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)

Twelve immunocompromised children were treated with 13 courses of intravenously administered ganciclovir for severe cytomegalovirus disease. All children were allograft recipients; 6 received organ transplants (5 liver, 1 kidney) and 6 received bone marrow. They presented with one or more of the following forms of cytomegalovirus disease: pneumonitis, 9; hepatitis, 3; colitis, 2; peritonitis, 1; and retinitis, 1. Clinical improvement was observed in 7 (58%) of 12 patients during ganciclovir therapy. Cessation of active viral replication during therapy accompanied 69% of the treatment courses. Mild and transient increases in creatinine and liver function tests and/or decreases in neutrophil count accompanied 77% of treatment courses but neutropenia (less than 1000 cells/mm3) did not occur. Transient decreases in platelet counts accompanied therapy in 3 bone marrow allograft recipients, but greater than 50% decrease in lymphocyte count was not seen. We conclude that ganciclovir is safe and appears to have a beneficial effect on cytomegalovirus disease in some pediatric transplant recipients.
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PMID:Ganciclovir treatment of cytomegalovirus disease in immunocompromised children. 254 91

Eleven aged patients over 65 years of age with advanced lung cancer (mean age = 70.8 +/- 1.4, non-small cell:small cell = 9:2, stage III:IV = 5:6) were treated with combination chemotherapy consisting of cisplatin (50 or 80 mg/m2) and vincaloids (vindesine 3 mg/m2 or etoposide 80 mg/m2). To evaluate this cisplatin combination therapy, the aged group was compared with a young group consisting of eleven patients (mean age = 53.3 +/- 1.7, non-small cell:small cell = 9:2, stage III:IV = 5:6) matched for cell type, stage and dose regimen. The mean dose of cisplatin was 58.2 mg/m2 in the aged and 63.6 mg/m2 in the younger group. A notable reduction in tumor size was observed in 9.1% of the aged and 27.3% of the young, while one-year survival rate was 63.6% in the aged and 72.7% in the young. The common side effects were nausea and vomiting, while diarrhea was seen in 18.2% of the aged. Neutropenia, anemia and thrombocytopenia were found in both groups and the time course of myelosuppression in the aged (18.2 +/- 0.8 days) was significantly shorter than that in the younger patients (22.0 +/- 1.4 days, p less than 0.05). With regard to nephrotoxicity, creatinine clearance rate in the aged decreased remarkably from 56.9 to 38.9 ml/min, while there was no significant change in BUN, serum creatinine and urine NAG between the aged and the young. Disorders of electrolytes such as hypokalemia and hyponatremia were seen in 45.5% of the aged. We conclude that advanced lung cancer in the aged was effectively treated with cisplatin combination therapy with tolerable nephrotoxicity and myelosuppression.
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PMID:[Cisplatin combination chemotherapy in advanced lung cancer in the aged]. 260 73

Oxygen free radicals have been implicated in postischemic renal injury. However, the source of these oxygen free radicals has not been well defined. One potential source is activated neutrophils. Neutrophil depletion was produced in rats by using two different techniques, and the effect on ischemic injury was examined. Rabbit anti-rat neutrophil serum was prepared by immunizing a rabbit with a Percoll gradient centrifugation-purified (approximately 90%) suspension of rat neutrophils. Rats received antineutrophil serum in one of four protocols and were subsequently subjected to 40 minutes of renal artery occlusion. Control animals received nonimmune rabbit serum. The serum creatinine levels 24 hours after ischemia were not different between control and immune serum-treated rats in any of the protocols despite significant reductions in absolute neutrophil count. In a separate study, nitrogen mustard was administered 40 hours before ischemia. Nitrogen mustard-treated rats developed moderate neutropenia and 24 hours after ischemia had lower serum creatinine levels and higher inulin clearance. However, nitrogen mustard-treated rats lost 31.5 +/- 5 gm body weight in the 2 days after nitrogen mustard administration, whereas control animals gained 5.9 +/- 5.9 gm during the same interval. Furthermore, among nitrogen mustard-treated rats there was no correlation between neutrophil count and postischemic renal function. It is thus possible that the beneficial effects of nitrogen mustard were caused by a mechanism other than neutrophil depletion. In summary, in four protocols that used antineutrophil serum, neutropenia did not protect against ischemic injury. Nitrogen mustard provided protection, but probably by a neutrophil-independent mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of neutrophil depletion on ischemic renal injury in the rat. 292 43

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of enalapril maleate, a nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor, are reviewed. Enalapril is rapidly converted by ester hydrolysis to enalaprilat, a potent ACE inhibitor; enalapril itself is only a weak ACE inhibitor. Enalapril lowers peripheral vascular resistance without causing an increase in heart rate. In patients with congestive heart failure, enalapril has beneficial hemodynamic effects based on reduction of both cardiac preload and afterload. Approximately 60% of a dose of enalapril is absorbed after oral administration. Excretion of enalaprilat is primarily renal. Accumulation of enalaprilat occurs in patients with creatinine clearances less than 30 mL/min. Enalapril 10-40 mg per day orally has shown efficacy comparable to that of captopril in treating patients with mild, moderate, and severe hypertension, hypertension caused by renal-artery stenosis, and in congestive heart failure resistant to digitalis and diuretics. When given alone for hypertension, enalapril has efficacy comparable to that of thiazide diuretics and beta blockers. Side effects observed with enalapril have generally been minor. Captopril-associated side effects such as skin rash, loss of taste, and proteinuria have been observed in a small number of patients receiving enalapril to date; neutropenia less than 300/mm3 has been noted with captopril but not enalapril. The incidence of these side effects has been noted to be greatly decreased in patients on low doses of captopril. Enalapril appears to be similar in efficacy to captopril for treating hypertension and congestive heart failure. Whether enalapril is safer than low-dose captopril in patients at high risk for captopril-associated side effects will require further investigation.
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PMID:Enalapril, a nonsulfhydryl angiotensin-converting enzyme inhibitor. 298 41

The pharmacokinetics of the antiviral drug 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl]guanine (DHPG) were examined in six patients receiving 2.5 or 5.0 mg/kg every 8 or 12 hours for human cytomegalovirus (HCMV) pneumonitis or retinitis. Biexponential decay with a mean distribution t1/2 of 0.23 hours and terminal t1/2 of 2.53 hours was observed. Total clearance correlated well with and exceeded creatinine clearance by a factor of 2.4. Mean volume of the central compartment was 15.26 L/1.73 m2 and the volume of distribution at steady state was 32.8 L/1.73 m2. Peak (model predicted) and trough plasma concentrations were 4.75 to 6.20 micrograms/ml and less than 0.25 to 0.63 microgram/ml, respectively, in patients receiving 2.5 mg/kg. Peak concentrations are well above those needed to inhibit HCMV at the 50% level (ID50) and troughs are near this ID50. Cerebrospinal fluid concentrations of DHPG indicate a penetration of 24% to 67%. No accumulation of DHPG was apparent in these patients. However, dosage reduction is necessary in renal insufficiency. Neutropenia occurred in one patient. The plasma concentration profile of DHPG suggests potential beneficial activity against HCMV.
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PMID:Human pharmacokinetics of the antiviral drug DHPG. 301 30

Ganciclovir is a congener of acyclovir with in vitro activity against cytomegalovirus. Ninety-seven patients with the acquired immune deficiency syndrome (AIDS) and a serious cytomegalovirus infection received ganciclovir, 3.0 to 15 mg/kg per day. Viremia cleared during drug therapy in 88 percent of patients. Viral shedding from urine and throat ceased or became inapparent during treatment in 78 percent and 68 percent of patients, respectively. Among patients with cytomegalovirus retinitis, 87 percent of evaluable patients had improvement in (30 of 60) or stabilization (22 of 60) of their disease. However, when the drug was discontinued, progression or recurrence of disease always occurred. Long-term suppressive therapy with ganciclovir, 5.0 mg/kg five to seven times weekly, prevented the recurrence of cytomegalovirus disease (p less than 0.001). The drug was eliminated by renal excretion, and in patients without renal impairment (creatinine clearance rates of more than 60 ml/minute/1.73 m2), ganciclovir has a mean half-life of 4.2 hours. Significant neutropenia and leukopenia occurred in 55 percent and 32 percent of patients, respectively.
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PMID:Ganciclovir for the treatment and suppression of serious infections caused by cytomegalovirus. 303 41

Fifty patients with histologically proven squamous-cell carcinoma of the head and neck, recurrent after surgery and/or radiation therapy, were treated with a triple-drug combination of methotrexate (MTX), 250 mg/m2 intravenously (IV) on day 1, followed by 5-fluorouracil (5-FU), 600 mg/m2 IV on days 1 and 2, followed by cisplatin, 50 to 60 mg/m2 IV on days 3 and 4. Patients were randomly assigned to receive cisplatin either in 300 mL of 3% saline or with standard mannitol diuresis along with appropriate hydration. The courses of treatment were repeated every 3 to 4 weeks. Among 47 evaluable patients, there were four complete responses (CRs) and 17 partial responses (PRs) (9% and 36%, respectively). The median duration of response was 23 weeks and the overall survival was 7 months. The median survival of responders v nonresponders was 12 months and 6 months, respectively. Nausea and vomiting was experienced by all patients and diarrhea was experienced by 36% of patients. Neutropenia occurred in 37 patients (79%) and resulted in fever or infection in 11 patients (23%) and death in two patients. Mild renal failure (persistent serum creatinine greater than 1.5 mg/ dL) was observed in ten patients (21%), six treated with 3% saline and four treated with mannitol. The median cumulative dose of cisplatin that lead to the development of renal impairment was 485 mg/m2 in the hypertonic saline arm and 550 mg/m2 in the mannitol arm (P = .40). The antitumor activity of this regimen was not superior to that of sequential MTX and 5-FU. The use of hypertonic saline was not effective in reducing the renal toxicity of cisplatin.
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PMID:Sequential methotrexate, 5-fluorouracil, and cisplatin in the treatment of recurrent squamous-cell carcinoma of the head and neck: failure of hypertonic saline to reduce the nephrotoxicity of cisplatin. 309 3

Twenty-six patients with histologically proven lung cancer, treated with carboplatin at the National Cancer Center Hospital between October 1985 and October 1986, were retrospectively analyzed to determine the hematologic toxicity of carboplatin (CBDCA) and to develop guidelines for dose modification. A total of 34 courses of CBDCA were administered, of which 21 were adequate for assessment of the myelosuppression in relation to the renal function. One of three doses of CBDCA was administered by iv drip infusion over one hour (450 mg/m2, 19 courses; 400 12; 300, 3). Myelosuppression was dose-limiting, with thrombocytopenia being more sensitive than leukopenia, neutropenia or anemia. No significant correlation of the absolute count of platelets, white blood cells, polymorphoneutrophils, or hemoglobin with patient's creatinine clearance (Ccr) and dose of CBDCA administered was found. However, the percent reduction in platelets, white blood cells, polymorphoneutrophils, or hemoglobin correlated well with the relative dose of CBDCA [RD = total dose of carboplatin administered (mg/m2)/pretreatment Ccr/m2]. As thrombocytopenia was dose-limiting, we have developed an equation for modification of the dose of CBDCA from the relationship between the relative dose and percent reduction at platelet count nadir: Dosage (mg/m2) = (Ccr/m2/5.34) x [(1-desired platelet count nadir/pretreatment platelet count) x 100-12.9]. After consideration of the range of thrombocytopenia, we have further developed a simple equation to use CBDCA easily and safely: Dosage (mg/m2) = (1/10) x Ccr/m2 x desired % reduction in platelet count nadir = 10 x Ccr/m2 x (1-desired platelet count nadir/pretreatment platelet count. The clinical validity of these two equations is now being evaluated in prospective studies.
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PMID:Prediction of hematologic toxicity of carboplatin by creatinine clearance rate. 311 53

Ten patients with progressive hairy cell leukemia were treated with 2'deoxycoformycin (dCF) by intravenous bolus (4 mg/m2) given every other week. All ten patients are evaluable for response and nine of the ten patients have achieved a complete remission. In addition to clearing of hairy cells from the bone marrow, eight patients had resolution of their monocytopenia. Seven of the nine patients remain in unmaintained remission with a median duration of 6.2 months. Two patients have had relapse in the bone marrow alone and continue to have normal peripheral blood counts. They are being followed without treatment. Toxicity was minimal at this low dose with one patient having a mild reversible reduction in creatinine clearance. Four other patients had reversible neutropenia. There were no significant infections associated with treatment. Low-dose deoxycoformycin administered intravenously every other week represents an extremely effective treatment for hairy cell leukemia.
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PMID:Low-dose deoxycoformycin in the treatment of hairy cell leukemia. 349 Feb 87

We conducted a phase II clinical trial using ifosfamide (IFX) as a single agent in cisplatin-refractory male germ cell tumor. Thirty patients with measurable disease were treated with IFX, 2 g/m2 intravenously (IV) for 5 consecutive days every 3 weeks. N-acetylcysteine, 2 g orally every 4 hours, was given as a uroprotective agent. All patients had previously been treated with cisplatin, vinblastine, and bleomycin, and all except two also had previously received etoposide. There were six partial responses (PR) and one complete response (CR) for an overall objective response rate of 23%. The median duration of response was 3.5 months (range, 2 to 5.5 months). The median survival time was 3.5 months (range, 2 to 14+ months). The toxicity of the regimen consisted of hematuria (65% of the patients), nausea and vomiting (43%), neutropenia (WBC less than 2,000; 52%), thrombocytopenia (platelet count less than 50,000; 20%), and nephrotoxicity (12%). Hematuria was dose related, occurring in 48% of courses using 2 g/m2/d v only 5% of courses at lower doses. Serious nephrotoxicity (creatinine level greater than 6.0 mg/mL) was observed in three patients with an elevated pretreatment serum creatinine level. In conclusion, IFX is an active agent in this heavily pretreated population with advanced refractory germ cell tumor.
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PMID:Ifosfamide in refractory male germ cell tumors. 351 Feb 80


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