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Biomedical subjects

M Thomas

Publications and source records attributed to M Thomas.

At least 451 records · Page 25Linked to original sources
PubMed1995

The effects of L-dihydroxyphenylalanine on alertness and mood in alpha-methyl-para-tyrosine-treated healthy humans. Further evidence for the role of catecholamines in arousal and anxiety.

Treatment with alpha-methyl-para-tyrosine (AMPT), a catecholamine synthesis inhibitor, has been shown to produce pronounced increases in sleepiness and mild increases in negative mood and anxiety when administered to healthy male adults. The present study was conducted to ascertain whether these effects of AMPT are secondary to decreases in brain catecholamines or whether they represent nonspecific drug effects. Forty-one healthy males were randomized to one of four treatment groups. (1) Treatment with AMPT alone (AMPT/placebo); (2) treatment with AMPT plus L-dopa/carbidopa (AMPT plus L-dopa/carbidopa); (3) treatment with L-dopa/carbidopa alone (placebo plus L-dopa/carbidopa); or (4) treatment with placebo alone (placebo plus placebo). Repeated measures of alertness, mood, and anxiety were obtained over a three-day period of drug treatment and following drug discontinuation. As before, AMPT treatment led to increased sleepines. In addition, AMPT treatment led to decreased calmness, increased tension and anger, and a trend for increased depression. Replacement of catecholamine stores with L-dopa reversed the effects of AMPT and was associated with a more rapid recovery from AMPT's effects. These findings indicate that AMPT's effects on alertness and anxiety are catecholamine-specific. Further, they provide additional evidence that catecholamines are involved in the regulation of normal states of arousal, and they are consistent with the view that brain catecholaminergic dysregulation is involved in pathological anxiety states.

Adult↗
PubMed1995

Nebulization of fluids of different physicochemical properties with air-jet and ultrasonic nebulizers.

PURPOSE: Empirical formulae relate the mean size of primary droplets from jet and ultrasonic nebulizers to a fluid's physicochemical properties. Although the size selective "filtering" effects of baffling and evaporation may modify the secondary aerosol produced, this research sought to evaluate whether viscosity and surface tension of nebulized fluids influenced the aerosol's size and output characteristics. METHODS: Fluid systems of different surface tension and viscosity (glycerol and propylene glycol solutions [10-50% (v/v)] and a range of silicone fluids [200/0.65 cs-100cs]) were nebulized in three jet and two ultrasonic nebulizers. Secondary aerosol characteristics were measured with a Malvern 2600C laser diffraction sizer and the nebulization times, residual volumes and percentage outputs were determined. RESULTS: While the droplet size appeared to be inversely proportional to viscosity for jet nebulizers, it was directly proportional to viscosity for ultrasonic nebulizers. Although fluid systems with lower surface tensions generally produced slightly smaller MMDs, the relationship between surface tension and droplet size was complex. The more viscous fluids required longer nebulization times and were associated with increased residual amounts (lower outputs). The ultrasonic nebulizers did not effectively, and were on occasion unable to, nebulize the more viscous fluids. CONCLUSIONS: It follows that there are cut-off values for viscosity and/or surface tension above or below which ultrasonic devices fail to operate. Moreover, jet nebulizers generated an aerosol with an optimum respirable output from median-viscosity fluids.

Aerosols↗
PubMed1995

Differential effects of depleting agents on cytoplasmic and nuclear non-protein sulphydryls: a fluorescence image cytometry study.

The intracellular distribution of glutathione (GSH) was measured by a quantitative image cytometry method, using the sulphydryl-reactive agent mercury orange. This readily forms fluorescent adducts with GSH and other non-protein sulphydryls (NPSH), but reacts much more slowly with protein sulphydryls. Under optimum staining conditions mean integrated mercury orange fluorescence per cell was closely correlated with a standard biochemical assay for GSH. Use of the DNA dye DAPI as a counterstain allowed measurement of nuclear NPSH. The mean nuclear-cytoplasmic ratio was 0.57 +/- 0.05. Isolation of nuclei under aqueous conditions resulted in the loss of approximately 90% of mercury orange fluorescence, compared with nuclear fluorescence from intact cells, suggesting that background labelling of protein sulphydryls or other macromolecules is low. Depletion of GSH with N-ethylmaleimide or diethylmaleate decreased mercury orange fluorescence in the nucleus and cytoplasm to a similar extent. In contrast, mercury orange fluorescence in the nucleus was much more resistant to DL-buthionine-S,R-sulphoximine (BSO) depletion than that in the cytoplasm. This finding is compatible with a distinct pool of GSH in the nucleus that is comparatively resistant to BSO depletion. Alternatively, the retention of fluorescence in the nucleus following GSH depletion by BSO treatment might be due to accumulation of cysteine. These findings have implications for cancer treatment since the level of NPSH in the nucleus might be a more important determinant of resistance to DNA-damaging agents than that in cytoplasm. The image cytometry method described here is quantitative, allows a measure of tumour cell heterogeneity and can be applied to small biopsy samples obtained by fine-needle aspiration. Thus it appears suitable for prospective clinical studies in cancer patients, and for monitoring the effects of GSH-depleting agents used as adjuncts to cancer chemotherapy or radiotherapy.

Animals↗
PubMed1995

The effects of the somatostatin analogue octreotide on ovulatory performance in women with polycystic ovaries.

The elevated luteinizing hormone (LH) and androgen concentrations characteristic of women with polycystic ovaries (PCO) are considered crucial factors in their infertility. The somatostatin analogue octreotide lowers LH and androgen concentrations in women with PCO. The effects of octreotide given concurrently with human menopausal gonadotrophin (HMG) were therefore compared with that of HMG alone in 28 infertile women with PCO resistant to clomiphene. In 56 cycles of combined HMG and octreotide therapy there was more orderly follicular growth compared with the multiple follicular development observed in 29 cycles in which HMG was given alone (mean number of follicles > 15 mm diameter on the day of human chorionic gonadotrophin (HCG) administration: 2.5 +/- 0.2 and 3.6 +/- 0.4 respectively; P = 0.026). There was a significantly reduced number of cycles abandoned (> 4 follicles > 15 mm diameter on day of HCG) in patients treated with octreotide+HMG, so that HCG had to be withheld in only 5.4% of cycles compared to 24.1% with HMG alone (P < 0.05). The incidence of hyperstimulation was also lower on combined treatment. Octreotide therapy resulted in a more 'appropriate' hormonal milieu at the time of HCG injection, with lower LH, oestradiol, androstenedione and insulin concentrations. Although growth hormone concentration was similar on both regimens, significantly higher insulin growth factor-I concentrations were observed on the day of HCG in women on combined therapy than on HMG alone.

Adult↗
PubMed1995

The effects of oral sumatriptan, a 5-HT1 receptor agonist, on circulating ACTH and cortisol concentrations in man.

1. The effects of oral sumatriptan (50, 100 and 200 mg), a 5-HT1 receptor agonist, and placebo, on circulating adrenocorticotrophic hormone (ACTH) and cortisol concentrations were determined over 24 h after dosing, in 26 healthy male subjects. ACTH was measured by immunoradiometric assay and cortisol by radioimmunoassay. 2. After sumatriptan all subjects displayed a normal diurnal rhythm for circulating ACTH and cortisol compared with placebo. 3. There was a reduction in the trough circulating ACTH concentration over 0-4 h which was 18% with 100 mg (P = 0.002), and 25% with 200 mg (P < 0.001). The 5 h, post-prandial, peak ACTH concentration was reduced by 21% with 100 mg (P = 0.018) and by 20% with 200 mg (P = 0.024). The weighted mean ACTH over 24 h was reduced by 8% with 100 mg (P = 0.029) and by 8% with 200 mg (P = 0.018). The nadir concentration of ACTH over the 24 h and the ACTH concentration 24 h after sumatriptan were not, however, significantly reduced. All results are compared with placebo. 4. There was a reduction in the trough circulating cortisol concentration over 0-4 h which was 15% with 50 mg (P = 0.015), 14% with 100 mg (P = 0.022) and 24% with 200 mg (P < 0.001). The 5 h, post-prandial, peak cortisol concentration was reduced by 16% with 100 mg (P = 0.012) and by 15% with 200 mg (P = 0.017).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Neutrophil elastase-alpha 1-antitrypsin in middle ear fluid in chronic otitis media with effusion.

Neutrophil elastase-alpha 1-antitrypsin was quantified in samples taken from middle ear effusions collected at operation from 17 children attending for elective myringotomy and grommet insertion. At the time of surgery the effusion was classified as serous or mucoid. Children with a recent history of infection or antimicrobial therapy were excluded. The quantification of immunoreactive neutrophil elastase was by means of enzyme-linked immunosorbant assay (ELISA). The mean value of neutrophil elastase-alpha 1-antitrypsin was 50.6 +/- 38.3 (SD) micrograms/ml in mucoid effusions, which was significantly higher (P < 0.05) than that in serous effusions (5.3 +/- 4.8 micrograms/ml). These results indicate that a mucoid effusion may reflect a more severe inflammatory response and that persistence of neutrophil activity in the middle ear mucosa may contribute to the persistence of at least one group of middle ear effusions.

Child↗
PubMed1995

Pulmonary infiltrates in patients with haematologic malignancies: clinical usefulness of non-invasive bronchoscopic procedures.

In a prospective study 90 patients with haematologic malignancies (57 acute leukaemias, 6 Hodgkin's Diseases, 15 Non-Hodgkin Lymphomas, 12 other diseases), with fever exceeding 38.4 degrees C and newly developed pulmonary infiltrates underwent bronchoscopy obtaining bronchoalveolar lavage, bronchial washings and protected brush specimen (n = 71). Pneumonias due to gram-negative bacteria (n = 38) and fungi (n = 34) were most frequent. Bronchoscopic specimens yielded 226 isolates (2 different organisms/bronchoscopy on average). 112 organisms were finally regarded as causing pneumonia. Sensitivity of bronchoscopy in diagnosing infectious episodes was 66%, but only 4 out of 13 non-infectious pulmonary infiltrates could be identified. Bronchoscopy was most effective in the diagnosis of pneumocystis carinii and herpes virus pneumonia, whereas sensitivity and specificity of detecting fungal and bacterial pneumonia were low. Empirical antimicrobial therapy was verified by evaluation of bronchoscopic samples in 25 out of 90 cases. Empirical therapy was successfully changed according to the results of invasive samplings in 34 out of 90 cases. Early identification of causative pathogens had a significant impact on survival.

Adolescent↗
PubMed1995

Dysphagia, a reversible cause not to be forgotten.

An 84-year-old man presented with dysphagia two years after the onset of symptoms. Repeated assessments at both ENT and neurology clinics had not recorded any of the more classical signs of Parkinson's disease and these did not become apparent until intercurrent illness had been treated. Once diagnosed, treatment was started and dramatic improvement was seen.

Aged↗
PubMed1995

The use of opiate antagonists for recurrent self-injurious behavior.

Despite a plethora of studies on the behavioral and pharmacologic treatment of self-injurious behavior, and despite our best efforts, many patients continue to harm themselves. The authors review the literature on the use of opiate antagonists for the treatment of self-injurious behavior.

Adolescent↗
PubMed1995

Opiate antagonists for recurrent self-injurious behavior in three mentally retarded adults.

Opiate antagonists have shown promise for treating a subset of self injurious patients. The authors report on the use of naltrexone with three mentally retarded adults who had long histories of self-injurious behavior and unsuccessful behavioral and drug treatments; for all three, the self- injurious behavior was substantially decreased. The authors have found a positive response for half the self-injurious patients for whom naltrexone has been tried. Before any drug therapy is initiated, environmental reinforcers of the behavior should be sought out and modified, and any reversible medical and psychiatric disorders should be treated.

Adult↗
PubMed1995

Immunophenotyping of lymphocytes in bronchoalveolar lavage fluid. A new flow cytometric method vs standard immunoperoxidase technique.

Characterizing lymphocyte subsets in bronchoalveolar lavage fluid (BALF) by flow cytometry (FC) proper gating of the lymphocyte subpopulation being analyzed is crucial. In order to test lymphocyte gate quality for the first time we used a DNA-dye to evaluate plasmamembrane integrity and thus to mark off fluorescent but not DNA-containing particles (eg, debris). A comparative prospective study between this newly developed FC technique and a standard peroxidase anti-peroxidase (PAP) method was performed. Samples of BALF from 50 patients with various pulmonary diseases were examined. After determination of the total cell yield, a differential cell count was performed. Subsequently, the immunophenotype of pan T lymphocyte CD3-, T-helper lymphocyte CD4-, and T-suppressor lymphocyte CD8-positive lymphocyte subsets was assessed with FC as well as with the PAP method. Both methods showed excellent correlation (CD3: r = 0.81; CD4: r = 0.97; CD8: r = 0.96; p < 0.05, respectively). Comparing the mean +/- SEM, FC tends to overestimate CD3+ cells (90.6 +/- 1.0% vs 85.8 +/- 1.3%). For CD4 (45.0 +/- 3.4% vs 44.4 +/- 3.4%) and CD8 (48.1 +/- 3.5% vs 46.7 +/- 3.5%), there was good agreement. In a clinical setting, the reliability of both methods was equivalent, and FC using a DNA-dye to test lymphocyte gate quality offered a rapid and reliable determination of lymphocyte subsets in BAL.

Bronchoalveolar Lavage Fluid↗
PubMed1995

Valproate-associated pancreatitis and cholecystitis in six mentally retarded adults.

BACKGROUND: Pancreatitis is usually considered a rare side effect of valproate. We describe five cases of pancreatitis and one case of cholecystitis associated with the use of valproate. METHOD: Through chart review, we identified all patients in our facility treated with valproate between 1989 and 1994, and all cases of pancreatitis and cholecystitis identified during that same period in our population of 322 mentally retarded patients. We also searched MEDLINE for all published cases of pancreatitis or cholecystitis associated with valproate treatment. RESULTS: Five (7%) of 72 valproate-treated patients experienced pancreatitis, and one experienced cholecystitis; all recovered fully. This brings the total number of reported cases of valproate-associated pancreatitis to 55. CONCLUSION: Pancreatitis may occur more frequently than previously recognized in mentally retarded adults treated with valproate. Developmentally disabled patients should be carefully monitored for this potentially lethal side effect.

Adult↗
PubMed1995

Exchange reamed intramedullary nailing for delayed union and nonunion of the tibia.

Twenty-eight tibial fractures, initially treated with nonreamed interlocking nails, were exchanged to reamed intramedullary nails to promote union. Initially, there were 8 closed fractures with compartment syndromes; 5 Type 2 open fractures; 6 Type 3 A injuries; and 6 Type 3B injuries. Exchange nailing was performed if followup radiographs did not show callus formation between 3 and 5 months after injury. Originally, 16 of the 28 nailings were statistically locked. Twenty-five of 27 fractures united after exchange nailing. In 2 patients with bone loss, additional bone grafting was required. Infection developed in 3 patients after exchange nailing (11%). Exchange nailing is a useful method to promote union of tibial fractures when slow consolidation occurs after initial treatment with a nonreamed nail. This method should be combined with autogenous bone grafting in patients with bone loss. The procedure is safe and effective in closed and minor open fractures; however, caution should be exercised in patients with prior Grade 3B open fractures because of the risk of infection.

Bone Nails↗