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M D Reed

Publications and source records attributed to M D Reed.

At least 73 records · Page 4Linked to original sources
PubMed1991

Survivor-victim status, attachment, and sudden death bereavement.

This research examines the significance of the survivor-victim relationship in understanding grief following sudden death bereavement. Data for this study come from medical examiner's reports and mailed self-report surveys of survivors of suicide and accidental death. In general, the results show that survivor-victim attachment is more important than survivor's status in explaining grief reactions. Also, suicide survivors experience significantly less emotional distress and shock, but greater feelings of guilt/shame and rejection, than survivors of accidental death. This paper concludes by directing future research to explore more fully the importance of survivor-victim relationships in understanding grief following bereavement.

Accidents↗
PubMed1991

Use of nondepolarizing neuromuscular blocking agents in mechanically ventilated patients.

The pharmacology and history of development of nondepolarizing neuromuscular blocking agents are presented, and the pharmacokinetics and pharmacodynamics of these agents, administration guidelines for mechanically ventilated patients, adverse effects, factors affecting paralysis, and methods for blockade reversal are reviewed. Nondepolarizing neuromuscular blocking agents (tubocurarine, metocurine, pancuronium, vecuronium, and atracurium) are frequently used to induce prolonged pharmacologic paralysis in patients in the intensive-care unit (ICU). These agents are poorly absorbed after oral administration and must be administered by injection, preferably by the i.v. route. Individualized adjustment of the dose is necessary to maintain the desired degree of paralysis. Dosing modifications may be necessary in patients with underlying renal or hepatic diseases and in pediatric and geriatric patients. Patients with thermal burns require larger doses of these drugs than other patients. These agents can cause several important adverse effects, including histamine release, cardiovascular changes, and muscle atrophy. Pathophysiologic variables and drug interactions can affect the degree of paralysis. Generally, patients no longer requiring paralysis in the ICU will be allowed to spontaneously regain muscle function after drug therapy has been discontinued. If the effects of the nondepolarizing neuromuscular blocking agents must be reversed more rapidly, acetylcholinesterase-inhibiting agents such as physostigmine, neostigmine, pyridostigmine, and edrophonium can be used. Nondepolarizing neuromuscular blocking agents can be used to paralyze mechanically ventilated patients, facilitating optimal oxygenation and ventilation.

Aged↗
PubMed1990

Clinical pharmacology of imipenem and cilastatin in premature infants during the first week of life.

The first-dose and multidose pharmacokinetics of imipenem and cilastatin were evaluated in 41 premature infants during their first week of life. Premature infants (gestational age, less than or equal to 37 weeks) were assigned to receive 10-, 15-, 20-, or 25-mg/kg doses of imipenem-cilastatin (1:1) as a single- or multiple-dose regimen. A total of 39 infants received a single dose, whereas 18 infants received multiple doses. No differences were observed in pharmacokinetic parameter estimates for either agent relative to the dose administered or infant body weight; thus, the data were pooled. Elimination half-life, steady-state volume of distribution, and body clearance averaged 2.5 h, 0.5 liter/kg, and 2.5 ml/min per kg, respectively, for imipenem and 9.1 h, 0.4 liter/kg, and 0.5 ml/min per kg, respectively, for cilastatin. Similar values for these parameter estimates were observed after multidose administration, although substantial accumulation of cilastatin in serum was observed. A total of 21% of the imipenem and 43% of the cilastatin were excreted unchanged in the urine over a 12-h collection period. Corresponding renal clearances averaged 0.4 and 0.2 ml/min per kg for imipenem and cilastatin, respectively. Substantial differences were observed in the route by which imipenem was cleared from the body compared with data from adult volunteers. These data suggest that infants should receive an imipenem dose of 20 mg/kg administered every 12 h for the treatment of bacterial infections outside the central nervous system.

Cilastatin↗
PubMed1989

Developmental pharmacology: ontogenic basis of drug disposition.

Our understanding of clinical pharmacology in pediatrics, although limited, is continually increasing. This increase in our database reflects the supportive perspective of our colleagues, but more importantly, the recognition that specific pharmacokinetic and pharmacodynamic data in children are necessary for the provision of optimal care. In this review, we have focused on the many predictable influences of body maturation on drug disposition. These data underscore the importance of the many patient-specific variables that directly influence a patient's clinical response to drugs and, thus, the design of appropriate pharmacotherapeutic regimens.

Aging↗
PubMed1989

Percutaneous transluminal aortic angioplasty: techniques and results.

Percutaneous transluminal angioplasty of the infrarenal abdominal aorta has been reported by a few authors. In the present series, aortic stenoses in 32 patients were treated with various percutaneous angioplasty techniques. Isolated aortic stenoses and primary aortic stenoses extending into the iliac arteries were successfully dilated. The initial success rate was 100%, without evidence of rupture, thrombosis, dissection, or distal embolization. In only three of the 28 patients who returned for follow-up did symptoms recur or noninvasive vascular laboratory indexes deteriorate (mean follow-up, 25 months). Percutaneous transluminal aortic angioplasty has proved safe and efficacious in the treatment of atherosclerotic aortic stenoses.

Adult↗
PubMed1989

Clinical pharmacokinetics in infants and children. A reappraisal.

A significant increase in the knowledge base in paediatric clinical pharmacology has occurred over the past 2 decades and has largely been the result of important scientific and sociological advancements pertaining to paediatric therapeutics. Although the data on drug disposition in infants and children have increased considerably over the past few years, pharmacokinetic-pharmacodynamic interactions, particularly the effect of development on pharmacodynamics, remain poorly understood. The impact of developmental physiology on drug absorption, distribution, metabolism and elimination in infants and children is reviewed and contrasted to the determinants of clinical pharmacokinetics in neonates. The most notable differences in drug disposition between infants and children when compared with neonates and young adults centre around alterations in body water and serum protein composition and the affinity/capacity for hepatic biotransformation of xenobiotics. As opposed to examining the effect of age on the disposition of specific compounds, the differences in developmental pharmacology are highlighted by the review of important and/or emerging pharmacokinetic-pharmacodynamic controversies in infants and children. These include the issues of altered drug distribution and metabolism in cystic fibrosis, pharmacokinetic determinants of successful antimicrobial therapy in bacterial meningitis and the pharmacokinetic determinants of immunosuppression treatment with cyclosporin. The pharmacological differences which are characteristic of development in both infants and children are also reviewed by examination of considerations for clinical pharmacokinetic evaluations such as specific routes and techniques for both drug administration and determination of sampling strategies. Clinical pharmacokinetics will continue to function as a bridge between the generation of new information and the practical application of this knowledge. Consequently, pharmacokinetics provides a pharmacological tool for use in research and clinical care. The clinical application of this tool is examined by a review of the pertinent assumptions and limitations, as well as useful mathematical techniques for use in paediatric patients. Additionally, 'non-traditional' uses of clinical pharmacokinetics (forensic application and use to evaluate organ function) in infants and children are discussed as are considerations for research use of clinical pharmacokinetic data.

Adolescent↗
PubMed1988

Lack of unique ciprofloxacin pharmacokinetic characteristics in patients with cystic fibrosis.

The single-dose pharmacokinetics of oral ciprofloxacin 750 mg were evaluated in six subjects with cystic fibrosis (CF subjects) and six age, sex and approximate weight-matched control subjects (controls). In addition, the effect of concurrently administered oral pancreatic enzyme replacement on the pharmacokinetics of ciprofloxacin was studied in 12 CF subjects. Ciprofloxacin t1/2, VSSF, CLF, and CLR in the matched CF subjects averaged 4.5 hours, 2.8 L/kg, 2.73 mL/min/kg and 5.7 mL/min/kg, respectively. Forty-two percent of the ciprofloxacin dose was excreted in the urine (0-48 hours) as the parent compound. No statistically significant differences in these ciprofloxacin pharmacokinetic parameter estimates were observed between CF and control subjects. In three CF subjects and two controls, the urinary excretion of ciprofloxacin and four of its metabolities were similar. In contrast, CF subjects demonstrated a prolonged tmax (2.3 versus 1.3 hours P less than .05) though ciprofloxacin Cmax was similar (4.7 versus 3.8 mg/L, NS). The concurrent administration of oral pancreatic enzyme replacement had no effect on the pharmacokinetics of ciprofloxacin. Apparent ciprofloxacin pharmacokinetic parameters in sputum were similar to those observed in serum. Sputum ciprofloxacin concentrations lagged behind serum concentrations but, on average, exceeded serum concentrations for 20 hours of the 24-hour sampling period. These sputum ciprofloxacin concentrations exceeded the reported MIC90 for Pseudomonas aeruginosa for approximately 15 hours. These data suggest an oral ciprofloxacin dose of 750 mg administered q8h to promote accumulation and maintenance of sputum drug concentrations well above pathogen MICs for the majority of a dosing interval in patients with CF.

Adolescent↗
PubMed1988

A versatile computational method for the determination of areas under the curve and moment curve following multidose drug administration.

The accurate determination of area under the biologic fluid concentration-time curve (AUC) and area under the first moment curve (AUMC) are important in the calculation of a compound's pharmacokinetic parameter estimates. Although numerous mathematical methods exist for the calculation of both AUC and AUMC under varying conditions, some permit direct computation of areas, whereas others only approximate the true areas. In this study, we describe an alternative mathematical method which allows the direct calculation of either the AUC or AUMC after any dose of drug administered by any route. Simulated data with known areas were used to assess the accuracy of the proposed method and compared to area calculations obtained from widely used published methods. Experiments were also performed under conditions of varying elimination half-lives and reduced numbers of concentration-time values. Under any experimental condition, the newly proposed method was the most accurate in determining both the AUC and AUMC. Percent deviations from exact area values were less than or equal to 0.11% with the proposed method, whereas as much as 30% deviation was observed using other methods of calculation. These findings support the accuracy of the proposed method in calculating the AUC or AUMC and its utility in data analysis.

Infusions, Intravenous↗
PubMed1988

An evaluation of optimal sampling strategy and adaptive study design.

We have evaluated the utility of optimal sampling strategy coupled with adaptive study design in the determination of individual patient and population pharmacokinetic parameter values. In 9 patients with cystic fibrosis receiving a short (1 minute) infusion of ceftazidime pharmacokinetic parameter values were determined with a nonlinear least-squares estimator analyzing a traditional, geometrically spaced set of 12 postinfusion serum samples drawn over 8 hours. These values were compared with values generated from four sample subsets of the 12 obtained at optimal times and analyzed by nonlinear least-squares estimator, as well as a maximum a posteriori probability Bayesian estimator with prior distributions placed on beta and clearance. The four sampling times were determined according to an adaptive design optimization technique that employs sequential updating of population prior distributions on parameter values. Compared with the 12-point determination, the four optimal points analyzed with the maximum a posteriori probability Bayesian estimator faithfully reproduced both microscopic and hybrid pharmacokinetic parameter values for individual patients and, consequently, also produced accurate measures of population central tendency and dispersion. This has important implications in being able to more efficiently derive target patient population pharmacokinetic information for new drugs. This should also allow generation of better concentration-effect relationships in populations of interest.

Adolescent↗
PubMed1988

The effect of exocrine pancreatic function on chloramphenicol pharmacokinetics in patients with cystic fibrosis.

The effect of exocrine pancreatic function on the pharmacokinetics of the choramphenicol oral capsule (CAP-base), chloramphenicol palmitate oral liquid (CAP-P), and chloramphenicol succinate intravenous (CAP-S) formulations was evaluated in 10 patients, aged 16-30 yr, with cystic fibrosis. Pancreatic insufficiency was assessed in each patient by measuring the absorption of p-amino-benzoic acid after oral administration of N-benzoyl-L-tyrosyl-p-aminobenzoic acid which requires chymotrypsin to cleave p-aminobenzoic from the parent molecule. In a controlled cross-over design, the overall biodisposition of each formulation was assessed in each patient with or without concurrent administration of oral pancreatic enzymes. The relative amounts of active chloramphenicol available in systemic circulation was CAP-base greater than CAP-S greater than CAP-P. Pancreatic enzyme replacement had little effect on the biodisposition parameters for the CAP-base and CAP-S formulation, but significantly increased the peak concentration and bioavailability of the CAP-P formulation. Although pancreatic enzyme replacement improved the absorption characteristics of the CAP-P formulation, absorption remained prolonged and unreliable. Serum concentration-time profiles for either CAP-base or CAP-S consistently exceeded the MIC of important nonpseudomonal pathogens. This finding was not observed after CAP-P administration independent of pancreatic enzyme replacement. The results of this study support the continued clinical use of either CAP-base or CAP-S, but the cautious use of CAP-P formulations in CF patients with concurrent pancreatic insufficiency.

Administration, Oral↗
PubMed1988

Principles of drug biodisposition in the neonate. A critical evaluation of the pharmacokinetic-pharmacodynamic interface (Part I).

Rational pharmacotherapy is dependent upon an understanding of the clinical pharmacokinetic and pharmacodynamic properties of the drugs employed. Although the available data on drug biodisposition and action in the neonate have increased considerably in the last few years, pharmacokinetic-pharmacodynamic interactions for many drugs remain poorly understood. The ontogeny of drug absorption, distribution, metabolism, and elimination are addressed in this review. Drug absorption from any site depends upon both the physicochemical properties of the drug and a variety of patient factors. Absorption of orally administered drugs may be affected by changes in gastric acidity and emptying time as well as by bile salt pool size, bacterial colonisation, and extraintestinal disease states such as congestive heart failure. Factors affecting drug absorption following intramuscular, percutaneous, and rectal administration are also discussed. Drug distribution in the neonate is influenced by a variety of important and predictable age-dependent factors. The developmental aspects of protein binding and body water compartments are described. Additionally, hepatic drug metabolism assumes an important role in understanding the pharmacokinetic and pharmacodynamic properties of many compounds. Certain biotransformation pathways, including hydroxylation by the P450 mono-oxygenase system and glucuronidation, demonstrate only limited activity at birth, while other pathways, such as sulphate or glycine conjugation, appear very efficient at birth. Elimination of drugs excreted unchanged in the urine is dramatically reduced in the newborn, compared with older infants and children, due to immaturity of both glomerular filtration and tubular secretory processes. The glomerular filtration rate remains markedly reduced prior to 34 weeks gestational age, increasing as a function of post-conceptual age until adult values are achieved by approximately 2.5 to 5 months of age. Tubular secretory capacity is also limited at birth, approaching adult values by approximately 7 months of age. Published reports describing the pharmacokinetics and pharmacodynamics of commonly used drugs in the neonatal period, as well as differences in drug biodisposition among premature infants, full term neonates, and older infants and children, are reviewed. Our recommendations for neonatal drug therapy are based upon a critical interpretation of these data, an understanding of fetal development and maturational processes, and an understanding of how disease states may affect drug biodisposition in the neonate.

Absorption↗
PubMed1988

Urologic pharmacology in the office setting.

The authors discuss two areas of therapeutics employed commonly in office practice, namely, anti-infective therapy and therapy for disorders of micturition. In anti-infective therapy, the pharmacodynamic aspects of drug action, as exemplified by the in-vitro susceptibility of various pathogens to antibiotics, are often known before the drug is administered to the patient. Thus, therapeutic failures generally result from a lack of knowledge of the individual patient's pharmacokinetics. In contrast, drug therapy for disorders of micturition is directed against a variety of often conflicting mechanisms and is seldom based on any pharmacokinetic tenets.

Ambulatory Care↗
PubMed1987

Comparison of the prophylactic effects of 2-deoxycytidine and prednisolone for high-dose intravenous cytarabine-induced keratitis.

In a double-masked, randomized fashion, 11 patients with hematologic malignancies received 13 courses of high-dose cytarabine therapy, intravenously (3 g/m2 every 12 hours for five to six days). Each patient received topical prednisolone phosphate 1% in one eye and 2-deoxycytidine 100 microM in the other eye every six hours. Topical therapy was initiated 12 hours before the first cytarabine dose and continued for up to ten days (until four to five days after completion of cytarabine therapy). Slit-lamp biomicroscopy was performed before therapy and then weekly for one month. 2-Deoxycytidine was equally as effective as the topical corticosteroid therapy in reducing photophobia and pain, microcysts, and punctate epithelial erosions, and each treatment gave results significantly better when compared historically to placebo-treated eyes.

Administration, Topical↗
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

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↗