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Biomedical subjects

R P Lewis

Publications and source records attributed to R P Lewis.

At least 19 recordsLinked to original sources

Reduced Leydig cell volume and function in adult rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin without a significant effect on spermatogenesis.

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to alter testicular function. However, its effect on the efficiency of spermatogenesis or on Leydig cell volume has not been determined in adult rats. In two replicas, adult male rats received a single intraperitoneal injection of TCDD at a rate of 0, 12.5, 25.0, or 50.0 micrograms/kg body weight. Rats were sacrificed 4 weeks after treatment. The cytosolic Ah receptor in the testis was estimated at 10.3 +/- 1.2 fmol/mg protein in these adult rats. The presence of the Ah receptor at this concentration in the testis reveals that the testis is a possible target organ for TCDD-induced responses. Left testes were homogenized and testicular spermatids were counted by phase contrast cytometry to determine daily sperm production. Right testes were vascularly perfused with glutaraldehyde, embedded in Epon 812, sectioned at 0.5 micron, stained with toluidine blue and evaluated by stereology for germ cells or Leydig cells. Body weight was reduced (P < 0.01) in a dose-dependent fashion. Testicular weight and daily sperm production per testis were not significantly reduced by TCDD. Androgen receptor concentrations in the testis and prostate were not affected. Weights of two androgen-sensitive organs (seminal vesicles and epididymis) were reduced (P < 0.01) in a dose-dependent fashion and serum concentrations of testosterone were reduced in a dose-dependent fashion in Replica 2. Due to low numbers of animals in Replica 1, the reduced Leydig cell volume was not significant after TCDD treatment; however, in Replica 2 there was a dose-dependent reduction (P < 0.01) in volume per testis of Leydig cell cytoplasm, nuclei, or total Leydig cell volume. Production of testosterone was sufficient to maintain spermatogenesis quantitatively; however, TCDD caused a dose-dependent reduction in Leydig cell function and Leydig cell volume per testis. This study showed for the first time that TCDD-induced androgen deficiency of male rats may be explained by the loss of total volume of Leydig cell cytoplasm. This study also further illustrates the reserve capacity of Leydig cell function to maintain spermatogenesis when the volume of these cells is significantly reduced.

Animals

Clinical use of serum digoxin concentrations.

The development of the radioimmunoassay for digoxin by Smith and coworkers in 1969 was a landmark in digitalis therapy. Since then, the complex pharmacokinetics of digoxin have been defined. As a result, the incidence of digitalis toxicity has markedly decreased. To use the digoxin assay properly, however, the relation of this pharmacokinetic parameter to digoxin pharmacodynamics must be known and the limitations of the assay itself understood. Systolic time intervals (STI) are uniquely useful to quantitate the inotropic effect of digitalis preparations. This technique can demonstrate the onset and magnitude of the inotropic effect for both oral and intravenous digitalis administration. By defining the mathematical relation between STI and simultaneous serum digoxin concentrations following intravenous administration of 1 mg digoxin, computer simulations can be made of the effect of dosing changes on blood and tissue concentrations. The serum digoxin assay has technical problems relating to quality control, interference by metabolites, and cross-reactions with endogenous digitalis-like substances. Further, a standard time for measurement following dosing has not been established. Physical activity can significantly after the serum digoxin concentrations by increasing skeletal muscle binding. Numerous drugs can interfere with digoxin absorption or elimination. Using the serum digoxin assay is the only way to assess these interactions. Computer surveillance (ideally with physician or pharmacist interaction) has been used to monitor digitalis but has not yet gained widespread acceptance. This is clearly a method in need of further testing.

Digoxin

Syncope.

Syncope is a clinical entity of diverse cause. The historical features surrounding the syncopal event and the presence or absence of heart disease are the most important features in establishing the cause for syncope. Passive head-up tilt study provides a means of identifying many patients with vasodepressor syncope. Electrophysiologic study is important in the elucidation of syncope in patients who have syncope undefined after noninvasive evaluation. With proper use of the modalities available, few patients will have an undefined cause for syncope.

Cardiac Pacing, Artificial

Pethidine as a spinal anaesthetic agent--a comparison with plain bupivacaine in patients undergoing transurethral resection of the prostate.

This study compares the anaesthetic effects of intrathecal pethidine or bupivacaine in patients undergoing surgery for transurethral resection of the prostate. Patients were randomly allocated to receive 3.5 ml of 0.5% plain bupivacaine or 1 mg kg-1 of 5% pethidine. The onset, extent and duration of sensory and motor blockade were studied. The cardiovascular and respiratory variables and frequency of side-effects were noted, both in the intra-operative period and the first 24 h of the post-operative period. There were no significant differences in intra-operative conditions or post-operative complications. The duration of block was significantly shorter with pethidine but was not associated with a difference in post-operative pain or analgesic requirements; this may have advantages when early post-operative mobility is indicated. We conclude that spinal pethidine is a satisfactory agent for transurethral resection of the prostate.

Aged

Maintenance of anaesthesia with propofol--a comparative study of a stepdown infusion of propofol and a low dose infusion supplemented by incremental doses.

Forty-four patients, ASA Grade I or II, had anaesthesia induced with propofol at 100 mg min-1 followed by a maintenance rate of 6 mg kg-1 h-1 or a stepdown regimen of 10 mg kg-1 h-1 for 10 min, 8 mg kg-1 h-1 for the next 10 min and at 6 mg kg-1 h-1 thereafter. Anaesthesia was maintained with propofol infused using an Ohmeda 9000 pump supplemented by nitrous oxide and oxygen (2:1) in a Bain circuit with spontaneous ventilation. Incremental doses of 20 mg of propofol were given to both groups as clinically indicated to maintain anaesthesia. Both methods provided satisfactory maintenance of anaesthesia but significantly more incremental doses were required in the group receiving the steady rate infusion. However, a lower cumulative dose was required up to 30 min in this group but not by 40 min. A comparable fall in systolic and diastolic blood pressure and heart rate was seen in both groups. There was no difference in the recovery times between the groups and the total dose did not correlate with time to recovery.

Adult

The use of the Penlon Nuffield 200 in a monoplace hyperbaric oxygen chamber. An evaluation of its use and a clinical report in two patients requiring ventilation for carbon monoxide poisoning.

We modified a Penlon Nuffield 200 for use in a monoplace hyperbaric oxygen chamber by feeding back the chamber pressure to the reducing valve of the Nuffield 200. This provides a compensating mechanism, allowing the ventilator to deliver adequate tidal volumes at pressures of up to 3 atmospheres. We report the laboratory testing of the ventilator and our experience of ventilating two patients with carbon monoxide poisoning. Although compensation is not complete the modification is adequate for short-term clinical use in patients in whom the airway is compromised but who need hyperbaric oxygen therapy.

Adult

Paracetamol metabolism after general anaesthesia.

Paracetamol metabolism was compared between nine patients after general anaesthesia and nine healthy volunteers. Each subject received 1.5 g of paracetamol orally, and paracetamol concentrations in venous blood were measured by HPLC at intervals over 12 h. Urine samples collected over 24 h were analysed by HPLC for cysteine, mercapturic acid, sulphate and glucuronide metabolites. There were no significant differences in the area under the concentration-time curve for paracetamol, or plasma half-life. Statistically significant differences were observed in the median percentages of unchanged paracetamol (volunteers 2.9%, patients 2.0%) and mercapturic acid (volunteers 4.5%, patients 6.5%) excreted in 24 h. The percentage of sulphate excreted was significantly lower in the 8-24-h period, although there was no difference over the total 24 h.

Acetaminophen

Effect of different rates of infusion of propofol for induction of anaesthesia in elderly patients.

The effect of changing the rate of infusion of propofol for induction of anaesthesia was studied in 60 elderly patients. Propofol was administered at 300, 600 or 1200 ml h-1 until loss of consciousness (as judged by loss of verbal contact with the patient) had been achieved. The duration of induction was significantly longer (P less than 0.001) with the slower infusion rates (104, 68 and 51 s), but the total dose used was significantly less (P less than 0.001) in these patients (1.2, 1.6 and 2.5 mg kg-1, respectively). The decrease in systolic and diastolic arterial pressure was significantly less in the 300-ml h-1 group at the end of induction and immediately after induction (P less than 0.01). The incidence of apnoea was also significantly less in the slower infusion group.

Aged

Pharmacology of modalities of treatment.

"Diagnosing congestive heart failure and establishing the etiology are necessary first steps. Perhaps more critical, however, are assessing the severity of heart failure, prognosticating, and initiating pharmacotherapy."

Adrenergic beta-Antagonists

Digitalis: a drug that refuses to die.

Use of digitalis declined in the 1970s, especially among younger physicians, but several recent studies have conclusively documented the hemodynamic and symptomatic benefits of digitalis in patients with class III and IV heart failure resulting from left ventricular systolic dysfunction. The S3 gallop is a useful marker for a subset with a highly favorable response. Symptomatic benefit cannot be shown in most patients with class I and II heart disease (e.g., most myocardial infarction patients). When patients are monitored carefully for evidence of toxicity with serum digitalis assays and for factors that may affect drug bioavailability or clearance, digitalis is well tolerated.

Autonomic Nervous System

Extension of the serum digoxin concentration--response relationship to patient management.

The purposes of this investigation were to demonstrate how computer simulations may be employed to extrapolate data obtained from a single intravenous digoxin dose to multiple oral dosing patterns and how these simulations may apply to clinical situations. The intravenous data were obtained from a previous study of the pharmacokinetics of serum digoxin and its inotropic response (derived from systolic intervals) in 12 normal male volunteers. The simulations were applied to various clinical situations including variations in oral dosing, alternate loading doses, no loading versus loading dose, and intravenous versus oral dosing. A nonlinear relationship was found between response and the post-distribution serum digoxin concentration in the therapeutic range. Thus, the increase in inotropic response is less than proportional to the increase in digoxin concentration in serum. This nonlinear relationship has several important clinical implications for loading and maintenance dosing protocols. Such concepts may be important relative to more rational clinical use of digoxin and to decreasing digoxin toxicity.

Computer Simulation

Erythromycin for anaerobic pleuropulmonary and soft-tissue infections.

Erythromycin has been reported to be active in vitro against most anaerobic bacteria. We found it effective in treating 14 of 17 patients with mild to moderately severe anaerobic or mixed aerobic/anaerobic pleuropulmonary of soft-tissue infections when adjunctive measures (eg, drainage, débridement, and the use of additional antibiotics to treat important aerobic pathogens) were employed. Erythromycin offers a reasonable therapeutic alternative to penicillin in the treatment of a penicillin-allergic patient who has a mild or moderately severe anaerobic or mixed aerobic/anaerobic infection not involving Bacteroides fragilis or fusobacteria.

Aerobiosis

Effectiveness of advanced paramedics in a mobile coronary care system.

The mobilized coronary care system in Columbus, Ohio, began with operation of a single vehicle with a physician in attendance. Currently, advanced emergency medical technician-paramedics work without direct physician supervision. When both experiences are compared, the results indicate that advanced emergency medical technician-paramedics working independently perform as well as physician counterparts.

Allied Health Personnel

Beneficial effect of continuation of propranolol through coronary bypass surgery.

The safety and beneficial effect of continuation of propranolol (Pr) through coronary bypass surgery (CBS) was studied in two groups of patients. In the control group (50 patients) Pr was discontinued 24 h before CBS without reinstitution afterwards. In the propranolol group the drug was maintained up to 4 to 10 h before surgery and was restarted within 24 h afterwards. The incidence of subendocardial myocardial infarction was significantly lower in the Pr group (1 out of 30 vs 10 out of 50, p less than 0.05) while the incidence of transmural infarction was the same in both groups (3 out of 30, 10%, vs 5 out of 50, 10%). The incidence of supraventricular tachycardias during the first three postoperative days was significantly lower in the propranolol group compared to control (5% vs 30%, p less than 0.01). The 24 h urinary epinephrine and norepinephrine excretion was significantly greater than normal the day before surgery (136 +/- 12 vs 39 +/- 4 micrograms/24 h, p less than 0.01), and was still high two weeks after surgery (115.1 +/- 14 micrograms/24 h). There were no complications related to propranolol. The left ventricular function as measured from the systolic time intervals was the same pre- and postoperatively in both groups. The results of this study show that administration of propranolol up to 4 h before coronary bypass and reinstitution immediately afterwards is safe and beneficial.

Adult