics after intravenous infusion. 22 39

Electrochemical disturbances of skeletal muscle cells in untreated uremia are characterized by an increase in the intracellular sodium and chloride content, a decrease in intracellular potassium, and a low resting membrane potential. In this study, we have reexamined the foregoing and, in addition, have examined the effects of hemodialysis. Three groups of patients were studied. In the first group of 22 uncomplicated uremic patients, whose creatinine clearance (Ccr) ranged from 2 to 12 cm(3)/min per 1.73 m(2), resting transmembrane potential difference (Em) of skeletal muscle cells was measured. In each of the nine patients whose Ccr ranged between 6.3 and 12 cm(3)/min, the Em was normal (i.e., -90.8+/-0.9 mV, mean+/-SEM). However, as Ccr dropped below 6.3 cm/min, the Em became progressively reduced and assumed a linear relationship with the Ccr. In the second study, nine individuals with end-stage renal disease, whose mean Ccr was 4.3 cm(3)/min, underwent measurement of Em and intracellular electrolyte concentration before and after 7 wk of hemodialysis. Before dialysis, the Em was -78.5+/-2.1 mV, intracellular sodium and chloride were elevated, and the intracellular potassium was reduced. After 7 wk of hemodialysis the Em rose to -87.8+/-1.3 mV, and the intracellular sodium, chloride, and potassium became normal. In the third study, seven patients who were stable on 6-h thrice-weekly dialysis were studied before and after reduction of dialysis to 6 h twice weekly. In those individuals whose Em remained normal after 6 wk, dialysis time was reduced further. On thrice-weekly dialysis the Em was -91.2+/-1.0 mV. With reduced dialysis, the Em fell to -80.1+/-0.8 mV (P < 0.001). In each case, the Em became abnormal before significant signs or symptoms of uremia were noted. These findings demonstrate that end-stage renal disease is associated with serious electrochemical changes in the muscle cell which are reversed by hemodialysis and recur when dialysis time is reduced. Thus, serial observations of muscle Em may be a potentially powerful tool to assess adequacy of dialysis therapy.
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PMID:Resting skeletal muscle membrane potential as an index of uremic toxicity. A proposed new method to assess adequacy of hemodialysis. 42 69

An original method which uses in vitro anaerobic incubation at 37 degrees C followed by centrifugation, ultrafiltration, and ion exchange chromatography is described; it shows that faecal material suspended in physiological saline can destroy added creatinine. The rate of breakdown by suspensions from uraemic subjects (mean 780 mumol h-1kg-1 SEM 70) was slightly faster than in normal subjects (mean 550 mumol h-1kg-1 SEM 80). Methylamine concentration increased over eight hours as creatinine was metabolised and sarcosine appeared as an intermediate. The rates of these reactions varied within and between individuals and were inhibited by oxygen and centrifugation but not by oxytetracycline. Concentrations of free amino acids did not change significantly despite the formation of ammonia. This approach should be useful in studying the metabolic inter-relationships between intestinal contents and the host organism in health and disease.
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PMID:In vitro metabolism of creatinine, methylamine and amino acids by intestinal contents of normal and uraemic subjects. 48 52

Despite methodologic problems, endogenous creatinine clearance is commonly used as an estimation of glomerular filtration rate (GFR). Inulin clearance was compared to endogenous creatinine clearance in a group of low birthweight infants to establish the validity of the latter. Thirty-three low birthweight infants (birthweight mean = 1600 g, gestational age mean = 33 wk) were studied between 10 hr and 10 days of age to simultaneously measure GFR by inulin and endogenous creatinine clearances. Inulin and creatinine clearances correlated directly (r = 0.738, P greater than 0.001). The slope of the regression line suggested an overestimation of GFR (inulin clearance) by creatinine clearance at the low GFR range and an underestimation at the high GFR range. The data were divided into two groups by the median inulin clearance (12.5 ml/min/1.73m2). The ratio of creatinine to inulin clearance was significantly higher in the low GFR group (1.28 +/- 0.16 vs. 0.89 +/- 0.04 SEM, n = 19, P less than 0.05). There was no difference between the two groups in plasma creatinine, birthweight, gestational age, incidence of respiratory distress, or oxygen requirements at the time of the studies. Endogenous creatinine clearance represents a good estimation of GFR (inulin clearance) in low birthweight infants. However, at the low GFR range, it represents an overestimation and at the high GFR range, an underestimation.
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PMID:Validity of endogenous creatinine clearance in low birthweight infants. 50 52

To delineate the potential role of disordered glucose and glucose-precursor kinetics in the abnormal carbohydrate metabolism of chronic renal failure, alanine and glucose production and utilization and gluconeogenesis from alanine were studied in patients with chronic compensated renal insufficiency and in normal volunteers. With simultaneous primed injection-continuous infusions of radiolabeled alanine and glucose, rates of metabolite turnover and precursor-product interrelationships were calculated from the plateau portion of the appropriate specific activity curves. All subjects were studied in the postabsorption state. In 13 patients with chronic renal failure (creatinine = 10.7+/-1.2 mg/100 ml; mean+/-SEM), glucose turnover was found to be 1,035+/-99.3 mumol/min. This rate was increased 56% (P = 0.003) over that observed in control subjects (664+/-33.5 mumol/min). Alanine turnover was 474+/-96.0 mumol/min in azotemic patients. This rate was 191% greater (P = 0.007) than the rate determined in control subjects (163+/-19.4 mumol/min). Gluconeogenesis from alanine and the percent of glucose production contributed by gluconeogenesis from alanine were increased in patients with chronic renal failure (192% and 169%, respectively) as compared to controls (P < 0.05 for each). Alanine utilization for gluconeogenesis was increased from 40.2+/-3.86 mumol/min in control subjects to 143+/-39.0 mumol/min in azotemic patients (P < 0.05). The percent of alanine utilization accounted for by gluconeogenesis was not altered in chronic renal insufficiency. In nondiabetic azotemic subjects, mean fasting glucose and immunoreactive insulin levels were increased 24.3% (P = 0.005) and 130% (P = 0.046), respectively.These results in patients with chronic renal failure demonstrate (a) increased glucose production and utilization, (b) increased gluconeogenesis from alanine, (c) increased alanine production and utilization, and (d) a relative impairment to glucose disposal. We conclude that chronic azotemia is characterized by increased rates of glucose and glucose precursor flux and by a relative impairment to glucose disposal. These findings may suggest an underlying hepatic and peripheral insensitivity to the metabolic action of insulin in patients with chronic renal insufficiency.
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PMID:Abnormal carbohydrate metabolism in chronic renal failure. The potential role of accelerated glucose production, increased gluconeogenesis, and impaired glucose disposal. 65 34

Creatinine appearance, defined as the sum of daily creatinine excretion in urine (average over 5 days) plus accumulation in body water, measured over the same interval, was calculated in 27 patients with severe chronic renal failure (creatinine clearance less than 0.15 liter/kg/day). Creatinine appearance per kg body weight in patients with the lowest clearances decreased to values as low as one third of values predicted from age and sex. The absolute value of measured cratinine accumulation was only 11 +/- 2% of creatinine appearance and thus could not account for such deficits in appearance and therefore renal excretion. One explanation for these results is that extrarenal clearance, CM, remains constant, that is, that the quantity of creatinine degraded, M, is proportional to serum creatinine, S: CM = M/S. When the values for extrarenal clearance necessary to account for the measured deficit in creatinine appearance were calculated, they were found to be quite constant: 0.042 +/- 0.004 liter/kg/day (SEM, n=13) in males and 0.041 +/- 0.004 liter/kg/day (SEM, n=14) in females. Renal creatinine clearance in these patients, predicted from age, sex, serum creatinine, and the assumed constant value for extrarenal clearance, corresponded closely to observed clearance (r = 0.93). From these calculations, decreased creatinine appearance (and excretion) of uremic patients may be explained by a constant extrarenal clearance, indicating degradation.
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PMID:A proposed mechanism for reduced creatinine excretion in severe chronic renal failure. 71 98

Plasma renin activity (PRA) was measured during the administration of clonidine (0.1 mg twice daily) to 11 patients with essential hypertension. After eigth weeks a trend toward an increase in PRA was noted. This increase was significant in "low renin" subjects (less than 1 ng Al/ml/hr, n = 7) in whom PRA (ng/ml/hr +/- SEM) rose from a control value of 0.7 +/- 0.1 to 2.0 +/- 1.1 at one week, 5.6 +/- 2.1 at four weeks, and 4.4 +/- 1.0 at eight weeks (p less than 0.05). In contrast, in a small group of "normal renin" patients (n = 4), PRA did not change significantly but tended to decrease on clonidine therapy from 9.2 +/- 3.4 at control to 3.3 +/- 2.0 at one week, 3.4 +/- 0.6 at four weeks, and 4.7 +/- 1.7 ng Al/ml/hr at eight weeks. Plasma renin substrate and serum and urinary electrolytes did not change significantly in either group and blood pressure reduction was comparable in the two groups. A strong negative correlation (r = -0.84, p less than 0.001) was found between changes in creatinine clearance and changes in PRA. Previous studies have implicated alpha-adrenergic receptors as the site of clonidine actions on blood pressure and renin release. The observed renin stimulation during chronic administration of clonidine to "low renin" patients with essential hypertension may imply an altered intrarenal alpha-receptor function in "low renin" essential hypertension.
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PMID:Renin stimulation during clonidine therapy in "low renin" essential hypertension. 72 16

To learn whether a single dialysis can acutely improve the intravenous glucose tolerance (i.v.GTT) of chronically dialyzed patients, a standard i.v.GTT was performed on 10 nonobese uremic subjects on maintenance hemodialysis for 27 +/- 9 (mean +/- SEM) mo, and on a control group of 13 normal subjects. The uremic patients were tested first 0.2-17 (range) hr, and then 65-109 hr, from last dialysis. In the uremic sera, plasma glucose was analyzed by 4 methods; 2 reducing (neocopurine and ferricyanide) and 2 enzymatic (hexokinase and glucose oxidase). The reducing methods markedly overestimated plasma glucose concentration because of the presence of nonglucose reducing substances (notably, creatinine). This inteference was significantly cut down by dialysis. A single dialysis, on the other hand, failed to improve the glucose fractional decay rate (KG) computed from the glucose oxidase data (1.69 +/- 0.2%/min before and 1.35 +/- 0.1 after dialysis, versus 1.47 +/- 0.1 of the normal subjects). The same conclusion was derived from the data measured by the other 3 methods of glucose assay. Fasting plasma insulin concentrations were, on average, above normal (5.5 +/- 0.6 muU/ml) both before (12.3 +/- 2.7, p less than 0.05) and after (17.2 +/- 3.5, p less than 0.01) a single dialysis. Likewise, the area under the glucose-induced plasma insulin curve was significantly greater than normal (1.46 +/- 0.21 mU/ml . min) both before (2.26 +/- 0.34, p less than 0.05), and after (2.86 +/- 0.43, p less than 0.01) dialysis. A single dialysis had little effect on either basal or glucose-stimulated insulin release, and no significant difference in the insulinogenic index (insulin area/glucose area) was found between the control and the uremic group in either test. Insulin response was not correlated with KG, whereas it was significantly associated with higher triglyceride levels. Creatinine, urea or methylguanidine did not appear to have any influence on KG, but lower serum potassium levels were significantly associated with poorer i.v.GTT's. Plasma calcium bore a reciprocal relation to the insulinogenic index. Chronically dialyzed subjects show some degree of tissue insulin resistance, which a single dialysis fails to correct. Electrolyte disturbances may play a role in this metabolic derangement.
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PMID:The response to intravenous glucose of patients on maintenance hemodialysis: effects of dialysis. 76 47

Urinary total, isomer I and isomer III coproporphyrin excretion was determined in 11 patients with Rotor's syndrome, 23 phenotypically normal family members, 16 patients with the Dubin-Johnson syndrome and 20 normal control subjects. Control subjects excreted 24.8 +/- 1.3 per cent (mean SEM) of urinary coproporphyrin as isomer I. Patients with the Dubin-Johnson syndrome excreted 88.9 +/- 1.3 per cent as urinary coproporphyrin I, and patients with Rotor's syndrome excreted 64.8 +/- 2.5 per cent as urinary coproporphyrin I, significantly different from the control subjects and the patients with the Dubin-Johnson syndrome (p less than 0.001). Eight phenotypically normal parents and children of patients with Rotor's syndrome excreted 42.9 +/- 5.4 per cent as urinary coproporphyrin I, intermediate between results in patients with Rotor's syndrome and control subjects (p less than 0.001). Total urinary coproporphyrin excretion was markedly increased in patients with Rotor's syndrome (332 +/- 86 mug/g creatinine) as compared to that in control subjects (p less than 0.001) or obligate heterozygotes (p less than 0.025). With respect to urinary coproporphyrin excretion, Rotor's syndrome and Dubin-Johnson syndrome are both inherited as autosomal recessive traits and are separate pathophysiologic entities. Study of rare but distinct inheritable disorders, such as these, provide insight into the functional dissociation of hepatic transport mechanisms.
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PMID:Rotor's syndrome. A distinct inheritable pathophysiologic entity. 76 21


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