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Inactivation of poliovirus type 1 by the Kelly-Purdy ultraviolet seawater treatment unit.

Three experiments were conducted to determine the effect of ultraviolet (UV) radiation on poliovirus-contaminated seawater. In two of the experiments, the effectiveness of the Kelly-Purdy UV Seawater Treatment Unit to inactivate poliovirus type 1 (T(1)) suspended in continuously flowing seawater was determined. In experiment 1, the observed survival ratio of poliovirus T(1) was 2.3 x 10(-4) (99.98% reduction) in 15.7 sec. No virus was detected (<0.2 plaque-forming unit/ml) in 20.6 seconds. The calculated half-life value was 1.29 sec. In experiment 2, the observed survival ratio of poliovirus T(1) was 5.9 x 10(-4) (99.94% reduction) in 11.7 sec. No virus was detected in 15.7 sec. The calculated half-life value was 1.37 sec. In experiment 3, a laboratory-controlled UV experiment designed to closely simulate the geometry of the continuously flowing seawater system, the observed survival ratios of poliovirus T(1) were 9.7 x 10(-3) (99.03% reduction) and 3.6 x 10(-4) (99.96% reduction) in 15 and 30 sec, respectively; the calculated half-life value was 2.38 sec. A statistically significant difference was found between the inactivation rates of poliovirus T(1) in the two test systems. This rate difference was attributed primarily to UV dosage and stirring effects. The data indicated that UV radiation effectively inactivated poliovirus T(1) in flowing seawater. These results validate the efficacy of the Kelly-Purdy UV Seawater Treatment Unit for use in commercial depuration systems.

Bacteriological Techniques↗

Down's syndrome: cost, quality and value of life.

Routine prenatal screening is based on the assumption that it is reasonable for prospective parents to choose to prevent a life with Down's syndrome. This paper questions whether Down's syndrome necessarily involves the costs, limitations and suffering which are assumed in the prenatal literature, and examines the lack of evidence about the value and quality of life with Down's syndrome. Tensions between the aims of prenatal screening policies to support women's personal choices, prevent distress, and reduce the suffering and costs of disability, versus the inadvertent effects of screening which can undermine these aims, are considered. Strengths and weaknesses in medically and socially based models of research about disability, and their validity and reliability are reviewed. From exploratory qualitative research with 40 adults who have congenital conditions which are tested for prenatally, interviews with five adults with Down's syndrome are reported. Interviewees discuss their relationships, education and employment, leisure interests, hopes, aspects of themselves and of society they would like to change, and their views on prenatal screening. They show how some people with Down's syndrome live creative, rewarding and fairly independent lives, and are not inevitably non-contributing dependents. Like the other 35 interviewees, they illustrate the importance of social supports, and their problems with excluding attitudes and barriers. Much more social research with people who have congenital conditions is required, if prenatal screening policies and counselling are to be evidence based.

Abortion, Eugenic↗

The comparative pharmacokinetics of H1-receptor antagonists.

H1-receptor antagonists appear to be absorbed rapidly after oral administration, with peak serum concentrations being reached one to three hours after a dose. For most of these drugs, the absolute bioavailability is unknown because no intravenous formulations are available for comparative purposes. The serum elimination half-life values of these agents are variable: a few hours for terfenadine and triprolidine; about 9 hours for cetirizine, azatadine, and loratadine; from 20 to 25 hours for hydroxyzine, chlorpheniramine, and brompheniramine; and from 5 to 14 days for astemizole. Few pharmacokinetic studies of H1-receptor antagonists in children have been reported. However, it is known that chlorpheniramine, hydroxyzine, cetirizine, and terfenadine have shorter elimination half-life values in children than in adults. Regardless of the age of patients, for most of the H1-receptor antagonists the apparent volumes of distribution and total body clearances appear to be large (3.4 to 18.5 L/kg and 4.4 to 32.1 mL/min/kg, respectively). Cetirizine is an exception, with values of 0.8 L/kg and 0.5 mL/min/kg. Urinary excretion of unchanged antihistamine is higher after cetirizine (60% of dose) than any other H1 blocker. For H1-receptor antagonists with long half-life values, steady state may not be reached for several days (chlorpheniramine and brompheniramine) or several weeks (astemizole), and significant accumulation of drug occurs if the dosing interval is more frequent than every half-life. There is no evidence for the introduction of metabolism of H1-receptor antagonists, even after months of treatment.

Adult↗

A microcomputer program for individualizing factor VIII dosage in hemophilia patients undergoing major surgery.

A pharmacokinetic program that allows individualization of Factor VIII dosage regiments in hemophilia patients undergoing major surgery is described. The program, which is designed for the IBM PC microcomputer and compatible machines, is based upon the one-compartment open model with instantaneous input. In the framework of such a pharmacokinetic model, it is assumed that the elimination of Factor VIII is faster during the early post-operative period and that it decreases progressively over the following days. Since Factor VIII half-life is dependent on the time elapsed since the operation (short half-life values during the early post-operative period, longer half-life values thereafter), the pharmacokinetic model is a nonlinear one. A first-order 'variation' rate constant is used to describe the prolongation of Factor VIII half-life from the initial value immediately after surgery to the final value achieved several days later. Individualized estimation of the patient's kinetic parameters (initial half-life, 'variation' rate constant and volume of distribution) is performed through the Bayesian method. Therefore, for such estimation the program exploits the Factor VIII plasma levels measured in the individual patient as well as the population pharmacokinetic data of Factor VIII. After estimating the individual's Bayesian parameters, the program predicts the dosage regimen that will elicit the desired time-course of Factor VIII plasma levels. If requested, the program is able to calculate the least-squares estimates for the parameters of the pharmacokinetic model and dosage prediction can also be made on the basis of such estimates. The least-squares estimates are useful for calculating population pharmacokinetic parameters according to the Standard Two-Stage method. Some examples of clinical use of the program are presented.

Computers↗

The value of life.

Explore the source record for details and available documents.

Abortion, Induced↗

Influence of sialic acid groups on the retention of glycosphingolipids in blood plasma.

The removal of several glycosphingolipids from the circulation and their disposal in different tissue and fluid compartments was studied in adult rats. 3H-labeled dihydro analogs of several glycosphingolipids were injected intravenously and radioactivity was measured in arterial blood samples at subsequent time intervals, to obtain half life values for the labeled compound in the plasma. Half life values of less than 1 min were obtained for neutral glycosphingolipids whereas the half lives of labeled gangliosides were much longer and ranged from 3.8 to 21 h. The prompt removal of labeled neutral glycosphingolipids but not of the gangliosides indicates that sialic acid groups play a significant role in the retention of glycosphingolipids in the circulation. The results suggest that neutral glycosphingolipids are rapidly exchanged with their counterparts in a large extraplasma pool and that a major portion of this exchange could occur between plasma and liver. The detection of only a minute fraction of the injected glycosphingolipids in the cerebrospinal fluid indicates that a blood-cerebrospinal fluid barrier exists for these compounds in the rat.

Animals↗

Ultrasound measurement of quadriceps muscle in the first year of life. Normal values and application to spinal muscular atrophy.

Using real-time ultrasound imaging normal values were obtained for quadriceps muscle thickness and subcutaneous tissue depth in the first year of life from 120 normal infants. These values were corrected for weight and height by introduction of a "correcting factor". In addition, a "modified muscle index" was calculated by multiplying the ratio of muscle to subcutaneous tissue thickness with the correcting factor and showed a steady increase from birth (mean 2.1) to the end of the first year (mean 4.8). The study of 12 patients with spinal muscular atrophy type I (SMA I) revealed that 9 out of 12 SMA I patients failed to reach the 3rd percentile for the muscle to subcutaneous tissue ratio and 10 out of 12 were well below the 3rd percentile for the modified muscle index due to their muscle atrophy. Only the two youngest SMA I patients aged 4 and 6 weeks reached values on the 3rd percentile. In contrast, 10 patients with myopathy and one patient with holoprosencephaly showed values within the normal percentiles even in the presence of severe clinical muscle weakness and signs of atrophy on muscle histology. In the differential diagnosis of early onset myopathy, atrophy of the quadriceps muscle during the first months of life in the absence of markedly increased echodensity seems to be a pathognomonic finding for SMA.

Body Weight↗

Pharmacokinetic study of 5-fluorouracil in a novel dialysate solution: a long-term intraperitoneal treatment approach for advanced colorectal carcinoma.

Five patients with advanced colorectal and gastric carcinoma with peritoneal deposits were treated by continuous weekdays intraperitoneal (i.p.) instillation of 5-fluorouracil (5-FU) 200 mg m-2 day-1 in a novel dialysate solution that ensures maximal exposure of peritoneal areas liable to bear tumours for 24 h. A solution of icodextrin, a glucose polymer, in a 21 twin-bag delivery system allowed a single daily exchange and demonstrated the feasibility of long-term continuous ambulatory treatment with up to 17.4 g of 5-FU, delivered intraperitoneally, in this initial study. During the entire study, there were 235 fluid exchanges or 470 connections and disconnections and no bacterial peritonitis or exit site infection were observed. There was no treatment-associated toxicity worse than WHO grade 2. Drug concentrations in both peritoneal and plasma compartments followed a first-order model with similar half-life value of 1.3 h. 5-FU pharmacokinetic parameters (half-life values, total body clearance, peritoneal clearance and pharmacological advantage of the i.p. route) with this novel icodextrin carrier solution were similar to those obtained in other referenced pharmacokinetic studies with other carrier solutions (dextrose dialysate and lactated Ringer's solutions). This confirms that icodextrin solution is physiologically neutral, drug compatible and allows adequate dwell times with constant fluid balance for long-term continuous intraperitoneal chemotherapy. The pharmacokinetic parameters from this study will be used to design a loading dose infusion schedule in an attempt to maintain steady-state i.p. 5-FU levels in a new multicentre phase I trial.

Colorectal Neoplasms↗

Clearance of intravitreal 3H-fluorouracil.

The clearance of intravitreally administered 5-fluorouracil (5-FU) was studied under five experimental conditions. The same nontoxic dose resulted in similar initial intravitreal concentrations and cleared rapidly from all eyes (approximately 90% clearance within eight hours). Half-life values ranged from 46 to 168 minutes. The longest half-life occurred in aphakic-vitrectomized eyes in which hyaluronic acid (Healon) was substituted for vitreous (168 minutes). A similar half-life was found in normal eyes (150 minutes). The shortest half-life occurred in aphakic-vitrectomized eyes postoperatively (46 minutes). Intermediate half-life values occurred in vitrectomized but phakic eyes postoperatively (67 minutes) and in aphakic-vitrectomized "quiet" eyes (at least two weeks postoperatively) (82 minutes).

Animals↗

The cost-effectiveness of lifesaving interventions in Sweden.

In this article, we discuss under what conditions an estimated cost per statistical life saved can be interpreted as an implied lifevalue. Furthermore, we state optimality conditions with respect to variation in implied lifevalues. The cost-effectiveness, together with references, are presented for 165 lifesaving interventions in Sweden. The cost-effectiveness of interventions has been found in publicly available analyses, or in some cases been calculated by us. Several of these interventions produce net savings for society. The most expensive interventions cost several hundred million SEK, or more, per life saved. To improve the comparability of the interventions, certain criteria have been used to standardize the estimates. Still, dissimilarities in the calculation of implied life values remain and the quality of the original data is in some cases uncertain. Despite this and the fact that the interventions are not a representative sample, it is nevertheless possible to conclude that implied life values vary greatly both within and between different sectors of the Swedish society, much in the same manner as in current U.S. analyses.

Accident Prevention↗

A CLINICAL STUDY OF ISONIAZID INACTIVATION.

The rate of inactivation of isoniazid (INH) in a host organism varies widely, probably because of genetic factors. A simple chemical test was used to determine INH levels in 24 tuberculous patients three and six hours after oral administration of the drug. Results are expressed in terms of half-life values of free INH in the body. Seven of the 24 patients inactivated INH rapidly (half-life average: 64 minutes); the remaining 17 metabolized INH at a slower rate (half-life average: 186 minutes). The range of individual half-life values was 30 to 305 minutes. A provisional half-life limit of 110 minutes was used to define "fast inactivators"; 110-160 minutes, "moderate inactivators"; and over 160 minutes, "slow inactivators". Although INH inactivation may not be directly related to therapeutic failure, the security margin of the treatment may be diminished in those patients who inactivate INH rapidly.

Administration, Oral↗

Metabolism and disposition of buspirone.

The metabolism and disposition of buspirone have been studied in the rat, the monkey, and in more than 150 human subjects. Buspirone is well absorbed, but is subject to first-pass metabolism. The mean systemic availability is approximately 4 percent. Buspirone is eliminated primarily by oxidative metabolism, which produces several hydroxylated metabolites, including 5-hydroxy-buspirone and 1-pyrimidinylpiperazine. The latter metabolite is from 1 to 20 percent as potent as buspirone in a variety of pharmacologic tests; 5-hydroxybuspirone is essentially inactive. In humans, the systemic exposure to buspirone increases linearly in relation to the oral dose. Food increases the bioavailability of buspirone by decreasing first-pass metabolism; absorption is not markedly altered. The pharmacokinetics of buspirone were not significantly different in men and women or in individuals 21 to 40 years old compared with those over 65 years of age. Half-life values observed in healthy volunteers ranged from two to 33 hours. Mean half-life values observed in healthy volunteers in the 14 studies conducted to date ranged from 2 +/- 1 to 11 +/- 3 hours. The half-life in women tended to be slightly longer than in men, but the difference was not significant. Hepatic cirrhosis resulted in a marked decrease in the clearance of buspirone, which correlated with serum alkaline phosphatase activity. Renal disease produced a modest decrease in buspirone clearance, which could not be correlated with an objective clinical measurement reflecting the severity of renal impairment. Buspirone was not removed by hemodialysis. Buspirone is highly protein bound (more than 95 percent), interacting with both albumin and alpha-acid glycoprotein. However, buspirone did not displace dilantin, propranolol, digoxin, or warfarin from plasma proteins. In rats, buspirone neither inhibited nor induced hepatic mixed-function oxidases. Co-administration of buspirone with amitriptyline or diazepam did not alter the disposition of these agents or their demethylated metabolites.

Absorption↗

Plasma pharmacokinetics of adriamycin and antipyrine and its relation to the therapeutic and toxic effects.

After a simultaneous administration of adriamycin and antipyrine to 19 tumor patients, the plasma kinetics of both drugs, the therapeutic effect and the reaction to white blood cells were determined. Antipyrine was given orally at a dose of 875 mg, whereas adriamycin was administered by means of intravenous infusion for 20 min at 60 mg/m2. This application was repeated in eight patients after three weeks. Nine patients had a normal liver function. In ten patients, slight increases were found in individual liver function parameters. All patients were free from metastases of the liver and had bilirubin levels within the normal range. Antipyrine followed an open one-compartment model, whereas adriamycin followed an open two-compartment model. In the mean, t1/2 el and Cl tot of antipyrine were found to be 16.1 h and 32.9 ml/min, t1/2 beta and Cl tot of adriamycin were 23.1 h and 877 ml/min. For antipyrine and adriamycin, these parameters varied interindividually by the factors 2.8 and 3.1, respectively. No correlations were found between the liver function parameters, and the kinetic elimination parameters and the areas under the curves of both drugs. However, significant positive correlations were found to exist between t1/2 el antipyrine and t1/2 beta adriamycin and between the areas under the curves of the two drugs. A relationship between the AUC adriamycinol/AUC adriamycin ratio (which was 0.52 in the mean) and the antipyrine elimination rate did not exist. As compared to 12 persons with no response or progression, the seven patients with partial or complete response had a significantly higher AUC and a significantly lower Cl tot of adriamycin. As compared to the patients with elimination half-life values of less than 20 h, five patients with antipyrine elimination half-life values of more than 20 h had a significantly longer adriamycin elimination beta-phase and a stronger depressive effect on the white blood cells. The results obtained suggest that the antipyrine kinetics in patients with normal or slightly impaired liver function is a useful parameter for an assessment of the depression of white blood cells and the dose adjustment for adriamycin.

Administration, Oral↗