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Biomedical subjects

J E Wallace

Publications and source records attributed to J E Wallace.

At least 19 recordsLinked to original sources

Pharmacokinetics of SCH-39304 in human immunodeficiency virus-infected patients following chronic oral dosing.

The pharmacokinetics of SCH-39304, an investigational, orally active, broad-spectrum antifungal agent, were evaluated in 17 adult, human immunodeficiency virus-positive males. Patients were studied on days 1 and 16 and were divided into the following three treatment groups: (i) patients with culture-proven oropharyngeal candidiasis who were not receiving concurrent zidovudine therapy and who were treated with 50 mg of SCH-39304 daily (n = 6); (ii) patients with culture-proven oropharyngeal candidiasis who were receiving concurrent zidovudine therapy and who were treated with 50 mg of SCH-39304 daily (n = 5); and (iii) patients with or without oropharyngeal candidiasis who were receiving concurrent zidovudine therapy and who were treated with 200 mg of SCH-39304 daily (n = 6). All patients received a single daily dose of the study medication for 16 days. Plasma samples for SCH-39304 concentration measurement were collected for 6 h following the initial dose and for 504 h following the day 16 dose. Urine was collected for 24 h following SCH-39304 administration on days 1 and 16. All samples were assayed for SCH-39304 by gas chromatography. Wide intersubject variations in SCH-39304 plasma concentration-versus-time profiles were observed on each study day. Absorption appeared to be slow, with mean day 1 peak plasma SCH-39304 concentrations of 1.2 micrograms/ml at 2.1 h (50 mg) and 3.9 micrograms/ml at 4.0 h (200 mg) after drug administration. Mean peak plasma SCH-39304 concentrations on day 16 were 7.6 micrograms/ml at 4.3 h (50 mg) and 17.2 micrograms/ml at 3.2 h (200 mg) after drug administration. Mean elimination half-lives on day 16 for the 50- and 200-mg daily dosages were 100 and 89 h, respectively. SCH-39304 was cleared primarily unchanged in the urine. Mean areas under the plasma concentration-versus-time curve (from 0 to 24 h) on day 16 reflect a lower than expected increase with the 200-mg/day regimen (314.5 microgram.h/ml) compared with that for the 50-mg/day regimen (139.9 microgram.h/ml), suggesting the potential for reduced bioavailability at higher dosages. No significant effect of concurrent zidovudine therapy on the kinetics of SCH-39304 was observed.

Administration, Oral

Assay of fluconazole by high-performance liquid chromatography with a mixed-phase column.

A mixed-phase liquid chromatographic column was used to assay fluconazole in plasma, serum, and cerebrospinal fluid. The assay was linear from 0.2 to 20 micrograms/ml, with an average coefficient of variation of less than 5%. The partitioning of the drug between serum and cerebrospinal fluid was determined for 34 patients. The method was demonstrated to be suitable for both pharmacokinetic studies and monitoring of patients receiving treatment with this antifungal agent.

Chromatography, High Pressure Liquid

Effect of high-flux hemodialysis on quality of life and neuropsychological function in chronic hemodialysis patients.

The objective was to evaluate the effect of high-flux hemodialysis on quality of life, intra- and interdialytic symptoms and neuropsychological function. The study was double-blind single cross-over with random allocation to order of treatment. The patients were stable adult hospital hemodialysis patients. Both the conventional and high-flux membranes were cellulose acetate, the dialysate was bicarbonate, and dialysate sodium was held constant. The high-flux membrane had an ultrafiltration rate of 15 ml/h/mm Hg transmembrane pressure, a B12 clearance of 88 ml/min and a beta 2-microglobulin clearance of 11.4 ml/min. The values of the conventional membrane were 3.5-5.0, 34-45 and negligible. Each treatment period was 4 months. Twenty-two patients completed both phases of the cross-over. The KT/V value was higher during high-flux than conventional treatment; 1.42 versus 1.27(p < 0.05). There were no differences between high-flux and conventional treatment with respect to quality of life. Symptoms during dialysis were less severe during high-flux than conventional treatment for 12/14 items. Only 3 items reached statistical significance (0.05 > p > 0.01) and none were clinically significant. Symptoms between dialyses were less severe during high-flux than conventional treatment for 18/20 items. No single item had a statistically significant improvement but 3 had clinically important improvement. Among the 23 neuropsychological variables, none demonstrated statistically significant changes.

Adolescent

Induction of type I diabetes by Kilham's rat virus in diabetes-resistant BB/Wor rats.

Type I diabetes mellitus is an autoimmune disease resulting from the interaction of genetic and environmental factors. A virus that was identified serologically as Kilham's rat virus (KRV) was isolated from a spontaneously diabetic rat and reproducibly induced diabetes in naive diabetes-resistant (DR) BB/Wor rats. Viral antigen was not identified in pancreatic islet cells, and beta cell cytolysis was not observed until after the appearance of lymphocytic insulitis. KRV did not induce diabetes in major histocompatibility complex-concordant and discordant non-BB rats and did not accelerate diabetes in diabetes-prone BB/Wor rats unless the rats had been reconstituted with DR spleen cells. This model of diabetes may provide insight regarding the interaction of viruses and autoimmune disease [corrected]

Animals

Accuracy of common drug screen tests.

Forty consecutive urine specimens, obtained from patients seen in the emergency center, positive for either cocaine and/or marijuana, were analyzed using five methods of analysis. A new latex agglutination inhibition assay, Abuscreen OnTrak, (Roche Diagnostic Systems, Nutley, NJ), was compared with four other drug abuse assays: mass spectrometry, (Hewlett-Packard Co, Richardson, TX); an automated homogeneous enzyme immunoassay technique, ETS System, (Syva Co, Palo Alto, CA); a manual enzyme multiplied immunoassay technique; EMIT-st, (Syva); and a fluorescence polarization immunoassay, TDx, (Abbott Laboratories, Chicago, IL). For statistical purposes, mass spectrometry was the reference point for the presence or absence of a specific substance. All instrument sensitivities, with the exception of mass spectrometry, were set with the same "cut off" point of 100 micrograms/L for marijuana and 300 micrograms/L for cocaine and its metabolites. Efficiency in the detection of cocaine and its metabolites was 95% by all methods. Efficiency for the detection of marijuana and its metabolites ranged from 70% (Roche's OnTrak) to 90% (Syva's ETS). Simple to use, assays of minimal cost are presently available for rapid, accurate drug of abuse screening.

Evaluation Studies as Topic

A comparison of evaluative indices of quality of life and cognitive function in hemodialysis patients.

In the setting of end-stage renal disease, the reproducibility and responsiveness of three health-related quality-of-life instruments were evaluated. The Time Trade Off instrument (TTO) is a generic instrument used to evaluate the utility of a health state. The Hemodialysis Quality-of-Life questionnaire (HQL) is a disease-specific instrument. A series of function-specific tests evaluated neurocognitive function. The TTO and HQL instruments are patient centric in that patient values define the health status while the neurocognitive function tests reflect the values of healthcare professionals. Forty-seven chronic hemodialysis patients participated. Those with adequate dialysis, defined as a Kt/V (a measure of small solute removal during hemodialysis) above 1.0 were maintained at the level for two administrations of the three instruments separated by six to eight weeks. The test-retest intraclass correlation coefficient exceeded 0.90 for all five domains of the HQL questionnaire and exceeded 0.70 for nine neurocognitive function tests. Patients with inadequate dialysis (Kt/V less than 0.8) had Kt/V increased to above 1.0. The TTO was not responsive. For the HQL questionnaire, an item was considered responsive if a 1-point improvement, on a 7-point Likert type scale, occurred significantly more often among those with an improvement in hemodialysis treatment compared to those without improvement. Only one item had such a change and therefore the HQL cannot be considered responsive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Tuberculosis.

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England

1,25-Dihydroxycholecalciferol in human serum and its relationship with other metabolites of vitamin D-3.

A competitive protein binding assay for 1,25-dihydroxycholecalciferol has been developed using the hormone's nuclear receptor protein from chick intestinal mucosa. This nuclear receptor protein can be stored at -70 degrees C for several months and bound and free hormone can be separated easily with dextran coated charcoal. Results obtained using this assay agree well with those reported by other groups of workers. Serum levels of other vitamin D-3 metabolites, namely 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol have also been measured and are shown in relation to 1,25-(OH)2D3 levels.

Animals

Emotional disturbance and cognitive deficits in hyperthyroidism.

Assessment of cognitive and emotional variables in 19 females with hyperthyroidism was made pretreatment, at 3 weeks, and after euthyroidism was established. A matched group of normal controls was similarly tested. Group differences on cognitive measures did not reach statistical significance, but cognitive deficits and symptoms of emotional disorder were significantly associated with the severity of thyroid toxicity previous to treatment. Measures of cognitive function and personality features moved towards control group values as euthyroidism was established. The implication of these findings is discussed in the context of a review of previous literature. The observed cognitive disturbance and emotional distress appear to be reflections of thyroid toxicity.

Age Factors

Analysis for diazepam and nordiazepam by electron-capture gas chromatography and by liquid chromatography.

We describe the use of electron-capture gas chromatography or reversed-phase "high-performance" liquid chromatography for concurrent analysis for diazepam and nordiazepam in serum. In the gas-chromatographic analysis our use of a new chemically deactivated stationary liquid phase, SP 2250-DB (Supelco, Inc.), resulted in improved chromatographic sensitivity and peak symmetry for the two benzodiazepines as compared to that obtained with either OV-17or OV-1 phases. Steady-state concentrations of diazepam and nordiazepam in serum as determined by gas-liquid chromatography correlated closely with those found by liquid-liquid chromatography.

Chromatography, Gas

Incidence of cocaine metabolites in urine specimens from medical examiners' cases.

Isobutane CIMS is useful for determining the molecular weight of morphine and its derivatives, as well as for identifying labile acyl substituents on morphine's O-6 position. Furthermore, this technique will provide information relating to the presence or absence of pi-bonding on the C-7 carbon. The spectra of morphine derivatives can be further simplified by employing ethylenediamine as a reagent gas. This approach proves useful for eliciting or confirming molecular weight information from the CI spectrum. In our laboratory extended use of ethylenediamine has been accomplished without any deleterious effect on the mass spectrometer's source or its vacuum system. The utility of isobutane and ethylenediamine CI rests with its ability to supply the analyst with structure elucidation data that may be used to complement more detailed information extractable from either EI or CE spectra. This aspect of mass spectrometry is especially useful when one is dealing with an unknown member of a particular class of organic compounds.

Cadaver

Electron-capture gas-liquid chromatographic determination of ethosuximide and desmethylmethsuximide in plasma or serum.

We describe the determination of ethosuximide and desmethylmethsuximide, simultaneously or separately, in 50 to 100 microliter of plasma or serum. Derivatives of ethosuximide and desmethylmethsuximide formed by reaction with pentafluorobenzoyl chloride are extremely sensitive to the electron-capture detector of a gas-liquid chromatograph. The sample, with added internal standard and ammonium sulfate as a pH-adjusting and salting-out agent, is extracted with ethyl acetate/benzene (20/80 by vol). The extract is evaporated and the derivatives are formed. Analytical recoveries of ethosuximide and desmethylmethsuximide exceed 99%, and the relative standard deviation (CV) between analyses is usually less than 4.0%. alpha-Methyl-alpha-propylsuccinimide is used as the internal standard for ethosuximide, 2-phenylsuccinimide as the internal standard for desmethylmethsuximide.

Chromatography, Gas

Microdetermination of procainamide in human serum.

An electron-capture GLC method to measure procainamide (0.1-1 microgram/sample) in human serum was developed. An internal standard, p-amino-N-[2-(dipropylamino)ethyl]benzamide, is added to the serum before the sample is alkalinized with pH 10.5 phosphate buffer and extracted with ethyl acetate. The ethyl acetate phase is evaporated to dryness, and the residue is reacted with pentafluoropropionic anhydride. N-Pentafluoropropionyl derivatives of the drug and the internal standard had retention times of 5 and 8 min, respectively, when chromatographed at 235 degrees on a 1-m (4-mm i.d.) glass column packed with 5% OV-17 (carrier gas flow of 40 ml/min). The coefficient of variation was less than 5% for spiked standards. Furthermore, N-acetylprocainamide added to samples did not interfere. One hundred and eighty-six samples from 16 patients receiving procainamide intravenously were assayed by this GLC procedure and by a standard colorimetric method. Linear regression analysis yielded a correlation coefficient of 0.985 (slope, 1.040; intercept, 0.015).

Chromatography, Gas

The absence of 24,25-dihydroxycholecalciferol in anephric patients.

1. In subjects with normal renal function there was a strong positive correlation between serum concentrations of 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol, as measured by competitive protein-binding assay. 2. The 24,25-dihydroxycholecalciferol concentration was about 7% of the prevailing 25-hydroxycholecalciferol concentration. 3. In contrast, sera from anephric patients contained very low or undetectable amounts of 24,25-dihydroxycholecalciferol even after the serum 25-hydroxycholecalciferol concentrations in these patients had been elevated by oral administration of 25-hydroxycholecalciferol. 4. In a further group of anephric patients, all having normal serum 25-hydroxycholecalciferol concentrations, no radioactively labelled 24,25-dihydroxycholecalciferol was formed from an injected pulse dose of [3H,14C]cholecalciferol. 5. These results indicate that in man the kidney is the major site of 24-hydroxylation of 25-hydroxycholecalciferol.

Adult

Putative role of isoquinoline alkaloids in alcoholism: a link to opiates.

Although the isoquinoline hypothesis has stimulated and even tantalized the scientific inquiry of a small number of investigators, it has been an area of widespread controversy. For the most part, until recently, alcohol researchers would ascribe very little importance to the role played by insoquinolines in alcohol actions or in the disease state known as alcoholism. To most, there was adequate evidence that these condensation amines had potent pharmacologic properties but little was known about their biochemical and behavioral interaction with ethanol or opiates. As pointed out here, there is an increasing amount of evidence that indicates the putative role of isoquinolines as regulators of alcohol dependence. There is even evidence that suggests a possible "link" to opiates. If this turns out to be the case, then it is rational to consider the possibility that when one imbibes alcohol a central opiate-like substance is, in essence, produced. It would appear that the sum total of evidence to date supports the notion that there are common territories between the two highly addictive classes of drugs--alcohol and opiates. Although still not definite, future studies may well confirm the intermediacy of the TIQ compounds.

Alcoholism

Improved ultraviolet spectrophotometry of serum theophylline.

We present an improved method for ultraviolet spectrophotometry of theophylline in serum. We studied various extraction techniques aimed at eliminating interferences from co-extractable serum constituents. In the resulting modified procedure, 1 ml of serum is required and a salt-solvent pair of ammonium sulfate and chloroform/hexane is used for extraction. The solvent forms the top phase after extraction, the lower phase after back-extraction, thereby permitting easy removal of the appropriate phase from culture tubes. The use of ammonium sulfate coupled with the added specificity of the extraction solvent results in an extract with low background absorption and a well-defined spectrum for the extracted theophylline.

Humans

Analysis for carbamazepine in serum by electron-capture gas chromatography.

We describe an analytical method for determining carbamazepine in serum by electron-capture gas chromatography. A single-step extraction is followed by formation of the N-pentafluorobenzamide derivative with pentafluorobenzoyl chloride. For quantitation either of two internal standards may be used: 10-methoxy carbamazepine or 7-chloro-5,11-dihydrodibenz[b,e] [1,4]-oxazepine-5-carboxamide (Squibb Compound No. 10996). The procedure requires 0.5 ml of serum. Analytical recoveries are 96%. Coefficients of variation routinely are less than 2% for concentrations of carbamazepine that are within the therapeutic range.

Carbamazepine