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)

A patient who developed chronic salicylism associated with salicylate therapy for treatment of juvenile rheumatoid arthritis is described, and the clinical presentation and treatment of chronic salicylism are reviewed. A 5 1/2-year-old boy was receiving aspirin 150/mg/kg/day for treatment of juvenile rheumatoid arthritis. While on salicylate therapy, the patient developed tachypnea and became increasingly hyperthermic, lethargic, and disoriented. The patient developed a maculopapular rash, weakness, and a decreased level of consciousness during the 11 days before admission to the hospital. Physical examination and laboratory determinations revealed that the patient had hypoprothrombinemia, hypoglycemia, and severe hepatic encephalopathy secondary to long-term salicylate toxicity. The patient was treated for hypoglycemia, electrolyte imbalances, thrombocytopenia, and anemia and was discharged after 24 days. Diagnosing chronic salicylism with hepatic dysfunction was difficult because the symptoms are similar to those of stage I to stage II Reye's syndrome. Liver enzymes, including aspartate aminotransferase (also called SGOT), alanine aminotransferase (also called SGPT), alkaline phosphatase, and lactate dehydrogenase, may be elevated in juvenile arthritis patients with hepatic dysfunction. Liver dysfunction usually improves when salicylate therapy is discontinued. Supportive therapy should always be used in symptomatic patients. Children on long-term, high-dose salicylate therapy should be monitored closely, and baseline liver function tests should be performed. The clinical effectiveness of administering sodium bicarbonate in attempts to alkalinize urine and increase salicylate elimination is controversial. In patients with juvenile rheumatoid arthritis who develop chronic salicylism, careful analysis of the patient's medication history, laboratory values, and clinical presentation are necessary to rule out Reye's syndrome.
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PMID:Chronic salicylism in a patient with juvenile rheumatoid arthritis. 370 82

CB3717 is a quinazoline antifolate whose cytotoxic activity is mediated by inhibition of thymidylate synthase (TS). A phase I clinical trial commenced in September 1981 and 99 patients have received 296 treatments. Doses were dissolved in 0.15 mol/L NaHCO3 (pH 9.0) at a concentration of 4 mg/mL infused over one hour or in a total volume of 1 L infused over 12 hours. Doses were repeated every 3 weeks. The starting dose of 140 mg/m2 was escalated to 600 mg/m2. Renal toxicity, detected by a decrease in the 51Cr EDTA clearance, was dose-related and occurred in seven of ten patients receiving greater than 450 mg/m2. Reversible hepatic toxicity often associated with malaise occurred in 223 of 288 assessable courses (77%). Fifty-nine courses (20%) were associated with increases in alanine transaminase (ALT) levels to greater than 2.5 times the upper limit of the normal laboratory range. Increases in alkaline phosphatase levels also occurred, but were less marked. The severity and prevalence of these elevations were unaffected by the duration of the infusion. A self-limiting rash appeared in 12 patients and a radiation recall reaction was seen in two. Leukopenia developed in 17 patients (WBC less than 3 X 10(9)/L), and thrombocytopenia occurred in six patients (platelets less than 100 X 10(9)/L). The mean leucocyte nadir occurred on day 10 and was followed by recovery at 11 to 19 days. Neither the incidence nor the severity of any of these latter toxicities was dose related. The maximum tolerated dose was in the region of 600 mg/m2 with renal toxicity being dose limiting, although the inter-patient variation did not allow a precise definition. Seventy-six patients were evaluable for response. Responses occurred at doses greater than or equal to 200 mg/m2 and were ovary, one complete response (CR), one partial response (PR), seven minor responses (MR) in 30 cases; breast, two PRs and one MR in eight cases; adenocarcinoma of the lung, one MR in 5 cases; mesothelioma, one PR in five cases; and colon, two MRs in four cases. CB3717 has activity in heavily pretreated patients. The recommended phase II dose for good-risk patients is 400 mg/m2 using the one-hour infusion schedule of administration.
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PMID:A phase I evaluation of the quinazoline antifolate thymidylate synthase inhibitor, N10-propargyl-5,8-dideazafolic acid, CB3717. 373 49

CI-921, a 4,5-disubstituted analog of amsacrine, has been selected for clinical testing because of its experimental activity in vitro and in vivo against solid tumors as well as leukemias. In studies conducted by Baguley and co-workers, CI-921 demonstrated activity against Lewis lung carcinoma in vivo, producing marked increases in life span and a high proportion of 60-day survivors. An intermittent schedule of administration was more effective than a daily X 5 or daily X 9 schedule. In pharmacokinetic studies in dogs, CI-921 achieved higher plasma concentrations and was cleared more slowly than amsacrine. CI-921 is readily soluble in water and may have antitumor activity when administered orally. Animal toxicology studies indicate that dose-related, reversible leukopenia and thrombocytopenia occur, as well as gastrointestinal toxicity, elevation of alkaline phosphatase and generalized lymphoid depletion. Phase I clinical testing of a parenteral formulation is in progress.
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PMID:CI-921: an analog of amsacrine with experimental activity against solid tumors. 375 24

Young rats were force-fed a lysine + arginine-devoid diet or a complete diet for 3 days, and selected biochemical and morphologic studies were conducted. Rats force-fed the experimental diet in comparison with those force-fed the control diet for 3 days showed decreased body weight gain, hepatomegaly with periportal fatty liver, pancreatic and splenic atrophy, and enhanced 14C-leucine incorporation into hepatic proteins. Differences in the experimental animals were observed in the free amino acid levels of serum (decreased lysine, arginine, and ornithine) and liver (decreased ornithine), in blood chemistries (decreased levels of ammonia N2, uric acid, cholesterol, protein, albumin, alkaline phosphatase, LDH and SGOT) and in hematologic findings (leukocytopenia and thrombocytopenia after a morning feeding). The experimental findings in young rats force-fed the lysine + arginine-devoid diet were compared with those reported to develop in children with lysinuric protein intolerance (LPI), an autosomal recessive defect in diamino acid transport. Children with LPI as described by others reveal a number of similarities as well as a number of differences in comparison to the findings in the experimental animals. The comparison suggests that some of the pathological manifestations of LPI may be related to a deficiency of diamino acids but others must be due to different alterations in this complex human disease.
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PMID:Chemical pathology of diamino acid deficiency: considerations in relation to lysinuric protein intolerance. 393 96

Rocky Mountain spotted fever (RMSF) or ehrlichiosis was diagnosed in dogs on the basis of specific immunofluorescent testing for each disease. Comparisons between clinical and laboratory findings were made between the 2 diseases. The incidence of RMSF tended to be more seasonal and it affected younger dogs. Purebred dogs appeared to be more susceptible to both diseases. In general, RMSF had a more rapid and severe course of clinical illness than did ehrlichiosis, but acute ehrlichiosis was difficult to differentiate from RMSF. Both diseases were characterized by fever, depression, lymphadenopathy, and signs of neurologic dysfunction; petechial hemorrhages or other signs of hemorrhagic diathesis were evident only in a small proportion of cases. Anemia, leukopenia, and thrombocytopenia were more common in dogs with ehrlichiosis, whereas those with RMSF more often had leukocytosis and thrombocytopenia. Hypoalbuminemia was found in dogs with both diseases, but those with ehrlichiosis usually had concurrent hyperglobulinemia. High serum alkaline phosphatase activity and serum cholesterol concentration, and low serum calcium concentration were more common in dogs with RMSF than with ehrlichiosis. Rising serum titers or positive direct immunofluorescence for Rickettsia rickettsii in skin biopsy specimens were used to confirm RMSF, whereas a single serum titer for Ehrlichia canis enabled detection of ehrlichiosis. In the absence of neurologic deficits and when dogs were treated with tetracycline, dogs with RMSF made a more rapid and consistent recovery than did dogs with ehrlichiosis.
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PMID:Rocky Mountain spotted fever in dogs and its differentiation from canine ehrlichiosis. 397 6

The clinical picture of 60 cases of primary liver cancer is reported. Distended abdominal veins found in a substantial number of cases, often point to collateral circulation due to a membrane in the inferior vena cava (budd-Chiari syndrome). Alpha-foetoprotein, alkaline phosphatase and gamma-glutamyltranspeptidase were the only reliable laboratory pointers to the disease. Ultrasound study proved to be very helpful. Thrombocytopenia was found in 5 out of 12 of our patients.
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PMID:Primary liver cancer in the Transvaal. 617 70

A microplate immune-enzymatic method was developed for detecting serum antiplatelet antibodies. The method involves the use of antigen-coated platelets and alkaline phosphatase-labeled antihuman immunoglobulin. Linear correlation was obtained between the titer of platelet antibodies and substrate conversion. Twenty-four patients with immune thrombocytopenia and 40 normal controls were studied. Eighteen patients and one control were positive. Therefore, sensitivity and specificity were 75% and 97% respectively. ELISA also was found to be more sensitive than the indirect antiglobulin consumption assay (ACA) and appears to be a practical and easy method for routine evaluation of antiplatelet antibodies.
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PMID:A microplate enzyme-linked immunospecific assay (ELISA) detecting unbound anti-platelet antibodies. 620 1

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

To identify a group of patients who are likely to have specific liver damage (a risk group), 88 patients with lymphogranulomatosis were examined. The examination program included clinical studies, liver scanning, peripheral blood analysis, blood serum biochemistry, study of the bone marrow, liver biopsy in all the patients. Eleven patients manifested specific liver damage. In all the patients with liver lymphogranulomas, the disease ran an unfavourable course; they frequently demonstrated the symptoms of intoxication enlargement of the liver size, focal changes on the scanogram and concurrent damage to the bone marrow. According to the biochemical tests, high activity (over 200 U/l) of alkaline phosphatase was recorded exclusively in patients with the lymphogranulomatosis-induced liver damage. Nevertheless, none of the above-enumerated signs regarded separately cannot serve as criterion of the diagnosis of lymphogranulomatosis metastases to the liver. Analysis of the rate of association of individual clinical symptoms and laboratory findings demonstrated that the most informative were associations of high alkaline phosphatase activity and enlargement of the liver size, as well as association of thrombocytopenia and anemia. However, histological study of liver biopsies is the most reliable method of diagnosis of lymphogranulomatosis metastases to the liver, particularly in patients with clinical stages I-II, since in such patients with lymphogranulomatosis, specific liver damage runs an asymptomatic course.
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PMID:[Early diagnosis of specific lesions of the liver in lymphogranulomatosis]. 649 95

Clinical and radiological studies of seven patients with autosomic recessive malignant osteopetrosis are presented. Diagnosis was established before the age of 3 months in six cases and at 7 months in one. In all cases the presenting signs were pallor and hepatosplenomegaly with associated neurological involvement in five. All patients had normocytic normochromic anemia, leucopenia and thrombocytopenia with features of extramedullary hematopoiesis. Radiological studies revealed increase in the density of bones with "mask" appearance of facial bones and diminished size of optic foramina. Long bones showed absence of normal trabeculae and anomalies in modeling with methaphiseal bands and "bone within bone" images. There was hypocalcemia and hypophosphatemia with slight increases in alkaline phosphatase; parathormone was normal. Clinical course was characterized by progressive pancytopenia, recurrent infections and neurological deterioration with convulsions, nistagmus and optic atrophy. Five out of the seven patients died after a median of 3 months, due to infections or haemorrhage. The patient diagnosed at 7 months of age presented bilateral optic atrophy and moderate anemia; no other complications appeared after 2 year follow-up. Histological findings included substitution of bone marrow by chondro-osseous tissue; focal obsteoblastic and osteoclastic activity in calcified cartilage, and myeloid metaplasia in liver, spleen, lymph nodes and kidneys. The lesions are in agreement with the concept of a defect in bone formation-resorbtion balance; dysfunction of both osteoclasts and osteocytes is implicated in the pathogenesis. Unlike experimental disease, osteopetrosis in man is probably an heterogeneous disease and appropriate therapy should be individualized. Nevertheless, at present, the only favorable results have been obtained with bone-marrow transplantation.
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PMID:[Juvenile malignant osteopetrosis. Clinico-radiological study of 7 cases]. 663 10


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