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Biomedical subjects

R Forney

Publications and source records attributed to R Forney.

At least 19 recordsLinked to original sources

Treatments for common superficial fungal infections.

Fungal infection of keratinized tissue is caused by any of the dermatophyte species. The topical allylamines and benzylamines have been especially effective in treating these infections because of their in vitro fungicidal activity and short treatment duration. With the development of new oral azoles and allylamine antifungal agents, there has been a renewed interest in treating superficial skin fungal infections. The use of topical and oral antifungal agents in treating cutaneous fungal infections is examined.

Antifungal Agents↗

Using lasers in diabetic wound healing.

Lasers are a treatment choice that appeals to patients. Early research suggests that laser therapy may have a role in hastening wound healing. Attempts have been made to use helium neon, CO2, and KTP lasers in encouraging wound healing in diabetics. We will review the English literature related to laser use in diabetic wound healing and discuss the concept of the use of nondestructive lasers for biostimulation. Further research is needed to assess effectiveness of biostimulation for diabetic wound healing.

Animals↗

Jamaican vomiting sickness in Toledo, Ohio.

The endemic illness of Jamaica known as ackee poisoning is reported for the first time in the United States. The toxic exposure resulted from the consumption of canned ackee. The epidemiology, diagnosis, theoretical mechanism, and possible therapy of this disease are discussed.

Adipates↗

The influence of storage temperature and chemical preservation on the stability of succinylcholine in canine tissue.

Succinylcholine (SCh) has been detected six months postmortem in liver, kidney, and injection site muscle of rats given 10 to 200 mg/kg by intramuscular injection. SCh stability was studied in canine tissue to evaluate three storage temperatures and two chemical preservatives at three time periods after injection. Nine mongrel dogs weighing 17.2 to 28 kg were divided equally into three groups and administered either 0.5, 1.0, or 5.0 mg SCh/kg intravenously into the cephalic vein. Liver, kidney, and gastrocnemius muscle were removed 90 min post-injection and divided into twelve portions. Each portion was treated with embalming fluid, physostigmine, the combination (50/50), or nothing. Chemically treated tissues and nontreated tissues were then stored at either 27, 5, or -20 degrees C for a period of up to forty days. Tissue portions were analyzed using ion-pair extraction, chemical demethylation, and gas chromatography with nitrogen phosphorous detection. Stability of SCh was greatest for samples stored at -20 degrees C and preserved with the combination of embalming fluid plus physostigmine. Kidney concentrations of SCh were significantly higher than those in liver or muscle at all doses. SCh was detected 24 h post-injection in all cases. By 40 days, only trace amounts of SCh, if any, could be detected in samples stored at room temperature with no chemical preservatives.

Animals↗

Correlation of plasma concentration and effects of succinylcholine in dogs.

The study was undertaken to determine the pharmacokinetic values for half-life, volume of distribution, and clearance for succinylcholine (SCh) based on measurements of the drug in plasma. Three intravenous (i.v.) doses (0.5, 1.0, and 5.0 mg/kg) were compared to study the time course of paralysis and recovery and to describe the relationship of plasma concentration (Cp) and the pharmacologic effects of SCh in canines. The physiologic response to the neuromuscular blocking drug was monitored using train-of-four stimulation of the left sciatic nerve and recording the response of the corresponding gastrocnemius muscle. Time courses for paralysis and recovery were monitored, and the results were used to predict the kinetic values for the pharmacologic effects. Blood samples were taken following drug administration for direct pharmacokinetic estimations. SCh determinations were performed using ion-pair extraction, chemical demethylation, and gas chromatography with nitrogen phosphorous detection. Both kinetic analyses showed the beta half-life for SCh to be approximately 5 min for all doses. SCh has a distribution half-life of less than 1 min. There appears to be a threshold Cp below which neuromuscular function returns. Recovery following SCh induced paralysis had a rapid onset, but the duration of paralysis and the rate of recovery were especially prolonged for the 5.0-mg/kg treatment group.

Animals↗

Experience with a computer-based technique for estimating pharmacokinetic constants from limited data.

A computer-based approach for estimating pharmacokinetic data and predicting plasma drug concentrations based on two measurements of plasma drug concentrations was compared with a standard two-point method for estimating aminoglycoside (AG) pharmacokinetic parameters. The computer-based technique was also used to predict a theophylline steady-state nadir from two preceding ones. The computer-based and standard two-point methods provided similar estimates for mean (+/- SD) values of elimination rate constant (lambda) (0.172 +/- 0.103 h-1 and 0.179 +/- 0.010 h-1, respectively) and apparent volume of distribution (V) (22.7 +/- 9.9 L and 23.3 +/- 11.5 L, respectively). The mean (+/- SD) of predicted AG troughs was 1.3 +/- 0.5 mg/L for the standard method and 1.3 +/- 0.6 mg/L for the computer-based method. Neither was significantly different from the actual AG trough mean of 1.3 +/- 0.7 mg/L. Both methods exhibited a slightly negative bias in their predictions of actual AG troughs. When applied to theophylline data from patients or subjects receiving multiple-dose theophylline, the computer-based method effectively predicted trough theophylline concentrations for three formulations of theophylline. Mean prediction errors ranged from 0.1 to 0.5 mg/L, and root mean squared error ranged from 1.1 to 1.2 mg/L. This computer-based technique may be useful in dose individualization since relatively few constraints are placed on the type of data required for its application.

Aminoglycosides↗

Theophylline kinetics: dose dependency and single sample prediction of clearance.

Theophylline clearance was measured at 3 doses (2, 4 and 6 mg/kg) in 10 young, healthy adult subjects. Clearance decreased as the dose of theophylline increased going from 0.064 +/- 0.016 to 0.052 +/- 0.011 1.h-1.kg-1 at the 2 and 6 mg/kg doses, respectively (p less than 0.02). A simplified method for estimating theophylline clearance was tested using single plasma concentrations of theophylline and assuming a constant value (0.5 l/kg) for volume distribution of theophylline. This method gave the best results when samples were drawn at 12 or 24 h after a 2 or 4 mg/kg intravenous dose of theophylline, respectively, and was effectively applied in estimating the quantitative impact of cimetidine administration on theophylline clearance.

Adult↗

Phenytoin as a probe of drug metabolism. Predicting clearance with a salivary sample.

Phenytoin (PHT) was administered in single 300-mg doses to each of 12 healthy, male subjects. Serial blood samples and salivary samples were collected for the next 48 h, and concentrations of plasma total PHT, unbound plasma PHT (plasma ultrafiltrates), and salivary PHT (salivary ultrafiltrates) were measured by immunofluorescence polarization. The following parameters were estimated: CLint/F, CL'int/F, V/F, and total and unbound PHT plasma disappearance half-lives. Estimates of CL'int/F (CL'int/F) were calculated from single 48-hour salivary PHT measurements. Mean (+/- SD) values were 0.026 +/- 0.009 1 . h-1 . kg-1, 0.385 +/- 0.148 1 . h-1 . kg-1, 12.6 +/- 3.5 l/kg (referenced to unbound drug), 28.0 +/- 12.1 h, and 25.9 +/- 13.5 h, respectively. When V/F referenced to unbound PHT was set at 14 l/kg, CL'int/F estimates were good predictors of the actual CL'int/F values demonstrating a mean prediction error of -9.012 1.h-1.kg-1. These data demonstrate that under specified conditions, intrinsic unbound PHT clearance can be estimated from a single PHT measurement in saliva, thereby permitting PHT to be used safely and sampled simply and noninvasively as a probe of hepatic mixed function oxygenase activity in humans.

Adult↗

Hepatitis B vaccine and antipyrine clearance.

The impact of hepatitis B vaccine on hepatic mixed function oxidase activity was studied using antipyrine as a probe. Fifteen health care workers who elected to take the vaccine due to occupational risk were the subjects. Each subject received all three vaccinations over a period of six months. Antipyrine (500 mg) was administered orally prior to the first vaccination, 1 week subsequent to each vaccination, and one month after the final vaccination, and antipyrine clearance, CL/F was estimated from concentrations of antipyrine in saliva collected 24 hr after each antipyrine dose. The mean (+/- SD) pre-vaccination CL/F was 3.65 (+/- 0.75) 1/hr. Post vaccination mean CL/F values deviated by no more than 8.8% and none of the post vaccination values were significantly different from the pre-vaccination mean. It is inappropriate to extrapolate findings concerning one antiviral vaccine and its putative effect on drug metabolism to other antiviral vaccines.

Adult↗

Use of plasma unbound drug concentrations in adjusting phenytoin doses.

The application of a Bayesian feedback algorithm for phenytoin (PHT) dosing adjustments was modified empirically to take advantage of measurements of plasma unbound PHT concentrations in the estimation of Km values. Doses were calculated to achieve steady-state unbound PHT nadirs of 1.2 mg/L with an allowable range of 0.9-1.5 mg/L. The success of this approach was compared with that of a routine strategy encompassing the use of monitored total plasma PHT concentrations and no estimates of kinetic parameters. Allowing up to a double feedback of monitored values, the Bayesian approach was better than the routine procedure in predicting doses that led to PHT concentration within the targeted range (p less than 0.005). The approach to optimizing PHT dosing described herein offers the advantage of rapidly converging on near-optimal therapy for those patients who are already on PHT but whose seizures are not suitably controlled, and may be useful even for patients who exhibit abnormal PHT plasma protein binding, such as those who also must take valproic acid.

Adolescent↗

The effect of erythromycin on the disposition kinetics of warfarin.

Erythromycin is generally regarded as innocuous in regard to adverse interactions with other drugs. Recently, however, its potentiation of theophylline and warfarin has been reported. The present investigation defined more specifically the kinetics of the interaction between erythromycin and warfarin. Warfarin kinetics were evaluated in 12 normal subjects who took a single 1 mg/kg dose of warfarin with and without erythromycin. Erythromycin (250 mg p.o.) every 6 h for 8 days decreased warfarin clearance by 14% (p less than 0.001). Warfarin's apparent volume of distribution was not affected. Further, the effect of erythromycin was greatest among subjects whose control phase warfarin clearance was relatively slow, and least among those whose control phase warfarin clearance was relatively fast. The magnitude of the decrease in warfarin clearance correlated negatively with control warfarin clearance (r = -0.89, p less than 0.005). These data are consistent with the interpretation that erythromycin can potentiate warfarin-induced hypoprothrombinemia by slowing warfarin clearance.

Adult↗

Selectivity of cholestyramine treatment on hepatic mixed function oxidase activity.

The possibility that oral cholestyramine treatment might indirectly increase hepatic drug oxidations was investigated in rats using pentobarbital, antipyrine, zoxazolamine, and aminopyrine as probes of the hepatic mixed function oxidase system and in humans using amobarbital and antipyrine as probes. Cholestyramine pretreatment of rats for 5 days (87.5 mg/kg twice daily by stomach tube) shortened pentobarbital sleep times, decreased antipyrine-induced hypothermia, but did not influence either zoxazolamine paralysis times or the in vitro N-demethylation of aminopyrine. Neither pentobarbital nor antipyrine pharmacokinetics in rats were affected by the cholestyramine pretreatment. Similarly, in two-way crossover studies with human subjects, a 5-day oral cholestyramine pretreatment (4 g 3 times daily) had no demonstrable effect on the pharmacokinetics of single doses of amobarbital (200 mg i.v.) or antipyrine (500 mg per os). After cholestyramine pretreatment, a trend toward diminished CNS depression produced by amobarbital was observed, but the effect was not statistically significant. The results suggest that hepatic mixed function oxidases in rats for which aminopyrine, antipyrine, pentobarbital, and zoxazolamine are substrates and that hepatic mixed function oxidases in humans for which amobarbital and antipyrine are substrates are not significantly affected by cholestyramine pretreatment.

Adult↗

The combined effect of marihuana and dextroamphetamine.

The studies in mice indicated that locomotor activity could be stimulated THC and that this would enhance the effect produced by MAMP. We have previously shown that when 3, 6, or 9 mug/kg THC were administered to young adult males by MJ smoking, a dose-related impairment in standing steadiness (WB) and attentive motor performance (PM) resulted, although DAF and subjective evaluations were insensitive to these treatments. These same testing procedures after d-AMP 5, 10, and 15 mg/70 kg revealed no important performance effect. Systolic blood pressure was elevated with 15 mg/70 kg d-AMP, and subjective detection was positive and dose related. A combination of 25 mug/kg THC delivered by smoking an appropriate MJ cigarette and 10 mg/70 kd d-AMP taken orally produced subjective effects and psychomotor performance decrements not different from those with the MJ alone. The doses used were modest, yet most subjects believed their driving performance, a representative motor and metal skill, would be impaired. This judgment is supported by the laboratory measurements made. It is reasonable that realistically higher doses may not only have adverse psychological and cardiovascular effects but increase an accident potential.

Adult↗