Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to investigate the suggestion that hyperparathyroidism in patients with familial MEA I has a mild and nonprogressive clinical course, we have compared clinical, biochemical, roentgenologic and histologic features of 29 patients with hyperparathyrodism originating from six families with the MEA I syndrome with those of 28 unselected patients with isolated nonfamilial hyperparathyroidism. The patients from the families with MEA I were significantly younger, had lower serum calcium and inorganic phosphate concentrations and a lower incidence of elevated alkaline phosphatase levels. Furthermore, they had multiple enlarged parathyroid glands and recurrence of the disease significantly more often. There was, however, no significant difference in the incidence of renal impairment, urolithiasis, subperiosteal resorption or large bone cysts on roentgenograms, histologic changes in bone biopsy specimens or mortality due to hyperparathyroidism. Therefore, the suggestion that this type of hyperparathyroidism has a milder clinical course is not confirmed in the present study.
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PMID:Clinical significance of hyperparathyroidism in familial multiple endocrine adenomatosis type I (MEA I). 3 99

Furosemide is frequently used for ascites and causes adverse reactions (AR). In an intensive prospective drug monitoring study of 1,920 patients, 172 (8.9%) had cirrhosis of the liver and received furosemide. Mean age was 53 years, and 66.3% were male; and 87% had alcoholic cirrhosis. Eighty-eight (51.2%) had 221 events that by consensus of the monitoring team and attending physicians were either definitely of probably related to furosemide. No AR was fatal but 24% of patients had severe reactions. Almost all reactions were dose-related (96%). The most common were electrolyte disturbances (23.3% of patients) and volume depletion (14%). Furosemide-induced coma occurred in 20 (11.6%) patients and was more frequent in patients with prior hepatic encephalopathy (p less than 0.0005). Higher total doses (p less than 0.001), hyerbilirubinemia (p less than 0.05), prolonged prothrombin time (p less than 0.02), and longer hospital stay (p less than 0.001) were associated with higher frequencies of AR to furosemide. The frequency of hypokalemia did not decrease when potassium chloride or potassium-sparing diuretics were added to furosemide therapy. Frequdncy of AR did not correlate with age, sex, renal impairment, serum albumin, transaminase, or alkaline phosphatase.
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PMID:Furosemide-induced adverse reactions in cirrhosis of the liver. 75 67

A report is given on advances in our knowledge of the ototoxicity of aminoglycoside antibiotics. The pharmacokinetics of gentamicin, tobramycin, sisomicin and amikacin in the inner ear, cerebrospinal fluid, compartments of the eye and serum were determined by means of pharmacokinetical investigations. The influence of long-term treatment, and the effects of otitis media and uremia were also studied. Furthermore, the influence of therapeutic methods on ototoxic damage was investigated, and the ototoxicity of these antibiotics was compared. The experiments were performed in guinea pigs, concentrations of the antibiotics being measured by a microbiological method and confirmed by investigations with C14 labeled gentamicin. The hair cell degeneration pattern after administration of the new aminoglycosides was determined using surface preparations. The prophylactic effect upon ototoxicity of the administration of dimercaptopropanol or of dividing up the daily dosage was examined. Studies were made of ototoxicity in children, and in patients with otitis media or renal impairment, and the effect of simultaneous ethacrynic acid or noise was assessed. The problem of delayed and progressive ototoxicity, and the reversibility of ototoxic damage caused by these antibiotics was examined histologically, and the ototoxicity of gentamacin, tobramycin, sisomicin and amikacin was compared. The influence of the new aminoglycoside antibiotics upon the amount of acidic and alkaline phosphatase and unspecific esterases in the inner ear was studied. The clinical importance of the latest experimental findings is emphasised. The clinical picture of ototoxic damage after administration of the new aminoglycoside antibiotics shows no special characteristics. The ototoxicity of these antibiotics after topical use is mentioned. Attention is drawn to guidelines for the prevention of ototoxic damage by aminoglycosides.
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PMID:[Ototoxicity of the aminoglycoside antibiotics (author's transl)]. 101 84

Hyperparathyroid bone disease is a common complication of end stage renal failure, particularly in patients on maintenance haemodialysis. Several studies have, however, shown a near absence of hyperparathyroid bone disease in diabetic patients who have been receiving haemodialysis for periods of up to 4 years. We have studied biochemical indices of mineral metabolism in 54 consecutive pre-dialysis patients with moderate to severe renal impairment. Deteriorating renal function was associated with developing hypocalcaemia and hyperphosphataemia. Hypocalcaemia was strongly related to increased severe alkaline phosphatase activity (p less than 0.001), suggesting the development of hyperparathyroidism. Five patients with hypocalcaemia and increased alkaline phosphatase were studied in detail. All had elevated serum concentrations of parathyroid hormone and histological signs of hyperparathyroidism on bone biopsy. Three of the patients had low serum 25 hydroxyvitamin D levels with associated osteomalacia, the other 2 patients were notable for their long duration of renal failure. In the long-term (greater than 4 years) we also observed the development of hyperparathyroidism in a small group of diabetic patients maintained on haemodialysis. We conclude that diabetic patients are not uniquely protected against renal osteodystrophy. Although the prevalence of hyperparathyroidism may be lower in diabetic patients than in those with other types of renal disease, the same factors which predispose to bone disease in non-diabetic patients (long duration of renal failure, low serum 25 hydroxyvitamin D and long periods on haemodialysis) also operate in the diabetic population.
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PMID:Hyperparathyroid bone disease in diabetic renal failure. 213 93

This study represents the first randomized prospective, double-blind, placebo-controlled trial of the efficacy of 1,25(OH)2D3 on bone histology and serum biochemistry in patients with mild to moderate renal failure. Sixteen patients with chronic renal impairment (creatinine clearance 20 to 59 ml per min) received either 1,25(OH)2D3, at a dose of 0.25 to 0.5 microgram daily (eight patients), or placebo. Transiliac crest bone biopsies were performed before entrance into the study and after 12 months of experimental observation. None of the patients were symptomatic or had radiological evidence of bone disease. Of the thirteen patients who completed the study, initial serum 1,25(OH)2D levels were low in seven patients and parathyroid hormone levels were elevated in seven patients. Bone histology was abnormal in all patients. 1,25(OH)2D3 treatment was associated with a significant fall in serum phosphorus and alkaline phosphatase concentrations as well as with histological evidence of an amelioration of hyperparathyroid changes. In contrast to previous reports, no deterioration of renal function attributable to the treatment occurred, perhaps because a modest dose of 1,25(OH)2D3 was employed combined with meticulous monitoring. Further investigation is required to determine whether alternative therapeutic strategies (smaller doses or intermittent therapy) may avoid the potential for suppressing bone turnover to abnormally low levels in the long term.
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PMID:1,25(OH)2D3 administration in moderate renal failure: a prospective double-blind trial. 265 58

The value of calcitriol administration in the management and prevention of renal bone disease was studied in a prospective double-blind manner in 16 patients with chronic renal impairment (creatinine clearance 20 to 59 ml per min). They were given either calcitriol at a dose of 0.25 to 0.5 micrograms daily (eight patients), or placebo. Transiliac crest bone biopsies were performed before entrance into the study and after 12 months of experimental observation. None of the patients were symptomatic or had biochemical or radiological evidence of bone disease. Of the thirteen patients who completed the study, initial serum 1,25(OH)2D levels were low in seven patients and parathyroid hormone levels were elevated in seven patients. Bone histology was abnormal in all patients. Calcitriol treatment was associated with a significant fall in serum phosphorus concentrations and alkaline phosphatase levels as well as with histological evidence of an amelioration of hyperparathyroid changes. In contrast to previous reports, no deterioration of renal function attributable to the treatment occurred, perhaps because a modest dose of calcitriol was employed combined with meticulous monitoring. Further investigation is required to determine whether alternative therapeutic strategies (smaller doses or intermittent therapy) may avoid the potential for suppressing bone turnover to abnormally low levels in the long term.
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PMID:Early therapy of renal bone disease with calcitriol: a prospective double-blind study. 269 94

The incidence and magnitude of false-positive serum digoxin concentrations (SDCs) determined by three digoxin assays in patients with liver disease were studied. Patients with biochemical evidence of liver disease were enrolled in the study if they had never received a cardiac glycoside, were not pregnant, were not receiving spironolactone, did not have moderate to severe renal impairment, and did not have transient elevations in liver function test results. Blood specimens from each patient were assayed for apparent SDCs in triplicate using a fluorescence polarization immunoassay (FPIA, TDx Digoxin II, Abbott) and a digoxin radioimmunoassay (RIA, GammaCoat I125, Clinical Assays) and in duplicate using a fluorometric enzyme immunoassay (Dade Stratus, American Dade). Forty-two patients met the study criteria. The percentage of patients exhibiting detectable apparent SDCs (greater than or equal to 0.2 ng/mL) was 57% with RIA, 55% with FPIA, and 28% with the fluorometric enzyme immunoassay. Apparent SDCs ranged from 0.2 to 0.6 ng/mL (RIA), 0.2 to 1.56 ng/mL (FPIA), and 0.2 to 0.38 ng/mL (fluorometric enzyme immunoassay). Values obtained using the fluorometric enzyme immunoassay were significantly different from the apparent SDCs determined using RIA and FPIA; however, no significant difference was found between the values obtained using RIA and FPIA. Significant correlations were found between the apparent SDCs determined using RIA and serum bilirubin values and between the apparent SDCs determined using the fluorometric enzyme immunoassay and alkaline phosphatase values. Of the three assay methods tested, the fluorometric enzyme immunoassay showed the least cross-sensitivity to digoxin-like immunoreactive substance (DLIS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:False-positive serum digoxin concentrations determined by three digoxin assays in patients with liver disease. 340 79

Sixty-eight patients with mild primary hyperparathyroidism were studied for a mean period of 4.5 years (median 3.3). Seven of these patients presented with renal colic while the rest had no symptoms. There was no significant deterioration in mean serum creatinine, total calcium or ionized calcium concentrations during this period. No patient had progressive renal stone or parathyroid bone disease. Hypertension was defined as a systolic or diastolic blood pressure greater than one standard deviation from the age-sex mean, or if hypotensive drugs were required. Thirty-nine per cent were hypertensive at presentation and 42 per cent became hypertensive later. Four patients died from causes unrelated to hypercalcaemia and three required parathyroidectomy when serum calcium concentration rose above 3.0 mmol/l. Patients over 55 with mild asymptomatic primary hyperparathyroidism may be managed conservatively for several years without significant renal impairment, progressive stone disease, parathyroid bone disease or worsening hypercalcaemia. We suggest that observation in these patients could be restricted to six-monthly checks of physical state, blood pressure and serum biochemistry, particularly concentration of calcium creatinine and alkaline phosphatase.
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PMID:The conservative management of primary hyperparathyroidism. 345 52

The metabolism and disposition of buspirone have been studied in the rat, the monkey, and in more than 150 human subjects. Buspirone is well absorbed, but is subject to first-pass metabolism. The mean systemic availability is approximately 4 percent. Buspirone is eliminated primarily by oxidative metabolism, which produces several hydroxylated metabolites, including 5-hydroxy-buspirone and 1-pyrimidinylpiperazine. The latter metabolite is from 1 to 20 percent as potent as buspirone in a variety of pharmacologic tests; 5-hydroxybuspirone is essentially inactive. In humans, the systemic exposure to buspirone increases linearly in relation to the oral dose. Food increases the bioavailability of buspirone by decreasing first-pass metabolism; absorption is not markedly altered. The pharmacokinetics of buspirone were not significantly different in men and women or in individuals 21 to 40 years old compared with those over 65 years of age. Half-life values observed in healthy volunteers ranged from two to 33 hours. Mean half-life values observed in healthy volunteers in the 14 studies conducted to date ranged from 2 +/- 1 to 11 +/- 3 hours. The half-life in women tended to be slightly longer than in men, but the difference was not significant. Hepatic cirrhosis resulted in a marked decrease in the clearance of buspirone, which correlated with serum alkaline phosphatase activity. Renal disease produced a modest decrease in buspirone clearance, which could not be correlated with an objective clinical measurement reflecting the severity of renal impairment. Buspirone was not removed by hemodialysis. Buspirone is highly protein bound (more than 95 percent), interacting with both albumin and alpha-acid glycoprotein. However, buspirone did not displace dilantin, propranolol, digoxin, or warfarin from plasma proteins. In rats, buspirone neither inhibited nor induced hepatic mixed-function oxidases. Co-administration of buspirone with amitriptyline or diazepam did not alter the disposition of these agents or their demethylated metabolites.
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PMID:Metabolism and disposition of buspirone. 351 29

The overfed rat served as the animal model for examining the influence of obesity on the hepatotoxic and nephrotoxic potential of metabolically activated drugs, and acetaminophen served as the prototype drug. Weanling Sprague-Dawley rats were given a standard pellet diet or semisynthetic, energy-dense diet designed to produce obesity. After 24 weeks, when overfed rats outweighed controls by more than 50%, animals received 710 mg/kg of acetaminophen i.p., based on total body weight. Toxicity evaluation included biochemical signs of organ injury over the first 24 hr and histopathologic changes in tissue morphology at 48 hr. Both enzyme release (alanine aminotransferase into plasma, alkaline phosphatase into urine) and frank cellular necrosis in liver and kidney of obese rats greatly exceeded that in pellet-fed controls. Contributing to the potentiation of injury were higher peak plasma concentrations of acetaminophen in obese animals resulting from total body weight dosing. However, liver and kidney injury and mortality remained elevated when peak plasma concentrations were matched by fat-free mass dosing, indicating that increased toxicity also was related to obesity. Incomplete recovery of acetaminophen and metabolites from obese animals (45 vs. 71% in control rats) caused by a functional renal impairment made it impossible to determine the metabolic fate of acetaminophen in overfed animals from the analysis of urine collections. Drug products measured in urine were summed with amounts remaining in carcass at sacrifice, computed as terminal plasma concentrations times respective distribution volumes. These results showed obese rats to form more glucuronide and less sulfate conjugate than did pellet-fed controls, coinciding with clinical evidence for enhanced glucuronidation in obese humans.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Obesity as a risk factor in drug-induced organ injury: increased liver and kidney damage by acetaminophen in the obese overfed rat. 359 8


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