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Enzyme
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Target Concepts:
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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)
Netilmicin, a new semisynthetic aminoglycoside, was used in the treatment of 42 patients with serious gram-negative bacterial infections. Of the 40 evaluable patients, 24 (60%) were cured, and 8 (20%) had a favorable clinical response, for a total clinical response rate of 80%. Eight patients failed to respond; of these, three had undrained abscesses and two had severe
granulocytopenia
. Three of the patients who failed had organisms in which resistance to netilmicin developed during therapy, and in two of these three netilmicin was the only aminoglycoside to which resistance developed. Of the 37 patients evaluable for toxicity, 8 (22%) developed renal insufficiency. Two patients had mild but persistant elevation in serum creatinine. Three patients had nephrotoxicity while on gentamicin in the past. Pre- and posttherapy audiograms were done on 26 patients; none had hearing loss. Four patients had mild, transient asymptomatic elevations in
alkaline phosphatase
. The pretreatment clinical isolates were tested for in vitro susceptibility. The median minimal inhibitory concentration of netilmicin, gentamicin, and tobramycin ranged between 0.5 and 2 mug/ml. The median minimal inhibitory concentration of amikacin was approximately twofold higher. No clear in vitro superiority of one aminoglycoside over another was observed.
...
PMID:Netilmicin in gram-negative bacterial infections. 42 6
Absolute counts for the
alkaline phosphatase
positive (AP+) fraction of potentially AP+ neutrophils were measured cytochemically during the course of chronic granulocytic leukaemia (CGL), from the clinical onset of the disease. In a previous study of different kinds of severe
granulocytopenia
, the AP positivity of circulating neutrophils appeared to indicate a kinetic parameter. Early release of mature, non-stored bone marrow granulocytes apparently furnished more AP+ neutrophils, whereas release of stored cells furnished more AP- cells. If we consider enzyme activity to indicate a kinetic parameter, its differential diagnostic usefulness would be less than generally supposed. One hundred and forty eight determinations in 74 CGL patients showed that low AP values are valid for CGL statistically, especially between the 2nd to 5th years of clinical disease, but normal or higher counts of circulating AP+ fraction of mature neutrophils could be found in one fourth of advanced cases (blastic metamorphosis excluded), and even more (17/37) in the earliest period of the CGL process. A similar tendency appears to be detectable in the absolute counts for circulating AP- cells.
...
PMID:Absolute alkaline phosphatase positive and negative neutrophil counts in chronic granulocytic leukemia. 107 10
Four of six siblings, offspring of Sicillian first cousins, developed a clinical disorder in early adulthood affecting the hematopoietic and immunoglobulin-producing systems. A female sibling died at age 21 with myeloid aplasia and
agranulocytosis
. A male sibling, at age 17, presented with erythroid and plasma cell aplasia with hypogammaglobulinemia. Two other female siblings, ages 21 and 35, had a lymphoproliferative disorder associated with hypogammaglobulinemia. In two of the affected subjects there was complete absence of the enzyme leukocyte
alkaline phosphatase
. Electron microscopic studies of the peripheral leukocytes from these two subjects and from one of the two asymptomatic siblings showed curious intranuclear and intracytoplasmic linear "crystalloid" structures in the mature neutrophils. It is postulated that the family contains a genetic defect, transmitted as an autosomal recessive by the heterozygous parents, that produces a stem-cell disorder manifested by myeloid, erythroid, and plasma cell aplasias, unique electron microscopic findings, and morphologic and functional abnormalities in later generations of cells.
...
PMID:Myeloid, erythroid, and immune system defects in a family. A new stem-cell disorder? 113 61
We report on two patients with acute leukemia and prolonged
granulocytopenia
after cytotoxic therapy in whom the diagnosis hepatosplenic candidiasis was made. Both patients developed upper abdominal discomfort with elevated
alkaline phosphatase
after resolution of
granulocytopenia
. The diagnosis was established by demonstration of multiple abscesses in liver and spleen on ultrasound and computed tomography. Both patients were initially treated with amphotericin B i.v., one of them received liposomal amphotericin B (cumulative dose of 2,530 mg and 570 mg, respectively). Thereafter, therapy was continued for months with oral fluconazole. The treatment of hepatosplenic candidiasis was successful, however, the patients died from relapse and progression of leukemia.
...
PMID:Hepatosplenic candidiasis, a fatal disease? 129 53
Paroxysmal nocturnal hemoglobinuria, first described in the late 19th century, is an acquired disorder characterized by hemoglobinemia and hemoglobinuria. The major clinical manifestation of PNH is chronic intravascular hemolysis of various severity. Patients-mostly young adults - may also present with episodes of abdominal or back pain. Common cause of death is thrombosis especially of the hepatic veins.
Granulocytopenia
and thrombocytopenia may be the initial manifestation of PNH, indicating that the disorder is a primary bone-marrow disease, affecting not only the erythrocytes but also other peripheral blood cells and the haematopoietic stem cell. The course of the disease is variable. Partial complete recovery was described, but also fatal thrombosis. The major phenotypic expression of PNH is an increased susceptibility of the erythrocytes to the lytic action of complement in vitro. The enhanced complement susceptibility is most probably due to membrane defects: two membrane proteins regulating the complement cascade in PNH cells were missing, the decay-accelerating factor, DAF, inhibiting the activation of the lytic complement complex and the C8 binding protein, C8bp, which interferes with the lytic process. Aside from the lack of the complement regulators also other membrane defects have been described (e.g. of acetylcholinesterase or
alkaline phosphatase
). The proteins as well as DAF and C8bp are linked to the cell membrane via a phosphatidylinositol (PI) anchor, leading to the speculation that the disease results from a deficiency in the post-translational PI anchoring mechanism. The diagnosis of PNH is based on the Hamtest, but will be extended to the quantitation of the above described membrane proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:[Paroxysmal nocturnal hemoglobinuria]. 218 38
Congenital
agranulocytosis
is a disorder characterized by severe neutropenia and a profound deficiency of identifiable neutrophil progenitors in bone marrow. In an attempt to stimulate neutrophil production and thereby reduce the morbidity and mortality associated with this disease, we administered recombinant human granulocyte colony-stimulating factor (rhG-CSF) in doses of 3 to 60 micrograms per kilogram of body weight per day to five patients with congenital
agranulocytosis
. In all five patients, an increase in the number of neutrophils was noted eight to nine days after the initiation of the effective dosage (the dose at which the neutrophil count reached 1000 cells per microliter or more and the bone marrow showed granulocyte maturation beyond the myelocyte stage). The absolute neutrophil counts rose from less than 100 to between 1300 and 9500 cells per microliter. Marrow aspirates obtained after 14 days at the effective dosage showed maturation to the mature neutrophil stage. The side effects that were observed were medullary pain, splenomegaly, and an elevation of levels of leukocyte
alkaline phosphatase
. All five patients have had sustained neutrophil counts of 1000 cells per microliter or more for 9 to 13 months while receiving subcutaneous maintenance therapy. Preexisting chronic infections have resolved clinically, and the number of new infectious episodes and the requirement for intravenous antibiotics have decreased. We conclude that treatment with rhG-CSF can lead to a large increase in the numbers of functional neutrophils in patients with congenital
agranulocytosis
.
...
PMID:Effects of recombinant human granulocyte colony-stimulating factor on neutropenia in patients with congenital agranulocytosis. 247 Oct 75
Most cancerocidal agents have myelosuppression as their major toxicity. In some clinical studies it has been possible to show a relationship between the amount of administered drug and the therapeutic efficacy. Within any defined protocol, however, there may be much variability in the severity of myelosuppression. We attempted to determine whether the tumor response might be related to this toxicity. We evaluated a total of 177 patients with small cell bronchogenic carcinoma, treated by five successive regimens of combination chemotherapy, consisting of either cyclophosphamide and vincristine alone or with doxorubicin or doxorubicin plus bacillus Calmette-Guerin (BCG) or doxorubicin plus methotrexate, for a number of prognostic factors (age, sex, extent of disease, performance status, sites and number of metastases, serum LDH and
alkaline phosphatase
, weight loss, leukopenia, and thrombopenia). Leukopenia (mean 415 +/- 478/mm3, range 0-2000/mm3) had a weak influence on the incidence of complete remission, which was highest with the least severe nadir (P = 0.027). Thrombopenia was a nonsignificant factor (P = 0.738). Both leukopenia and thrombocytopenia had no influence on the overall survival. Because these drug combinations were based on cyclophosphamide, which requires metabolic activation, we evaluated the relationship of myelosuppression and the incidence of response in a second group of patients with small cell bronchogenic carcinoma treated with a VP16, cyclophosphamide, doxorubicin, vincristine sulfate protocol. In this analysis, no relationship could be detected between remission and myelosuppression.
Granulocytopenia
or thrombocytopenia also-showed no significant influence on the achievement of long-term survival beyond 36 months.
...
PMID:Relationship between myelosuppression and chemotherapeutic response in small cell bronchogenic carcinoma. 298 16
We studied changes in peripheral blood and bone marrow biopsy specimens obtained before, during, and after recombinant alpha 2b-interferon (IFN-alpha 2b) therapy in 25 patients with hairy cell leukemia. During therapy, only 1 patient showed no improvement in at least one of the parameters monitored.
Granulocytopenia
, thrombocytopenia, and monocytopenia resolved in 19/20, 14/15, and 17/18 patients, respectively. In 18/21 patients with Hb less than 12g/dl before treatment, the anemia became less severe. Hairy cells disappeared or decreased in numbers in the peripheral blood in all patients. In the bone marrow, numbers of hairy cells decreased and numbers of granulocytic, erythroid, and megakaryocytic cells increased usually within 3-6 months after the start of therapy. In no patient were hairy cells ever completely absent from the bone marrow. After cessation of IFN-alpha, the median Hb value, WBC, and platelet counts changed little for up to 12 months, but the absolute neutrophil count and absolute monocyte count decreased. Hairy cells reappeared in the peripheral blood of three patients. In the bone marrow the percentage of hairy cells increased, whereas the percentage of granulocytic and erythroid cells decreased. Neutrophil
alkaline phosphatase
(NAP) scores were abnormally high in 18/18 patients studied prior to IFN-alpha, but became normal in 17 of these during therapy and were normal in seven first studied during therapy. The median NAP score doubled by 3 months after cessation of therapy and was abnormal in 17/19 patients followed for 6 months. NAP score may be useful in predicting changes in the bone marrow in patients treated with IFN-alpha. We did not find any parameter in the pretherapy specimens that would have allowed us to predict individual response.
...
PMID:Changes in peripheral blood and bone marrow specimens during and after alpha 2b-interferon therapy for hairy cell leukemia. 366 60
Cefmenoxime was evaluated in an open trial consisting of 41 patients. Forty infections in 36 patients could be evaluated. Thirteen patients had pyelonephritis due to Escherichia coli (two bacteremic), Pseudomonas aeruginosa, Klebsiella pneumoniae, or Streptococcus faecalis; all improved and 12 of 13 were clinically cured, but one relapse (S. faecalis) occurred at two weeks. Six patients with cystitis due to E. coli, Citrobacter freundii, Serratia marcescens, P. aeruginosa, or S. faecalis all improved, but relapse or reinfection, or both, occurred in five due to P. aeruginosa, S. faecalis, C. fruendii, or E. coli. Neurogenic bladder or other complications were present in five of 13 patients with pyelonephritis and five of six with cystitis. Ten patients with pneumonia and one with tracheobronchitis due to Hemophilus influenzae, S. pneumoniae, S. agalactiae, or Neisseria meningitidis all improved and seven had resolution without relapse, but P. aeruginosa emerged in two patients, one of whom died. Eight soft tissue infections due to Staphylococcus aureus, Peptococcus prevotti, Streptococcus species, or infections of mixed origin resolved in six. Sterility of blood cultures was obtained in one patient with endocarditis due to S. anginosus, but other therapy was substituted. Clinical resolution of the toxic shock syndrome and subsequent negative endocervical cultures for S. aureus occurred in one.
Granulocytopenia
of unverified cause in four (with less than 1,500 mm3) and two (with less than 2,000 mm3) was reversible. Headache during treatment occurred in six patients and a possible disulfiram-like effect in three. Elevations of serum glutamic oxalacetic transaminase and
alkaline phosphatase
occurred in five, Coombs' positivity in two, and diarrhea in three. Clinical efficacy of cefmenoxime was significant. Possible side effects require further study.
...
PMID:Cefmenoxime: clinical evaluation. 609 26
Administration of lithium carbonate, 750 mg daily, during 10 days to 25 patients with essential
granulocytopenia
, induced an increase of the total leukocyte count, of the absolute count of neutrophils and of the number of neutrophils phagocytizing Staphylococcus aureus Oxford in vitro. An enhancement of acid phosphatase activity in the neutrophils was noted both in the patients and the healthy subjects in the control group. In the patients, the counts of neutrophils exhibiting a positive enzymatic reaction with regard to beta-glucuronidase, myeloperoxidase and
alkaline phosphatase
were also increased after treatment with lithium carbonate. Based on these results, the authors recommend the clinical application of this treatment in patients with
granulocytopenia
.
...
PMID:Effect of lithium carbonate on the functional state and the enzymatic equipment of neutrophils in patients with granulocytopenia. 624 67
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