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)

Ametantrone is the third of a family of anthracene derivatives to undergo a phase I trial in man. Sixteen patients received 33 courses of drug as a single iv dose given every 3 weeks. Escalations proceeded from 120 to 180 mg/m2. Predictable and reversible leukopenia was the dose-limiting toxic effect. Four patients developed thrombocytopenia. Nonhematologic toxic effects included a marked cumulative blue discoloration of the skin seen in all patients receiving more than three courses of the drug. This cumulative cosmetic effect may also be dose-limiting. Other nonhematologic toxic effects included: blue urine (all patients), nausea (two), vomiting (one), a blue stool (one), and reversible elevations of either SGOT or alkaline phosphatase (two). No objective responses were seen in this study. A dose of 140-160 mg/m2 is recommended as the starting dose for phase II trials in patients who have received prior chemotherapy or radiotherapy.
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PMID:Phase I investigation of ametantrone. 664 May 57

Thirty-one patients with measureable metastatic colorectal cancer refractory to 5-fluorouracil-containing regimens received dihydroxyanthracenedione (DHAD, NSC 301739) on a 5-day I.V. schedule administered every 4 weeks. Good-risk patients received DHAD at the starting daily dose of 4 mg/m2 while patients who had had therapy with radiation or myelosuppressive drugs such as mitomycin C or a nitrosourea compound received an initial daily dose of 3 mg/m2. There were no complete or partial remissions in this study. Eight of 30 evaluable patients had disease stabilization. The dose-limiting toxic effect was myelosuppression; neutropenia was more severe than thrombocytopenia. The myelosuppression was more severe in patients who had poor bone marrow reserves and abnormal pretreatment liver functions (serum alkaline phosphatase and serum glutamic oxaloacetic transaminase) levels greater than or equal to 1.5 times normal). DHAD administered by the 5-day dose schedule as used in this study is not effective against colorectal cancer.
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PMID:Phase II evaluation of dihydroxyanthracenedione (DHAD, NSC 301739) in patients with metastatic colorectal cancer. 683 6

Local inflammation was induced in rats by single (1 x 4 ml/kg) or multiple (14 X 0.2 ml/animal) infections of turpentine. The induction of inflammatory processes in both groups resulted in anemia and granulocytosis following an initial leukopenia. Thrombopenia on the second day, followed by thrombocytosis, was also observed in both groups. Studies on blood chemistry parameters revealed a decline in serum albumin; elevation of alkaline phosphatase in serum was observed only after multiple injection of turpentine. In these animals an elevation in the weights of spleen and adrenals and a reduction in the weight of thymus were also found.
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PMID:[Systemic reactions in rats following the initiation of a local inflammatory process by subcutaneous administration of spirits of turpentine]. 689 Dec 53

Paroxysmal nocturnal hemoglobinuria is characterized by chronic hemolytic anemia, leukopenia, and thrombocytopenia. The increased hemolysis and hemoglobinuria associated with sleep have been observed so frequently that these features have been incorporated into the syndrome's name. Infections, especially of the respiratory and urinary system, can cause hemolytic episodes. Patients with paroxysmal nocturnal hemoglobinuria have increased susceptibility to infections. Some PNH patients are leukopenic, but many are not. It has been reported that leukocyte alkaline phosphatase of granulocytes in patients with PNH is low. As Hartmann and Kohlhouse point out, "The principles of treating infection in PNH seem no different than the therapy of infections in any group. "If major surgery is indicated, preparation should include saline-washed red cells, which would increase the patient's number of circulating normal red blood cells, if necessary. The prognosis is variable. A small percentage of patients with PNH develop leukemia. However, in at least half of all patients, the number of complement sensitive cells decreases, and many of these patients live a fairly normal life.
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PMID:Paroxysmal nocturnal hemoglobinuria: report of case with odontogenic infection. 693 60

Although it is widely accepted that patients with immune thrombocytopenia produce platelet antibodies, the demonstration of such antibodies has been difficult and time consuming. A simple and quick enzyme linked immunoassay for platelet antibodies is presented. The platelet associated IgG is coupled with alkaline phosphatase labeled anti-IgG. The resultant complex is determined spectrophotometrically using p-nitrophenyl phosphate as substrate. With this technique, excess of IgG on platelets was detected in 24 out of 33 patients (72 percent) with immune thrombocytopenic purpura and four out of four thrombocytopenic patients with systemic lupus erythematosus. The results of this assay correlate quantitatively with Dixon er al3 complement lysis inhibition assay (r = 0.82).
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PMID:Enzyme labeled immunosorbant assay (ELISA) for detection of platelet antibodies. 703 90

A retrospective was designed to analyse the mode of presentation, clinical signs and haematological and biochemical abnormalities in 225 consecutive Black (Zulu) patients who were admitted to a general medical ward between the years 1970 and 1981 and in whom cirrhosis was later diagnosed. The most common presenting complaint was swelling of the body (60% of the patients), followed by abdominal pain (32%) and episodes of bleeding, mainly from the gastrointestinal tract (19%). On examination, hepatomegaly was encountered in 66% of the patients, with moderate to massive enlargement in 40%. Ascites was detected in 56%, with tense abdominal distension in 34%. Jaundice was present in 38% and emaciation, mental disturbance and splenomegaly in over 25%. Spider naevi (found in 2 patients) and Dupuytren's contracture (found in 1) were very rare. Thrombocytopenia and a high ESR were common. Over 90% of patients had low albumin and high globulin concentrations (albumin less than 20 g/dl and globulin greater than 60 g/dl in 25%). Bilirubin and alkaline phosphatase levels and the prothrombin index were found to be within normal limits in 32%, 24% and 52% of cases respectively. Histologically the lesion was most commonly micronodular (73%) with variable deposits of fat and iron. Peritoneoscopy was the most useful special investigation in the diagnosis of cirrhosis, leading to a correct diagnosis in 77% of cases. In conclusion, the clinical signs, biochemical abnormalities and histological features suggest that the factors causing cirrhosis in the community studied are mixed; it may result from the combined effects of alcohol abuse, malnutrition and chronic viral (e.g. hepatitis B) infections.
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PMID:Clinical presentation and biochemical abnormalities in black (Zulu) patients with cirrhosis in Durban. 707 88

We review the clinical and pathologic features of 39 cases of nodular regenerative hyperplasia of the liver and include two new cases. This is an uncommon but distinct pathological entity characterized by regenerative hepatocytic nodules without fibrosis. Portal hypertension that often leads to hemorrhage from esophageal varices is the most important clinical manifestation. Characteristically, manifestations of hepatic failure are lacking, but a number of patients have elevated alkaline phosphatase of hepatic origin. Felty's syndrome is the entity most often associated with nodular regenerative hyperplasia. Anemia, leukopenia, and thrombocytopenia are frequent hematologic abnormalities secondary to hypersplenism. The etiology and pathogenesis of nodular regenerative hyperplasia of the liver are unknown.
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PMID:Nodular regenerative hyperplasia of the liver: report of two cases and review of the literature. 724 Jun 92

An enzyme linked immunoassay incorporating antihuman globulin coupled with alkaline phosphatase has been developed to measure platelet associated IgG (PAIgG). Using a method in which platelet IgG is extracted into the fluid phase after appropriate procedures, we were able to bind the 'solubilized' PAIgG to commercially obtained antihuman IgG (AHG) which had previously been coated onto polystyrene. The amount of PAIgG thus bound was subsequently measured by the addition of the enzyme reagent using p-nitro phenyl phosphate as substrate. With this technique platelets from normal donors were found to have 2.6-17.4 ng/10(6) platelets (mean +/-2 SD). These values are higher than those obtained when assay systems using intact platelets are employed. Platelets from patients with immune thrombocytopenia had PAIgG values of 8.2-98.0 ng/10(6) platelets. In a few patients with disorders other than autoimmune thrombocytopenia (AITP) increased levels of PAIgG were also demonstrated. The assumption that increased PAIgG always represents platelet autoantibody may not be valid. The relevance of PAIgG as a parameter in the diagnosis and clinical management of patients with AITP is discussed.
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PMID:Enzyme linked immunoassay for the detection of platelet associated IgG. 724 90

Coupling of anthracyclines to high-molecular-weight carriers may alter drug disposition and improve antitumor effects. We have performed a clinical phase I trial of doxorubicin coupled to dextran (70000 m.w.). The drug was administered as single dose i.v. every 21-28 days. Thirteen patients have received a total of 24 courses (median 2; range 1-3). At the starting dose of 40 mg/m2 doxorubicin equivalent (DOXeq), WHO grade IV thrombocytopenia was noted in 2/2 patients. WHO grade IV hepatotoxicity and WHO grade III cardiotoxicity were noted in a patient with preexisting heart disease. Five patients were treated with 12.5 mg/m2 DOXeq. Maximal toxicity at this dose level was WHO grade III thrombocytopenia and local phlebitis (WHO grade II) in 1/5 patients, elevation of alkaline phosphatase (WHO grade III) and WHO grade III vomiting in another patient. Subsequently, five patients received 20 mg/m2 DOXeq. Hepatotoxicity was noted in 5/5 patients (1 x WHO grade IV, 1 x WHO grade III). Thrombocytopenia was noted in 3/5 patients (1 x WHO grade IV, 2 x WHO grade III). At 12.5 mg/m2 DOXeq, a patient diagnosed with a malignant fibrous histiocytoma had stable disease for 4 months. Pharmacokinetic analyses of total and free doxorubicin were performed in plasma and urine. The maximum peak plasma concentration (ppc) for total DOX was 12.3 micrograms/ml at 40 mg/m2 DOXeq. The area under the plasma concentration time curve (AUC) ranged from 28.83-80.21 micrograms/ml*h with dose-dependent elimination half lives (t1/2 alpha: 0.02-0.87 h; t1/2 beta: 2.69-11.58 h; t1/2 gamma: 41.44-136.58 h).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I clinical and pharmacokinetic trial of dextran conjugated doxorubicin (AD-70, DOX-OXD). 750 68

11 patients suffering from an isolated leucopenia during fractionated radiotherapy were treated with granulocyte colony stimulating factor (G-CSF). 4 of the patients received radiotherapy alone, and 7 patients received concomitant chemotherapy. G-CSF treatment was initiated at the occurrence of leucopenia and maintained for the duration of radiotherapy. The applied daily dose was 5 micrograms/kg subcutaneously. 10 of the 11 treated patients reacted with an increased leucocyte count, from an average of 1342 leucocytes per microliter (+/- 502/microliters) to 24,568 leucocytes per microliter (+/- 950/microliters). Neutrophil counts increased on average from 64.9% (+/- 13.9%) to 91.1% (+/- 2.3%) (n = 7). In 1 patient thrombocytopenia occurred during the continued radiotherapy. 1 other patient reacted with an unexplained fall of leucocytes after two doses of G-CSF and one fraction of mediastinal irradiation. Side-effects observed during G-CSF treatment consisted of mild bone pain (1/11) and transient increases of serum alkaline phosphatase levels (4/11). Our observations indicate that G-CSF treatment is well tolerated during continuous fractionated radiotherapy. Therefore, we conclude that G-CSF can be used clinically to alleviate neutropenia caused by radiotherapy or by combined radio-chemotherapy.
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PMID:Granulocyte colony-stimulating factor treatment of leucopenia during fractionated radiotherapy. 750 58


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