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Biomedical subjects

R D Leff

Publications and source records attributed to R D Leff.

51 records · Page 3Linked to original sources
PubMed1983

Host factors influencing the response to antimicrobial agents.

When the desired clinical response to an antibiotic therapeutic regimen is not achieved, despite appropriate antibiotic selection and organism sensitivity, the clinician must be aware that several host factors exist that may influence the outcome. Examples of the influence of host-related factors on drug disposition have been briefly reviewed in this article. It should be noted, however, that further investigation is needed to determine whether these factors truly exert a significant influence on the outcome of antibiotic utilization.

Anti-Bacterial Agents↗
PubMed1983

A prospective analysis of the arthritis syndrome and immune function in jejunoileal bypass patients.

Fifty-two patients undergoing jejunoileal bypass surgery were prospectively evaluated to determine: 1) the incidence of the associated arthritic syndrome; 2) whether we could identify patients at risk for arthritis prior to surgery; and 3) changes in immune function. The incidence of arthritis was 28% and was frequently associated with dermatitis. No preoperative clinical or laboratory parameters identified those patients at risk to develop rheumatic problems. Circulating immune complexes were found in both arthritis and non-arthritis patients after surgery. Mean serum levels of IgA rose significantly after surgery only in patients who developed arthritis, but remained within the normal range. No other immunologic abnormalities were noted.

Adult↗
PubMed1982

Effect of intravenous fluid and drug solution coadministration on final-infusate osmolality, specific gravity, and pH.

The effects of i.v. fluid rates and i.v. drug delivery rates on osmolality, specific gravity, and pH of the resulting infusate were examined. Selected drug solutions of various osmolalities and 5% dextrose and 0.2% sodium chloride injection or Ringer's injection, lactated, were administered simultaneously using a drug delivery system capable of controlling the flow rates independently. The i.v. fluid and drug infusion rates were varied from 4 to 46 and from 2 to 31 ml/hr, respectively. Osmolality, pH, and specific gravity of the drug solutions and final infusate were measured. Using alligation, the osmolality, pH, and specific gravity of the final infusate were calculated; correlations between observed and calculated values were computed. Guidelines for achieving an osmolality of the final infusate less than 500 mOsm/kg water were calculated. The observed and calculated osmolality and specific gravity of the final infusate were significantly correlated (r = 0.91, p less than 0.001, and r = 0.99, p less than 0.01, respectively). The pH of the final infusate was dependent on the pH of the original drug solution and was not affected by i.v. fluid and drug delivery flow rates. Osmolality may be an important factor to consider when establishing ideal drug solution infusion rates or concentrations. The infusate osmolality can be controlled by adjusting the concentration of the drug solution, drug infusion rate, or the i.v. fluid flow rate.

Hydrogen-Ion Concentration↗
PubMed1981

Aminoglycoside dosage in pediatric patients:considerations regarding pharmacokinetic-based dose adjustment in patients requiring high versus low dose therapy.

Pharmacokinetic-based adjustment of individual aminoglycoside dosage regimens is currently being utilized in the clinical setting in an attempt to avoid toxicity and/or enhance efficacy. In this report, comparison have been made between initial and adjusted aminoglycoside dosage employed in toddlers and older children with cystic fibrosis or leukemia (high daily dose) and neonates (low daily dose) with suspected or proven infection. The initial versus adjusted mean aminoglycoside dosage was 14.1 and 17.0 mg/kg/day, respectively, in toddlers and older children with cystic fibrosis, and 7.1 and 11.5 mg/kg/day, respectively, in toddlers and older children with leukemia. Neonates with suspected or proven infection had an initial mean total daily dose of 7.4 mg/kg/day and the adjusted mean daily dose was 5.4 mg/kg/day. The use of a single pharmacokinetic dosing model for all patients, irrespective of evidence of increased or decreased drug elimination, results in widely differing drug dosages. Important and serious questions must be considered regarding the balance between efficacy and toxicity resulting from the rigid manner by which dosage adjustment protocols are employed.

Adolescent↗
PubMed1981

Profile of a unique community-based clinical pharmacy family practice program.

The provision of clinical pharmaceutical services in family practice offices has aroused considerable national interest among both pharmacists and physicians. Many of these clinical pharmaceutical services and educational programs have been university-funded and/or rely on colleges of pharmacy for fiscal support. Few examples of community-funded, ambulatory care clinical pharmaceutical programs have been reported. Community Health Care, Inc., and Davenport Medical Education Foundation, Inc., are two health care programs which sponsor an innovative ambulatory care clinical pharmacy program. Community Health Care is a nonprofit corporation which utilizes a multidisciplinary team concept to provide comprehensive ambulatory care services to patients. Davenport Medical Education Foundation is a nonprofit corporation that provides a community-based family practice residency program. Because the two separate parent organizations have distinct goals requiring individualized clinical pharmaceutical services, the responsibilities of the clinical pharmacist have evolved to be comprehensive in scope.

Family Practice↗
PubMed1978

Pharmacokinetic considerations in exchange transfusion in neonates.

Neonates undergoing blood exchange often receive concomitant therapy. Questions may be raised whether dosage regimen alterations are necessary to replace drug lost as a result of the exchange procedure. Our study reports the changes in plasma concentration of kanamycin during an exchange transfusion and a pharmacokinetic analysis of the effect of the exchange on drug elimination. The relationships of the volumes of distribution, elimination rate constant, and time after dosing on the fraction of the dose eliminated in the blood exchange are developed on the basis of a one-compartment body model. Computer simulations using the equations developed were used to estimate the fraction of a dose that might be removed as a result of an exchange transfusion. As the disposition rate constant or the apparent volume of distribution increase, i.e., the clearance of the drug increases, the fraction of the dose removed by the exchange process decreases. Thus, significant amounts of drug removal may occur in an exchange transfusion for drugs with low clearance when the exchange is initiated early in the drug dosing interval. In our study, only 3% of the kanamycin dose was removed as a result of the exchange process, and dosing adjustment would not be required. This was in part due to initiation of the exchange late in the dosing interval, although the maximum calculated percentage of the dose which could have been removed under the exchange conditions employed was only 10%.

Exchange Transfusion, Whole Blood↗
PubMedDate not supplied

Mechanism of action, antimicrobial activity, pharmacology, adverse effects, and clinical efficacy of cefotaxime.

Cefotaxime sodium, a parenteral cephalosporin antibiotic, exerts its bactericidal action through inhibition of bacterial cell wall synthesis. Chemical structure modifications have enabled this compound to be resistant to the action of Richmond I, III, IV, and V beta-lactamase enzymes. Excellent activity against many gram-negative bacilli, especially Enterobacteriaceae, has been demonstrated. Antipseudomonal activity is generally poor, however. Activity against gram-positive cocci, with the notable exception of Streptococcus fecalis, is adequate. Anaerobic activity is variable, particularly against Clostridia and Bacteroides species. Acute, subacute, and chronic toxicity studies in animals were generally unremarkable. No mutagenic effects or reproductive toxicity have been noted in animals. In man, cefotaxime is desacetylated to a microbiologically active metabolite. Urinary excretion is approximately 50-60% and 15-20% of a dose for the parent compound and desacetyl metabolite, respectively. The elimination half-life of cefotaxime is about one hour, with the total body clearance being approximately twice that of the renal clearance. Severe renal dysfunction causes a prolongation of the elimination half-life of cefotaxime and particularly desacetyl cefotaxime. A relatively low degree of protein binding in part attributes to a wide bodily distribution of cefotaxime. Cefotaxime is effective in a variety of infectious processes caused by susceptible organisms. Local reactions at the injection site and hypersensitivity phenomena are the most common adverse effects. Comparative trials attesting to cefotaxime's clinical utility over other parenteral cephalosporins or amino-glycosides are very limited. Based on the available evidence, cefotaxime should be most useful in combating serious gram-negative infections, because of its excellent activity against most of these organisms and its low toxicity profile.

Adult↗
PubMedDate not supplied

Iodixanol pharmacokinetics in children.

The objective of this report was to study the elimination pharmacokinetics of iodixanol in children. Iodixanol (Visipaque, Nycomed Inc., Wayne, PA, USA) is a new iso-osmolar iodinated radiocontrast agent. We hypothesized that elimination of this agent would be dependent on age-related differences in renal clearance. Seven centers enrolled 43 patients. Cardiac catheterization was performed in 41 patients and cranial computed tomography in 2. Patients were entered into 5 age groups: newborn to <2 months, 2 to <6 months, 6 months to <1 year, 1 to <3 years, and 3 to 6 months of age that is comparable to normal adults. Prolonged elimination in children <6 months of age is related to renal immaturity.

Age Factors↗
PubMedDate not supplied

Simplified gentamicin dosing in neonates: a time- and cost-efficient approach.

A nomogram-based method for monitoring gentamicin therapy in neonates was developed and evaluated prospectively. Gentamicin dosage adjustment, based on analysis of a single blood sample collected between 8 and 12 hours after dose administration, resulted in satisfactory serum levels in 79% of the neonates. When compared to dosage adjustment methods requiring multiple blood samples, the nomogram method is a cost-effective and time-efficient technique for screening the appropriateness of gentamicin dosages in neonates.

Bacterial Infections↗
PubMedDate not supplied

Arthritis in Indian country: determining the prevalence and effects.

OBJECTIVE: This project was designed to determine the prevalence of self-reported arthritis and its effect on the daily lives of Chippewa Indian people on tribal lands in Wisconsin. DESIGN AND METHODS: After review and approval by the LCO Tribal Council and the University of Minnesota Human Subjects Committee, face-to-face interviews with randomly selected tribal residents were conducted, followed by focus group formation, and medical chart reviews. RESULTS: Eighty-one percent (N = 82) of the eligible sample were interviewed. Fifty-six percent (N = 46) self-reported a diagnosis of arthritis, either by physician report or description of symptoms confirmed by a rheumatologist. Seventy-eight percent of this group (N = 36) reported limitations in their activities that can be attributed to arthritis. Only half of the medical charts included the diagnosis of arthritis or any tests to document its diagnosis. CONCLUSIONS: In this Chippewa population, the prevalence of and limitations due to arthritis are extremely high. Reasons for this need further investigation. The implications of these findings for tribal and health planning include housing, community activities, and medical services to accommodate the needs of this group.

Aged↗
PubMedDate not supplied

Relationship between pain severity and serum beta-endorphin levels in postoperative patients.

STUDY OBJECTIVE: To examine the relationship among postoperative pain severity, serum beta-endorphin level, and serum morphine level in pediatric patients after posterior spinal fusion with instrumentation. DESIGN: A prospective study. SETTING: University-based medical center. PATIENTS: Ten patients age 13-17 years admitted for posterior spinal fusion with instrumentation. INTERVENTIONS: Each subject was administered an initial dose of intravenous morphine 100 micrograms/kg, followed by a constant infusion of 50 micrograms/kg/hour. The primary physician was allowed to titrate the dosage as required to meet the patient's requirement for analgesia. Whole blood was obtained for the analysis of serum morphine and beta-endorphin levels preoperatively, after the initial morphine dose, 24 hours after initiation of the infusion, and before any change in dosage. At each blood sampling time, pain severity ratings were obtained from the subject, nurse, and parent using a 10-point linear scale. MEASUREMENTS AND MAIN RESULTS: No statistical difference between serum beta-endorphin values preoperatively and after the initial dose of morphine was observed; mean values were 68 and 60 pg/ml, respectively. The relationships between serum beta-endorphin level and pain scores were statistically significant only for self (subject) pain scores (p = 0.014, r = 0.30). Mean serum morphine level was 21.9 ng/ml for patients with self pain scores of 4 or less. CONCLUSION: The clinical usefulness of serum beta-endorphin as a measure of pain severity was not established under the experimental conditions of this study.

Adolescent↗