Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemorrhagic fever with renal syndrome is an acute febrile nephropathy caused by several viruses of the genus Hantavirus of the family Bunyaviridae. During the past 8 years, 32 cases of hemorrhagic fever with renal syndrome have been diagnosed. Nine out of the 32 patients (28%) had raised (twofold upper normal limits) transaminases during hospitalization. Four out of the nine patients (44%) died. In contrast, only three out of the 23 patients (13%) without raised transaminases died. Five patients had slightly increased serum alkaline phosphatase and gamma-glutamyl-transpeptidase, whereas six patients had prolonged prothrombin time. Liver histology showed midzonal necrosis in hepatic lobules with extravasation of red cells and mild mononuclear infiltrate. Liver involvement seems to be an ominous prognostic factor in such patients and is correlated with severe renal failure and thrombocytopenia.
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PMID:Liver involvement in hemorrhagic fever with renal syndrome. 810 72

We compared the biochemical effects and safety of pamidronate (30 mg a day for 3 consecutive days) versus clodronate (300 mg a day for 3 consecutive days) via intravenous infusion in 14 patients with Paget's disease of bone (PDB). Both drugs induced a decrease in serum alkaline phosphatase levels as well as the elimination of hydroxyproline from urine, an effect most marked in the group treated with pamidronate. The response was maintained for 6 months after the infusion in the majority of the patients. No relevant side effects were found, except post-infusion febricula and in one patient, self-limiting thrombopenia 6 months after the infusion. We conclude that the intravenous infusion of either of the two drugs may constitute a safe and effective alternative for treatment of PDB with marked biochemical activity or resistant to conventional therapy.
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PMID:[The treatment of Paget's disease of bone with second-generation bisphosphonates via intravenous infusion]. 810 76

Bone marrow bilateral biopsy was done in 106 small cell lung cancer patients before treatment. Full blood count, serum alkaline phosphatase activity, serum albumin concentration and serum Na+ concentration were compared according to presence or absence of bone marrow metastases. Decreased red cell count and elevated alkaline phosphatase activity were found significantly more often in the group of patients with bone marrow involvement. Thrombocytopenia and "blast" smear occurred only in patients with bone marrow metastases. Although bone marrow was found more often in association with low albumin level, this was not significant. It was impossible to anticipate the presence of bone marrow metastases on the base of total blood count, examination increased serum alkaline phosphatase activity or decreased serum Na+ or albumin levels. However in the presence of thrombocytopenia and "blastic" smear bone marrow metastases are very probable.
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PMID:[Frequency of bone marrow involvement in patients with small cell lung carcinoma before treatment based on selected laboratory parameters]. 811 24

We characterized urinary excretion of C3 fragments among patients with systemic lupus erythematosus (SLE) as a possible indicator of renal involvement. 28 patients, representing a broad range of disease activity were admitted to our study. Urinary proteins were separated on 4-20% gradient SDS-PAGE gels, under reducing conditions, and transblotted to nitrocellulose. Western blots were developed with a polyvalent goat-anti-human C3d antiserum, and an alkaline phosphatase-conjugated rabbit anti-goat IgG. Three patterns were obtained: 1) no bands detected; 2) bands suggesting the presence of intact C3; and 3) samples with additional low molecular (< 4 x 10(4)) bands. The 12 patients with no C3 bands had minimal disease activity (e.g. fatigue, arthralgia, arthritis, rash, oral ulcers). The seven patients with intact C3 patterns also had minimally active disease. Their primary clinical findings included fatigue, pleurisy, renal disease which had been treated, hemolytic anemia, and arthritis. Patients with low molecular weight C3 fragments in their urine formed two sub-sets, based upon their presenting features. The first group had severe disease and contained all patients with active lupus nephritis (n = 4), while the second consisted of non-renal patients with primary clinical findings of moderate disease activity (e.g. thrombocytopenia, pneumonitis, arthritis). Our results suggest urinary excretion of low molecular weight C3 fragments correlates with active renal disease, but is a variable finding among SLE patients with non-renal manifestations of disease activity.
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PMID:Complement C3 fragments in urine: detection in systemic lupus erythematosus patients by western blotting. 819 18

Ribavirin, a broad-spectrum antiviral agent active in vitro against a number of RNA and DNA viruses, has been associated with moderate toxicity in laboratory animals and humans. Clinically, ribavirin has been used effectively in persons primarily to treat life-threatening viral diseases such as acute haemorrhagic fever or viral pneumonia of infants. In order to evaluate the feasibility of using this antiviral agent in cats, the effects of oral (p.o.), intramuscular (i.m.) and intravenous (i.v.) doses of ribavirin in 27 9-month-old specific-pathogen-free cats were evaluated by haematology, clinical chemistries, bone marrow biopsies and histopathology. Ribavirin was administered once daily for 10 consecutive days at a dose of either 11, 22, or 44 mg/kg after which all cats were euthanatized and necropsied. Most cats receiving 22 or 44 mg of ribavirin/kg became anorectic and suffered some degree of weight loss (0.2 to 0.6 kg), and about one-third of the cats developed diarrhoea and/or mucous membrane pallor. Icterus or haemorrhage was not observed. The most profound and consistent haematologic change, particularly among the moderate and high dosage groups regardless of route of administration, was a significant and severe thrombocytopenia (range, 33-78% reduction in mean platelet counts vs. baseline). Other changes, particularly reductions in total WBC and neutrophils and reductions in RBC and PCV, tended to occur at lower ribavirin dosages, but generally they were not statistically significant. Cats given 44 mg of ribavirin/kg i.v. showed significant decreases in leukocyte variables, including total WBC (P = 0.016), neutrophils (P = 0.026) and lymphocytes (P = 0.047). Mild-to-moderate increases in serum alanine aminotransferase and alkaline phosphatase activities occurred at doses of 22 and 44 mg/kg. Evaluation of bone marrow biopsies before and after treatment revealed that cats given 11 mg of ribavirin/kg had mild megakaryocytic (MK) hypoplasia, whereas cats receiving 22 or 44 mg/kg had progressively severe degrees of MK hypoplasia and dysplasia, asynchronous MK maturation, and increased myeloid:erythroid ratio. Pathologic changes in ribavirin-treated cats generally were mild and included primarily enteritis (seven cats) and hepatocellular vacuolation and/or centrilobular necrosis (seven cats). Results of this study in cats indicated that daily administration of ribavirin at a dose range of 11 to 44 mg/kg induced a dose-related toxic effect on bone marrow, primarily on megakaryocytes and erythroid precursors, and at the higher dosages is suppressed numbers of circulating leukocytes.
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PMID:Toxicologic effects of ribavirin in cats. 823 Apr 1

This study reviews the clinicopathologic features of 25 adult patients without a known history of malignancy presenting with metastatic carcinoma in the bone marrow. The disease mainly affected middle-aged to elderly males (mean age, 61.6 years). Bone pain, generalized or confined to the back, was a common presenting complaint. Organomegaly was often absent. Laboratory abnormalities included anaemia, leukocytosis, thrombocytopenia and a leukoerythroblastic blood picture. Serum alkaline phosphatase level was raised in the majority of cases. In about one-third of the cases, malignancy was not suspected clinically, and bone marrow aspiration was carried out because of incidental finding of abnormal blood counts. The marrow aspirate findings were characterized by numerous to sparse cohesive tumour clusters with nuclear moulding. Over two-thirds of the patients had metastatic adenocarcinoma, and the lung was found to be the commonest site of primary disease. We conclude that since the marrow infiltration can be subtle, marrow smears should be carefully scrutinized for tumour cells in patients with leukoerythroblastic blood picture, in particular those with an elevated serum alkaline phosphatase level.
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PMID:Solid tumour with initial presentation in the bone marrow--a clinicopathologic study of 25 adult cases. 832 25

So far, no curative treatment is available for hormone-refractory prostate carcinoma. Therapy is thus focused on alleviating symptomatic tumor progression with the aim of improving quality of life. Therefore, anthracyclin-derived mitoxantrone was administered to 25 patients with hormone-refractory prostate carcinoma and symptomatic progressive disease. After a median treatment of 13 weeks, a median of 4 cycles and a follow-up of 14 months, 48% of the patients (12/25) reported improvement in tumor-related pain; in 60% (15/25) there was improvement of the self-assessment symptom score and 32% of the patients (8/25) gained weight. Additionally, partial tumor response with regression of lymph-node metastases occurred in 3/25 patients (12%). In 10/25 patients the serum level of prostate-specific antigen (PSA) decreased as well as the alkaline phosphatase (AP) in 7/25 patients. Side effects subsequent to chemotherapy were leucopenia WHO grade III in 25% of the patients and thrombocytopenia WHO grade III in 3/25 and grade V (treatment-related death) in 1/25 patients. Non-hematological toxicity occurred in 2 patients (cardiotoxicity n = 1, nephrotoxicity n = 1, WHO grade II each).
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PMID:[Therapy of hormone refractory prostate carcinoma with mitoxantrone. A clinical phase II study]. 865 Aug 48

Seventeen Minnesota and Wisconsin dogs with granulocytic ehrlichosis were studied. The diagnoses were made by finding ehrlichia morulae in peripheral blood neutrophils. Eight dogs were studied retrospectively, and nine dogs were studied prospectively. The medical records of all dogs were reviewed. Eighty-eight percent of the dogs were purebred and 76% were spayed females. The median age was 8 years. Sixty-five percent of the cases were diagnosed in October and November. Fever and lethargy were the most common clinical signs. The most frequent laboratory findings were lymphopenia, thrombocytopenia, elevated activities of serum alkaline phosphatase and amylase, and hypoalbuminemia. No dogs seroreacted to Ehrlichia canis or Ehrlichia chaffeensis antigens, which are cross-reactive. Seventy-five percent of the dogs tested during the acute phase of disease and 100% of the dogs tested during convalescence were seropositive for E. equi antigens. Granulocytic ehrlichial 16S rRNA gene DNAs from six dogs were amplified by PCR. Sequence analysis of a 919-bp sequence of the ehrlichial 16S rRNA gene amplified by PCR from the blood of two dogs revealed the agent to be identical to the agent of human granulocytic ehrlichiosis in Minnesota and Wisconsin and to be very similar to E. equi and Ehrlichia phagocytophila and less similar to E. canis, Ehrlichia ewingii, and E. chaffeensis. The geographic, clinical, serologic, and molecular evidence indicates that granulocytic ehrlichiosis in Minnesota and Wisconsin dogs is not caused by E. ewingii, but suggests that it is a zoonotic disease caused by an agent closely related to E. equi and that dogs likely contribute to the enzootic cycle and human infection.
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PMID:Geographic, clinical, serologic, and molecular evidence of granulocytic ehrlichiosis, a likely zoonotic disease, in Minnesota and Wisconsin dogs. 874 70

The true incidence of sarcoidosis in common variable immunodeficiency (CVID) is unknown. We report here 8 cases of sarcoidosis among 80 patients with CVID followed in our clinics, along with 22 well-documented cases reported in the literature. Sarcoidosis, therefore, represents an important entity to consider among patients with CVID who exhibit clinical, radiographic, laboratory, and biopsy findings compatible with sarcoidosis. Conversely, the diagnosis of CVID should be considered in patients with sarcoidosis who do not exhibit the characteristic hypergammaglobulinemia and who have a history of recurrent infections. Although many features of sarcoidosis are similar in patients with CVID to those in patients with sarcoidosis alone, there are many important differences. Patients with CVID in whom sarcoidosis develops present with hypogammaglobulinemia rather than hypergammaglobulinemia and have a higher prevalence of recurrent infections, thrombocytopenia, and splenic involvement. Steroids, in most cases, appeared helpful in reducing adenopathy and splenomegaly, improving uveitis, lowering serum alkaline phosphatase, and reversing hematologic abnormalities. The underlying pathophysiology responsible for the association of these 2 disorders in the same patient remains obscure. However, as more patients are identified, it may be possible to gain a better understanding of the immunologic defect responsible for the dual presentation of these 2 relatively uncommon diseases.
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PMID:Sarcoidosis and common variable immunodeficiency. Report of 8 cases and review of the literature. 886 47

The tolerability and efficacy of four courses of paclitaxel and ifosfamide plus cisplatin every 3 weeks was evaluated in patients with residual or refractory ovarian cancer. Additionally, supportive haematological effects of recombinant human interleukin 3 (rhIL-3) and recombinant human granulocyte colony-stimulating factor (G-CSF) were studied. Paclitaxel starting dose was 135 mg m(-2) (day 1), with ifosfamide dose 1.2 g m(-2) day(-1) (days 2-4) and cisplatin dose 30 mg m(-2) day(-1) (days 2-4). All 16 patients received 5.0 microg kg(-1) day(-1) G-CSF (days 7-16) and, in addition, eight patients were randomized to receive 10 microg kg(-1) day(-1) rhIL-3 (days 5-9). Paclitaxel and ifosfamide doses were reduced when grade IV haematological toxicity occurred. In the absence of grade IV haematological toxicity and normal recovery of haematopoiesis, paclitaxel dose was escalated. Toxicity was evaluable in 56 courses, with haematological effects in 52. Despite antiemetic treatment, nausea and vomiting (> or = grade I) occurred in 50 courses. Five patients had persisting peripheral neuropathy. Renal and liver function were not affected. Grade IV neutropenia occurred in 12 out of 52 courses, with neutropenic fever in two patients, both of whom died from fatal septicaemia. Grade IV thrombocytopenia without bleeding was observed in 15 courses. Grade IV haematological toxicity was associated with hepatic metastases and concurrent increases in alkaline phosphatase (P <0.001) and gamma-glutamyltransferase (P=0.007). No relation was found between haematological toxicity and pharmacokinetic parameters of paclitaxel. Patients treated with rhIL-3 showed a tendency to a faster platelet recovery (not affecting platelet nadir), and the cisplatin dose intensity was higher (P=0.025). Six of the nine evaluable patients had a tumour response. The overall median progression-free survival was 7 months and the overall mean survival was 13 months. In conclusion, this potentially interesting combination as second-line treatment showed a low tolerability with unexpected mortality, while rhIL-3 administration tended to induce a more rapid platelet recovery.
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PMID:Paclitaxel, ifosfamide and cisplatin with granulocyte colony-stimulating factor or recombinant human interleukin 3 and granulocyte colony-stimulating factor in ovarian cancer: a feasibility study. 904 28


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