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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
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

Penetration of SCH-39304, a new antifungal triazole, into cerebrospinal fluid of primates.

We characterized the cerebrospinal fluid (CSF) penetration and pharmacokinetics of SCH-39304 in adult rhesus monkeys receiving a single oral dose of SCH-39304 (2.0 mg/kg of body weight). The mean CSF-to-plasma area under the curve ratio was 0.63 (+/- 0.18, standard error of the mean); maximum concentrations were 1.34 micrograms/ml (+/- 0.18) in CSF and 1.96 micrograms/ml (+/- 0.43) in plasma. The mean plasma half-life was 45.7 h (+/- 11), and mean CSF half-life was 38.7 h (+/- 3.5). The mean levels of SCH-39304 at 24 h were 1.48 micrograms/ml (+/- 0.3) in plasma and 0.96 microgram/ml (+/- 0.12) in CSF. We conclude that SCH-39304 effectively penetrates into CSF and achieves concentrations considered active against many opportunistic yeasts and that these concentrations are sustained in CSF for greater than or equal to 24 h.

Animals↗
PubMed1989

Assay of free and total tocainide by high performance liquid chromatography (HPLC) with ultraviolet (UV) detection.

A rapid high performance liquid chromatographic (HPLC) method for the determination of tocainide, using N-(2,6-dimethylphenyl)-2-amino-butanimide as an internal standard, was developed. A methylene chloride extraction involving salting out at pH 9.0 was employed. An 85:15 mixture of 0.025M monobasic potassium phosphate at pH 3.0 and acetonitrile was used as the mobile phase. The separation and quantitative analysis of tocainide was performed on a mixed phase column with a 1.0-mL/min flow rate and detection at 210 nm. Separation of tocainide from some of its metabolites required the use of heptane sulfonic acid as an ion-pairing reagent. For the free-drug assay, the specimen was centrifuged through an Amicon Centrifree filter before being processed.

Anti-Arrhythmia Agents↗
PubMed1988

Can psychological assessment address borderline phenomena?

Literature about psychological test findings in borderline disorders reflects changes in the meaning of the term and can be confusing when viewed from today's prespective. Most descriptions have referred to a concept of borderline schizophrenia. This paper reviews psychological assessment of borderline patients by means of the Rorschach, by using WAIS/Rorschach patterns, and, post-DSM-III, by using the MMPI. It focuses on the Rorschach's sensitivity to several dimensions relevant to borderline pathology. The concept that borderline disorders can include mild forms of affective and schizophrenic illness was examined by applying a Rorschach content scoring system to a borderline sample. The findings demonstrate Rorschach ability to identify borderline subtypes and offer independent validation of affective and schizotypal subtypes in the borderline realm.

Borderline Personality Disorder↗
PubMed1987

Regional brain [Met]-enkephalin in alcohol-preferring and non-alcohol-preferring inbred strains of mice.

Scrutiny of the data from these studies reveals that the C58/J alcohol-preferring mice have significantly lower baseline methionine-enkephalin levels in both the corpus striatum and hypothalamus compared to C3H/CHRGL/2 non-alcohol-preferring mice. In other brain regions in these two strains, specifically, pituitary, amygdala, midbrain, and hippocampus, analysis of methionine-enkephalin levels did not show any significant differences. This suggests that the hypothalamus may indeed be a specific locus involved in the regulation of alcohol intake, via the molecular interaction between neuroamines, opioid peptides, as they are influenced by genetics and environment.

Alcohol Drinking↗
PubMed1987

Bioequivalence and pharmacokinetic profile of promethazine hydrochloride suppositories in humans.

A bioequivalence study of promethazine hydrochloride (10-[2-(dimethylamino)propyl]-phenothiazine monohydrochloride) was conducted in 20 male human subjects with the purpose of comparing, under blind condition, the human serum levels of promethazine in three different formulations. The formulations tested were a 50-mg promethazine hydrochloride polyethylene glycol suppository, a 50-mg promethazine hydrochloride cocoa butter-white wax suppository, and a 50-mg oral dose of promethazine hydrochloride syrup. Each subject received single doses of each of the three formulations on each of three different days on a crossover basis. From the measured serum levels, estimates of the bioavailability parameters (area under the serum concentration versus time curve, time-to-peak serum concentration, and peak serum concentration) were obtained by least-squares digital computer fitting. Also, a one-compartment pharmacokinetic open model with two consecutive first-order input steps is proposed. Statistical analysis of the results was performed by using a linear multiple regression approach for the analysis of variance. No significant differences between the syrup and the polyethylene glycol suppositories were obtained (p greater than 0.05) for the above three bioavailability parameters. However, the polyethylene glycol suppositories provided statistically higher peak serum concentration, shorter time-to-peak serum concentration, and larger area under the serum concentration versus time curve than the cocoa butter-white wax suppositories.

Adult↗
PubMed1985

In vitro precipitation of calcium phosphate under intracellular conditions: formation of brushite from an amorphous precursor in the absence of ATP.

Release of mitochondrial calcium has been shown to occur concomitant with mineral ion loading of matrix vesicles at the onset of mineralization in epiphyseal growth plate cartilage. Matrix vesicles contain amorphous calcium phosphate (ACP), a mineral form that usually results from rapid precipitation at high initial levels of Ca2+ and/or inorganic P (Pi). Since the cytosol of growth plate chondrocytes has been found to contain high levels of Pi, rapid release of mitochondrial Ca2+ into the cytosol may cause local precipitation of calcium phosphate and thus be coupled with matrix vesicle formation. Studies were carried out to determine the kinetics and nature of mineral formation that occur when small amounts of Ca2+ are added under various conditions to a Pi buffer composed of electrolytes matched in concentrations and pH to that of the cytosol of epiphyseal chondrocytes. Depending on the manner in which Ca2+ was added, ACP, dicalcium phosphate dihydrate (DCPD), or apatite (HA) first formed. In the presence of ATP, ACP was the only solid phase detected, being stable for at least 24 h. However, in its absence, ACP rapidly transformed into DCPD. Increasing the pH of the reaction buffer from 6.9 to 7.5 increased the amount of ACP initially formed, but DCPD was consistently found upon ACP transformation. Yet at pH 8.0, ACP persisted for at least 24 h. The amount of precipitate formed was proportional to the level of added Ca2+; precipitates formed when as little as 1.0 mmole was added per liter of buffer. Our findings support the possibility that rapid release of mitochondrial Ca2+ may cause localized intracellular precipitation of ACP. Since nascent ACP is known to stimulate membrane fusion and blebbing of vesicles, these findings may explain the presence of ACP in matrix vesicles. The rapid conversion of ACP to DCPD in the absence of ATP under these conditions may also explain the reported occurrence of DCPD in samples of early mineralizing tissue.

Adenosine Triphosphate↗
PubMed1979

Tuberculosis.

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England↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗