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Biomedical subjects

W A Watson

Publications and source records attributed to W A Watson.

At least 91 records · Page 5Linked to original sources
PubMed1988

The increase in urinary alanine aminopeptidase excretion associated with enflurane anesthesia is increased further by aminoglycosides.

Urinary excretion of alanine aminopeptidase (AAP) is an extremely sensitive indicator of drug-induced renal tubular damage. The urinary excretion of AAP was determined in patients after enflurane anesthesia with or without concurrent aminoglycoside administration to determine if enflurane enhances the nephrotoxic potential of aminoglycosides. Twenty-two patients with normal renal function were studied. Ten received enflurane alone, eight received enflurane plus gentamicin or tobramycin, and four patients who underwent nitrous oxide and narcotic anesthesia were the control group. Preoperative values ranged from 1010 to 2461 microU/24 hour. Urinary AAP excretion increased significantly in both enflurane groups 2 days postoperatively (P less than 0.025). Patients who received both enflurane and aminoglycosides had significantly greater urinary AAP excretion on postoperative day 2 than did patients given enflurane alone: 21,342 +/- 4074 microU/24 hour and 6336 +/- 1496 microU/24 hour, respectively (mean +/- SEM, P less than 0.005). There was no change in AAP excretion in the control group compared to baseline; on day 3 AAP was 1412 +/- 710 microU/24 hour. No changes in blood urea nitrogen or serum creatinine levels were observed. These data suggest that enflurane increases the renal tubular effects of aminoglycosides, possibly increasing the risk of aminoglycoside renal toxicity.

Adult↗
PubMed1987

Repeated oral doses of activated charcoal and the clearance of tobramycin, a non-absorbable drug.

Factors which determine the ability of activated charcoal to increase systemic drug clearance include adsorption characteristics, the extent of back diffusion, and biliary excretion into the gut. Orally absorbed drugs diffuse back into the gut, but it is not known whether non-absorbed agents also diffuse back. Tobramycin was studied with a highly activated charcoal to determine whether this occurs. Five volunteers received a single IV dose of tobramycin on two occasions. Using a randomized, crossover design, subjects received 10 g of activated charcoal (as SuperCharR suspension) 2 hr prior, and at 0, 2, 6, and 8 hr after tobramycin administration during one of the study days. In vitro, tobramycin adsorbed to charcoal at pH 5.6, but not at pH 2.6. A 20:1 charcoal:tobramycin ratio resulted in 34.9% of tobramycin adsorbed to activated charcoal. Blood (0-12 hr) and urine (0-24 hr) were collected and tobramycin concentrations determined. Urinary tobramycin recovery, renal and total drug clearance, half-life, and volume of distribution were calculated. There were no differences in these parameters between the two groups. We conclude that activated charcoal has no effect on tobramycin distribution or elimination in normal volunteers, and that back diffusion does not occur with this drug.

Administration, Oral↗
PubMed1987

Factors influencing the clinical efficacy of activated charcoal.

The use of activated charcoal as part of the treatment of intoxicated patients has increased dramatically over the last ten years. Activated charcoal is currently suggested as therapy to prevent the absorption of orally ingested compounds, and is gaining popularity as a method of increasing systemic drug clearance. This review presents variables that should be considered when activated charcoal is used in the treatment of intoxicated patients. Variables that may alter the efficacy of charcoal therapy include the preparation and dose of charcoal used, the intoxicants involved, stomach contents, the gastrointestinal pH, concurrently administered materials, and time from toxin ingestion to charcoal administration. As a general guideline, a single, large dose should be administered with a cathartic as soon as possible after oral ingestion to prevent drug absorption. When charcoal is used to enhance systemic drug clearance, the dosage regimen should be individualized, based on the drugs involved and the patient's gastrointestinal tract function, fluid and electrolyte status, and the severity of intoxication.

Charcoal↗
PubMed1986

Gastrointestinal obstruction associated with multiple-dose activated charcoal.

The development of a gastrointestinal obstruction associated with multiple doses of activated charcoal is described. A carbamazepine-intoxicated patient received 240 g of activated charcoal and a total of 600 mL magnesium citrate with the development of an ileus and a small-bowel obstruction. The patient also had episodes of emesis associated with charcoal administration. This case suggests that the use of multiple doses of activated charcoal may be associated with gastrointestinal obstruction, a previously unreported adverse effect. Further evaluation of the incidence of adverse effects associated with activated charcoal is needed to determine optimal therapeutic regimens.

Adult↗
PubMed1986

Practical value of a new serum digitoxin assay.

The purpose of this study was to evaluate a new fluorescence polarization immunoassay, TDx, for digitoxin by comparing the results of this assay with those of a radioimmunoassay (RIA). Thirty-three serum samples were obtained from 15 patients during, and for 4 weeks after, a 4-week course of digitoxin therapy. Each sample was separated by centrifugation, coded, and frozen until analysis. At the time of analysis, each sample was divided and analyzed simultaneously by TDx and RIA. Nine samples yielded results less than 2 ng/ml (limit of assay sensitivity) by one or both methods and were excluded from further data analysis. Linear regression analysis of the results of the remaining 24 paired samples (x = TDx, y = RIA) revealed a strong correlation coefficient of r2 = 0.95, slope = 0.95, and a y intercept of -0.99 (y = -0.99 + 0.95x). Additionally, the TDx results were lower than the RIA values in only five of 33 paired samples; and these occurred in four patients who had a significantly lower mean estimated creatinine clearance than that of the other 11 patients (39.0 +/- 9.1 ml/min/1.73 m2 vs. 63.3 +/- 11.8 ml/min/1.73 m2, p less than 0.01). The TDx system is a comparable alternative to the RIA method, but differences in specificity and sensitivity may exist and should be evaluated more thoroughly.

Aged↗
PubMed1986

Blood pentobarbital concentrations during thiopental therapy.

The desulfuration of thiopental to pentobarbital has previously been shown to be a relatively minor pathway of thiopental metabolism. In two cases, we observed significant conversion, resulting in blood pentobarbital concentrations up to 50 percent of total blood barbiturate (thiopental and pentobarbital) concentrations. Both patients received continuous infusions of thiopental and had present a condition (hypothermia) or drug (cimetidine) known to inhibit hepatic microsomal enzyme activity. It is suggested that inhibition of hepatic microsomal enzyme activity may prevent thiopental's metabolism to its major metabolite, a carboxylic acid analogue, and increase the amount of thiopental desulfurated to pentobarbital. Inhibition of hepatic microsomal metabolism also decreases the metabolism of pentobarbital. Until further elucidation of the causes of altered thiopental metabolism is available to identify patients more likely to have elevated concentrations of pentobarbital, monitoring of blood drug concentrations in patients receiving thiopental should include determination of both thiopental and pentobarbital concentrations.

Adult↗
PubMed1985

Spinal cord and cerebral blood flow responses to subarachnoid injection of local anesthetics with and without epinephrine.

Subarachnoid anesthesia with lidocaine, mepivacaine, or tetracaine with and without added epinephrine (1:100 000) produced no demonstrable changes in average cerebral (CBF) or segmental spinal cord blood flow (SCBF) in 38 cats anesthetized with pentobarbital. Blood flow was measured by the injection of radioactive microspheres. Seven groups of cats received either lidocaine 15 mg, lidocaine 15 mg with epinephrine, mepivacaine 10 mg, mepivacaine 10 mg with epinephrine, tetracaine 5 mg, tetracaine 5 mg with epinephrine, or saline with epinephrine 1:100 000. Mean arterial pressure (MAP) decreased significantly (P less than 0.05) in Groups I-VI. Added epinephrine had no effect on the decrease in MAP. Amplitude of the somatosensory cortical evoked response decreased significantly in Groups I-VI, but did not change from control in Group VII. No significant change in CBF or SCBF was demonstrated in any group at any time. Plasma lidocaine and mepivacaine levels were significantly less at 5 min after subarachnoid injection in the groups receiving epinephrine compared to those not receiving epinephrine (P less than 0.05). The data appear to support the hypothesis of a vasoconstrictive reduction in systemic absorption of intrathecal local anesthetics, but suggest that significant segmental spinal cord ischemia does not occur. Maintenance of total flow in the face of a decrease in MAP suggests that autoregulation in brain and spinal cord may be maintained. Changes in regional SCBF or CBF may have been present but were not examined in this study. Further studies of brain and spinal cord blood flow dynamics, regional flow changes, and regulation of flow after intrathecal agents are necessary.

Anesthesia, Spinal↗
PubMed1984

Phenotypic and genotypic characterization of monoclonal anti-digoxin antibodies.

Eleven hybridoma cell lines secreting monoclonal anti-digoxin antibody have been produced. They are primarily gamma heavy chain and kappa light chain molecules. Affinity constants for digoxin range from 2 X 10(6) to 3.5 X 10(8) liters/mole. Fine specificity analysis using a series of digoxin congeners demonstrates that an unsaturated lactone ring attached to the aglycone at the C-17 position is necessary for hapten recognition. The impact of other changes in digoxin's structure on antibody binding were also studied. DNA hybridization analysis demonstrates that there are at least three different variable region gene arrangements used to produce the heavy chains of the different hybridoma antibodies. Correlations between antigen binding characteristics and antibody V-gene arrangements are demonstrable.

Animals↗
PubMed1984

Cimetidine kinetics during resuscitation from burn shock.

Severely burned patients suffer from rapidly changing metabolic and hemodynamic abnormalities that could alter drug kinetics. The kinetics of cimetidine, commonly used in the prophylaxis of acute stress erosions, were studied during fluid resuscitation of 11 patients with mean burn sizes of 45% total body surface area. Six patients were studied after the completion of fluid resuscitation. Total clearance, steady-state volume of distribution, and cimetidine t1/2 did not change between the early period after burn and after fluid resuscitation, but before the completion of fluid resuscitation patients had lower renal and greater nonrenal cimetidine clearance than after resuscitation. The increase in nonrenal cimetidine clearance resulted in decreased urinary recovery of unchanged drug, 50.7 +/- 14% during fluid resuscitation and 81.0% +/- 6% after resuscitation.

Adult↗
PubMed1983

The volume of a swallow: correlation of deglutition with patient and container parameters.

The study purpose was to evaluate the relationships between average volume of a swallow (AVS) and age, height, weight, sex, and container-opening diameter (COD) to confirm and expand the work of Jones and Work. Forty-five males and 50 females between two and 18 years of age were studied. Each subject drank five swallows from each of four containers. AVS for each subject under each condition was calculated and the joint relationship with the independent variables analyzed by multiple regression. Age, height, and weight were highly intercorrelated, and each had similar correlations with AVS. COD was important; between 24 and 90 months of age, swallows from the 6.5 cm COD had a three- or four-fold larger AVS than swallows from the 1.5 cm COD. Sex differences in AVS were noted in subjects over seven years of age. These findings suggest that determination of the child's age and number of swallows ingested may be useful in estimating the fluid volume ingested and the potential toxicity of an exposure.

Adolescent↗