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)

An 11-year-old boy with chronic granulomatous disease caused by cytochrome b deficiency developed right upper lung lobe aspergillosis. Intracerebral lesions developed on maximum doses of flucytosine and amphotericin B. Treatment with 16 mg/kg oral itraconazole was followed by a dramatic clinical improvement and almost complete disappearance of the intracerebral lesions. Plasma itraconazole levels were between 40 and 3440 ng/ml depending on concomitant medication. Toxicity was restricted to transient elevation of alkaline phosphatase and gamma glutamyl transferase. We conclude that further trials with itraconazole are justified in high risk patients in whom conventional therapy has failed.
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PMID:Control of proven pulmonary and suspected CNS aspergillus infection with itraconazole in a patient with chronic granulomatous disease. 165 60

The influence of immunosuppression by T-2 mycotoxin on the fungal disease aspergillosis was investigated in rabbits. Four groups of rabbits (groups 1A, 1B, 3A, and 3B) were given 0.5 mg of T-2 toxin/kg of body weight/day, PO; in addition, rabbits of groups 3A and 3B were exposed to aerosols of Aspergillus fumigatus conidia from days 7 through 16. Rabbits of groups 2A and 2B were exposed to A fumigatus aerosols, but were not given T-2 toxin, and rabbits of group 0 served as controls. Two rabbits of group 1A, 1 rabbit of group 1B, and 1 rabbit of group 3A died before scheduled necropsy. Rabbits of groups 1A, 2A, and 3A were killed and necropsied on day 17, and the remaining rabbits (groups 0, 1B, 2B, and 3B) were killed and necropsied on day 28. Changes caused by T-2 toxin included leukopenia, marginal anemia, and increased number of and morphologic changes in nucleated erythrocytes by day 21, followed by a regenerative hematologic response. Serum alkaline phosphatase and sorbitol dehydrogenase activities and antibody response to A fumigatus (as measured by an indirect hemagglutination test) were decreased by T-2 toxin ingestion. Rabbits with aspergillosis had leukocytosis, increased PCV, and increased antibody response to A fumigatus. Histologic lesions consisting of centrilobular hepatocellular swelling, portal and periportal fibrosis, and lymphocyte necrosis and/or depletion within secondary lymphoid tissue were observed in most rabbits treated with T-2 toxin. Normal defense mechanisms against A fumigatus infection were compromised by T-2 treatment, as evidenced by the severity and extent of lung lesions, greater number of hyphal elements observed, and greater number of colonies of A fumigatus isolated from rabbits of groups 3A and 3B. There were no significant changes in group-0 rabbits.
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PMID:Pathologic, hematologic, and serologic changes in rabbits given T-2 mycotoxin orally and exposed to aerosols of Aspergillus fumigatus conidia. 307 Nov 96

Radiostrontium ((85)Sr) skeletal scintiscanning was done on 640 cases and 520 were included in a review. Forty-eight percent of 359 patients with biopsy-proved malignant disease had secondary skeletal involvement; in 17 percent the involvement was identified by scintiscanning alone. False-negative scintiscans were recorded in 0.9 percent. Unusual (85)Sr localization was found in a bone infarct, in proteus bursitis and in a pulmonary aspergillosis infiltrate. Serum alkaline phosphatase levels were found to be of little value in the evaluation for osseous metastasis, and normal acid phosphatase values in patients with prostatic carcinoma did not exclude the possibility of spread to the skeleton. Both the scintiscan and roentgenograms are essential in the evaluation of patients for metastatic bone disease.
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PMID:Review of a 5-year experience with the radiostrontium bone scintiscan. 503

To evaluate procedures used for epidemiologic analysis of outbreaks of aspergillosis, we analyzed a collection of 35 Aspergillus fumigatus isolates using three typing methods: isoenzyme analysis (IEA), random amplified polymorphic DNA (RAPD) analysis, and restriction endonuclease analysis (REA). Twenty-one isolates were from a single hospital, with four isolates coming from different patients. Three clinical isolates came from a different hospital, and 11 clinical or environmental isolates were derived from a culture collection. With IEA, the patterns of alkaline phosphatase, esterase, and catalase discriminated nine types. In contrast, 22 types were obtained with five different RAPD primers, and 21 types could be detected with three of these (R108, R151, and UBC90). Restriction endonuclease analysis of genomic DNA, digested with either XbaI, XhoI, or SalI, detected 3, 17, and 13 different REA types, respectively, and 22 types were identified by combining the data from the XhoI and SalI REAs. Twenty-eight types were obtainable with a combination of REA, IEA, and RAPD patterns. Overall, the results pointed to substantial genetic variation among the isolates. Though two isolates had markedly distinct genotypes, their morphologic features and exoantigens were consistent with their being A. fumigatus. The analysis will help in planning epidemiologic studies of aspergillosis.
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PMID:Comparison of three typing methods for clinical and environmental isolates of Aspergillus fumigatus. 858 42

Comparative studies were performed to assess the stability and lot-to-lot variation of Blastomyces dermatitidis yeast and mycelial phase lysate antigens. Four lots were prepared from each growth phase of B. dermatitidis strain T-58 (canine isolate) during a 14-month period. Serum specimens from dogs with blastomycosis, histoplasmosis, coccidioidomycosis, cryptococcosis and aspergillosis were assayed for antibody content using an alkaline phosphatase enzyme-linked immunosorbent assay (ELISA). The four lots of the yeast phase reagents were similar with respect to sensitivity and specificity, and the absorbance readings were approximately four times greater with sera from dogs with blastomycosis than with histoplasmosis or coccidioidomycosis. Even less cross-reactivity was evidenced when the sera from dogs with cryptococcosis and aspergillosis were assayed. In contrast, the four lots of the mycelial lysate reagents were considerably less reactive and more cross-reactive than the yeast phase antigens and, as above, the four reagents retained their activity after prolonged storage. Therefore the results indicated that the lysate antigens exhibited a great deal of stability and lot-to-lot variations in activity were not observed.
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PMID:Comparative stability, sensitivity and specificity studies with different lots of Blastomyces dermatitidis yeast and mycelial lysate antigens. 789 10

Aspergillosis, candidiasis, and zygomycosis were diagnosed in tissues from three lovebirds (Agapornis roseicollis) using indirect enzyme-immunohistochemical techniques. In these techniques, the first antibody was raised against fungal antigen. A second antibody, which was raised in another animal species, was added to link the first antibody to enzyme-immunocomplexes. The reactivity of specific monoclonal and polyclonal antibodies was visualized by immunoreactivity of alkaline phosphatase anti-alkaline phosphatase and peroxidase anti-peroxidase immunocomplexes. All three birds examined had dermal candidiasis. In addition, one of the birds was diagnosed with concomitant acute ocular aspergillosis, and another bird was diagnosed with chronic zygomycotic myocarditis.
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PMID:Application of enzyme-immunohistochemistry for the diagnosis of aspergillosis, candidiasis, and zygomycosis in three lovebirds. 825 96

To improve the immunohistopathological diagnosis of systemic bovine mycoses, we have evaluated the utility of antifungal polyclonal and monoclonal antibodies, and peroxidase and alkaline phosphatase staining techniques. A rabbit polyclonal antibody to mannan from Candida albicans was specific for candidosis. The diagnosis of aspergillosis was accomplished using a rat monoclonal antibody to the galactofuran side chains of Aspergillus galactomannan. A murine monoclonal antibody reacting with weakly Con-A binding 41 and 46 kDa somatic antigens from Absidia corymbifera was used for immunostaining of zygomycetic hyphae. Peroxidase antiperoxidase (PAP) and alkaline phosphatase antialkaline phosphatase (APAAP) complexes were visualized using aminoethylcarbazole and fast red substrates. A green staining of PAP reactions with dioctyl sulfosuccinate sodium and 3,3',5,5'-tetramethylbenzidine (DONS/TMB) was effective for the demonstration of fungi in dual and triple infections. Tissue sections of experimentally infected mice were used to determine the sensitivity and specificity of the antibodies. Tissues obtained from 161 bovine mycotic lesions previously studied by indirect immunofluorescence staining were further evaluated using the three antibodies. In all of 45 lesions solely affected by aspergillosis and in three solely affected by candidosis the diagnoses were confirmed by the new evaluation. In 85 of 96 cases of single infections with zygomycetes the diagnosis was confirmed, while none of the antibodies reacted with fungal elements in the remaining 11 lesions. Aspergillus hyphae were detected in all three lesions with dual aspergillosis and zygomycosis, whereas zygomycetic material was confirmed in only two of these cases. A mixed infection of candidosis and zygomycosis in a lymph node was confirmed too. In 13 cases in which a diagnosis had not hitherto been obtained, aspergillosis and zygomycosis were recorded each in three cases.
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PMID:Enzyme immunohistochemistry with mono- and polyclonal antibodies in the pathological diagnosis of systemic bovine mycoses. 839 91

The efficacy and safety of Amphotericin B Colloidal Dispersion (ABCD) have been investigated on 572 patients in five Phase I/II clinical trials. The patients were all selected to present a challenging test; having a fungal infection superimposed on severe illness. In 442 cases ABCD was used after amphotericin B, which had been withdrawn. One hundred and forty patients had pre-existing nephrotoxicity. Most patients received doses of 3-6 mg/kg/day of ABCD. Complete or partial recovery was reported in 149/260 (57.3%) patients evaluable for therapeutic response. Patients with Candida infection responded better than those with systemic aspergillosis showing 70.1% recovery vs. 48.8%. ABCD therapy made no difference to serum creatinine levels, even in patients with pre-existing renal failure, nor to liver function as measured by SGOT, alkaline phosphatase and total bilirubin levels in serum. Infusion-related adverse events were the most frequently reported side effects of ABCD. However these studies show clearly that ABCD can be administered safely to patients without the risks of renal toxicity, even when renal toxicity had already developed following therapy with conventional amphotericin B deoxycholate.
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PMID:Safety and efficacy of amphotericin B colloidal dispersion. An overview. 1039 23

Invasive Fungal Infections (IFI) remain a severe and major complication among patients with hematologic diseases, but the recent availability of new antifungal agents (echinocandins and new azoles) have improved the chance of cure. Caspofungin (Cancidas-Merck) is a large lipopeptide molecule able to inhibit the enzyme complex 1,3-d-glucan synthetase; this action specifically damages the fungal cell wall. Caspofungin (CAS) is active, in vitro and in vivo, against most Candida species and Aspergillus species. We report on our experience with this drug as first-line therapy for proven or probable pulmonary IFI in immunocompromised patients with hematologic malignancies. Thirty-two consecutive patients (20 males and 12 females, with a median age of 52 yr) have been treated with CAS (27 acute leukemias, 1 chronic leukemia, 3 lymphomas and 1 multiple myeloma). Sixteen patients (50%) had a relapsed or resistant hematologic disease, while 12 patients were in complete remission and 4 were at onset of disease; 8/32 (25%) developed IFI after a hematopoietic stem cell transplant (HSCT) procedure. Seven out of 32 patients (22%) had a proven pulmonary IFI (7/7 Aspergillosis) and 25 (78%) had a probable IFI with pulmonary localization as defined according to international consensus. Thirty-one patients (97%) had less than 1000 granulocytes/mL at onset of infection and at the start of CAS therapy. The CAS was given at the dose of 70 mg on day 1, followed by 50 mg/day. Median duration of CAS therapy was 20 d (range 8-64); all the 31 neutropenic patients received concomitant granulocyte colony-stimulating factor (G-CSF). The overall response rate was 56% (18/32) with 12/18 complete responses and 6/18 partial responses; two patients (6%) had a stable disease. Twelve out of 32 (38%) did not respond and seven died of mycotic infection. Univariate analysis showed that granulocytes recovery (>500/mL vs. <500/mL) and status of hematologic disease (remission/onset vs. refractory/relapsed) were significantly associated to favourable outcome. No clinical adverse events (AE) were reported and only a grades I and II transient increase of serum alkaline phosphatase and/or transaminases occurred in 4/32 (12%) patients. After CAS therapy six non-responders and six cases with a partial or stable response were rescued with voriconazole. Two out of six patients (33%) in the former group and 6/6 (100%) in the latter obtained a complete resolution of IFI. Our experience suggests an efficacy of CAS, in combination with G-CSF, as first-line treatment of proven or probable IFI with pulmonary localization. The drug was well tolerated and there were no significant hepatic AE even in patients receiving CAS with cyclosporine after a HSCT. A significant proportion of non-responders or partial responders to CAS can be rescued with a subsequent voriconazole-based therapy.
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PMID:Caspofungin as first line therapy of pulmonary invasive fungal infections in 32 immunocompromised patients with hematologic malignancies. 1610 79

The aim of this study was to evaluate the efficacy and safety of caspofungin in patients treated in Finland during the period 2001-2004. The medical records of 78 adult patients treated with caspofungin in five major hospitals were reviewed retrospectively. Fifty-nine (76%) patients had proven invasive fungal infection, of whom 22 (28%) had aspergillosis and 37 (47%) had candidiasis. Nineteen (24%) patients were treated empirically; only 13 (17%) patients received caspofungin as primary therapy. A favourable response was achieved in 52 (67%) patients. The response rate was 78% in patients with candidiasis, and 50% in patients with aspergillosis. At the end of the study period, 40 (51%) patients remained alive; of the 38 deaths, nine (24%) were caused by fungal infection. The response rates were lower, although not significantly, for patients with high (>20) vs. low (< or =20) Acute Physiology and Chronic Health Evaluation (APACHE II) scores (response rate 50% vs. 68%, p 0.48, respectively), and were also lower in patients with long-term (>20 days) vs. shorter duration (< or =20 days) neutropenia (55% vs. 73%, p 0.32, respectively), and in those with an underlying haematological malignancy vs. patients with other diseases (59% vs. 73%, p 0.2, respectively). In five (6%) patients, caspofungin therapy was discontinued prematurely because of adverse drug reactions (ADRs) (elevated liver enzyme values in three patients, neuropathic pain in one, and skin rash in one). Serious ADRs occurred in two (3%) patients (severe hepatic insufficiency with consequent death, and eosinophilia with elevated alkaline phosphatase levels), and laboratory abnormalities, mostly mild and reversible, in 24 (31%) patients. In this unselected patient population, caspofungin was safe, well-tolerated, and had an efficacy comparable to that in previous reports from prospective trials.
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PMID:A retrospective nationwide case study on the use of a new antifungal agent: patients treated with caspofungin during 2001-2004 in Finland. 1737 26


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