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Biomedical subjects

H Russo

Publications and source records attributed to H Russo.

13 recordsLinked to original sources

HIPAA Creating privacy protection that works.

All health care providers, clearinghouses, and health plans that transmit health information electronically in connection with a standard transaction (e.g., claims, coordinating benefits, payment and remittance advice, claims status, etc.) are subject to compliance under the Health Insurance Portability and Accountability Act of 1996 (HIPAA). The effective date of the regulations was April 14, 2001, and all health providers must be in full compliance by April 2003. It is extremely important that you and your organization understand HIPPA and the final privacy rule and begin working toward compliance now.

Computer Communication Networks↗

Application service providers. Home care's new software stores.

Do you want simpler, inexpensive applications that can help manage your business? From scheduling to billing, clinical care to electronic medical records, data capture, analysis, and reporting as well as just-in-time access to information, application service providers (ASPs) provide organizations with a menu of options and "pay as you use" service.

Home Care Services↗

Window of opportunity for home care nurses: telehealth technologies.

Multiple telehealth technologies are currently available for nurses working in home care and other community settings. Furthermore, the rate at which new electronic technologies, which can promote home care nursing, are introduced continues to increase. This article addresses the need for increased use of information technologies in home care nursing, describes how information technologies are changing the way we give nursing care, provides examples of telehealth nursing in home care, and discusses the future of telehealth technologies in nursing.

Community Health Nursing↗

Leveraging health care processes using technology applications.

Providers are being encouraged to deliver health care services differently, and use resources more efficiently while maintaining or improving patient outcomes and satisfaction. Agencies should understand how to use information technology in leveraging the health care industry's ability to improve access to care, facilitate collaboration in delivering care and health information, and decrease costs related to the rendering of care.

Costs and Cost Analysis↗

Pharmacodynamics and pharmacokinetics of thiopental.

Thiopental is an ultra short-acting barbiturate which remains the standard against which other induction agents are judged; it is also indicated for the therapy of brain hypoxic-ischaemia injuries and status epilepticus. Aspects of drug distribution that govern the onset and end of drug effect have been intensively studied to determine which parameters (in patient characteristics, diseases and administration modalities) influence effective dose and concentrations in individual patients. Thiopental has been used as a reference for pharmacokinetic and/or pharmacodynamic models in the study of rapid and short acting effect drugs. In anaesthesiology the pharmacokinetics of thiopental are described as linear; when doses and duration of treatment increase, nonlinear pharmacokinetics occur because of the saturation and/or the induction of the metabolism.

Adult↗

High-performance liquid chromatographic assay for thiopental in human plasma. Application to pharmacokinetic studies.

A simple assay method for the measurement of thiopental by reversed-phase high-performance liquid chromatography (HPLC) with ultraviolet absorbance detection was developed. The method involved a protein precipitation with methanol. Carbamazepine was used as internal standard. The mobile phase was acetonitrile-water (32:62, v/v). The elution was isocratic and the column temperature was ambient. Linear detection response was obtained for concentrations ranging from 1-100 microg ml(-1). Recovery from plasma averaged 88%. Precision, expressed as coefficient of variation (%), was in the range of 0.2-8%. Percent recovery was at least 93%. Stability studies showed that plasma samples should be processed as promptly as possible. This method has been used in therapeutic monitoring and for the determination of pharmacokinetic parameters of thiopental in patients treated with a high dose over a long time to decrease intracranial pressure.

Anesthetics, Intravenous↗

Population pharmacokinetics of high-dose thiopental in patients with cerebral injuries.

Thiopental monitoring was performed in 95 critically ill patients hospitalized for neurologic damage, High-dose thiopental was infused during long-term treatment. Total dose of 333 +/- 144 mg/kg (449 +/- 185 mg/kg for females and 302 +/- 113 mg/kg for men) were given in 125 +/- 43 hours. Plasma concentration-time data were analyzed according to a population pharmacokinetic approach with an initial group of 65 patients. Clearance (CL) and central volume of distribution (Vc) were modeled alone and under the influence of demographic covariates, assuming a two-compartment open model with first-order elimination. The final population models were as follows: CL (L/hr) = 11.7.weight (kg).age (yr)/(2136 + age2) and Vc = 1.52.weight (kg) + 44.8. Mean CL and Vc mean population estimates were 8.01 L/hr (133 ml/min or 2.02 ml/min/kg) and 145 L (2.19 L/kg). The predictive performance of the population modeling and parameters was evaluated with a bayesian fitting procedure in an independent validation set of 30 patients with similar physical and clinical characteristics. There was no statistically significant bias or imprecision between measured and predicted thiopental plasma concentrations in this validation group. Moreover, there was a good adequation (r = 0.939) between individual CL values predicted from the population formula and estimated with the bayesian approach.

Adolescent↗

Time-dependent pharmacokinetics of high dose thiopental infusion in intensive care patients.

PURPOSE: In patients with severe head injuries receiving long-term infusion for reducing intracranial pressure, a decline in concentrations was apparent following attainment of an initial steady state. This could be explained by an increased rate of elimination. An adequate modeling of the plasma disposition curves was used to demonstrate clearly the metabolic induction. METHODS: The concentration-time data of 17 patients were fit by a one compartment pharmacokinetic model in which the decline of plasma concentration during infusion was due to an increase in the clearance rate of thiopental following a latency period. This time-dependent clearance model provided estimates of initial and final clearance rates. RESULTS: This study demonstrated that large interindividual variations were observed during the course of the thiopental time-dependent pharmacokinetics. Depending on the patient, one or two steps of induction occurred. The mean initial and final clearance rates were 1.22 +/- 0.82 mL/min/kg and 10.5 +/- 23 mL/min/kg. The latency period for the first induction averaged 69 +/- 56 h. For 6 subjects, the rate of thiopental metabolism continued to change with time and there was a second step of induction. CONCLUSIONS: Induction of thiopental metabolism occur within therapeutic ranges, but it was not established that attainment of individual limits in dosing rate, total dose, or treatment duration occur in the process. Thus, monitoring is needed for achievement of a target plasma concentration.

Adolescent↗

Pharmacokinetics of high-dose thiopental in pediatric patients with increased intracranial pressure.

This study was conducted on 10 pediatric patients in whom intracranial hypertension stemming from head injury was reduced by high-dose thiopental administered for a prolonged period. All children showed a favorable recovery of their neurological functions. The total dose normalized to body weight averaged 335 +/- 135 mg/kg, and the mean treatment duration was 93.0 +/- 37.1 h. Data analysis was modeled for each patient to cover all the doses on the whole plasma thiopental concentration-time curve, according to a one-compartment open model. A better fit was obtained using a linear model rather than a Michaelis-Menten elimination model. Model selection was guided by evaluation of the minimum objective function, the weighted residuals, and the Akaike criterion. Thiopental pharmacokinetic parameters in pediatric patients were compared with those determined in an adult control group with similar total doses and durations of treatment. No significant difference was found between the two groups in spite of a 33% decrease of the elimination half-life in children (11.7 +/- 5.7 h) compared with adults (17.5 +/- 9.03 h). The mean values obtained were 2.42 and 2.19 ml/min/kg for total clearance and 2.18 and 2.90 L/kg for Vd in pediatric and adult groups, respectively. The linear regression of pharmacokinetic parameters in terms of age was not significant. When high doses of thiopental were administered over a prolonged period, the pharmacokinetic parameters computed for pediatric patients did not differ from those obtained in adults.

Adolescent↗

Pharmacokinetics of thiopental after single and multiple intravenous doses in critical care patients.

Thiopental was administered to neurosurgical patients for cerebral protection and its pharmacokinetic parameters were determined after a single bolus of 540, 1000 or 1500 mg (3 subjects) or after multiple doses of 250 mg (5 subjects) and 500 mg (2 subjects) every two hours for up to 7 days. The data were analysed by a two- or three-compartment model and linear kinetics. After a single iv bolus, the mean initial volume of distribution (V1) was 0.481 l.kg-1, and the steady-state volume of distribution (Vss) was 2.16 l.kg-1. The distribution (t1/2 alpha) and elimination (t1/2 beta) half-lives were 0.590 and 5.89 h, respectively, and the mean residence time (MRT) was 7.44 h. The clearance was 5.41 ml.min-1.kg-1. With repeated injections, the pharmacokinetic parameters for each patient were estimated taking into account all administered doses and blood samples, which were taken whenever possible daily at steady state and after the last dose. The variability observed in the pharmacokinetic parameters of thiopental reflected by the coefficient of variation (CV%) was wide but was of similar magnitude within patients (CVintra) as it was between patients (CVinter). The steady-state trough plasma concentration (Cmin obs) ranged from 4.8 to 30 mg.l-1 (mean 16.0 mg.l-1 and median 14.3 mg.l-1). Peak concentrations (Cmax obs) ranged from 8.35 to 45 mg.l-1 (25.4 mg.l-1, and median 23.3 mg.l-1). The values of V1 and Vss were similar to those obtained after a single dose. For V1, the mean was 0.333 l.kg-1. The mean Vss was 2.68 l.kg-1, with a CVintra of 12.6 to 56% and a CVinter of 13.2%. A shorter distribution half-life t1/2 alpha was noted on multiple dosing; the mean value was 0.122 h. The elimination half-life t1/2 beta and the mean residence time became longer due to a decrease in clearance. For t1/2 beta the mean value was 16.3 h. The mean MRT was 21.9 h, CVintra 9.19 to 48.5%, and the CVinter 35.3%. The mean clearance was 2.16 ml.min-1.kg-1, CVintra 7.28 to 25.5%, and the CVinter 20.4%. This value is 50% lower than after a single dose. Identification of the kinetic parameters of thiopental allows simulation of the effects of doses on subsequent plasma levels and will permit a priori prediction of day to day adjustment of drug dosage.

Adolescent↗

Variability of thiopental clearance in routine critical care patients.

Thiopental was administered to neurosurgical patients as a drug for cerebral protection for up to 9 days either by continuous infusion (seven subjects) or repeated intravenous bolus (nine subjects). The efficient levels of thiopental measured at steady state ranged between 5 and 63 mg.l-1. Steady-state clearance evidenced considerable interindividual variability. Overall mean plasma clearance was lower than 1 ml.min-1.kg-1 for one subjects, ranged between 1 and 2 ml.min-1.kg-1 for six subjects, between 2 and 3 ml.min-1.kg-1 for seven subjects and was up to 5 ml.min-1,kg-1 for one subject. Extreme values for apparent daily clearance were 0.268 ml.min-1.kg-1 and 5.40 ml.min-1.kg-1. Daily intersubject CV gradually increased from day to day, increasing from 37% on day 1 to 51% on day 7. During the treatment for seven subjects, variations were minimal and clearance was considered to be constant; the maximum variation of clearance expressed as a percentage of the initial value was lower than 21% over a period longer than 3 days. For the other subjects, clearance was not stable with time. A decrease in clearance was evidenced for four subjects over a period of 7 days and more; the maximum variation of clearance was greater than -35%. An increase in clearance was noted for three subjects after 2 days of treatment; the maximum variation of clearance was greater than +44%. Evaluation of clearance at steady state made it possible to analyse interindividual variability and its clinical implications.

Adolescent↗

Displacement of thiopental from human serum albumin by associated drugs.

Displacement of thiopental from its binding sites to 4% human serum albumin solution was studied in vitro. Experimental conditions were selected to reproduce a physiological situation. Associations were studied according to the therapeutic conditions of use of the substances (drug and protein concentrations). The unbound fraction of thiopental was obtained by equilibrium dialysis at 37 degrees C and pH 7.4. Eleven drugs were associated with thiopental in 50 combinations of drugs and molar ratios. Bromhexine, citocoline, dextromoramide, dexamethasone, and methotrimeprazine had no effect on thiopental binding. The unbound fraction of thiopental significantly increased with cefamandole, cefazolin, diazepam, desmethyldiazepam, furosemide, and fentanyl. At usual therapeutic drug concentrations, the unbound fraction increase was < 5%. Higher values, however still < 10%, were found with associated drugs that were added at maximal concentrations observed in therapy. The displacement of thiopental from its albumin binding by drugs that are normally associated with the treatment of intracranial hypertension does not modify the pharmacokinetic parameters or pharmacological effect of thiopental.

Binding, Competitive↗

Growth of a human carcinoma (HEp3) in nude mice: rapid and efficient metastasis.

Our aim was to identify conditions which would permit the development of spontaneous metastasis of a human tumor in nude mice in a rapid and predictable manner and to explore ways to quantitate metastasis. Using a human squamous carcinoma--HEp3--we determined that invasiveness and metastasis were influenced by the host. HEp3 cells grew very rapidly and without a significant lag period in Balb/c and NIH(S)-II nude mice kept in aseptic conditions; a much longer lag period was observed in NIH-Swiss mice kept in conventional conditions. The HEp3 tumor displayed a highly invasive behavior in N-NIH(S)-II mice, in which it invaded the body wall, gaining access to the peritoneal cavity. Microinvasion was noted in all strains of mice inoculated with HEp3 cells. To prolong survival of the mice until metastases became evident, primary tumors were excised when they weighed 1-2 gm. N-NIH(S)-II and Balb/c nude mice, maintained in germ-free conditions, were most receptive to the development of metastases-lung metastases developed in 80% of these mice. Over 60% of all metastases were present within 4 weeks following the removal of the primary. Only 26% of tumor bearing NIH-Swiss developed lung metastases. Lung metastases were observed in some mice in the absence of local microinvasion, local tumor recurrence, and regardless of the presence of lymph node involvement. They were also noted in mice from which primary tumors were not excised. We compared three methods of lung metastasis detection: histology, detection of tumor cells in the cultures of lung minces, and the measurement of the levels of human urokinase-type plasminogen activator directly in the lysates of lungs. The detection of tumor cells in cultures of lung minces appeared to be the most sensitive of these methods and the determination of enzyme in lung lysates seemed to hold most promise for a quantitative approach. These data indicate that, the type of tumor, as well as the genetic background and the maintenance conditions of the host, have to be carefully selected to ensure the successful outcome of the particular tumor-host interaction being studied. Adherence to these guidelines allowed us, in the case of the HEp3 tumor, to develop a rapid, predictable, and efficient model in which to study factors affecting metastasis of this human tumor.

Animals↗