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)

Two hundred and seventy-six hospitalized patients with severe infection (complicated UTI, pneumonia, skin and soft tissue infection or septicaemia) were randomly allocated to receive either 1g or 2g cefpirome bd. Two hundred and seventy-four patients were evaluable for tolerance, 210 for bacteriological efficacy. The two groups were similar in terms of underlying disease, age, sex, and general condition on admission. The overall clinical and bacteriological response rates were 97/103 (94%) and 68/76 (90%) respectively in the 1g group, compared with 102/107 (95%) and 67/71 (94%) in the 2g group. There was no significant difference between the treatment groups. Eighteen adverse events, possibly or probably drug related, were reported (7 in the 1g group, 11 in the 2g group). This resulted in discontinuation of therapy in four cases (two in each group). Fourteen of the adverse events were local (five receiving 1g, nine receiving 2g), mainly phlebitis or pain at the injection site. Thirteen patients died during the study period (up to 14 days after the last dose) but in no case was death attributed to cefpirome. A review of routine laboratory parameters revealed no abnormalities which could definitely be attributed to cefpirome although in four cases a relationship was considered possible; these included two increases in serum creatinine, one increase in SGPT, and one episode of neutropenia. Cefpirome administered as 1 or 2g twice daily was a well tolerated, effective agent for the treatment of severe sepsis in hospitalized patients.
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PMID:Prospective randomized phase II study of intravenous cefpirome 1g or 2g bd in the treatment of hospitalized patients with different infections. Cefpirome Study Group. 160 64

We review our experience with low-dose intravenous pulse cyclophosphamide as treatment of biopsy-proven lupus nephritis. Seventeen patients were treated with 2-4 (mostly 3) weekly low-dose intravenous pulses of cyclophosphamide (500 mg) and moderate doses of prednisolone (0.5 mg/kg/day), followed by an oral immunosuppressive drug (either azathioprine or cyclophosphamide). As compared with the classical monthly high-dose cyclophosphamide regimen, this weekly low-dose regimen induced neutropenia in one patient only. The incidence of herpes zoster was very low (6%). At the end of the follow-up period (15 +/- 8 months), two patients required chronic ambulatory peritoneal dialysis. The 14 patients that could be evaluated improved their mean serum albumin from 30 +/- 7 to 37.5 +/- 7 g/l (mean +/- SD; P < 0.01) and their mean serum creatinine fell from 125 +/- 119 to 101 +/- 66 mumol/l (not significant). Mean DNA binding dropped from 71 +/- 29 to 26 +/- 27% (P < 0.001) and mean complement fraction C4 levels increased from 14 +/- 8 to 28 +/- 18 mg/dl (P < 0.05). The mean daily prednisolone dose was dramatically reduced from 26 +/- 8 to 10 +/- 4 mg (P < 0.001). Although this preliminary and retrospective study clearly needs validation with a larger cohort followed for a longer period, it seems that a treatment combining moderate doses of steroids and 3-4 weekly low-dose intravenous pulses of cyclophosphamide, followed by oral immunosuppression, is well tolerated and beneficial--at least in the short term--for most patients with severe lupus nephritis.
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PMID:Short course of weekly low-dose intravenous pulse cyclophosphamide in the treatment of lupus nephritis: a preliminary study. 184 61

Data from clinical trials with benazepril suggest that the safety profile of benazepril is similar to that of other angiotensin-converting enzyme (ACE) inhibitors. Treatment-related side effects occurred in 20% of benazepril-treated patients and in 18% of patients receiving placebo. The most commonly reported side effects with benazepril were headache, dizziness, and fatigue. The incidence of side effects was not affected by the degree of hypertension, age, gender, race, dosage, or the degree of renal impairment. Side effects believed to be related to the pharmacologic action of ACE inhibitors as a class include symptomatic hypotension, which occurred at a relatively low rate with benazepril, and hyperkalemia and elevation of serum creatinine, which occurred to the same extent with benazepril as has been noted with other ACE inhibitors. The mechanism of cough as an ACE inhibitor side effect is unknown; the incidence was similar to that with other ACE inhibitors. Rash and taste disturbance have occurred rarely with benazepril. The incidence of neutropenia and of proteinuria was the same in both the benazepril and placebo groups. Renal failure in hypertensive patients treated with benazepril has not been reported. Overall, benazepril is generally well tolerated by hypertensive patients. The incidence of most side effects is comparable to that with other ACE inhibitors and placebo.
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PMID:Safety profile of benazepril in essential hypertension. 189 40

A phase I study of cis-diammine(glycolato)platinum (254-S; NSC 375101D) was conducted in 15 patients with refractory or relapsing malignancy by 5-day continuous i.v. infusion. Three to 5 patients per dose were given 50, 75, 87.5, or 100 mg/m2/120 h (10-20 mg/m2 daily for 5 days). Toxicity evaluation and pharmacokinetic analysis were performed in 15 and 14 patients, respectively. Thrombocytopenia and neutropenia were the dose-limiting toxicities at the maximum tolerated dose of 87.5 mg/m2/120 h (17.5 mg/m2/day); however, nonhematological toxicities including renal toxicity, nausea and vomiting, and peripheral neuropathy were mild and well tolerated. The nadir of platelets and neutrophils was observed 4 and 5 weeks, respectively, after the initiation of drug infusion. Plasma and urine samples were obtained during and after infusion for quantification by atomic absorption spectrophotometry of total and free platinum levels derived from 254-S. The maximum level of total platinum was obtained after 120 h of infusion, whereas the steady state concentration of free platinum in the patients given 75 mg/m2 or more was over 0.1 microgram/ml. Free platinum levels declined monophasically, with half-lives of 0.65-2.56 h/100 mg/m2 dose. The mean area under the concentration versus time curve (AUC) in the patients treated with 75 mg/m2 was 1069 micrograms/ml, which was similar to that obtained in the patients receiving 100 mg/m2 of 254-S by i.v. drip infusion over 30 min. There was a direct correlation between the dose administered and the AUC of platinum (R = 0.757, P = 0.002) or the steady state plasma concentration of free platinum (R = 0.763, P = 0.002). The percentage of platinum excreted in urine 144 h after the initiation of infusion ranged from 73.1 to 100% for each dose level. No significant relationship was established between creatinine clearance in patients before treatment and the AUC or steady state concentration of free platinum. The plasma platinum AUC showed a linear correlation with the percentage of change in leukocytes [formula: see text] (R = 0.736, P = 0.003). In conclusion, the recommended phase II dose for a continuous infusion of 254-S is 75.5 mg/m2/120 h every 6 hours.
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PMID:Phase I study and pharmacological analysis of cis-diammine(glycolato)platinum (254-S; NSC 375101D) administered by 5-day continuous intravenous infusion. 199 85

We performed a phase I-II trial of escalating doses of cisplatin (CDDP: 50-100 mg/m2 per course) plus carboplatin (CBDCA: 300-400 mg/m2 per course) as a potential way in which to maximize platinum doses without causing excessive toxic effects in patients with advanced ovarian cancer. Thirty-three patients with nonoptimally debulked disease of FIGO (International Federation of Gynecology and Obstetrics) stages IIc-IV [median age: 60 yr; median WHO (World Health Organization) performance status: 2; no prior chemotherapy] received a median of six courses of therapy. CBDCA was infused on day 1 and CDDP on day 2 with an aggressive 48-hour hydration regimen. Myelosuppression was dose-limiting: at the highest dose levels, WHO grade 4 neutropenia and thrombocytopenia led to dose reduction and/or treatment delay in 45% of the patients. Nonhematologic toxic effects included acute nausea and vomiting (97% of the patients), mild alopecia (45%), ototoxic effects (39%), neurotoxic effects (21%), and renal toxic effects (serum creatinine greater than 1.5 mg/dL: 12.5%). The pathologic complete response rate was 22%. We conclude that CBDCA and CDDP can be given safely in combination at reasonably high doses (CBDCA at 300 mg/m2 per course and CDDP at 100 mg/m2 per course) over a 6-month period, provided a close hematologic follow-up is conducted. Randomized clinical trials are needed to define whether this regimen is any better than standard combination chemotherapy.
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PMID:Cisplatin combined with carboplatin: a new way of intensification of platinum dose in the treatment of advanced ovarian cancer. Belgian Study Group for Ovarian Carcinoma. 218 Nov 52

Thirty patients with advanced breast cancer, previously treated with anthracycline and 5 fluorouracil in bolus administration, were evaluated with a chemotherapy regimen generally used in head and neck cancer. Treatment schedule consisted of: cisplatin 100 mg/m2 on d 1 and 5 fluorouracil 1000 mg/m2 continuous infusion on d 2-3-4-5 every 21 d. With all measurable lesions and 27 evaluable patients, the response rate was 29% (95% confidence interval: 12-47%), with 5 complete responses (3 soft tissue - 2 lung) and 3 partial responses (1 lung - 2 liver). The median duration of response is 4.5 months (range 2-11 months). The 30 patients (93 courses) are evaluable for toxicity. Hematologic toxicity was mild: anemia 68% grade 0, neutropenia 68% grade 0 and thrombocytopenia 83% grade 0. Nausea and vomiting were severe 83% grade 3 + 4 at d 1. Others side effects were mild including 5/91 mucositis grade 2 + 3, peripheral neuropathy 1/31 grade 2 and 2/91 reversible rise in serum creatinine greater than 1.5 mg/dl.
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PMID:[Phase II trial as 2nd line chemotherapy with 5 fluorouracil and cisplatin (5FU-CDDP) for advanced breast cancer]. 220 69

Fostriecin, a novel anticancer antibiotic produced by Streptomyces pulveraecus, is believed to act via inhibition of topoisomerase II. Single-dose intravenous administration to rats at dose levels of 8.8 to 48 mg/kg resulted in lethality at dose levels of 35 mg/kg and higher. Major toxic effects were observed primarily at 17.5 mg/kg and higher, were reversible, and consisted of bone marrow hypocellularity, leukopenia, neutropenia, thrombocytopenia, and diffuse necrosis of various lymphoid tissues. The kidney was also identified as a target organ. Renal effects were observed primarily at 20 mg/kg, were reversible, and included increases in serum BUN, creatinine, and 24-hr glucose excretion. Twenty-four-hour excretion of Na+, K+ and urine osmolality were decreased postdosing at 10 and 20 mg/kg. Renal lesions, observed primarily at 20 mg/kg, consisted of vacuolization and necrosis of proximal and distal tubular epithelium at the corticomedullary junction extending into the medulla. Repeated daily intravenous administration of fostriecin for 5 days to rats at dose levels of 2.5 to 26.5 mg/kg resulted in death at 10 mg/kg and above and similar hematologic, bone marrow, lymphoid tissue, and renal changes as observed in the single-dose study. Hematological, bone marrow, lymphoid, and renal changes observed in rats were consistent with the cytotoxic mechanism of action of the compound.
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PMID:Preclinical toxicological evaluation of fostriecin, a novel anticancer antibiotic, in rats. 222 54

Interferon-beta-serine (IFN-beta-ser) is a muteine, recombinant IFN that is tolerated at a dose fivefold to 10-fold higher than IFN-alfa and interacts with the same cell membrane receptor as IFN-alfa. We hypothesized that at high doses IFN-beta-ser might induce a higher response rate than IFN-alfa in metastatic renal cell carcinoma. We undertook a phase II trial of IFN-beta-ser in patients with metastatic renal cell carcinoma. Patients were treated three times each week by a 2-hour intravenous infusion. Doses were escalated weekly (.25 to 5.5 mg, 1 mg = 180,000,000 U) until the maximum-tolerated treatment dose (MTTD) was determined. The MTTD is defined as one dose level less than that which caused grade 3 toxicity and was subsequently administered three times weekly for at least 4 weeks. Twenty-nine patients were entered, and 25 were assessable for response and toxicity. The performance status was 0-1 in all patients and only one patient received previous chemotherapy. The MTTD dose was 2.5 mg (range, 0.5 to 5.5 mg per treatment), although in 10 patients, doses were later deescalated because of cumulative toxicity. Initial dose-limiting toxicity and cumulative toxicity were fatigue, malaise, and fever in most patients. Hepatic transaminitis, neutropenia, and elevation of serum creatinine were also observed but were not dose-limiting. There was one complete response (CR) and four partial responses (PRs). All responses but one occurred in pulmonary metastases. The median time to response was 26 days (range, 17 to 102 days). These data demonstrate that IFN-beta-ser given in high doses exhibits significant antitumor activity in renal cell carcinoma; however, the objective response rate is 20%. This is no higher than previous IFN studies; therefore, we reject the hypothesis than IFN-beta-ser at high doses may induce a greater response rate than IFN-alfa. However, we did observe more responses than were seen in a similar trial undertaken with lower dose IFN-beta serine in renal cell carcinoma.
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PMID:Phase II trial of interferon-beta-serine in metastatic renal cell carcinoma. 233 72

Withholding iron dextran treatment normally given to pigs at 1-3 days of age to prevent anemia resulted also in neutropenia. Polyinosinic acid:polycytidylic acid (poly I:C) at 0.5 mg/kg IV at 25 days of age resulted in induction of putative interferon 2 to 24 hours later, with significantly (P less than 0.05) lower concentrations in iron-deficient (Fe-) female pigs than in iron-supplemented (Fe+) female pigs. Poly I:C caused several transient toxic manifestations, including elevations in blood urea nitrogen, creatinine, aspartate aminotransferase, potassium (K), total bilirubin and phosphorus (P), marked leukopenia (both neutropenia and lymphopenia), and declines in serum albumin, calcium, cholesterol, glucose and globulin. Certain blood chemistries before poly I:C were significantly (P less than or equal to 0.05) different: albumin, globulin, cholesterol and K were higher in females than in males; albumin, globulin, glucose, P and K were higher in Fe- than in Fe+ pigs; and total carbon dioxide was higher in Fe+ than in Fe- pigs.
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PMID:Effects of poly I:C in porcine iron deficient neutropenia. 241 Jan 86

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


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