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)

I.v. pentamidine is well known to cause severe multiorgan adverse effects and is usually given to hospitalized patients under close monitoring. The primary purpose of this retrospective quality assurance study is to assess the safety of administering i.v. pentamidine in the medical daycare unit (MDCU) for outpatients. Thirty-five outpatients infected with the HIV made 306 visits to the MDCU from January 1991 to December 1993. They received i.v. pentamidine in a dosage of either 300 mg once a month for prophylaxis or 4 mg/kg/d 5 days a week for treatment of Pneumocystis carinii pneumonia (PCP). BP was monitored every 15 to 30 min over 3 to 4 h and clinical side effects were noted. CBC count, BUN, creatinine, amylase, and blood glucose values were taken twice a week. The records were reviewed retrospectively and analyzed for clinical and biochemical derangement. GI side effects occurred in 59 of 306 (19%) visits; 43 (73%) of the side effects were nausea. Routine normal saline solution boluses before and after pentamidine infusion prevented the drop in BP and actually significantly elevated BP after i.v. pentamidine. The most common biochemical derangement was elevated BUN level in eight patients and creatinine in nine patients, but they were mild and required no intervention. Significant neutropenia occurred in three, anemia in two, hyponatremia in two, hyperamylasemia in two, and hyperglycemia in two patients. No palpitation or irregular pulse was encountered. No death was associated with the administration of i.v. pentamidine. Three patients required hospital admission. Only one hospital admission was definitely related to adverse drug effects. In conclusion, the side effects of i.v. pentamidine are common but minor. We conclude that it is safe to administer i.v. pentamidine in carefully selected patients with appropriate monitoring in an ambulatory setting. This has a major health economic implication, because ambulatory i.v. pentamidine can result in significant cost savings and can also enhance quality of life. Further studies regarding the feasibility of home administration of i.v. pentamidine is warranted as even further cost savings and improvement in the quality of life of HIV-infected patients may be achieved.
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PMID:The safety of i.v. pentamidine administered in an ambulatory setting. 868 17

Abelcet, or Amphotericin B lipid Complex, is unique formulation, comprising an equimolar mixture of amphotericin B complexed with two lipids. In preclinical studies, Abelcet was clearly demonstrated to be less toxic than amphotericin B desoxycholate and to be effective in models where amphotericin B was ineffective at its maximum tolerated dose. Pharmacokinetic studies in animals also showed that the concentration of Abelcet in blood is similar or reduced compared to levels seen with conventional amphotericin B, with accumulation in the liver, lungs and spleen. Phase I clinical trials determined the optimum tolerated dose of Abelcet to be 5 mg/kg d-1. Data are now available for 228 cases (including 51 paediatric cases) of invasive fungal infection treated with Abelcet in an open-label emergency-release protocol. All patients had to have failed on previous amphotericin B or other conventional antifungals, or to have unacceptable toxicity on amphotericin B, or underlying renal disease, or nephrotoxicity due to other drugs. Abelcet was administered at a dose of 5 mg/kg d-1 for 4 wk. Approximately one-third of patients had candidiasis, one-third aspergillosis and one-third other infections, including fusariosis. Of 183 cases evaluable for response, 126 (69%) had a clinical response (cure or improvement) which was mycologically confirmed in 55% (61/110 tested). Results in paediatric cases were similar to or better than those seen in the group as a whole. When comparisons were made between cases with different types of infection, underlying disease/immunosuppressive disorder, and degree of neutropenia, the response rates were very consistent from group to group. Treatment with Abelcet was well tolerated and mean serum creatinine levels actually declined during therapy, particularly in patients with pre-existing renal dysfunction.
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PMID:Amphotericin B Lipid Complex (Abelcet) in the treatment of invasive mycoses: the North American experience. 870 12

The experience with single-agent gemcitabine in advanced or metastatic breast cancer is reviewed. In all studies, gemcitabine was administered as a 30 min intravenous infusion in cycles once a week for 3 weeks followed by 1 week of rest. In the first European study (gemcitabine 800 mg/m2/week), of 40 evaluable patients, 14 were chemo-naive, 7 had received adjuvant chemotherapy, and 19 had received chemotherapy for metastatic disease. There were 3 complete responders and 7 partial responders (all independently validated by an external Oncology Review Board) for an overall response rate of 25.0% (95% CI: 12.7%-41.2%). The median time to declaration of response was 1.9 months and the median duration of survival for all 40 efficacy-evaluable patients was 11.5 months. Haematological and non-haematological toxicities were particularly mild. WHO grade 3 and 4 toxicities included leukopenia (6.8% and 2.3% of patients), neutropenia (23.3% and 7.0%), AST (6.8% and 2.3%), ALT (18.2% and 0%), infection (0% and 2.3%), nausea and vomiting (25.0% and 2.3%), alopecia (2.3% and 0%). There was no grade 3 or 4 creatinine, proteinuria or haematuria. In the smaller US study (18 evaluable patients, all but one having received prior chemotherapy for stage IV disease) there were no responders. However, the mean dose delivered was very low (577 mg/m2/injection). In an ongoing European trial, with a starting dose of 1000 mg/m2, a number of partial responders have been seen in soft tissue, lung and liver. Gemcitabine's modest toxicity profile and single-agent activity make it an attractive candidate for trial in combination therapy in advanced breast cancer where treatment is currently given to palliate symptoms and improve quality of life.
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PMID:Gemcitabine in advanced breast cancer. 871 26

Ciprofloxacin is a broad spectrum fluoroquinolone antibacterial agent. Since its introduction in the 1980s, most Gram-negative bacteria have remained highly susceptible to this agent in vitro; Gram-positive bacteria are generally susceptible or moderately susceptible. Ciprofloxacin attains therapeutic concentrations in most tissues and body fluids. The results of clinical trials with ciprofloxacin have confirmed its clinical efficacy and low potential for adverse effects. Ciprofloxacin is effective in the treatment of a wide variety of infections, particularly those caused by Gram-negative pathogens. These include complicated urinary tract infections, sexually transmitted diseases (gonorrhoea and chancroid), skin and bone infections, gastrointestinal infections caused by multiresistant organisms, lower respiratory tract infections (including those in patients with cystic fibrosis), febrile neutropenia (combined with an agent which possesses good activity against Gram-positive bacteria), intra-abdominal infections (combined with an antianaerobic agent) and malignant external otitis. Ciprofloxacin should not be considered a first-line empirical therapy for respiratory tract infections if penicillin-susceptible Streptococcus pneumoniae is the primary pathogen; however, it is an appropriate treatment option in patients with mixed infections (where S. pneumoniae may or may not be present) or in patients with predisposing factors for Gram-negative infections. Clinically important drug interactions involving ciprofloxacin are well documented and avoidable with conscientious prescribing. Recommended dosage adjustments in patients with impaired renal function vary between countries; major adjustments are not required until the estimated creatinine clearance is < 30 ml/min/1.73m2 (or when the serum creatinine level is > or = 2 mg/dl). Ciprofloxacin is one of the few broad spectrum antibacterials available in both intravenous and oral formulations. In this respect, it offers the potential for cost savings with sequential intravenous and oral therapy in appropriately selected patients and may allow early discharge from hospital in some instances. In conclusion, ciprofloxacin has retained its excellent activity against most Gram-negative bacteria, and fulfilled its potential as an important antibacterial drug in the treatment of a wide range of infections. Rational prescribing will help to ensure the continued clinical usefulness of this valuable antimicrobial drug.
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PMID:Ciprofloxacin. An updated review of its pharmacology, therapeutic efficacy and tolerability. 873 21

The pharmacokinetics of Amikacin were studied in 56 febrile episodes for 45 patients with severe neutropenia while using the USC*Pack PC Clinical Programs for adaptive control of their dosage regimens [223 drug levels]. The purpose of this study are: i] to estimate the pharmacokinetic parameters in this neutropenic population [56 episodes, I], ii] to evaluate the effect of the dosage regimen: once-a-day [22 episodes, II] versus bid or tid [34 episodes, III]. Patients [mean age 53.3 +/- 17.9], 23 men and 22 women, received amikacin [17.7 +/- 3.6 mg/kg/d at day 1] in a 30 minutes infusion. The mean estimated creatinine clearance [CCr] was 76 +/- 22.5 ml/min/1.73 m2 at day 1. The method used for the population modeling was the Non Parametric EM algorithm [NPEM2] which computes the complete probability density function for a 1 or a 2 compartment model. The parametrizations studied are: Clearance/Volume [CL/VOL], Elimination rate constant/Volume [Kel/VOL] and KS/VS with Kel = KS * CCr + 0.00693, VS = VOL/Weight for a 1 compartment pharmacokinetic model. The main results concerned CL and VS with: CL[I] = 4.94 +/- 2.71, CL[II] = 4.74 +/- 2.65, CL[III] = 5.14 +/- 2.75 l/h and VS[I] = 0.31 +/- 0.11, VS[II] = 0.34 +/- 0.10, VS[III] = 0.30 +/- 0.11 l/kg. Volume of distribution VS is not so large as expected and a slight difference appears between II and III. The pharmacokinetic parameters obtained for this population of neutropenic patients will be used thereafter for the daily adaptive control of Amikacine therapy in our haematologic/oncologic patients. The variability observed remains important and requires an individualization of the dosage regimen for each patient.
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PMID:[Assessment of pharmacokinetic parameters of amikacin in a group of neutropenic patients in onco-hematology]. 876 95

To determine the efficacy of pretreatment with amifostine in diminishing the hematologic and nonhematologic toxicities of cyclophosphamide and cisplatin in previously untreated patients with stage III/IV ovarian cancer, a multicenter randomized controlled trial of cyclophosphamide (1,000 mg/m(2)) and cisplatin (100 mg/m(2) with or without amifostine (910 mg/m(2)) was performed. Two hundred forty-two patients with stage III/IV epithelial ovarian cancer were enrolled. Following primary surgery, patients were stratified and randomized to either cyclophosphamide/cisplatin (CP; 120 patients) or amifostine plus CP (122 patients) every 3 weeks for six cycles. Patient characteristics were similar in both groups. Cytoprotective end points and tumor response were evaluated, including the need to delay or discontinue therapy because of toxicity and the incidence of febrile neutropenia with associated complications. Fourteen patients treated with CP discontinued protocol therapy because of hematologic or renal toxicity (eight hematologic and six renal). In contrast, only one patient treated with amifostine plus CP discontinued protocol therapy for hematologic or renal toxicity (P < .001). Forty-three percent of CP patients compared with 22% of amifostine plus CP patients had grade 4 neutropenia (P = .001); total days in hospital were reduced from 258 in the CP arm to 11 in the amifostine plus CP arm (P = .009, two-sided). Sixty-five percent of the CP patients and 41% of the amifostine plus CP patients (P = .004) had the next cycle of CP delayed because of an absolute neutrophil count below 1,500/microL at day 22. Platelet and red blood cell transfusion support were substantially reduced in the group that received amifostine. The serum creatinine failed to return to < or = to 1.5 mg/dL by day 22, requiring a delay in chemotherapy in 15% and 5%, respectively, of the CP and amifostine plus CP groups (P = .014). Over the six cycles, the incidence and severity of peripheral neuropathy were also significantly reduced in the amifostine-treated group (P = .029). Pathologic response rates and survival curves were equivalent. The significant reduction in the CP-induced acute and cumulative hematologic, renal, and neurologic toxicities by amifostine pretreatment with equivalent response and survival indicates selective cytoprotection. This selective effect has the potential to affect quality of life and medical economic considerations.
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PMID:Amifostine cytoprotection with chemotherapy for advanced ovarian carcinoma. 878 73

A randomized clinical trial was performed in children with cancer, fever and neutropenia, to evaluate the efficacy of amikacin once daily versus thrice daily dosing plus carbenicillin in both groups. Fifty patients were included, 25 patients in group A who received amikacin once daily and 25 in group B who received amikacin thrice daily. No intergroup differences were observed, i.e., fever diminished in a median of 6 days (2-8 days) vs. 7 days (3-12 days) in groups A and B respectively (p = 0.37);clinical improvement was observed in a median of 6 days (3-10 days) vs 7 days (2-14 days) (p = 0.68). One patient in group A and two in B died. The peak levels of amikacin on the 7th day of treatment were 10-60 and 7-25 micrograms/mL in groups A and B respectively, and the serum creatinine levels were 0.3 - 0.7 for group A and 0.2 - 0.8 mg/dL for group B; none of the patients presented a creatinine above 40% of the basal value. Three patients of group A had amikacin levels higher than 40 micrograms/mL without increasing the creatinine levels; our observations do not suggest that toxicity is higher. We conclude that the administration of aminoglycoside once daily seems to be as effective as the traditional dosing.
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PMID:[Amikacin in single daily doses in children with fever]. 881 81

We determined the safety and efficacy of deoxycholate-amphotericin B (d-AmB) mixed with Intralipid (IL) as the initial treatment of AIDS-associated cryptococcal meningitis in a phase II, multicentre, non-comparative open study, assessing two dosages of ILd-AmB: 1 mg/kg (group A, n = 9) and 1.5 mg/kg (group B, n = 6). Patients were treated daily for 2 weeks, then three times weekly for 4 weeks. The ILd-AmB dosage was decreased due to toxicity in three patients in each group. Serum creatinine increased significantly on day 14 in group A and on day 7 in group B. Nephrotoxicity, (serum creatinine level > 165 mumol/L) was noted in two and five patients in groups A and B, respectively. Nine adverse haematological events were noted (seven cases of anaemia requiring transfusion, and two cases of neutropenia < 750/mm). Two patients had an increase in serum alkaline phosphatase. In each cohort, 15% of the infusions were associated with fever and/or chills. Successful outcome was obtained in half of the patients. We conclude that, in AIDS patients with cryptococcosis, tolerance to ILd-AmB was acceptable when the daily dosage did not exceed 1 mg/kg, but the higher 1.5 mg/kg daily dosage was associated with an unacceptable rate of nephrotoxicity. Neither of these relatively high daily dosages of ILd-AmB achieved an improved rate of successful outcomes compared with lower daily dosages of conventional d-AmB in glucose.
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PMID:Amphotericin B in a lipid emulsion for the treatment of cryptococcal meningitis in AIDS patients. 885 63

We evaluated and compared hematologic, hepatic and renal cumulative toxicity of high dose methotrexate (HDMTX) repeated courses in two groups of pediatric patients: 22 patients affected by "non B" acute lymphoblastic leukemia (ALL) treated, in consolidation phase, with four courses of HDMTX 5 g/mq given intravenously over 24 hours infusion (for a total of 88 courses) according to the Italian Cooperative Protocols AIEOP LLA-88; 18 patients affected by non metastatic osteosarcoma of extremities (OST) treated, in preoperative and postoperative phases, with five courses of HDMTX 8 g/mq given intravenously over 6 hours infusion (for a total of 90 courses) according to CNR-NEO 2 protocol. Severe myelosuppression (neutropenia < 500/microliters and/or thrombocytopenia < 25000/microliters) was more frequently observed in ALL (7% of infusions) than in OST (3%). Hepatotoxicity (serum transaminase elevation > 350 IU/l) was significantly more frequent (p < 0.001) in OST (32% of courses) than ALL (6%). Nephrotoxicity was assimilable in the two groups and the elevation of serum creatinine was never higher than 1.9 mg/dl. We did not observe any increase of hematologic, hepatic and renal toxicity following the HDMTX courses repetition.
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PMID:[Toxicity of high dose methotrexate repeated infusions in children treated for acute lymphoblastic leukemia and osteosarcoma]. 892 55

Bone marrow transplant (BMT) recipients are at increased risk of invasive fungal disease as a result of the profound neutropenia associated with transplantation. Amphotericin B lipid complex injection (ABLC, ABELCET) was developed to preserve the broad spectrum and fungicidal activity of conventional amphotericin B while avoiding its associated nephrotoxicity. ABLC was made available to physicians in an emergency-use program to treat seriously ill patients with advanced fungal infections who had failed to respond to previous systemic antifungal therapy (mostly amphotericin B), had experienced nephrotoxicity or severe acute toxicity due to amphotericin B or other drugs, or had pre-existing renal disease. Of 59 clinically evaluable BMT recipients with presumed or confirmed fungal infections, 31 (53%) responded to treatment: 23 (39%) were cured and eight (14%) improved. For 38 mycologically evaluable patients, pathogens were eradicated in 19 (50%). For 30 patients who began ABLC treatment with a serum creatinine > 221 mumol/l, significant reductions were observed at weeks 1 to 3 (P < 0.01) and 6 (P < 0.001). Trends in serum creatinine during ABLC therapy between autologous and allogeneic transplant recipients were similar. In summary, the results of this evaluation indicate that ABLC appears to be less nephrotoxic than conventional amphotericin B as well as an effective treatment for BMT recipients with presumed or confirmed fungal infections.
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PMID:Efficacy of amphotericin B lipid complex injection (ABLC) in bone marrow transplant recipients with life-threatening systemic mycoses. 905 Dec 44


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