Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A total of 33 patients with bacterial meningitis were treated with single daily doses of ceftriaxone (CTR 100 mg/kg/day i.v.) for a median duration of 13 days. Pathogens isolated by culture and/or determined by latex agglutination were 15 Haemophilus influenzae b, 7 Neisseria meningitidis, 2 Streptococcus pneumoniae, 1 group B streptococcus, 2 Streptococcus viridans and 2 Staphylococcus epidermidis. In 4 cases a diagnosis of purulent meningitis could only be made by means of the inflammatory liquor parameters. All cerebrospinal fluid (CSF) drug levels even at the end of the dosing interval were at least 10-fold higher than the MICs of the respective bacterial isolates. The average penetration of CTR into the CSF was 6.6%. Within 12-46 h after the first dose, control spinal taps were performed. Cultures were sterile in all cases. Side effects encountered were diarrhea, exanthema, neutropenia and transient elevation of glutamic oxaloacetic transaminase, but none caused a change of therapy. One patient developed a biliary concrement. No patient died; 5 patients had prolonged fever (greater than 5 days), and 2 were left with persistent hearing deficiencies. CTR can be recommended as a safe and effective antibiotic agent for once daily treatment of bacterial meningitis in children.
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PMID:Ceftriaxone monotherapy for bacterial meningitis in children. 229 6

We have evaluated the use of high-dose intravenous ciprofloxacin as monotherapy in the empirical therapy of febrile episodes in neutropenic patients during the course of a randomized trial comparing ciprofloxacin with a standard combination regimen. Sixty-four episodes of fever were studied in a high risk population of 42 patients mostly undergoing intensive chemotherapy for leukaemia. Ciprofloxacin achieved clinical responses as follows: completely successful in 39%, partially successful in 20%, and unsuccessful in 41%. Infections were microbiologically documented in 37 (58%), with Gram-positive bacteria (of which 37% were coagulase negative staphylococci and 34% were streptococci) accounting for 81% of all organisms cultured. Responses in documented infections were as follows; completely successful in 32%, partially successful in 27%, and unsuccessful in 41%. One infection-related death occurred 30 h after starting ciprofloxacin, and a further three patients died before the resolution of neutropenia. The early death was caused by fulminant infection with a ciprofloxacin-resistant Pseudomonas aeruginosa. No other ciprofloxacin resistance was seen amongst eight Gram-negative isolates. There was no evidence of emerging ciprofloxacin resistance during the course of the study. Ciprofloxacin was associated with a low incidence of adverse events with skin rash (five cases) and nausea (one case) being reported as possibly or probably related to ciprofloxacin. We conclude that high-dose intravenous ciprofloxacin may be safely employed as monotherapy in the empirical treatment of febrile episodes in neutropenic patients. It has the additional advantages of twice daily administration, the availability of intravenous and oral presentations, and absence of cross-allergy in beta-lactam antibiotic hypersensitive patients.
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PMID:High dose intravenous ciprofloxacin in febrile neutropenic patients. 229 37

A prospective study on the effect of beta-lactam antibiotics on granulopoiesis was carried out in 29 consecutive patients with bacterial endocarditis. Fourteen patients received a high dose of benzylpenicillin, up to 18 g/day, but in only three of them could the treatment be fulfilled as planned, for a mean time of 25 days. In 11 benzylpenicillin treated patients treatment had to be discontinued because of fever, rash or neutropenia. Neutropenia appeared in seven patients after 14-24 (mean 22) days. No superinfection occurred during the neutropenic phase which lasted 2-12 days. Patients with neutropenia differed significantly from others in having a lowered pretreatment neutrophil count (3.2 vs 10.4). In 15 patients treated with other beta-lactams, three cases of fever and rash and one case of neutropenia were seen in patients treated with cloxacillin 12 g daily. It was concluded that a daily dose of 18 g of benzylpenicillin is too high for longer treatment periods and that patients with initial low counts of neutrophils have an increased risk of developing neutropenia.
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PMID:A prospective study of neutropenia induced by high doses of beta-lactam antibiotics. 233 21

Clinical studies of imipenem/cilastatin sodium (IPM/CS) were conducted in 40 pediatric patients. 29 out of the 40 patients were treated for infections and 11 for prophylaxis. The following results were obtained. 1. The response rate in 29 patients with infections was 79.3%. Among the 29 patients, 16 patients who presented with malignant diseases showed the response rate of 68.8%. The response rate was lower in patients with severe infections than in those with mild or moderate infections, and a lower response rate was associated with severe neutropenia. However, there were no differences in the response rates between patients who had previously been treated and those who had been untreated with other antibiotics. The response rate in 6 patients from whom causative organisms were isolated was 83.3% and that in the remaining 23 patients was 78.3%. 2. The response rate in 11 patients to whom IPM/CS was administered prophylactically was 63.6%. 3. As for side effects, a rash was observed in 1 patient and hematuria in another, and the abnormal laboratory test results observed were elevations of GOT and GPT in 1 patient. However, they were not clinically significant. From the above results, it appears that IPM/CS may be used as a drug of the first choice for the treatment of patients with severe infections in which the causative organisms are unknown, and for the prophylaxis of infection in patients with neutropenia.
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PMID:[Clinical study of imipenem/cilastatin sodium in children with severe infections]. 234 51

A Phase I study of bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was undertaken in 21 patients with advanced malignancy or neutropenia. rhGM-CSF was administered once daily by i.v. bolus injection (0.3 to 3 micrograms/kg/day) or 2-h i.v. infusion (3 to 20 micrograms/kg day) for 10 days. rhGM-CSF at all i.v. doses caused an immediate transient decrease in circulating neutrophils, eosinophils, and monocytes. By 6 h after rhGM-CSF, circulating leukocyte levels were restored. Daily i.v. bolus dosing (0.3 to 3 micrograms/kg/day) did not elevate leukocyte levels except in one neutropenic patient. Daily 2-h i.v. infusions (10 to 20 micrograms/kg/day) caused a dose-dependent leukocytosis with increased levels of neutrophils (up to 4.3-fold), eosinophils (up to 18-fold), and monocytes (up to 3.5-fold). Marrow aspirates showed increased proportions of promyelocytes and myelocytes during rhGM-CSF administration. Retreatment after 10 days without rhGM-CSF resulted in a more marked leukocytosis at doses greater than or equal to 10 micrograms/kg/day. Platelet levels decreased for the first 3 days and then increased during the first course of rhGM-CSF administration. Two patients with chronic lymphocytic leukemia had a transient reduction in lymphocytosis. Serum cholesterol and albumin levels decreased, and vitamin B12 levels increased during rhGM-CSF treatment. At doses of up to 15 micrograms/kg/day, rhGM-CSF was relatively well tolerated by the patients, but adverse effects included bone pain, lethargy, fever, rash, and weight gain. A first dose reaction characterized by hypoxia and hypotension was identified at dose levels greater than or equal to 1 microgram/kg. Dosing i.v. was less potent at inducing a leukocytosis than previously observed for equivalent s.c. doses and was associated with a higher incidence of generalized rash and first dose reactions. The maximal tolerated dose of i.v. rhGM-CSF was 15 micrograms/kg/day. Phase II studies in which the derived effect is to raise leukocyte levels should be undertaken at rhGM-CSF doses of 3 to 15 micrograms/kg/day.
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PMID:Phase I study of intravenously administered bacterially synthesized granulocyte-macrophage colony-stimulating factor and comparison with subcutaneous administration. 240 73

The human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) requires reverse transcriptase for viral replication. We treated 12 patients who had acquired immunodeficiency syndrome and active HTLV-III/LAV viremia with suramin, a potent competitive inhibitor of reverse transcriptase, in six weekly induction doses of 1 g, followed by weekly maintenance doses of 500 mg. Three of eleven evaluable patients had complete inhibition of viral reverse transcriptase levels, lasting at least 18 weeks in each. Two additional patients had marked reduction in reverse transcriptase activity. Nadir serum suramin levels at the end of the induction phase correlated with the level of reverse transcriptase reduction. Toxicity included hepatic transaminase elevation, fever, malaise, rash, proteinuria, paresthesias, reversible neutropenia, and adrenal insufficiency. Objective clinical improvement was documented in 1 patient, but no patient had improvement in immune function and 7 patients had recurrent opportunistic infections. Although suramin may suppress HTLV-III/LAV viremia, its significant toxicity and lack of effect on immune variables indicate that alternative therapy will be required.
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PMID:Suramin antiviral therapy in the acquired immunodeficiency syndrome. Clinical, immunological, and virologic results. 242 53

Agranulocytosis is an uncommon complication of beta-lactam antibiotic therapy. Two patients who developed absolute neutropenia and anemia after having received 168 g of cefotaxime are reported. There was fever and rash, and hematologic recovery too place 10 and 6 days after withdrawal of the drug. The bone marrow culture showed that the incubation of cells with cefotaxime (10 micrograms/ml) induced a 26 +/- 1% inhibition of the formation of granulocytic colonies (CFU-GM) in controls and a 47% and 48% inhibition, respectively, in the two patients with neutropenia. When serum was added to the culture, the control serum improved the in vitro granulopoietic response, while the serum from the first patient inhibited in 77 +/- 1.5% the formation of CFU-CM in the control marrow. The need for the monitoring of peripheral blood cells in patients receiving long term treatment with beta-lactam antibiotics emphasized, as we have shown the suppressor effect of cefotaxime on the hematopoietic precursors and the effect of an autoimmune mechanism in some cases.
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PMID:[Neutropenia secondary to cefotaxime use]. 249 Apr 62

Trimetrexate (TMTX) is a potent inhibitor of dihydrofolate reductase that circumvents the transport resistance seen with methotrexate and has a wide spectrum of preclinical activity. A total of 18 patients with advanced cancer were treated in a clinical and pharmacological phase I trial with TMTX given as a continuous 5-day intravenous infusion. Neutropenia, thrombocytopenia and stomatitis were the dose-limiting toxicities at the maximum tolerated dose of 50 mg/m2 per 120 h (10 mg/m2 per day for 5 days). There was one septic death associated with neutropenia. Other toxicities were mild rash, mild nausea and transiently raised serum transminase levels. Significant relationships between the dose given and the AUC of plasma TMTX and the steady-state plasma level were established. Significant, although weak, relationships between the percentage of change in neutrophils and platelets and both the AUC and steady-state plasma level of TMTX were also observed. No objective tumour responses were seen, although six patients had stable disease. The recommended phase II dose for a continuous infusion of trimetrexate is 40 mg/m2 per 120 h.
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PMID:A phase I study of trimetrexate (NSC 352122) administered by 5-day continuous intravenous infusion. 252 92

The safety of 738 high-risk patients treated with enalapril under various clinical programs was evaluated. High risk was defined as the presence of a collagen vascular disease; a renal disease, including renovascular hypertension; or either hypertension or refractory cardiac failure with serum creatinine greater than or equal to 1.7 mg/dl at baseline. Essential hypertension was the primary diagnosis in most of these patients. Treatment with enalapril in these patients usually continued without interruption for the length of the particular protocol. The incidence of adverse reactions resulting in discontinuation of treatment was comparable to that observed with other standard antihypertensive therapies in patients with milder forms of disease. No enalapril-related neutropenia, proteinuria, dysgeusia or ageusia were reported in these high-risk patients. The incidence of discontinuation due to rash was less than 0.5%. Resolution and/or improvement of captopril-related adverse effects was observed in many patients crossed over to treatment with enalapril. In patients with collagen vascular diseases and those with severe impairment of renal function (serum creatinine greater than or equal to 3.0 mg/dl), the incidence of discontinuation due to adverse experiences or death as well as the profile of reported adverse experiences was similar to those for the total group of high-risk patients. The data suggest that enalapril is efficacious and well tolerated by the high-risk patients.
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PMID:High-risk patients treated with enalapril maleate: safety considerations. 253 44

Patients with severe hypertension and/or congestive heart failure (n = 281) who were unresponsive to other therapies and intolerant to captopril received enalapril treatment (mean dose 19.5 mg/day) under study conditions as part of a Compassionate Use Program. Many of these patients had serious concurrent disorders known to predispose them to a greater risk of adverse experiences and death. The mean duration of enalapril treatment was 29 weeks, with a range of 1 day to approximately 3.5 years. Enalapril was generally well tolerated, and the estimated long term probability of patients terminating enalapril therapy because of adverse effects was low. 20 patients had discontinued captopril treatment because of low white blood cell counts; during subsequent enalapril treatment these reactions resolved in 14 patients, persisted in 2 patients, and could not be evaluated in 4 patients. Captopril-related proteinuria improved or resolved in 9 and persisted in 2 of 15 patients, taste disturbances resolved in 35 and persisted in 2 of 38 patients; and rash resolved in all but 7 of 178 patients during enalapril treatment. 18 patients (6%) discontinued enalapril treatment because of lack of efficacy; 6 of these 18 patients died due to a progression of heart failure, and another 11 patients died for other reasons. The deaths were considered unrelated to therapy with enalapril. Adverse reactions were the reason for discontinuation of enalapril treatment in 53 patients (19%). The most common adverse experiences that resulted in discontinuation of enalapril were: impairment of renal function (5%), hypotension (2%) and rash (2%). No neutropenia, proteinuria, or new taste disturbances were recorded as reasons for discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tolerability of long term therapy with enalapril maleate in patients resistant to other therapies and intolerant to captopril. 254 10


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