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Biomedical subjects

R L Stout

Publications and source records attributed to R L Stout.

At least 55 records · Page 3Linked to original sources
PubMed1987

The novel therapeutic implications of azlocillin's dose-dependent pharmacokinetics: contributing physiologic mechanisms and a prospective, cross-over designed trial.

Azlocillin is an important acylureido penicillin antibiotic for the management of complex gram-negative infections particularly those caused by Pseudomonas species. The current studies demonstrate that it manifests dose-dependent pharmacokinetics during the usual regimens of clinical dosing, that enterohepatic recirculation does not occur and that renal tubular secretion (maximum renal tubular secretory capacity 300 +/- 30 micrograms/min) and hepatic metabolism appear to be the dominant contributors to the dose-dependent nature of azlocillin. The possible therapeutic implications of azlocillin's dose dependency were evaluated by undertaking a six-day randomized, prospective, cross-over design study to evaluate the pharmacokinetic disposition of the drug during a 3-g q4h (typically used in adults) regimen versus a 5-g q8h regimen. By using the area under the serum-time concentration curve (AUC) as the major comparative parameter for these two regimens, the results demonstrate that both regimens provide approximately equal quantitative amounts of the drug systemically as a result of azlocillin's dose dependency. The AUC values, although not therapeutic end points, nonetheless correlate well with clinical response to antibiotic therapy. The 5-g q8h regimen was well tolerated. It is less disruptive for patients, requires half the number of intravenous administrations, 17% less drug, and is more cost effective than the 3-g q4h regimen.

Adult↗
PubMed1987

Calcium channel blockade in experimental aminoglycoside nephrotoxicity.

Calcium channel blocker therapy has proved protective in certain models of ischemic-induced acute renal failure. This effect may be related to the prevention of calcium influx into injured cells or by the vasodilatory effects of verapamil that may result in an improvement in renal blood flow. In the current study, the effect of verapamil treatment on the development of renal insufficiency and renal tissue calcium accumulation following aminoglycoside administration was investigated. The degree of functional damage and cortical tissue calcium accumulation after six or nine days of gentamicin administration (120 mg/kg body weight/day) was not significantly different in rats whose drinking water contained verapamil (10 mg/100 cc) than corresponding values in control animals. The tissue calcium accumulation correlated with the degree of reduction of creatinine clearance and probably reflects the extent of lethal tubular cell injury.

Animals↗
PubMed1987

Predictors of attrition from an outpatient alcoholism treatment program for couples.

Applicants (N = 105, 22 women) to an outpatient alcoholism treatment research program for married couples were categorized into three classifications: (1) treatment refusers (N = 37), (2) treatment dropouts (N = 23) and (3) treated subjects (N = 45). Discriminant analyses were performed to determine the best predictors of eventual category from baseline data. Compared with those who consented to treatment, refusers were found to be younger, have shorter drinking histories and were less likely to have personally initiated contact with the treatment program. Dropouts were less likely than treated subjects to have made their own initial contact with the program, more likely to have depressive symptoms not associated with alcohol use and were not employed full time. Remaining in treatment was most strongly associated with marital factors--assignment of the couple to a marital therapy condition versus a treatment in which the spouse was not fully involved and the spouse's initial satisfaction with the marriage. Results are discussed in terms of the treatment implications for spouse involvement in treatment.

Adult↗
PubMed1987

The influence of renal functional changes on the intrarenal distribution and urinary kinetics of amdinocillin.

The maintenance of effective therapeutic concentrations of antibiotics within the renal parenchyma is an important issue in the management of acute and chronic pyelonephritis. Available clinical data indicate that an important clinical-therapeutic correlation exists between the physiologic state of the kidney and the antibiotic concentrations that can be achieved in the medulla and papilla. Using a healthy canine model, we evaluated the influence of hydration and the state of acid-base balance upon the intrarenal distribution and urinary clearance of the semisynthetic penicillin amdinocillin. Renal physiologic activity significantly modulates the intrarenal distribution pattern of this compound. During the production of maximally acid and concentrated urine, the highest renal parenchyma levels of amdinocillin are achieved. During the latter circumstances the antibiotic undergoes distal tubular nonionic diffusion, which appears to be an important contributing factor to the high medullary and papillary concentrations of the drug. Nonetheless, at all levels of tested renal physiologic activity tissue and urine drug concentrations are adequate for the treatment of sensitive urinary pathogens.

Amdinocillin↗
PubMed1987

Parathyroidectomy increases peripheral vascular responsiveness to exogenous noradrenaline in the uraemic rat.

The effect of surgical parathyroidectomy and/or cyclo-oxygenase inhibition on noradrenaline-induced blood pressure (BP) responses were investigated in a rat model of chronic uraemia. The blood pressure responses to noradrenaline were significantly lower in uraemic rats when compared with the responses of non-uraemic animals. Blood pressure responses of previously parathyroidectomized uraemic rats were significantly greater than sham-operated uraemic rats, as were the responses of uraemic rats pretreated with the cyclo-oxygenase inhibitor, indomethacin. Pretreatment of uraemic rats with both indomethacin and parathyroidectomy improved blood pressure responses to a degree equal to either manoeuvre alone, but did not exhibit an additive effect. These data suggest a role for parathyroid hormone and prostaglandins in the pathogenesis of the diminished noradrenaline responsiveness in uraemia, and suggest a common mechanism.

Animals↗
PubMed1986

Selective inhibition of thromboxane synthesis in glycerol-induced acute renal failure.

It has recently been postulated that thromboxane A2 may participate in the pathogenesis of acute myohemoglobinuric experimental acute renal failure. To investigate this further, the effect of selective inhibition of thromboxane synthesis on the course of glycerol-induced acute renal failure was determined. Despite significant inhibition of thromboxane synthesis by 4-imidazole-yl-acetophenone, the functional and morphologic disturbance induced by glycerol was unaltered. Moreover, pretreatment with 4-imidazole-yl-acetophenone failed to prevent the fall in renal blood flow seen following glycerol administration. These results argue against a major role for thromboxane A2 in the pathogenesis of this form of experimental acute renal failure.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Comparative effectiveness of three types of spouse involvement in outpatient behavioral alcoholism treatment.

Treatment was provided to 53 alcoholics and their spouses in one of three outpatient behavioral treatment conditions: minimal spouse involvement (MSI) (N = 21), alcohol-focused spouse involvement (AFSI) (N = 13) or alcohol-focused spouse involvement plus behavioral marital therapy (ABMT) (N = 19). Subjects were followed for 6 months after treatment. All subjects markedly decreased their drinking and reported increased life satisfaction. ABMT subjects were more compliant than AFSI subjects with conjoint homework assignments, decreased their drinking more quickly during treatment, relapsed more slowly after treatment and maintained marital satisfaction better. ABMT subjects were more likely than MSI subjects to stay in treatment and maintained their marital satisfaction better after treatment. Clinical and theoretical significance of the findings are discussed.

Adaptation, Psychological↗
PubMed1985

Evaluating employee assistance policy in an HMO-based alcoholism project.

One aspect of successful employee assistance program (EAP) implementation is the adoption of a formal, written policy, reflecting company commitment to EAP guidelines and goals. This study of criteria predictive of such policy adoption was conducted at the occupational alcoholism project of a New England health maintenance organization (HMO). Data on nearly 400 organizations contacted by occupational program consultants (OPCs) over a 20-month period were collected by questionnaire and interview. One third of these organizations adopted employee assistance policies and set about establishing formal programs. Stepwise multiple regression is the principal method used to pinpoint the correlates of policy adoption. Two of the most important of these are the attitudes of contact persons within the organization toward alcoholism and employee assistance programs, particularly their admission of alcohol problems within their social networks; and the consultants' persistence and marketing skills. The adopting organizations also had reputations for being progressive, and actively concerned about employee welfare; they tended to be large, their executives autonomous, and their union membership rates high. Inhibiting policy acceptance were fears that a written policy would jeopardize the reputation and image of the organization, and that an employee assistance program would remove internal control of personal procedures. The adequacy of the evaluative data and methods are discussed, and recommendations are offered in the interests of streamlining the efforts of OPCs and of achieving greater penetration of targeted organizations.

Alcoholism↗
PubMed1985

Effectiveness of alcoholism treatment in partial versus inpatient settings: twenty-four month outcomes.

The authors examined the effectiveness of the partial hospital setting, in contrast to the inpatient setting, for the rehabilitation of alcohol abusers and alcoholics. Outcomes after 24 months in five life health areas indicated marked improvement from baseline for the entire follow-up period on almost all measures. There also was a strong relationship between drinking outcomes and outcomes in the other health areas. Although there were few between group differences on the clinical outcome measures, differences which were found favored the partial hospital setting. Furthermore, cost of treatment over two years clearly favored the partial hospital.

Activities of Daily Living↗
PubMed1984

The intrarenal distribution of aztreonam in healthy and diseased kidneys: clinical therapeutic implications.

Using a healthy canine model, we evaluated the influence of renal physiological activity on the stability, intrarenal distribution, and clearance of aztreonam and compared the results with the concentrations of aztreonam that can be achieved in the scarred devitalized renal tissues of patients with end-stage kidney disease. Renal physiological activity significantly modulates the intrarenal distribution of aztreonam. During the production of maximally acid-concentrated urine, urinary aztreonam levels, clearance rates, and inner zone renal tissue concentrations are increased. Aztreonam concentrations in the parenchyma of severely diseased kidneys are significantly reduced in comparison with healthy tissues; nonetheless, the values are similar to concurrent serum drug levels, a result suggesting that treatment may provide adequate coverage for aztreonam-susceptible organisms.

Animals↗
PubMed1983

Pharmacokinetics of azlocillin in normal renal function: single and repetitive dosing studies.

Systemic and urinary pharmacokinetic studies of the disposition of azlocillin were performed in seven male and six female healthy volunteers. Four separate studies identified the kinetics of the drug following a single 2, 3 or 4 g administration and during the repetitive administrations of 3 g of the drug over a five-day period. Peak plasma concentrations were 174 +/- 19 mg/l, 214 +/- 17 mg/l and 286 +/- 11 mg/l in the 2, 3 and 4 g single dose studies respectively. Trough values at 4 h post-dosing were 6 +/- 1 mg/l, 10 +/- 1 mg/l and 26 +/- 3 mg/l respectively. The plasma half-life of azlocillin was approximately 60 min. A dose-dependent phenomenon was observed. This was characterized by a slight but significant progressive increase in the plasma half-life of the drug as increasing amounts of drug were given and as the same amount was given repeatedly. No significant systemic accumulation of azlocillin was noted during the repetitive dosing study. The urinary excretion of the compound was prompt with most of the bioactive drug being eliminated in the first 4-6 h following dosing. The apparent volume of distribution of azlocillin was slightly greater than the extracellular fluid compartment. For the therapy of systemic infections in adults with normal renal function a 4 h or 6 h dosing cycle would be appropriate.

Azlocillin↗
PubMed1983

Azlocillin kinetics during extracorporeal haemodialysis and peritoneal dialysis.

The kinetic disposition of azlocillin in patients with end stage renal failure was evaluated in six individuals maintained on chronic extracorporeal haemodialysis and in six individuals on peritoneal dialysis. In the absence of renal function the plasma half-life of azlocillin was extended from the normal value of approximately 60 min to 235 +/- 30 min. During peritoneal dialysis the plasma half-life was reduced to 148 +/- 15 min and during extracorporeal haemodialysis it was further reduced to 112 +/- 11 min. Azlocillin was readily dialysed during haemodialysis but its removal rate during peritoneal dialysis was substantially less.

Adult↗
PubMed1983

An azlocillin dosing nomogram for renal insufficiency.

We have developed an azlocillin dosing nomogram suitable for use in patients with various degrees of renal functional impairment. A total of 50 kinetic studies undertaken by us and an additional 60 similar kinetic investigations as reported in the literature formed the basis for the construction of our nomogram. This renal failure dosing nomogram gives immediate information to the physician who needs to give azlocillin to a patient with renal failure.

Azlocillin↗
PubMed1982

Union-related correlates of employee referrals to an occupational alcoholism project in a health maintenance organization.

A number of union-related factors, including the degree of unionization and the skill level of the work force, the quality of union-management relations, the extent of union involvement in program development, as well as the provision of supervisory training, have been found to be important in explaining occupational alcoholism program outcome. This study attempted to determine the relationship of such factors to an unusual measure of program outcome, employee referrals to the treatment component of an occupational alcoholism project housed in the counseling department of a health maintenance organization. Multiple-regression techniques were used, with data collected for unionized companies that adopted formal, written employee assistance program (EAP) policies and those that did not. The adoption of an EAP policy seems more important than any other factor in predicting referrals to treatment, In unionized companies without policies, the union-related factors bear no relationship to referrals, while in unionized companies with policies, these variables, particularly the quality of union-management relations, are strong predictors. Supervisory training has only a modest positive effect on referrals. The adoption of an employee assistance policy itself was found to be crucial to program outcome, measured by increased chances of referrals.

Alcoholism↗
PubMed1979

Breath-by-breath variation of FRC: effect on VO2 and VCO2 measured at the mouth.

We examined breath-by-breath (B-B) variations of FRC (delta FRC) and their effect on measured O2 and CO2 gas exchange in 52 2- to 4-min segments of continuous air breathing obtained in 29 patients (age range 6--50 yr). Respiratory frequency ranged from 13 to 43 breaths/min, VE from 6.7 to 22.5 l/min (BTPS), and expired VT from 234 to 1,370 ml (BTPS). Computer analysis was based on the following source data measured at the mouth: inspired (VI) and expired (VE) gas flow, FN2, FO2 and FCO2. The analysis provides B-B evaluation of VI, VE, delta FRC in terms of VN2, and VO2 and VCO2 at the mouth and at the alveolar level, i.e., after correction for delta FRC. Significant B-B variations of FRC were found in all studies. delta FRC ranged from +360 to -360 ml (BTPS). For single respiratory cycles VI - VE is primarily a function of N2 exchange at the mouth (VMN2). VO2 and VCO2, uncorrected for delta FRC, are significantly more dispersed about mean values than the corrected gas uptakes (P less than 0.0005). The data support the view that the assumption of VIN2 = VEN2 is invalid for single respiratory cycles. Determination of breath-by-breath VO2 and VCO2 should therefore, not be based on steady-state gas uptake equations. It requires measurement of both inspired and expired breath volumes and evaluation of N2 gas exchange.

Adolescent↗