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Biomedical subjects

M Stafford

Publications and source records attributed to M Stafford.

11 recordsLinked to original sources

Human T lymphotropic virus type I-associated myelopathy. A report of 10 patients born in the United States.

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) (tropical spastic paraparesis/HAM) has rarely been reported in the United States. We present 10 well-documented cases with positive Western immunoblot test results and polymerase chain reactions for HTLV-I. The clinical and laboratory features of these American-born patients resemble those previously reported series of tropical spastic paraparesis and HAM from the Caribbean and Japan, but important differences were observed. In our study there were equal numbers of whites and blacks and of men and women. Age at onset was younger than that reported from the Caribbean and Japan. Rate of progression to paraparesis varied but was more rapid than previously reported. Half were transfusion recipients but six had multiple sexual partners, with one regularly interacting with prostitutes and reporting a history of drug abuse. Although more rapid progression was seen in the transfusion recipients, this did not explain the earlier age of onset in this group of patients. The HTLV-I, and the associated myelopathy, are endemic in Florida, suggesting that immigration from, and proximity, to the Caribbean basin are contributing risk factors.

Adult

tcPCO2 electrode design, calibration and temperature gradient problems.

Transcutaneous PCO2 electrodes habe been constructed and evaluated on adults and children. Glass pH and silver reference electrodes were used at 44--45 degrees C, with either circulating water and a copper jacket, or with internal electrical heating. The skin surface PCO2 at 44 degrees C is about 1.33 times PaCO2 plus 3 mmHg when measured with electrodes calibrated in gas at 44 degrees C. Three temperature effects combine in this ratio: Heating raises blood PCO2 4.5%/degrees C, skin metabolism adds about 3 mmHg, and the cooling of the electrode active surface by skin increases electrode reading. Response time to step changes of PaCO2 was about 3 min to 63%, of which 1.2 min was sensor delay, the remainder skin CO2 washout. It was found important to use ethylene glycol-water mixtures rather than water for electrolyte to avoid bubble generation and drift. Heat transfer through the pH glass electrode has been increased by enlarging the internal silver electrode to virtually fill the entire glass electrode. Time required for initial vasodilation and stabilization is similar to that of tcPO2 electrodes, and accuracy of determination of PaCO2 appears to be better than +/- mmHg.

Adult

The effect of jejunoileal bypass on the pharmacokinetics of digoxin in man.

Seven subjects who underwent jejunoileal bypass surgery for massive obesity participated in a study to examine the relative bioavailability of digoxin before and one to two months after surgery. They were given a loading dose of 1 mg digoxin in divided oral doses followed by oral maintenance doses of 0.5 mg daily. There were no significant differences in the area under the serum concentration time curve, steady state serum levels or 24 hour steady state excretion of digoxin before and after surgery. We conclude that the bioavailability of digoxin from the Lanoxin tablets employed is not impaired in these patients, although urinary d-xylose and 24 hour fecal fat excretion indicated moderate to severe malabsorption after surgery.

Digoxin

Profiles of volatile metabolities in body fluids.

A method for the analysis of volatile metabolites present in plasma, urine, breast milk and amniotic fluid collected from mother-infant pairs has been developed which requires only 100 mul of plasma, 3 ml of urine, 20 mul of breast milk and 500 mul of amniotic fluid. After extraction with diethyl ether, the volatile compounds were absorbed on glass wool in a special concentration tube and subsequently desorbed and transferred to a 100-m nickel capillary column for analysis by gas chromatography and gas chromatography-mass spectrometry. The separations, carried out by temperature programming, were complete in 90 min.

Alcohols

Elimination of antipyrine and benzo[a]pyrene metabolism in cultured human lymphocytes.

A strong correlation was found in a carefully selected homogenous population (n = 57) between antipyrine plasma half-life and the percent induction of aryl hydrocarbon hydroxylase by 3-methylcholanthrene in mitogen-stimulated lymphocytes from the same individual. The correlation coefficient of r = 0.923 indicates that antipyrine and benzo[a]pyrene share one or several common determinants that are responsible for the observed interindividual variation in the oxidation rates of the two compounds. When a heterogenous population (n = 80) was studied, the above correlation was not found (r = 0.425).

Adult

Digoxin bioavailability: formulations and rates of infusions.

The bioavailability of digoxin (lanoxin) tablets, oral aqueous solution of digoxin, and capsules containing a solution of digoxin was compared with digoxin given intravenously over 1 and 3 hr. The mean peak serum concentration of digoxin after the 1-hr intravenous infusion was 5 ng/ml, after the 3-hr infusion, 3.5 ng/ml, and after the oral solution, 2.0 ng/ml. There was an equivalent bioavailability of the oral solution and reference tablets of digoxin. The digoxin in capsules tended to be better absorbed than the reference tablets. There was 21% more digoxin excreted over 6 days after the 3 hr iv infusion than after the 1 hr iv infusion. This indicates that the calculated bioavailability of an orally administered dose of digoxin may vary with the rapidity of injection of the intravenous standard. It is estimated that an oral tablet of digoxin of 0.5 mg has about the same bioavailability as 0.35 of digoxin given by slow intravenous infusion (or 0.4 mg if calculated against a rapid intravenous injection).

Administration, Oral

The use of gas chromatographic-mass spectrometric-computer systems in pharmacokinetic studies.

Pharmacokinetic studies involving plasma, urine, breast milk, saliva and liver homogenates have been carried out by selective ion detection with a gas chromatographic-mass spectrometric-computer system operated in the chemical ionization mode. Stable isotope labeled drugs were used as internal standards for quantification. The half-lives, the concentration at zero time, the slope (regression coefficient), the maximum velocity of the reaction and the apparent Michaelis constant of the reaction were determined by regression analysis, and also by graphic means.

Chromatography, Gas

Atypical nuclear structures in the buccal mucosal cells of the rhesus monkey.

During evaluation of cytologic buccal samples obtained from nine female rhesus monkeys over a period corresponding to three menstrual cycles, unusual nuclear changes were observed in the exfoliated cells. The changes ranged from small nuclear protrusions to bi-lobed and multi-lobed structures.

Animals

Correlation of aryl hydrocarbon hydroxylase activity of human lymphocyte cultures and plasma elimination rates for antipyrine and phenylbutazone.

A high correlation was observed between the aryl hydrocarbon hydroxylase activities in short-term lymphocyte cultures of 23 individuals and their plasma half-lives of antipyrine and phenylbutazone. Individuals with low inducibility of aryl hydrocarbon hydroxylase activities had very long plasma half-lives of antipyrine and phenylbutazone, whereas subjects with high inducibility of aryl hydrocarbon hydroxylase activites had relatively short plasma half-lives. Individuals with intermediate aryl hydrocarbon hydroxylase activities displayed intermediate half-lives for both drugs. The observed correlation indicates determinants which are common to the elimination of antipyrine or phenylbutazone, and aryl hydrocarbon hydroxylase metabolism of hydrocarbons. The differences in rates of drug elimination are probably due to genetic differences and may have pharmacological and therapeutic significance.

Adult