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Biomedical subjects

M Thomas

Publications and source records attributed to M Thomas.

At least 595 records · Page 33Linked to original sources

Purification and characterisation of elastase from Staphylococcus epidermidis.

An elastase of Staphylococcus epidermidis was purified by ion exchange chromatography on CM-Sepharose and characterised. Its M(r) is c. 21 kDa, its optimal temperature for activity is 42 degrees C and the pH optimum is 6.8. The enzyme is activated by cysteine and other SH-donators and inhibited by L-trans-epoxy-succinylleucylamido-(4-guanidino)butane (E64), an inhibitor of cysteine proteases, but not by 3,4-dichloroisocoumarin (3,4-DCI), an inhibitor of serine proteases. This finding suggests that the elastase of S. epidermidis is a cysteine protease. Because S. epidermidis elastase degrades human sIgA, IgM, serum albumin, fibrinogen, and fibronectin, this enzyme may be regarded as a virulence factor.

Chromatography, Ion Exchange↗

Is acupuncture an alternative in idiopathic pain disorder?

This study investigated the pain-relieving effect of an intensive type of periosteal acupuncture stimulation in patients with idiopathic pain disorder. Twelve patients, 2 males and 10 females, with a mean age of 54, were included in the study. The average duration of their pain was 12.6 years. Each treatment consisted of brief but painful manual stimulation of 3 to 4 periosteal sites. Over a 3-8-month period each patient had between 4-11 treatments, an average of 7. Analgesic drugs that patients were on prior to the study were continued but no other physical or psychological treatment for their pain was applied. Ten patients had either no responses to treatment or only transient responses which were not maintained until the following treatment. Two patients benefitted from treatment, having long periods of substantial pain reduction. All responses were assessed on pain scales maintained daily before and during the entire period of treatments. For the majority (83%) of patients in this study, with an idiopathic pain disorder, periosteal acupuncture stimulation was not a treatment alternative.

Acupuncture Therapy↗

Development of prolonged focal cerebral edema and regional cation changes following experimental brain injury in the rat.

The present study examined the formation of regional cerebral edema in adult rats subjected to lateral (parasagittal) experimental fluid-percussion brain injury. Animals receiving fluid-percussion brain injury of moderate severity over the left parietal cortex were assayed for brain water content at 6 h, 24 h, and 2, 3, 5, and 7 days post injury. Regional sodium and potassium concentrations were measured in a separate group of animals at 10 min, 1 h, 6 h, and 24 h following fluid-percussion injury. Injured parietal cortex demonstrated significant edema, beginning at 6 h post injury (p less than 0.05) and persisting up to 5 days post injury. In the hippocampus ipsilateral to the site of cortical injury, significant edema occurred as early as 1 h post injury (p less than 0.05), with resolution of water accumulation beginning at 3 days. Sodium concentrations significantly increased in both injured cortex (1 h post injury, p less than 0.05) and injured hippocampus (10 min post injury, p less than 0.05). Potassium concentrations fell significantly 1 h post injury within the injured cortex (p less than 0.05), whereas significant decreases were not observed until 24 h post injury within the injured hippocampus. Cation alterations persisted throughout the 24-h post injury period. These results demonstrate that regional brain edema and cation deregulation occur in rats subjected to lateral fluid-percussion brain injury and that these changes may persist for a prolonged period after brain injury.

Animals↗

Measurement of vascular access recirculation without contralateral venous puncture.

The rate of recirculation is an important variable in calculating the correct dose of dialysis delivered to a patient. Traditionally it is calculated using blood results obtained from the arterial and venous lines and from venous puncture of the opposite arm. To avoid this venipuncture, cessation of the blood pump for 1 or 2 min was attempted to mimic the systemic circulation. This technique underestimated recirculation but was statistically correlated with the result obtained by the classical method, thus it is possible to derive a formula to obtain the recirculation value without contralateral venipuncture.

Adult↗

Effects of switching from a high-fat diet to a low-fat diet on tumor proliferation and cell kinetics of 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in rats.

We investigated the stimulatory effect of a high-fat diet on tumorigenesis, tumor proliferation and cell kinetics of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in Sprague-Dawley rats, and sought to determine whether switching the animals from a high-fat diet to a low-fat diet would suppress tumor proliferation and cell kinetics. The high-fat diet significantly stimulated tumorigenesis, tumor proliferation and cell kinetics. After the animals were switched from the high-fat diet to the low-fat diet, however, tumor growth decreased, the BrdUrd labeling indices of tumors significantly decreased, and the potential doubling times of tumors significantly increased. Therefore, switching from a high-fat diet to a low-fat diet may improve the prognosis of breast cancer.

9,10-Dimethyl-1,2-benzanthracene↗

Influence of a preadsorbed terpolymer on human platelet accumulation, fibrinogen adsorption, and ex vivo blood activation in hemodialysis hollow fibers.

Results are presented on kinetics of platelet accumulation in charged polyacrylonitrile (AN69) hollow fibers by continuous data recording under flow conditions (wall shear rate 108-1050 s-1), using suspensions of washed 111In-labeled human platelets in Tyrode's-albumin buffer, containing washed red blood cells (0-40%). Preadsorption of a terpolymer of acrylonitrile, poly(ethyleneoxide) methacrylate and trimethylaminoethyl chloride methacrylate leads to very efficient passivation with respect to platelet accumulation and fibrinogen adsorption. In human ex vivo tests, evaluation of complement peptide C3a, platelet beta-thromboglobulin, leucocyte-polymorphonuclear neutrophile elastase and fibrinopeptide A shows no detectable activation. Furthermore, preadsorption appears to result in simultaneous improvement in hemocompatibility of the blood lines leading to and from the dialysis module. This single pretreatment of dialysis membranes should allow injection of lower doses of anticoagulant to patients submitted to hemodialysis.

Acrylic Resins↗

Abnormal intracellular calcium ion concentration in platelets and lymphocytes of bipolar patients.

The authors measured intracellular Ca2+ concentrations in four manic and five bipolar depressed patients and seven comparison subjects. Platelet and lymphocyte intracellular Ca2+ concentrations were comparable. The patients' mean intracellular Ca2+ concentrations were higher than those of the comparison subjects and demonstrated more interindividual variation. These findings suggest a diffuse abnormality in mechanisms affecting intracellular calcium homeostasis in bipolar disorder.

Adult↗

Psychotic depression: advances in conceptualization and treatment.

Psychotic depression is a unique subtype of depressive illness in which mood disturbance is accompanied by delusions, hallucinations, or both. Once considered relatively uncommon, it is frequently encountered in clinical practice, particularly in treatment-resistant depressed patients. Psychotically depressed patients respond poorly to antidepressants, but remission is likely with neuroleptic-antidepressant combinations or electroconvulsive therapy. Psychotic depression may be unipolar or bipolar with early or late onset and may be more likely to occur in patients with a history of childhood psychic trauma. Much is known about the course and treatment response of obvious presentations of psychotic depression, but more must be learned about depressed patients who have intermittent, subtle, or mild psychotic symptoms and about the ways in which the capacity to become psychotic interacts with the capacity to become depressed to produce a syndrome greater than the sum of its parts.

Affective Disorders, Psychotic↗

Prolonged administration of oral etoposide in non-small-cell lung cancer: a phase II trial.

PURPOSE: The trial was undertaken to investigate the activity and toxicity of a prolonged schedule of oral etoposide in the treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between March 1989 and August 1990, 25 patients with advanced NSCLC were treated with oral etoposide 50 mg/m2/d for 21 consecutive days, repeated every 28 to 35 days. The median patient age was 60 years (range, 38 to 84 years); male:female ratio was 12:13. Eight patients had stage IIIB disease; 17 had stage IV. Seventy-six percent of patients had Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. No patient had received previous chemotherapy with standard agents; nine patients had received previous or concurrent radiation therapy. Plasma etoposide concentrations were measured to estimate etoposide bioavailability and kinetics. RESULTS: Five of 22 patients (23%; 95% confidence interval [CI], 10% to 43%) had partial responses. Median response duration was 5 months (range, 2 to 6 months). Four of five responders were female. Besides alopecia, which occurred in all patients, myelosuppression was the most common toxicity, but was mild or moderate in most patients. Median leukocyte nadir during course 1 was 3,200/microL; only four of 69 courses produced a leukocyte nadir less than 1,000/microL. Severe thrombocythemia (less than 75,000/microL) did not occur. Gastrointestinal toxicity was uncommon. Median peak etoposide concentration was 3.4 micrograms/mL. A mean serum etoposide concentration greater than 1 microgram/L was maintained for more than 13 hours; the plasma concentration-time curve (AUC) was estimated to be 90% of that predicted after an identical dose of etoposide given intravenously. CONCLUSIONS: Etoposide given by this dose and schedule has moderate activity as first-line systemic therapy for advanced NSCLC. In previously untreated patients, chronic oral etoposide is well tolerated, and incorporation into combination regimens should be feasible. Etoposide bioavailability may be increased at lower oral doses.

Administration, Oral↗

Combined effects of RU486 and tamoxifen on the growth and cell cycle phases of the MCF-7 cell line.

The antiproliferative effect of RU486 and its effect combined with tamoxifen on the growth and cell cycle kinetics parameters on the MCF-7 human carcinoma cells were investigated. When MCF-7 cells in the exponential growth phase were treated with RU486 (10(2) nmol/L), a time-dependent cell growth inhibition was observed which was significant 5 days after the beginning of treatment. This inhibition was accompanied by a time- and dose-dependent decrease in the percentage of S and G2-M phase cells and a concomitant increase in the percentage of cells in the G0/G1 phase of the cell cycle. With tamoxifen (10(5) pmol/L), growth inhibition was obtained after 4 days of treatment of cells, and the blockage of the cell cycle occurred in the G0/G1 phase. In the case of simultaneous treatment of MCF-7 cultures with RU486 (10(2) nmol/L) and tamoxifen (10(5) pmol/L), we observed a synergistic inhibitory effect on the proliferative rate for short treatment (less than or equal to 3 days), whereas RU486 or tamoxifen alone had no effect. For the intermediate treatment (4 days), the combined effect of RU486 and tamoxifen was not significant compared to the effect of tamoxifen alone. For the long treatment (greater than 4 days), there were no differences between the number of cells in the treated cultures under different experimental conditions, but all were inhibited compared to those in control cell cultures. This simultaneous treatment of cells does not induce any change in the distribution of cells in the different cell cycle phases compared to tamoxifen percentages. These results suggest that RU486 is a cell cycle phase-specific growth inhibitory agent, and a combination of antiestrogen/antiprogestin should be considered as a possible improvement in breast cancer endocrine therapy.

Breast Neoplasms↗

Vaginal bromocriptine--clinical and biochemical effects.

Adverse effects occur in over 50% of women taking oral bromocriptine, causing at least 10% to discontinue treatment. Although the drug is absorbed from the vagina and reportedly caused no side-effects in one patient intolerant of oral bromocriptine, long-term clinical effects of daily vaginal administration have not been assessed. We have now given bromocriptine vaginally for up to 2 years to 31 hyperprolactinemic and five normoprolactinemic women, 17 of whom were intolerant of oral bromocriptine. The drug was well absorbed from the vagina and a daily dosage of 2.5 mg lowered serum prolactin levels in 28 of the hyperprolactinemic women (in 11 to within normal limits), restored menstrual cyclicity, and abolished galactorrhea; one of the four infertile women conceived. Minor side-effects occurred in only three women. Vaginal administration is clinically effective, avoids the adverse effects of oral therapy and could be the first-line treatment for patients requiring bromocriptine.

Administration, Intravaginal↗

Client perceptions of the ideal addictions counselor.

Addicted persons in a residential treatment center rated the traits which they felt were the most positive and negative in a counselor. Lists of traits were developed by having one group of clients make a list, in their own words, of positive and negative traits. These traits were compiled into lists from which other groups of clients rated the top 10 positive and the top 10 negative counselor traits. Profiles were developed for eight subgroups (Males, Females, Black Clients, White Clients, Alcoholics, Cocaine Addicts, Younger Clients: 18-23 years old, and Older Clients: 43+ years). Significant differences were found in the type of counselor preferred by various groups within the sample. The data suggest that addicted persons, while using colorful and imprecise language, have definite preferences and aversions toward certain counselor traits. These findings should be useful to counselors as well as those involved in training programs.

Adolescent↗

A new device for specific extracorporeal immunoadsorption of anti-DNA antibodies. In vitro and in vivo results.

Selective removal of anti-DNA antibodies could be an alternative to therapeutic plasma exchange in patients with active systemic lupus erythematosus. The method is based on the immobilization by covalent binding of double-stranded, calibrated, 0.3-kb DNA fragments on a microporous, methylated, polyacrylonitrile membrane. This enables linkage of 60 micrograms of DNA per cm2 of apparent surface area. In vitro, perfusion of 100 ml of plasma maintained at 37 degrees C through 650 cm2 of dsDNA linked to the membrane, at a flow rate of 1.5 ml/min for 60 min, resulted in the removal of 49-89% of anti-DNA IgG without any changes in plasma protein or IgG levels. During a therapeutic plasma exchange, perfusion of the plasma through 1.5 m2 of membrane, at a flow rate of 25 ml/min, initially removed 92% of the anti-dsDNA antibodies entering the adsorbent and 25% at 120 min, indicating a progressive saturation of the binding capacity. Clinical immunoadsorption, at a plasma flow rate of 20-40 ml/min through 2 m2 of membrane, removed more than 50% of anti-dsDNA IgG within 60 min. Microporous membranes are able to irreversibly bind large amounts of antigenic ligands, and enable the selective removal of pathogenetic immunoglobulins or circulating factors.

Antibodies, Antinuclear↗

Effects of high and low dietary fat and indomethacin on tumour growth, hormone receptor status and growth factor expression in DMBA-induced rat breast cancer.

The effects of high and low dietary fat (20% vs. 0.5% corn oil), and of the prostaglandin synthetase inhibitor indomethacin (0.005% w/w), on tumour incidence, tumour growth, hormone-receptor status and growth-factor expression were examined in dimethylbenzanthracene (DMBA)-induced rat breast cancer. The high dietary-fat group showed a significantly higher tumour incidence, larger tumour size and larger number of bromodeoxyuridine(BrdU)-positive cells of tumours as compared with those in the low dietary-fat group. Indomethacin reduced tumour incidence significantly, but conversely increased the tumour size and the number of BrdU-positive cells in both the high and the low dietary-fat groups. No significant difference was noted in the hormone-receptor status of the tumours. Growth factors (TGF-alpha and IGF-II) were somewhat highly expressed in the high dietary-fat group as compared with the low dietary-fat group, but indomethacin rather reduced the growth-factor expression. It is concluded that high dietary fat stimulates tumour incidence and tumour proliferation, while indomethacin has dual effects: a stimulating effect on tumour proliferation, but an inhibiting effect on tumour incidence. It is also suggested that hormone-receptor status and growth-factor expression do not play an important role in their stimulating effects on tumour proliferation.

9,10-Dimethyl-1,2-benzanthracene↗

Carboplatin plus oral etoposide in the management of advanced, non-small cell lung cancer: preliminary results of a Vanderbilt trial.

Twenty-eight patients with unresectable, metastatic non-small cell lung cancer (NSCLC) were treated with carboplatin/oral etoposide. Carboplatin was administered intravenously on day 1 at a dose of 300 mg/m2 (12 patients) or 350 mg/m2 (16 patients); oral etoposide was administered at a dose of 50 mg/m2/d for 21 consecutive days. Treatment was repeated every 28 days. Patient characteristics included male:female ratio of 23:5, median age of 60 years, median Eastern Cooperative Oncology Group performance status of 1, weight loss of 5% or more in seven patients; stage IIIB disease in two patients and stage IV in 26. Twenty-five patients were evaluable for response and seven (28%) achieved a partial response (95% confidence interval, 14% to 48%). Median duration of response was 3+ months (range, 2+ to 6+) and median survival was 4+ months (range, 1+ to 10+). Myelosuppression was the predominate toxicity; leukocyte and platelet nadirs occurred between days 22 and 29, with median counts of 2,900/microL and 172,000/microL, respectively. The median interval between the start of cycle 1 and the start of cycle 2 was 33 days (range, 26 to 42). Carboplatin/oral etoposide is a moderately active regimen against advanced NSCLC that can be administered in an outpatient setting with manageable toxicity. Its impact on survival remains to be determined.

Administration, Oral↗