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Biomedical subjects

R J Davidson

Publications and source records attributed to R J Davidson.

At least 109 records · Page 6Linked to original sources

Toxicity of rapamycin--a comparative and combination study with cyclosporine at immunotherapeutic dosage in the rat.

Sprague-Dawley rats were treated for 14 days with rapamycin (RAP; 1.5 mg/kg/day i.p.), cyclosporine (15 mg/kg/day by gavage), both drugs in combination, or appropriate drug vehicles. Hematological parameters and biochemical indices of renal and hepatic function were determined throughout the experimental period, at the end of which the rats were killed and tissues examined histologically. There was a significant reduction in weight gain in RAP- but not CsA-treated animals, while rats given both drugs showed a reduction in body weight over the 14-day experimental period. There were no significant alterations in absolute or differential white blood cell counts or in T or B cell numbers, except in the drug combination group, in which an absolute lymphopenia was detected on day 14. Small but significant increases in urinary flow rate (UFR) were found with either drug alone, and there was a marked (4-fold) increase in UFR in response to drug combination. Both RAP and CsA caused a small elevation in serum creatinine concentrations, but only with CsA was there a significant elevation in urinary enzyme activity and reduction in 51Cr. EDTA clearance. The drug combination exacerbated renal impairment, the extent of which was greater than the additive effect of either drug alone. Hyperbilirubinemia of similar magnitude was observed in rats receiving either CsA alone or in combination with RAP. In contrast to its effect on renal function, however, the CsA+RAP combination was without additional effect on liver function compared with the minor changes seen with either drug alone. Plasma and urinary glucose levels were elevated in all drug treatment groups and especially in animals given both drugs. RAP administration did not significantly affect whole-blood CsA concentrations, although the possibility of a pharmacokinetic interaction cannot be totally excluded. Histological studies revealed striking thymic medullary atrophy in all drug-treated animals. In addition, all rats given RAP showed focal myocardial necrosis of overall mild-moderate severity. Kidneys of RAP-treated rats appeared normal, whereas mild, focal, acute tubular necrosis was evident in all CsA-treated animals. Pancreases of all drug-treated animals were normal.

Animals↗

Human serum enhances the postantibiotic effect of fluoroquinolones against Staphylococcus aureus.

The postantibiotic effect (PAE) of fluoroquinolones against Staphylococcus aureus was determined in Mueller-Hinton broth and normal human serum. At both 4X and 10X the MIC, serum significantly increased the duration of the PAE in all strains tested (P less than 0.05). Reducing the pH of the serum from 7.9 to 7.2 had no effect on the PAE. Heat treating the serum (56 degrees C, 30 min) reduced the PAE of ciprofloxacin at 10X the MIC approximately 25% (P less than 0.05). The PAE of cloxacillin was reduced approximately 80% in serum, and PAE experiments with gentamicin and cephalexin produced findings similar to those obtained with the fluoroquinolones. Serum increased the MICs of ciprofloxacin and norfloxacin less than twofold and increased the MIC of pefloxacin approximately fourfold. We conclude that normal human serum considerably increases the PAE of fluoroquinolones against S. aureus.

Anti-Infective Agents↗

Antimicrobial activity of subinhibitory concentrations of aminoglycosides against Pseudomonas aeruginosa as determined by the killing-curve method and the postantibiotic effect.

This investigation used the postantibiotic effect (PAE) and killing curves to provide data on the antimicrobial activity of subinhibitory (1/8x, 1/4x and 1/2x minimum inhibitory concentration; MIC) and inhibitory (1x MIC) concentrations of amikacin, gentamicin and tobramycin against Pseudomonas aeruginosa. Subinhibitory concentrations (1/4x and 1/2x MIC) of aminoglycosides demonstrated a reproducible PAE. At 1/4x MIC, the order of duration of the PAE was approximately 15 min for all aminoglycosides, while at 1/2x MIC all three aminoglycosides displayed a similar PAE of approximately 40 min. Killing-curve studies demonstrated that subinhibitory concentrations of aminoglycosides either decrease bacterial growth for several hours (1/4x and 1/2x MIC) or produce stasis of growth for several hours (1/8x MIC). Only inhibitory aminoglycoside concentrations (1x MIC) proved to be bactericidal. Subinhibitory concentrations of aminoglycosides decrease bacterial growth and produce a PAE against P. aeruginosa.

Amikacin↗

Influence of human urine on the in vitro activity and postantibiotic effect of ciprofloxacin against Escherichia coli.

The purpose of this investigation was to study the effects of human urine on the minimum inhibitory concentration (MIC) and the postantibiotic effect (PAE) of ciprofloxacin against Escherichia coli. MICs and the PAE were performed in Mueller-Hinton broth (MHB; pH 7.3 and 5.5) and in human urine (pH 5.5 and 7.3). In urine, pH 5.5, MICs increased 64-fold (from 0.016 to 1.024 micrograms/ml) and the PAE was abolished (from 101.6 to 3.7 min), when compared to MHB, pH 7.3. An acidic pH demonstrated the greatest effect on reduced susceptibility and PAE. Using ciprofloxacin concentrations adjusted for a higher MIC obtained in pH-adjusted urine and MHB, PAE values were similar for urine and MHB (approximately 280 min at 40 x MIC). This study demonstrated that the MIC and PAE of ciprofloxacin against E. coli are influenced by human urine and in particular its pH.

Ciprofloxacin↗

Reaction time measures of interhemispheric transfer time in reading disabled and normal children.

This experiment was designed to test whether reading disabled boys differ from matched controls on behavioral measures of interhemispheric transfer time (IHTT). Specifically, we proposed that language-disordered reading disabled children who had deficits in naming would show either faster or slower IHTTs compared with controls. From an initial group of 118 right-handed males, we selected a group of 25 disabled and 25 normal readers, matched on age. All subjects had to obtain a full scale IQ of 90 or above, a PIQ score of 85 or above, and a scaled score of 7 or above on the Block Design Subtest of the WISC-R. After meeting additional criteria for group assignment, manual reaction time (RT) measures of IHTT were obtained in response to simple visual and tactile stimuli during two laboratory testing sessions. Half the trials were conducted with the hands in an uncrossed orientation and half with the hands crossed in order to examine the effects of spatial compatibility on estimates of IHTT. The results revealed no overall group differences in IHTT for any of the conditions. However, correlations between IHTT measures and indices of cognitive performance indicated that faster IHTTs were significantly correlated with poorer performance on measures of reading and language function in the dyslexic group. These data are discussed within the context of a model of interhemispheric transfer deficits in disabled readers.

Child↗

Regional brain electrical asymmetries discriminate between previously depressed and healthy control subjects.

Baseline resting electroencephalogram (EEG) activity was recorded from 6 normothymic depressives and 8 controls using three different reference montages. Power in all frequency bands was extracted by Fourier transformation. Significant Group X Region X Hemisphere interactions were found consistently for alpha band power only. Previously depressed subjects had less left-sided anterior and less right-sided posterior activation (i.e., more alpha activity) than did never depressed subjects. Previously depressed subjects had no history of pharmacological treatment and did not differ from controls in emotional state at the time of testing. The pattern of anterior and posterior asymmetry in the previously depressed subjects is similar to that found in acutely depressed subjects and suggests that this may be a state-independent marker for depression.

Adult↗

Resting frontal brain asymmetry predicts affective responses to films.

This article assessed whether resting electroencephalographic (EEG) asymmetry in anterior regions of the brain can predict affective responses to emotion elicitors. Baseline EEG was recorded from 32 female adults, after which Ss viewed film clips preselected to elicit positive or negative affect. Resting alpha power asymmetry in the frontal region significantly predicted self-reported global negative affect in response to clips and predicted the difference between global positive and negative affect. Analyses of discrete emotions revealed a strong relation between frontal asymmetry and fear responses to films. Effects were independent of Ss mood ratings at the time at which baseline EEG was measured. Resting anterior asymmetry may be a state-independent index of the individual's predisposition to respond affectively.

Adolescent↗

Viewpoint: academic medical centers--it is time for a declaration of values.

America's academic medical centers have become big businesses, competing, diversifying, and pursuing new economic relationships with physicians and the private sector. Corporate values and ethics are being tested, and leaders of some institutions say they are troubled by emerging trends.

Academic Medical Centers↗

Adult mastocytosis: an immunophenotypic and flow-cytometric investigation.

Skin mast cells of five patients with mastocytosis/urticaria pigmentosa and from four normal controls were immunophenotyped with a panel of 17 monoclonal antibodies; peripheral blood mononuclear cells from the patients were similarly labelled and analysed by flow cytometry. Cutaneous mast cells expressed leucocyte common antigen and markers of macrophage/monocyte lineage suggesting a common progenitor in the ontogeny of the two cell types. The mast cells from the patients differed from the controls, expressing HLA-DR in four cases, and this may be a feature of proliferating cells. The patients' peripheral blood T lymphocytes showed a marked increase in the activation markers HLA-DR and CD25 suggesting a contributory role, possibly via cytokines, in driving mast-cell proliferation.

Adult↗

Asymmetrical brain electrical activity discriminates between psychometrically-matched verbal and spatial cognitive tasks.

This study compared the asymmetry of different features of brain electrical activity during the performance of a verbal task (word finding) and a spatial task (dot localization) that had been carefully matched on psychometric properties and accompanying motor activity. Nineteen right-handed subjects were tested. EEG was recorded from F3, F4, C3, C4, P3, and P4, referred to both CZ and computer-derived averaged-ears references, and Fourier transformed. Power in the delta, theta, alpha, and beta bands was computed. There were significant Task X Hemisphere effects in all bands for CZ-referenced data and for the alpha and beta bands for ears-referenced data. The effects were always either greater power suppression in the hemisphere putatively most engaged in task processing or greater power in the opposite hemisphere. Correlations between EEG and task performance indicated that CZ-referenced parietal alpha asymmetry accounted for the most variance in verbal task performance. Power within individual hemispheres or across hemispheres was unrelated to task performance. The findings indicate robust differences in asymmetrical brain physiology that are produced by well-matched verbal and spatial cognitive tasks.

Adult↗

Approach-withdrawal and cerebral asymmetry: emotional expression and brain physiology. I.

In this experiment, we combined the measurement of observable facial behavior with simultaneous measures of brain electrical activity to assess patterns of hemispheric activation in different regions during the experience of happiness and disgust. Disgust was found to be associated with right-sided activation in the frontal and anterior temporal regions compared with the happy condition. Happiness was accompanied by left-sided activation in the anterior temporal region compared with disgust. No differences in asymmetry were found between emotions in the central and parietal regions. When data aggregated across positive films were compared to aggregate negative film data, no reliable differences in brain activity were found. These findings illustrate the utility of using facial behavior to verify the presence of emotion, are consistent with the notion of emotion-specific physiological patterning, and underscore the importance of anterior cerebral asymmetries for emotions associated with approach and withdrawal.

Adolescent↗

The Duchenne smile: emotional expression and brain physiology. II.

Facial expression, EEG, and self-report of subjective emotional experience were recorded while subjects individually watched both pleasant and unpleasant films. Smiling in which the muscle that orbits the eye is active in addition to the muscle that pulls the lip corners up (the Duchenne smile) was compared with other smiling in which the muscle orbiting the eye was not active. As predicted, the Duchenne smile was related to enjoyment in terms of occurring more often during the pleasant than the unpleasant films, in measures of cerebral asymmetry, and in relation to subjective reports of positive emotions, and other smiling was not.

Adolescent↗

A survey and critical evaluation of a dual isotope (Dicopac) vitamin B12 absorption test.

The results of all dual isotope tests (2142) carried out on 1989 patients, 807 males (40.6%) and 1182 females (59.4%), during a 10 year period (1976-1985 inclusive) in the Grampian Health Board Area (population 497,272) have been reviewed. Patient age ranged from 5-95 years with 45.5% over 60 years. The referring specialties were Gastroenterology (47.6%), Haematology (11.3%), Paediatrics (2.1%) and all others (39.0%). According to the manufacturer's recommended criteria, results were classified as normal in 1054 (49.2%), abnormal in 659 (30.8%), equivocal in 337 (15.7%) and unsatisfactory in 92 (4.3%) tests. Vitamin B12 malabsorption of ileal type was indicated in 544 tests (25.4%) and of gastric type in 115 (5.4%). Of the latter, 76 were related to pernicious anaemia, 10 to previous gastric surgery and 2 to gastric carcinoma. Of the 337 patients with equivocal results, 138 patients were reviewed and 115 (83.3%) found to have a documented cause for gastric malabsorption (96 pernicious anaemia and 19 previous gastric surgery). In 172 patients with proven pernicious anaemia the manufacturer's recommended criteria for gastric malabsorption were completely satisfied in only 76 (44.3%) but 167 (96.5%) had an excretion ratio greater than or equal to 1.3 and 127 (73.8%) a ratio greater than or equal to 1.7. Unsatisfactory tests were mainly due to incomplete urine collection (91.3%) or contamination with another isotope (5.4%).

Anemia, Pernicious↗

Frontal brain asymmetry predicts infants' response to maternal separation.

Examined whether certain features of infant temperament might be related to individual differences in the asymmetry of resting frontal activation. EEG was recorded from the left and right frontal and parietal scalp regions of 13 normal 10-month-old infants. Infant behavior was then observed during a brief period of maternal separation. Those infants who cried in response to maternal separation showed greater right frontal activation during the preceding baseline period compared with infants who did not cry. Frontal activation asymmetry may be a state-independent marker for individual differences in threshold of reactivity to stressful events and vulnerability to particular emotions.

Anxiety, Separation↗

Visual evoked potential measures of interhemispheric transfer time in humans.

Four experiments testing right-handed adult males examined interhemispheric transfer time (IHTT) estimation with visual evoked potentials (EPs) elicited in response to hemiretinal presentations of checkerboard-flash stimuli. Experiment 1 was a study of the relation between reaction time (RT) and EP measures of IHTT. EP measures provided more valid estimates than RT measures because more subjects showed IHTT in the direction of anatomical prediction. Experiment 2 showed that EPs derived from lateral occipital sites provided more valid and longer estimates of IHTT compared with EPs from medial occipital sites. Experiment 3 showed no difference between random versus blocked hemiretinal stimuli. Experiment 4 showed that IHTT derived with a linked-ears reference provided more valid estimates than IHTT derived with a mid-frontal reference and that small changes in stimulus eccentricity did not influence IHTT. The findings of these experiments indicate that noninvasive estimates of visual IHTT can be obtained in humans.

Adult↗

Longitudinal study of circulating gastric antibodies in pernicious anaemia.

Temporal changes in gastric antibody response were investigated in 113 (51 men, 62 women) patients with confirmed pernicious anaemia. Their ages ranged from 31-92 years (mean (SD 13.2) 66). At diagnosis, parietal cell antibody and intrinsic factor antibody were detected in 90.9% and 39.1% of all patients, respectively. When the tests were repeated after a mean follow up of 70 months (range 14-137), parietal cell antibody and intrinsic factor antibody were positive in 82.8% and 58.7%, respectively. There was a definite but not significant trend for the organ specific parietal cell antibody to disappear; intrinsic factor antibody became more positive. These results may indicate that with progressive parietal cell destruction, the antigen is no longer available to sustain an immunological response. On the other hand, this hypothesis does not explain the increased prevalence of intrinsic factor antibody which is also a product of parietal cells.

Adult↗