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Biomedical subjects

J L Blumer

Publications and source records attributed to J L Blumer.

At least 109 records · Page 6Linked to original sources
PubMed1987

Ciprofloxacin monotherapy for acute pulmonary exacerbations of cystic fibrosis.

Ciprofloxacin has potent in vitro activity against Pseudomonas aeruginosa and Pseudomonas cepacia strains isolated from cystic fibrosis patients. Our previous single-dose pharmacokinetic and pharmacodynamic studies identified important differences between cystic fibrosis patients and age- and sex-matched controls. Based on these data, 30 acutely ill cystic fibrosis patients (aged 18 to 44 years) received 750 mg of ciprofloxacin orally every eight hours for 21 days. Multiple timed serum, urine, and sputum samples for pharmacokinetic analysis were obtained on Days 3, 12, 14, and 21 of the study. Estimates of steady-state pharmacokinetic parameters averaged (+/- SD): t1/2 beta, 3.8 (1) hours; Vd/F, 4.4 (2) liters/kg; Cl/F, 772.9 (301) ml/minute/1.73 m2; Fe, 46 percent; peak, 5.4 (2) mg/liter; and trough, 1.8 (0.8) mg/liter. Serum ciprofloxacin concentrations and pharmacokinetic estimates remained unchanged throughout the study. Sputum ciprofloxacin concentrations exceeded those observed in serum. Sputum cultures revealed 43 P. aeruginosa (MIC90 = 2 micrograms/ml) and 15 P. cepacia (MIC90 = 16 micrograms/ml) strains. Sputum ciprofloxacin concentrations exceeded the MIC90 for P. aeruginosa approximately fivefold, yet only eight isolates were fully suppressed. Posttreatment sputum cultures revealed 35 P. aeruginosa (MIC90 = 16 micrograms/ml) and 15 P. cepacia (MIC90 = 16 micrograms/ml). All patients showed clinical improvement based upon the results of pulmonary function tests and an acute clinical efficacy score (median pre 49/post 60). No patients experienced drug-related toxicity. Ciprofloxacin monotherapy is effective for the acute treatment of cystic fibrosis patients. The development of pathogen resistance during oral therapy may limit its utility in ambulatory patients.

Adolescent↗
PubMed1987

Pseudomonas aeruginosa as a primary pathogen in children with bacterial peritonitis.

This prospective study compared the efficacy of sulbactam/ampicillin and clindamycin/gentamicin in the treatment of children with bacterial peritonitis. Of the 29 children enrolled, 17 were evaluable; eight received sulbactam/ampicillin/gentamicin and nine clindamycin/gentamicin. Sixteen patients were previously healthy children with appendicitis. An average of 3.6 bacterial species were recovered from the peritoneal fluid of each patient. E coli and B fragilis were the most common aerobic and anaerobic isolates, recovered from 15 and ten patients, respectively. Pseudomonas aeruginosa was recovered from seven of 17 children; the three children with P aeruginosa infections randomized to the sulbactam/ampicillin group received gentamicin in addition to the investigational agents throughout the treatment course. Although the study groups were small, there was no difference in age, sex, number of pathogens per patient, duration of hospitalization, toxicity, or treatment failures between the two treatment groups or between children infected with P aeruginosa and controls. As a result of the high prevalence of P aeruginosa in the peritoneal exudate of otherwise healthy children with appendicitis, initial antimicrobial therapy in this patient population should include agents effective against this organism.

Adolescent↗
PubMed1987

Sultamicillin in the treatment of superficial skin and soft tissue infections in children.

Fifty-two children with superficial skin and soft tissue infections were randomized to receive sultamicillin or cloxacillin for 7 days. Twenty-one children in each group finished the study. A total of 16 of 21 in the sultamicillin group and 13 of 21 in the cloxacillin group were cured. One child in the sultamicillin group and two in the cloxacillin group failed therapy. Four children who received sultamicillin and six who received cloxacillin had recurrences of lesions. Differences were not statistically significant.

Abscess↗
PubMed1987

Randomized double-blind evaluation of ceftazidime dose ranging in hospitalized patients with cystic fibrosis.

Eighty-five patients with cystic fibrosis who were experiencing an acute infectious exacerbation of their disease were randomized in double-blind fashion to receive either 50 or 75 mg of ceftazidime per kg (body weight) per dose administered intravenously every 8 h for 14 days. Three patients were dropped from the study within 4 days of enrollment for reasons unrelated to drug administration. The total daily dose of ceftazidime administered was restricted by protocol design and was independent of the body weight of the patient. Thus, for datum analysis, patients were separated into three ceftazidime dosage groups (denoted as range of milligrams per kilogram per dose): group 1, 22 to 44.5; group 2, 46.3 to 56.6; and group 3, 66.7 to 80.6. Ceftazidime monotherapy had no effect on sputum colony counts for any Pseudomonas cepacia isolate. In contrast, a substantial reduction in Pseudomonas aeruginosa sputum colony counts was observed, and from 19 to 31% of isolates were suppressed greater than or equal to 10(5) CFU/ml after 14 days of therapy. Bacterial resistance in vitro was not observed, although a trend for increasing ceftazidime MICs was observed for group 1 patients (P less than 0.05). Overall, clinical response appeared independent of drug dose, and no relationship could be identified between the reduction in P. aeruginosa sputum colony counts and clinical outcome. Adverse effects of ceftazidime were mild and transient, necessitating drug discontinuation in one patient. These data suggest that the clinical response to ceftazidime in patients with cystic fibrosis may be maximal with 50 mg/kg per dose (150 mg/kg per day) up to a total daily dose of 6 g.

Adolescent↗
PubMed1987

The clinical pharmacology of vancomycin in seriously ill preterm infants.

The first dose and steady state pharmacokinetics of vancomycin were studied in 16 seriously ill preterm infants (less than or equal to 34 wk gestational age) with documented Staphylococcus epidermidis infections. One infant was dropped from the study due to peripheral flushing occurring during administration of the first dose. Individual vancomycin doses ranged from 9.8 to 17.8 mg/kg and were infused intravenously over 15-37 min. Fifteen infants were studied after the first dose of vancomycin, whereas only 12 of these 15 were able to be studied under steady state conditions. Vancomycin half-life, steady-state volume of distribution, and body clearance averaged 6.0 h, 0.53 liter/kg, and 1.22 ml/min after the first dose and only slight differences were observed in these parameter estimates under steady state conditions. However, substantial accumulation of vancomycin in serum was observed with multiple dosing. Complete 8-h urine collections were possible in 12 of 15 premature infants after the first dose of vancomycin. Overall, 44.6% of the dose was recovered in the urine with a corresponding vancomycin renal ClR averaging 0.88 ml/min. Vancomycin body Cl correlated directly with renal ClR (r = 0.88, p less than 0.001) and body weight (r = 0.8, p less than 0.001). Vancomycin pharmacokinetic parameter estimates Vdss and Cl correlated directly with body weight, surface area, and postconceptional age. No significant relationships were observed between these parameter estimates and gestational age or postnatal age. Fourteen of 15 infants were treated successfully for their underlying infectious process. These data support the use of lower doses of vancomycin than previously recommended for the treatment of preterm infants.

Female↗
PubMed1986

Diuretic therapeutics in the pediatric patient.

Careful management of fluid and electrolytes has long been an intrinsic part of pediatric practice. However, the augmentation of these manipulations through the rational use of diuretic agents requires considerable skill. In pediatric medicine, the regulation of pharmacokinetic processes and their interface with pharmacodynamic processes show dramatic age-related changes. These ontogenetic processes and their modification by various disease states must be considered carefully before selection and application of diuretic agents. The available data concerning the ontogeny of renal function and the attempts to apply diuretic therapy to pediatric disease are reviewed. It is concluded that results obtained to date suffer from the absence of a rigorous attempt to answer the fundamental therapeutic questions: What drug? What dose? What duration of therapy? A rational "target-effect" strategy is proposed for the application of diuretic agents to pediatric medicine.

Acid-Base Equilibrium↗
PubMed1986

Cephalosporin therapeutics in cystic fibrosis.

Cephalosporins modified at the C-3 and C-7 positions of the cephem-nucleus have high antimicrobial activity and are safe. With evolution through first, second, and third generations, they have gained increasing gram-negative activity, but often at the expense of potency against gram-positive organisms. All third-generation cephalosporins have some intrinsic anti-Pseudomonas activity, indicating their potential benefit in the treatment of acute pulmonary exacerbations in patients with cystic fibrosis. Rational therapy in this clinical setting requires recognition of the pharmacodynamic and pharmacokinetic idiosyncrasies intrinsic to this patient population. When these priorities are recognized, only two of the available agents, cefsulodin and ceftazidime, appear to be of any therapeutic value. Both agents have been evaluated extensively in the treatment of acute pulmonary exacerbation in cystic fibrosis, and both have been found to be safe and effective.

Cefsulodin↗
PubMed1986

Developmental pharmacology and therapeutics of piperacillin in gram-negative infections.

Twenty children ranging in age from 1 week to 19 years with documented or suspected bacterial infections arising outside the central nervous system were studied. Pharmacokinetic analysis was possible in 15 children; 8 after the first dose, 6 during steady-state conditions, and 4 on both occasions. Data were obtained utilizing noncompartmental pharmacokinetic methods. Peak piperacillin serum concentrations ranged from 51 to 232 mg/l and correlated directly (r = 0.75) with the dose administered. In children with normal renal function, there was an age-dependent decrease in elimination half-life and apparent steady-state volume of distribution, whereas plasma clearance increased logarithmically. All but 1 child responded favorably to piperacillin therapy, and 1 child with a urinary tract infection relapsed 10 days after discontinuation of the therapy. Although improved clinically, piperacillin monotherapy failed to eradicate pathogens in 2 children. No adverse clinical or biochemical effects were observed in any child.

Adolescent↗
PubMed1986

DNA damage in L5178YS cells following exposure to benzene metabolites.

Because DNA modification may be a prerequisite for chemical carcinogenesis, the DNA-damaging potential of benzene and its metabolites was examined in order to identify the proximate DNA-damaging agent associated with benzene exposure. A DNA synthesis inhibition assay previously identified p-benzoquinone as the most potent overall cellular toxin and inhibitor of DNA synthesis, but failed to discriminate among the hydroxylated metabolites. Therefore, the ability of benzene and its metabolites to induce DNA strand breaks in the mouse lymphoma cell line, L5178YS, was examined in order to provide a more accurate indication of the DNA damage associated with benzene and its metabolites. Cells were exposed to benzene, hydroquinone, catechol, phenol, 1,2,4-benzenetriol, or p-benzoquinone over a 1000-fold concentration range (1.0 microM-1.0 mM). Concentrations of benzene, phenol, or catechol as high as 1.0 mM did not increase the percentage of single-stranded DNA observed. Concentrations of hydroquinone as high as 0.1 mM were also ineffective. In contrast, both p-benzoquinone and 1,2,4-benzenetriol produced DNA breaks in a dose-related fashion. Of the two, benzoquinone proved to be more potent with an ED50 of approximately equal to 2.5 microM compared with 55.0 microM for benzenetriol. The DNA damage induced by 6.0 microM benzoquinone was maximal within 3 min of exposure and yielded approximately 70% single-stranded DNA after alkaline denaturation. By contrast, the single-stranded DNA observed after benzenetriol exposure required 60 min of exposure to achieve the same extent of damage as that found with benzoquinone. These results suggest that the benzene metabolites, benzenetriol and benzoquinone, may cause DNA damage and that the mechanisms responsible for the damage associated with these two compounds may be different.

Animals↗
PubMed1986

Continuous nasogastric administration of activated charcoal for the treatment of theophylline intoxication.

Two adolescents with serum theophylline concentrations in excess of 100 mg/L were treated with continuous nasogastric infusion of activated charcoal after an intentional overdose. In both cases, nasogastric boluses of 20 to 50 gm of charcoal resulted in prompt emesis of stomach contents despite the presence of a functional nasogastric tube. For nasogastric infusion, activated charcoal was diluted in 0.9% sodium chloride and infused at a rate of 0.25 to 0.5 gm/kg/hr up to a maximal rate of 50 gm/hr. Despite the high initial serum concentrations, the theophylline elimination half-lives during the first 20 hours after the start of charcoal were 7.7 and 13.5 hours. Subsequently, this decreased to 2.6 and 3.2 hours. No serious neurologic, cardiovascular, or metabolic derangements were observed. Continuous nasogastric infusions of activated charcoal may be safe and effective alternatives to charcoal hemoperfusion in patients with theophylline overdose.

Administration, Intranasal↗
PubMed1985

Ceftazidime therapy in patients with cystic fibrosis and multiply-drug-resistant pseudomonas.

The in vitro activity of ceftazidime against Pseudomonas aeruginosa and P. cepacia isolates from patients with cystic fibrosis was compared with that of other antipseudomonal drugs. Ceftazidime was as potent as imipenem against P. aeruginosa and the only drug effective against P. cepacia. An evaluation of the elimination kinetics of ceftazidime in 20 cystic fibrosis patients revealed an elimination half-life of 1.76 hours, an apparent distribution volume of 0.27 liters/kg, and a serum clearance rate of 133.9 ml/minute/1.73m2. Urinary recovery of ceftazidime was 87 percent within the first 24 hours after administration of the drug, with 65 percent recovered in the first two-hour fraction. Probenecid administration had no effect on the elimination kinetics of ceftazidime. Forty-three patients who had either shown no response to conventional therapy or had sputum Pseudomonas isolates that were susceptible only to ceftazidime received 75 courses of therapy. In 67 percent of these patients, the clinical response, when evaluated using an objective clinical efficacy scoring system, was considered favorable. Clinical failures were not associated with the development of drug resistance. Thus, ceftazidime can be recommended for the treatment of acute pulmonary exacerbations in patients with cystic fibrosis.

Adolescent↗
PubMed1985

Streptokinase dissolution of a right atrial thrombus.

A critically ill 20-month-old white male with severe bronchopulmonary dysplasia, cor pulmonale, and intolerance to enteral feeds, required a left percutaneous subclavian Broviac catheter. Echocardiogram showed a right atrial thrombus, resolution of which was demonstrated after infusion of streptokinase through the Broviac catheter for 16 hours. The catheter remained in place, functioning well, for a further 4 months. The patient suffered no bleeding complications, and was spared the prohibitive risk of right atrial thrombectomy. This use of streptokinase has not previously been reported.

Cardiac Catheterization↗
PubMed1985

Pharmacokinetic determination of ranitidine pharmacodynamics in pediatric ulcer disease.

The pharmacokinetics and pharmacodynamics of ranitidine were evaluated during three methods of administration in 12 children ranging in age from 3.5 to 16 years with documented gastric or duodenal ulcer disease. First, a continuous intravenous infusion of ranitidine was administered to determine the serum concentration necessary to suppress gastric acid secretion by at least 90%. From these data a therapeutic dose of ranitidine was calculated and administered on separate days via the intravenous bolus and oral routes. Half-life, volume of distribution, and clearance values for ranitidine were the same after intravenous bolus and oral doses (1.8 vs 2.0 hours, 2.3 vs 2.5 L/kg, and 794.7 vs 788.0 ml/min/1.73 m2, respectively). The bioavailability of ranitidine given orally averaged 48%. Serum ranitidine concentrations necessary to inhibit gastric acid secretion by at least 90% ranged between 40 and 60 ng/ml for all children studied. No adverse clinical or biochemical effects were observed in any child during the 6 weeks of orally administered treatment. Endoscopic reevaluation after 6 weeks indicated complete healing of initial ulcers.

Adolescent↗