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)

Ketoconazole has only recently been recognized as a cause of hepatic injury, with most reports coming from outside the United States. In order to characterize more fully the U.S. experience, we undertook an analysis of 54 reports of alleged ketoconazole-induced liver injury submitted to the Food and Drug Administration from the time of initial marketing in 1980. Thirty-three reports were considered likely instances of ketoconazole-induced hepatitis. The majority of these cases occurred in women more than 40 yr of age. Jaundice was recorded in 27 individuals after therapy of 11-168 days with an average daily dose of 200 mg. Anorexia, malaise, nausea, and vomiting accompanied liver injury in one-third of cases. No instances of rash or eosinophilia were recorded. Serum transaminase and alkaline phosphatase values were consistent with acute hepatocellular injury in 18 patients, with primarily cholestatic injury in 5 patients, and with a mixed pattern in 9 individuals. Only one death seemed attributable to ketoconazole. In that patient, the drug was continued after the appearance of clinical and biochemical evidence of hepatic injury and massive hepatocellular necrosis was present at autopsy. The incidence of symptomatic, potentially serious hepatic injury appears to be very low, perhaps 1 in 15,000 exposed individuals. The presumed mechanism of injury is metabolic idiosyncrasy, although hypersensitivity has not been completely dismissed in some cases reported in the literature. The incidence of mild, asymptomatic, reversible elevations in serum transaminases occurring in ketoconazole recipients has been estimated to be 5%-10%. Periodic biochemical testing and monitoring for symptoms of hepatitis during ketoconazole therapy is recommended to help prevent the development of serious or fatal hepatic injury.
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PMID:Hepatic injury associated with ketoconazole therapy. Analysis of 33 cases. 631 20

Early recognition of pyogenic liver abscess requires a high index of suspicion. The abrupt onset of hectic fevers and jaundice is rarely seen today; instead, an insidious progression of malaise, abdominal pain, and night sweats is more common. Biliary tract disease is the most frequent underlying disorder. An elevated alkaline phosphatase is a useful clue to the condition, but diagnosis depends on imaging of an abscess cavity followed by aspiration. Treatment involves antibiotics together with drainage, which can often be performed successfully by a nonsurgical percutaneous approach. However, prognosis continues to be poor unless the diagnosis is made promptly.
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PMID:Pyogenic liver abscess: new concepts of an old disease. 636 2

In a medical out-patient clinic, over a period of several years, atrial myxoma was diagnosed in four patients with ages ranging between 32 and 69 years. With the exception of one patient referred for assessment of ventricular premature beats, presentation was not primarily attributable to cardiac causes. In all patients, there was a latency period of years between the onset of symptoms and establishment of the diagnosis. The history of patients with atrial myxoma includes symptoms such as dizziness, syncope, transient cerebral ischemia, weight loss and malaise. The differential diagnosis may encompass consideration of neoplastic disease since laboratory findings can reveal evidence of an inflammatory reaction, accelerated sedimentation rate, anemia, abnormal electrophoresis, hypoproteinemia as well as elevated alkaline phosphatase. One patient had undergone numerous examinations to rule out the presence of malignant disease. Symptoms related to the cardiovascular system include exertional dyspnea, premature beats, tachyarrhythmias and nonspecific chest pain. Auscultatory findings are consistent with those of mitral stenosis. M-mode and two-dimensional echocardiography established the diagnosis in all patients and confirmed the usefullness of this examination technique in the assessment of patients in a general medical clinic.
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PMID:[Atrial myxoma in the patients of a general and internal medicine outpatient clinic]. 666 80

A phase I study of human lymphoblastoid interferon (IFN-alpha) was undertaken in patients with acute leukaemia and other malignancies. The pharmacokinetics of intravenous IFN-alpha were also investigated. IFN-alpha was administered to two patients by intravenous (IV) bolus injection at a dose of 5 X 10(6) U/m2; and to a further 37 patients (40 cycles) by continuous intravenous infusion (IVI) for 5, 7, or 10 days at doses ranging from 5 to 200 X 10(6) U/m2/day. Pyrexia, general malaise, anorexia, and rigors were observed at all dose levels; three patients became hypotensive. Myelosuppression occurred in all patients, including seven without bone marrow infiltration. Transient rises in alkaline phosphatase and transaminases (SGOT) were observed in patients receiving daily doses greater than 30 X 10(6) U/m2. Dose-limiting central nervous system toxicity, hyperkalaemia, and hypocalcaemia were encountered at 200 X 10(6) U/m2. In six patients with acute leukaemia there was a fall in the number of circulating leukaemic blasts and in one patient with acute myelogenous leukaemia (AML) the degree of bone marrow infiltration decreased from 99% to less than 5% with cellularity returning to normal. Serum levels of IFN above 1,000 U/ml were achieved with daily doses above 30 X 10(6) U/m2 given by IVI. The maximum safely tolerated daily dose, 100 X 10(6) U/m2 administered for 7 days, is appreciably higher than that used in most previous studies, although even at this level considerable toxicity may be encountered.
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PMID:A phase I study of human lymphoblastoid interferon administered by continuous intravenous infusion. 717 12

A 38-year-old black woman presented with a multisystem disease characterized by malaise, fever, sweats, and diffuse hyperpigmentation. Laboratory examinations showed anemia, elevated alkaline phosphatase, granulomas in the liver and bone marrow, and elevated porphyrins in the urine and feces, characteristic of porphyria cutanea tarda (PCT). A workup for an etiology of the granulomas was nonproductive, and the patient responded to systemic steroids.
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PMID:Porphyria cutanea tarda and sarcoidosis. 735 54

A case of Whipple's disease (WD) initially presenting with migrating arthralgia and later with weight loss, malaise, fever and abdominal discomfort is reported. On examination the patient showed signs of malnutrition, was anaemic and pyrexial (37.6-38.8) and had mild abdominal distention. Retroperitoneal lymph node enlargement was demonstrated by CT-scanning. Gastroduodenoscopy demonstrated white plaques and erosions in the 2nd and 3rd part of the duodenum. Repeated small bowed biopsies revealed pathological changes typical of WD. The patient was treated with parenteral penicillin 2 MIE t.i.d. for 14 days followed by sulfamethoxazole 800 mg and trimethoprim 160 mg b.i.d for a year. Response to treatment was satisfactory. Serum alkaline phosphatase levels were raised: 324-649 U/l (80-275) on admission and remained so following treatment.
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PMID:[Whipple disease]. 750 69

We report a patient with oligodendroglioma metastases 1 year after tumour debulking and postoperative radiotherapy to the parietal lobe primary. This treatment controlled the patient's tumour locally. Distant recurrence was manifest by back pain, weight loss and malaise. The serum alkaline phosphatase was raised and a bone scan showed generalized increased uptake. Bone marrow trephine revealed infiltration by oligodendroglioma. Bone marrow infiltration by gliomas is very rare. If the trephine had not been performed it might have been assumed that he had a disseminated second primary tumour.
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PMID:Bone marrow infiltration by a parietal lobe grade III oligodendroglioma. 858 60

Merbarone, NSC 336628, is an investigational anticancer drug with activity against experimental animal tumors including melanoma. This paper presents results of a Phase II clinical study of merbarone in patients with biopsy proven stage IV malignant melanoma without prior chemotherapy and with no evidence of CNS involvement. Thirty-five patients with median age 58 (range 27-81), with performance status 0-2 were treated with merbarone 1000 mg/m2/day for five days by intravenous continuous infusion repeated every 3 weeks. All patients (21 males and 14 females) were evaluable for toxicity. Two patients were not evaluable for response having been removed from protocol treatment due to toxicity and received other treatment during the first course of chemotherapy. Among the evaluable patients there was one complete response in a supraclavicular lymph node lasting four months and one partial liver response lasting three months. The remaining thirty-one patients were non-responders. Of these one had a stable disease lasting 21 months. The overall objective response rate was 6% (2/35) with a 95% confidence interval of 1%-19%. Twenty-six of the 35 patients have died. The estimated median survival of the entire group was 9 months with a 95% confidence interval six to eleven months. Renal toxicity was dose-limiting and manifested as increasing serum creatinine (54% of patients), proteinuria (51%) and hematuria (9%). One patient experienced grade 4 creatinine increase, proteinuria and acute renal failure. Other toxicities included nausea (71%), vomiting (51%0, malaise (23%), weakness (20%), alopecia (17%), diarrhea (17), anorexia (14%) transaminase (SGOT, SGPT) increase (14%), constipation (14%), alkaline phosphatase or 5'nucleotidase increase (9%), and fever (9%). Hematologic toxicity (granulocytopenia, leukopenia, and anemia) was generally mild and infrequent (29%, only one patient had grade 4 granulocytopenia). Overall 9 patients (26%) had at least one grade 3 toxicity. We conclude that merbarone at this dose and schedule has detectable but minimal activity in the treatment of metastatic malignant melanoma and given the significant renal toxicity this schedule does not merit further evaluation in this disease.
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PMID:Evaluation of merbarone (NSC 336628) in disseminated malignant melanoma. A Southwest Oncology Group study. 861 77

Parvovirus B19 (B19), also known as "erythema infectiosum", is a disease that occurs in smaller outbreaks during late winter and early summer; and in Denmark an epidemic occurs every three years. The symptoms vary from fever, fatigue and the characteristic maculopapoulous erythema to asymptomatic cases in 50% of the infected patients. Two-thirds of the Danish population have been infected. The virus has a broad spectrum of clinical manifestations ranging from erythema nodosum in children, arthralgia/arthritis (especially in adults), aplastic crisis in patients with haemolytic anaemia, chronic anaemia in immunocompromised patients, to hydrops foetalis following acute infection during pregnancy. In two adult females aged 41 and 35 years with persisting fatigue, malaise, transitory swelling and arthralgia we found elevated ALT and alkaline phosphatase (pt. 1), despite no serological evidence of hepatitis, cytomegalovirus (CMV), or Epstein-Barrvirus and no story of alcohol consumption or recent travelling outside Denmark. Ongoing B19 infection was diagnosed by ELISA and confirmed by B19 DNA PCR in case 2 and IgG avidity and epitope-type specificity in case 1, who was B19 DNA negative in three different samples. The concentrations of alkaline phosphatase and ALT returned to normal as the antibody response shifted from acute B19 infection to IgG positivity. In conclusion we suggest that a serological test and/or B19 DNA for B19 infection is a relevant test to undertake when screening patients for viral hepatitis especially during B19 epidemics and in exposed individuals.
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PMID:[Parvovirus B19 as a cause of acute liver symptoms in adults]. 981 Feb 42

Docetaxel has been reported to show promising anti-tumour activity in pancreatic ductal cancer (PC). This study was conducted to evaluate the activity and toxicity of moderate-dose (60 mg m(-2)) docetaxel in Japanese chemo-naive patients with measurable metastatic PC. The patients had a performance status of 0-2. They received docetaxel intravenously over a 1- to 2-h period without any premedication for hypersensitivity reactions. This treatment was repeated every 3-4 weeks with dose adjustments based on the toxic effects observed. Twenty-one patients were eligible and treated with docetaxel. The median number of courses was 2 (range, 1-4). None of the patients achieved an objective response; seven showed no change and 13 showed progressive disease. In one patient, the response was not assessable because of early death. The median survival time for all patients was 118 days. The main grade 3-4 toxicities by patient were leucocytopenia (67%) and neutropenia (86%). Other grade 3-4 toxicities included anaemia (10%), thrombocytopenia (5%), nausea/vomiting (29%), anorexia (29%), GOT/GPT increase (10%), alkaline phosphatase increase (14%), malaise/fatigue (33%) and alopecia (24%). In conclusion, docetaxel, administered on this schedule, did not show significant anti-tumour activity in patients with metastatic PC.
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PMID:Phase II study of docetaxel in patients with metastatic pancreatic cancer: a Japanese cooperative study. Cooperative Group of Docetaxel for Pancreatic Cancer in Japan. 1040 50


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