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)

Results of the isotretinoin (13-cis-retinoic acid, Ro 4-3780) German Cooperative Study Group, with 198 acne conglobata patients being treated in 19 departments are reported. For the first 12 weeks (phase I) there was an open assignment to 0.2, 0.5 or 1.0 mg/kilogram bodyweight (kg bw). This was followed by further 12 weeks (phase II). If there was at least a two-third improvement of lesions, the 0.2 mg/kg bw was continued, and the 0.5 mg/kg bw dose lowered to 0.2 mg/kg bw. If there was no such improvement, the dose was elevated to 0.5 and 1.0 mg/kg bw respectively. The initial high dose group of 1.0 mg/kg bw was divided after twelve weeks into 0.2 mg/kg bw maintenance therapy, or no therapy at all. Non-inflammatory and inflammatory acne lesions from the entire body were counted. Seborrhea was graded on a four scale (0 to 3+). Subjective side effects were registered. Laboratory data included hematological profile with differential counts, creatinin, SGOT, SGPT, alkaline phosphatase, total bilirubin, serum cholesterol and serum triglycerides, and urine analysis. For statistical analysis 171 patients were available, 27 dropped out of the study, mostly for reasons unrelated to the drug. At least 75 per cent improvement was seen, in the 0.2 mg/kg bw group in 73.7 and 59.5 per cent respectively; in the 0.5 mg/kg bw group in 72.5 and 61.2 per cent respectively; and in the 1.0 mg/kg bw group in 85.4 and 92 per cent respectively (phase I t12 and phase II t24 values, respectively). Sebum suppression was dose-related. Subjective side effects were fairly well dose-related, particularly those of skin and mucous membranes. Myalgia was rare. There was a dose-related elevation of triglycerides and cholesterol, but not significant for the means of each group. Single patients did show significant elevation of blood lipids. All other laboratory parameters did not change significantly. Isotretinoin is presently the most effective drug to control severe forms of acne, leading to long lasting remissions.
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PMID:[Oral treatment of acne conglobata using 13-cis-retinoic acid. Results of the German multicentric study following 24 weeks of treatment]. 622 51

Six cases of severe leptospiral infection with renal failure are described. Five of the six patients had acute oliguric renal failure requiring dialysis. Renal function recovered over three weeks and by two months all patients had plasma creatinine levels less than 200 mumol/litre. The initial diagnosis of leptospirosis depended on clinical and epidemiological features because serological confirmation was not possible during the first week of the illness. All the patients had either high risk occupations or a history of exposure to external sources of infection. All had fever, myalgia, jaundice and muscle tenderness. Although bilirubin levels were high (greater than 350 mumol/litre in five) the elevations of aspartate transaminase and alkaline phosphatase levels, and prolongations of prothrombin times were relatively slight. Thrombocytopenia occurred in five of the six cases. Leptospira complement fixation tests were weakly positive or negative on admission in five cases but rose to significant levels subsequently. Penicillin treatment resulted in Jarisch-Herxheimer reactions in three cases. The important complications were: upper gastro-intestinal haemorrhage (five cases), thrombocytopenia less than 30 000 platelets/mm3 (four cases), atrial fibrillation (three cases), drowsiness with asterixis (four cases). All six patients were seriously ill and required intensive supportive therapy. All survived.
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PMID:Acute renal failure due to leptospirosis: clinical features and outcome in six cases. 633 67

Side reactions following ivermectin treatment were evaluated in sixty males with high density bancroftian microfilaremia (GM 1388/ml). Following a single oral dose of ivermectin of different strengths (20, 50, 100 or 200 micrograms/kg), microfilariae clearance and side reactions were monitored in a double blind fashion. Microfilaria levels fell rapidly after ivermectin administration in all dosage groups and 98% of pretreatment microfilariae was cleared after 12 h of treatment. The rate of microfilaria (mf) clearance was slower with 20 micrograms/kg than with the highest dose (200 micrograms/kg) administered. Forty-six patients (77%) became amicrofilaraemic within 2 weeks of treatment. Side reactions were noted in 97% of cases. The most common reactions were fever, headache, weakness, myalgia and cough which appeared by 12 h and subsided by 72 h following treatment. The frequency and intensity of side reactions were related to pretreatment mf densities and were independent of the dose administered. Unusual side reactions were noted in a few patients with high density microfilaraemia. These included intense cough, shortness of breath, blood tinged mucoid expectoration associated with patchy pneumonitis of the lung. Itchy rashes, lymphatic nodules and raised alkaline phosphatase level were also observed in some patients. These side reactions were transient, self limiting and were not serious enough to warrant any treatment. These exaggerated unusual reactions were possibly due to allergic response of the susceptible host to rapid killing of large number of microfilariae.
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PMID:Side reactions following ivermectin therapy in high density bancroftian microfilaraemics. 790 35

Paclitaxel, a novel antimicrotubule agent that enhances tubulin polymerization and microtubule stability, was administered as a 24-hour infusion in a phase I study. Twelve patients received 32 courses at 50, 100, 150, and 200 mg/m2. A premedication regimen of dexamethasone, diphenhydramine, and ranitidine was used to prevent the acute hypersensitivity reactions (HSRs). The dose-limiting factor was leukopenia (granulocytopenia) associated with Grade 4 infection. The maximum tolerated dose was 200 mg/m2. Other non-hematological effects included peripheral neuropathy, myalgia, alopecia, and elevations of transaminase and alkaline phosphatase. Severe HSRs were not observed. The paclitaxel plasma concentration declined with a half-life of 10.0 to 24.9 hours. Excretion into urine within 72 hours was in the range of 7.28 to 11.34% of paclitaxel dosage. Two patients with breast cancer at the 200 mg/m2 dose level had partial responses. The recommended dose of paclitaxel for phase II study, when administered as a 24-hour infusion, is considered to be 150 mg/m2 every 3 weeks.
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PMID:[Phase I study of paclitaxel]. 794 84

Endemic skeletal fluorosis is characterized by bone, joint and muscle pain, progressive ankylosis of various joints and crippling deformities. Whole body skeletal scintigraphy with 99Tcm-methylene diphosphonate was performed for 17 symptomatic subjects suffering from this disorder. The fluoride content of drinking water ranged from 4.1 to 12.9 mg l-1 (normal < 1 mg l-1). Urinary and serum fluoride levels were markedly elevated. Serum calcium (total and ionized), inorganic phosphorus, creatinine and albumin were essentially normal while serum alkaline phosphatase was elevated in six subjects (mean +/- S.D. 206 +/- 106; range 22-1072 IU l-1). Skeletal radiology revealed a wide spectrum of bony abnormalities. Skeletal scintigraphy revealed a picture similar to metabolic 'superscan' in all subjects, i.e. increased tracer uptake in axial and appendicular skeleton, reduced soft tissue uptake, poor or absent renal images, prominent costochondral junction and 'tie' sign in sternum. Increased uptake was present in all subjects irrespective of age, water fluoride content, serum alkaline phosphatase level and radiological abnormalities. Our findings suggest the presence of a high bone turnover state in endemic skeletal fluorosis irrespective of other variables.
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PMID:Skeletal scintigraphic findings in endemic skeletal fluorosis. 851 Aug 79

Zoledronate (CGP 42446) is a third generation imidazole ring containing bisphosphonate that has been found in animal studies to be up to 850 times more potent than pamidronate. In this first study reporting the effects of this drug in humans, 16 patients with active Paget's disease of bone [baseline serum alkaline phosphatase activity (SAP) at least twice the upper limit of normal] were treated in a fixed ascending dose-ranging protocol with a single 1-hour infusion of either 24, 72, 216, or 400 microg of zoledronate (four patients per dose). SAP and two markers of bone resorption, 24-hour urinary hydroxyproline/creatinine excretion (OHP) and 24-hour urinary calcium/creatinine excretion, were measured at baseline, 24 hours postinfusion (day 1) and on postinfusion days 3, 7, 10, and 14. Safety parameters including vital signs, hemogram, and chemistries were measured at the same time points. At the 24- and 72-microg doses there were no consistent or meaningful changes in the bone resorption markers. However, with the 216 microg dose, urinary OHP decreased from baseline by a mean of 16-19% on days 3, 7, 10, and 14; with the 400 microg dose, OHP decreased by a mean of 33-48% at days 1, 7, and 10 and by 16% at day 14. Urinary calcium/creatinine decreased from baseline with the 216 microg dose by a mean of 15-40% on days 1, 3, 7, 10, and 14 and with the 400 microg dose by a mean of 55-71% on days 3, 7, 10, and 14. As expected, there was no reduction in SAP during the 14-day postinfusion period. There was no evidence of an acute phase reaction (pyrexia, myalgia, or arthralgia), leukopenia, or renal or hepatic toxicity. We conclude that single infusions of microgram amounts of zoledronate were capable of inhibiting bone resorption in patients with active Paget's disease during a 2-week study interval. This anti-bone resorbing effect was not associated with any clinically or biochemically observed toxicity. This potent new bisphosphonate appears to be a promising compound for the management of skeletal disorders characterized by increased bone resorption.
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PMID:Antiresorptive effect of a single infusion of microgram quantities of zoledronate in Paget's disease of bone. 911 57

Retinoids have been shown to be potent inhibitors of epithelial carcinogenesis. Recent evidence has demonstrated that retinoid actions are mediated through nuclear receptors, which are proteins encoded by the retinoic acid receptor and retinoid X receptor gene families. These receptors are activated by binding to specific retinoids; of the known naturally occurring retinoids, 9-cis retinoic acid is unique in its ability to bind to both receptor families. Because of its unique receptor-binding characteristics, 9-cis retinoic acid may have biological activity not possible with other retinoids. For this reason, we conducted a Phase I trial of 9-cis retinoic acid in adult patients with solid tumors. Twenty-two patients were treated twice daily with p.o. 9-cis retinoic acid at doses ranging from 20 mg/m2/day to 150 mg/m2/day. The patients had non-small cell lung cancer (n = 8), breast cancer (n = 5), colorectal cancer (n = 3), head and neck cancer (n = 2), nonmelanoma skin cancer (n = 2), or ovarian cancer (n = 2). The dose-limiting (WHO grade III) toxic effects, which occurred at the 150-mg/m2/day dose level, were headaches and diarrhea. Less severe (grades I and II) toxic effects included cheilitis, dry skin, conjunctivitis, fatigue, hypertriglyceridemia, alkaline phosphatase elevation, myalgia/arthralgia, and hypercalcemia. Of the 15 patients evaluable for tumor response, no objective responses were observed. Pharmacokinetic analysis revealed a reduction in peak 9-cis retinoic acid plasma levels with chronic administration. Based on this study, the recommended Phase II dose of 9-cis retinoic acid in adult patients with solid tumors is 100 mg/m2/day administered in a divided dose twice daily.
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PMID:Phase I trial of 9-cis retinoic acid in adults with solid tumors. 981 71

The safety and tolerability of quinupristin/dalfopristin were assessed in both comparative and non-comparative trials (2298 quinupristin/dalfopristin-treated patients). In comparative clinical trials, the most frequent systemic adverse events related to quinupristin/dalfopristin were nausea (4.6%), diarrhoea (2.7%), vomiting (2.7%) and skin rash (2.5%). The comparator group showed similar rates, except that nausea was significantly more common (7.2%; P = 0.01). In non-comparative trials, arthralgia and myalgia were reported most frequently but were reversible upon treatment discontinuation. The renal, inner ear, cardiovascular and central nervous systems were not implicated as significant target organs for toxicity. The most frequent local adverse events related to infusion of quinupristin/dalfopristin were inflammation, pain, oedema, infusion site reaction and thrombophlebitis. Results of laboratory tests while on therapy were comparable for quinupristin/dalfopristin and comparator groups, except that increases in conjugated bilirubin of >5 x the upper limit of normal were reported in 5.5% of quinupristin/dalfopristin recipients; increases in total bilirubin of >5 x the upper limit of normal occurred in 1.5%. Comparator recipients more frequently had increases in alanine aminotransferase and alkaline phosphatase. Quinupristin/dalfopristin inhibits the cytochrome P450 3A4-mediated metabolism of drugs including midazolam, nifedipine, terfenadine and cyclosporin. Therefore, plasma drug monitoring and/or dosage reduction of these agents is prudent. Concomitant administration of drugs that can prolong the electrocardiographic QTc interval should be avoided. Quinupristin/dalfopristin is visually and chemically compatible with commonly used drugs of various classes, but it is not compatible with sodium chloride solution and certain other drugs, including some antimicrobials. Therefore, when prescribing quinupristin/dalfopristin, clinicians should be aware of the potential for peripheral venous intolerance, arthralgias and myalgias, increases in conjugated bilirubin, interactions with drugs metabolized by the cytochrome P450 3A4 isoenzyme and certain physico-chemical incompatibilities. However, multiple studies have shown that the safety and tolerability of quinupristin/dalfopristin are generally favourable, and that it provides clear benefits to ill patients with severe gram-positive infections.
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PMID:Safety and tolerability of quinupristin/dalfopristin: administration guidelines. 1051 96

Vitamin D deficiency in immigrants has been known in the UK for 30-40 years. In Denmark, we have become aware of the problem only recently. Of 69 randomly chosen Palestinian women living in Denmark 85% were found to have very low levels of 25-hydroxyvitamin D (< 10 nmol/l). Vitamin D deficiency is caused by inadequate exposure to sunlight and a low dietary content of vitamin D and calcium. Typical symptoms are muscle pain, muscle spasms, diminished muscular strength, deep bone pain, and paraesthesias. The diagnosis can be tested by three blood tests: serum 25-hydroxyvitamin D, serum PTH, and serum alkaline phosphatase. If a combination of low 25-hydroxyvitamin D and secondary hyperparathyroidism is found, the treatment should be high-dose ergocalciferol or cholecalciferol (100,000 IU weekly). If only (isolated) low 25-hydroxyvitamin D is found, treatment with 1000 IU of ergocalciferol or cholecalciferol in combination with one gram of calcium daily will be adequate.
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PMID:[Vitamin D deficiency among immigrants]. 1110 65

Four cases of hypovitaminosis D were seen in a general practitioner's population in the Netherlands: a Somalian veiled woman aged 53 and her 11-year-old daughter, a dark-skinned Surinam woman aged 31, and a veiled Moroccan woman aged 56 years. This cause of myopathy has only been recently recognised and is more prevalent than often thought, especially in high-risk groups such as veiled and dark-skinned immigrants who lack sunlight in the Netherlands. Symptoms are muscle pain and mainly proximal muscle weakness resulting in difficulties in ascending a staircase or getting up out of a chair. The diagnosis is made on the basis of a detailed history and measurement of serum 25-hydroxyvitamin D. Calcium and serum alkaline phosphatase activity may be normal. Treatment with ergocalciferol is effective and cheap. As diagnosis and treatment are relatively simple, finding and treating hypovitaminosis D is a rewarding challenge to primary health care practitioners in the Netherlands.
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PMID:[Hypovitaminosis D: a veiled diagnosis]. 1178 59


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