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)

Consecutive patients with serious infections were randomized between gentamicin 4 mg/kg once daily i.v. or netilmicin 5.5 mg/kg once daily i.v. (with dosage reduction in case of renal dysfunction). Exclusion criteria were neutropenia or severe renal failure. Median first serum trough and peak concentrations were 0.4/9.5 mg/L and 0.4/12.2 mg/L, for gentamicin and netilmicin respectively. A good clinical response was observed in 50/54 (92.6%) evaluable patients treated with gentamicin and in 48/52 (92.3%) netilmicin-treated patients. Nephrotoxicity (a rise of serum creatinine > or = 45 mumol/L) developed in 5/72 (6.9%) gentamicin patients treated > or = 48 hours and in 10/69 (14.5%) netilmicin patients (difference 7.5%, 95% CI -3.9% to +16.2%). High-tone audiometry was performed when possible; no significant differences were found between the regimens with regard to hearing loss or prodromal signs of ototoxicity. We conclude that with once-daily dosing no benefit of netilmicin over gentamicin regarding nephro- or ototoxicity could be demonstrated.
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PMID:Once-daily gentamicin versus once-daily netilmicin in patients with serious infections--a randomized clinical trial. 805 1

Pulmonary invasive aspergillosis is a frequent and poor prognosis complication of immuno-deficiency and prolonged neutropenia. Its treatment is usually based on amphotericin B (0.7 to 1 mg/kg/d) given as intravenous infusions for at least 2 months. This therapy is limited by the side-effects of the drug including renal failure, myelosuppression, chills and fever. We present here the case of women with pulmonary invasive aspergillosis treated with a different modality of administration. The amphotericin B was given as a continuous infection at 2 mg/kg/d diluted in Intralipid, a triglyceridic mixture used in parenteral nutrition. Given by this way amphotericin B seems to have a good therapeutic efficiency and a mild toxicity limited to transient reduction in creatinine clearance with increased kaliuria. Other current approaches of invasive aspergillosis include the amphotericin B in liposomes, combination of amphotericin B with 5-fluorouracil and the triazolated compounds.
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PMID:[Pulmonary invasive aspergillosis: value of treatment with intravenous amphotericin B administered in a triglyceride emulsion for parenteral usage]. 805 44

The objectives of this study were: (a) to assess whether treatment outcome with gentamicin in pediatric oncology patients could be improved by a pharmacy based therapeutic drug monitoring (TDM) service that included pharmacokinetic interpretation; and (b) to describe the challenges in comparing treatment outcome from a prospective to a retrospective study when the merit of gentamicin therapeutic drug monitoring (TDM) was assessed in pediatric oncology patients. Two groups of pediatric oncology patients, aged 1-18 years, received empiric gentamicin therapy for fever and for confirmed or suspected infection, with the same inclusion and exclusion criteria. Group 1 consisted of patients from a prospective gentamicin pharmacokinetic study with a formalized pharmacy-based TDM service (n = 52). Group 2 consisted of patients admitted to the oncology units who had gentamicin levels analyzed in the TDM Laboratory without the formalized TDM Service (n = 25). Gentamicin dosage adjustments were recommended based on three blood samples (one pre- and two postdose concentrations) collected between the third and sixth doses from each patient in the TDM group, utilizing pharmacokinetic principles and the Sawchuk-Zaske method. In the non-TDM group, dosage adjustments based on two routine blood samples (one pre- and post-gentamicin dose) were performed by physicians without the help of the formalized TDM Service. Multiple regression analysis showed that time periods (TDM, non-TDM), duration of neutropenia, intravenous methotrexate, and types of cancer, e.g., hematologic malignancy vs. solid tumor, had significant effects on duration of fever. Initial absolute neutrophil count, insertion of central venous line, intravenous cloxacillin administration, bacteriologic cultures, and initial post gentamicin levels > or = 5 mg/ml had no significant effects on the duration of fever. Mean duration of fever in the TDM group (2.8 +/- 2.4 days) was significantly shorter than that in the non-TDM group (9.0 +/- 8.8 days) (p < 0.001). Therapeutic serum concentrations were achieved more promptly in the TDM group, with significantly fewer patients requiring dose changes and fewer sets of serum concentrations required. One patient from each group had a > 100% increase in serum creatinine on day 5 compared to baseline. No apparent nephrotoxicity was observed in other patients. Although there was an association of shorter duration of fever with prompt achievement of therapeutic gentamicin serum concentrations with the TDM Service, there were several unresolved factors that affected duration of fever. A randomized prospective and controlled study would be required to substantiate the merit of TDM in shortening the duration of fever in pediatric oncology patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Challenges in comparing treatment outcome from a prospective with that of a retrospective study: assessing the merit of gentamicin therapeutic drug monitoring in pediatric oncology. 808 78

Aminoglycosides are usually given in two or three divided doses. A once-daily regimen might be more effective and less toxic. We have conducted a randomised trial in consecutive patients with serious infections for whom an aminoglycoside seemed warranted. Exclusion criteria were neutropenia or severely impaired renal function. 123 patients were enrolled. For efficacy analysis only those patients were considered in whom treatment with the aminoglycoside was not stopped within 72 h (n = 67); toxicity was analysed on patients receiving aminoglycosides for more than 48 h and not using other nephrotoxic medication (n = 85). Gentamicin 4 mg/kg every day (OD) or gentamicin 1.33 mg/kg three times daily (MD) (with dose-reduction in case of renal dysfunction) were given intravenously. In almost all patients intravenous amoxycillin 1 g every 6 h was also started. Baseline characteristics were comparable in both arms. A good clinical response was observed in 32/35 (91%) of the OD and in 25/32 (78%) in the MD group (difference 13%, 95% confidence interval -6.4% to +26.9%). 2 patients in each group died with uncontrolled infection. An insufficient bacteriological response (persistent positive cultures, resistance, or superinfection) was observed in 2 patients with OD and 3 patients with MD. In patients treated for more than 48 h duration of therapy and mean doses were 7.0 days (1590 mg) and 7.4 days (1672 mg) in OD and MD respectively. Mean first serum trough/peak levels were 0.6/10.2 mg/L and 1.4/5.2 mg/L. Nephrotoxicity (a rise in serum creatinine of 45 mumol/L or more) developed in 2/40 (5%) in OD and 11/45 (24%) in MD (p = 0.016). Risk factors for nephrotoxicity were duration of therapy and baseline creatinine clearance rate. High-tone audiometry was performed when possible; no significant differences were found in hearing loss (3/12 and 3/11) or prodromal signs of ototoxicity (5/12 and 4/11). A once-daily dosing regimen of gentamicin is at least as effective as and is less nephrotoxic than more frequent dosing.
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PMID:Once versus thrice daily gentamicin in patients with serious infections. 809 33

We performed a phase I trial of cyclosporin A (CsA) in combination with doxorubicin (dox) to determine the maximally tolerated dose (MTD) of the combination in man, to define the quantitative and qualitative toxicities of the combination, and to determine the pharmacokinetics of the two drugs when used together. CsA was administered as a continuous infusion for 6 days, and dox was administered as a single 10-min infusion 24 h after the initiation of CsA. The starting CsA infusion rate was 5 micrograms/kg/min, and the dox starting dose was 30 mg/m2. Courses were administered every 4 weeks with first CsA and then dox being escalated in consecutive cohorts of patients until the MTD was determined. Twenty-three patients and 40 courses were evaluable for toxicity. Pharmacokinetic analysis was performed in 23 patients on the first course for whole blood CsA and plasma dox and doxorubicinol. The MTD of CsA was 6 micrograms/kg/min, and for dox it was 45 mg/m2. Dose-limiting toxicity was neutropenia. Serum creatinine and creatinine clearance did not change over the infusion period. Bilirubin increased from a median of 10 mumol/liter at the initiation of the infusion to a median of 40.4 mumol/liter at the end of the infusion but returned to normal before the next cycle of therapy. Nausea and vomiting were common and marked, whereas thrombocytopenia was mild. Two patients, one with small cell lung cancer and one with breast cancer, had stable disease while receiving treatment for 5 and 6 months, respectively. Mean whole blood steady state concentrations of CsA were 2210 ng/ml during the infusion with total body clearance of 0.177 liter/h/kg. The area under the concentration x time curve (AUC) increased linearly with dose of dox, and total body clearance was independent of dose. The mean total body clearance was 2.46 liters/h/m2, and terminal half-life was 49.6 h. The AUC for dox was greater and clearance was less than has been previously reported at the doses administered in this study. The ratio of AUC for doxorubicinol to AUC for dox was less than expected, suggesting that the metabolism and/or excretion of dox was decreased when administered with CsA. We conclude that dox can be combined with infusioned CsA but at a lower dose than when given alone. This may be due to altered metabolism and/or excretion of dox or increased bone marrow stem cell sensitivity to dox.
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PMID:Phase I pharmacokinetic study of cyclosporin A combined with doxorubicin. 840 70

We reviewed the effectiveness of Muromonab-CD3 (OKT3) and anti-thymocyte globulin (ATG) in the treatment of corticosteroid-resistant acute renal allograft rejection in 49 transplanted children. Reversal of rejection was successful in 22 of 23 patients (96%) treated with OKT3 and 21 of 26 (81%) treated with ATG (P = NS). Re-rejection episodes occurred within 1 month of cessation of therapy in 9 of 22 patients treated with OKT3 but only in 2 of 21 who received ATG (P < 0.05). In the patients with re-rejection, 7 of the 9 patients originally given OKT3 and 1 of the 2 who received ATG responded to a repeat course of high-dose corticosteroids; thus, at 1 month post treatment, the incidence of graft loss due to initial rejection or re-rejection was 13% for the OKT3 and 23% for the ATG group (P = NS). Graft survival was similar at 6 months: 82% for OKT3- and 73% for ATG-treated patients (P = NS); 100% patient survival was noted in both groups. Mean calculated creatinine clearance prior to, during, and at 1 and 6 months post rejection was similar in the OKT3- and ATG-treated groups. Neutropenia and thrombocytopenia occurred more frequently in the ATG group, but there was no significant difference in infectious complications. Two patients developed high (> or = 1:1,000) OKT3 antibody titers. In our experience, children with corticosteroid-resistant acute renal allograft rejection treated with OKT3 and ATG had similar allograft survival and level of renal function at 1 and 6 months, and number of infectious complications post therapy.
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PMID:Evaluation of OKT3 monoclonal antibody and anti-thymocyte globulin in the treatment of steroid-resistant acute allograft rejection in pediatric renal transplants. 851 94

In an attempt to circumvent clinical multidrug resistance, we conducted a Phase II trial of cyclosporin plus combination chemotherapy in patients with relapsed or refractory non-Hodgkin's lymphoma. Thirteen patients, all of whom had been previously treated with a doxorubicin-containing regimen, received doxorubicin 50 mg/m2 intravenous continuous infusion (IVCI) over 96 h (days 1-4), vincristine 2 mg i.v. (day 1), and etoposide 75 mg/m2 i.v. daily for 4 days (days 1-4). Four days prior to chemotherapy, patients received a loading dose of cyclosporin (0.88 mg/kg i.v. over 2 h), followed by a maintenance dose (1.8 mg/kg per day IVCI for 9 days). Cyclosporin dose escalation was permitted, conventionally defined therapeutic levels of cyclosporin were achieved; this drug was well tolerated at these doses. The study was closed due to a poor response rate; only one patient achieved a complete remission of 33 weeks' duration. Grade 3 and 4 toxicities included gastrointestinal haemorrhage (one patient), sensory neuropathy (two patients), stomatitis (two patients), and transaminase elevation (one patient). Asymptomatic grade 1-2 toxicities (elevated creatinine and transaminase levels) occurred in 33% of patients. There were no treatment associated deaths. Prolonged neutropenia and thrombocytopenia were the primary haematological toxicities. Although the addition of cyclosporin at this dose and schedule did not improve response rates in this patient group, future trials using higher doses of cyclosporin with combination chemotherapy may warrant further investigation.
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PMID:Cyclosporin plus doxorubicin, vincristine and etoposide in the treatment of refractory non-Hodgkin's lymphoma: a phase II study. 858 55

This study was designed to establish the toxicity and response rates o observed with a combination of high-dose cyclophosphamide, carboplatin, and etoposide with stem cell rescue in patients with breast carcinoma. Eligibility criteria included metastatic or locally advanced breast carcinoma ; aged < or equal to 60 years; performance status Eastern Cooperative Oncology Group (ECOG) 0-1; and creatinine clearance > or equal to 65 ml/min. Chemotherapy consisted of cyclophosphamide 25 mg/kg i.v. X 4 days, etoposide 400 mg/m(2) i.v. X 4 days, and carboplatin 375 mg/m(2) X 4 days. Bone marrow or peripheral blood stem cells were reinfused 48 h after completion of chemotherapy. Seventeen patients were treated in this study. The major toxicity was gastrointestinal (grades I and II). Fevers associated with neutropenia were observed in all the patients, but no episodes of bacteremia were documented. Hematopoietic toxicities were acceptable. No toxic deaths were observed. Six patients had chemotherapy-sensitive disease at time of transplant, nine had refractory disease, and two were untested. A response rate of 62% with 18% complete response (CR) was achieved. Two patients are free of disease at +7 and +9 months after transplantation. The combination of high-dose cyclophosphamide, carboplatin, and etoposide is well tolerated with a response rate comparable to previously reported high-dose chemotherapy regimens. However, in a poor prognostic risk group, namely patients with chemoinsensitive disease, this therapeutic approach seems to be of no advantage over standard chemotherapy.
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PMID:High-dose cyclophosphamide, carboplatin, and etoposide with autologous stem cell rescue in patients with breast cancer. 861 Jun 43

A study was conducted to examine the feasibility of cisplatin-based chemotherapy in elderly patients (> or = 75 years old) with advanced non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). Thirty-four patients were enrolled between September 1993 and December 1994. Patients with normal organ function and good performance status (PS) received cisplatin-based chemotherapy (cisplatin 80 mg/m2 on day 1 and vindesine 3 mg/m2 on days 2 and 8 for NSCLC, or cisplatin 80 mg/m2 on day 1 and etoposide 100 mg/m2 on days 2 to 4 for SCLC). Ten patients (29%) were eligible for this study, 7 with NSCLC and 3 with SCLC. Reasons for exclusion were ischemic heart disease in 14, poor PS (> or = 2) in 11, reduced creatinine clearance (Cer) in 10, abnormal electrocardiogram without ischemia in 9 and noncompliance with the protocol in 2 patients. Eight patients had two or more reasons. Nine of the 10 eligible patients were able to tolerate two or more courses of chemotherapy. All 3 patients with SCLC responded (1 complete response and 2 partial response), but only 1 of the patients with NSCLC achieved partial response. Toxicity was evaluated according to Japan Clinical Oncology Group criteria. All but one patient experienced grade 4 neutropenia, and 6 patients had infectious episodes requiring antibiotics. Grade 3 anemia and thrombocytopenia were observed in 1 and 2 patients, respectively. Non-hematological toxicities were mild. Only 10 of 34 patients (29%) satisfied our eligibility criteria and they experienced severe myelotoxicity. We conclude that chemotherapy should be given carefully to elderly patients even if they appear to have normal organ function.
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PMID:Prospective evaluation of the feasibility of cisplatin-based chemotherapy for elderly lung cancer patients with normal organ functions. 863 10

Neutropenia in solid organ transplant recipients may be caused by immunosuppressive therapy, antimicrobial therapy, as well as bacterial and viral infections. Filgrastim, a human granulocyte colony stimulating factor (G-CSF) is used for the reversal of neutropenia. Although its influence is principally restricted to neutrophil progenitors, the safety of G-CSF in terms of percipitating or aggravating allograft rejection and its efficacy in reversing neutropenia in kidney and combined kidney and pancreas transplant patients has not been studied or reported. In this study we retrospectively analyzed the use of G-CSF between March 1992 and May 1994 at the University of Cincinnati Medical Center, in patients who received either a kidney or a combined kidney and pancreas transplant. A total of 25 patients developed 35 episodes of neutropenia and received an average of 2.9 doses of G-CSF per episode. The mean WBC nadir was 2.6 x 10(3)/cu mm with an average peak WBC count of 15.5 x 10(3)/cu mm following treatment (p = < 0.00001). The average number of days to peak WBC after initiation of treatment was 4.6 days. The mean pre-treatment serum creatinine level was 2.3 mg/dl and the peak serum creatinine in the week following treatment remained the same. We conclude that G-CSF is an effective treatment in reversing neutropenia in renal transplant recipients and does not precipitate or aggravate allograft rejection.
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PMID:Role of granulocyte colony stimulating factor (G-CSF) in reversing neutropenia in renal allograft recipients. 865 92


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