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Biomedical subjects

M Frost

Publications and source records attributed to M Frost.

At least 37 records · Page 2Linked to original sources

Prevention and treatment of experimental autoimmune myasthenia gravis with anti-rabbit thymocyte serum and gammaglobulin in rabbits.

Twenty-two rabbits received Torpedo californica acetylcholine receptor (AChR) subcutaneously. Six rabbits were treated with 0.5 ml/kg/day of anti-rabbit thymocyte serum (ARTS), and four were treated with 5.0 mg/kg/day of anti-rabbit thymocyte gammaglobulin (ARTG) subcutaneously beginning concomitantly 1, 2 and 3 weeks after the initial AChR immunization. All 12 control animals died of experimental autoimmune myasthenia gravis (EAMG) within 52 days. None of the 10 treated rabbits developed clinical EAMG. ARTS- and ARTG-treated animals had significantly lower anti-AChR antibody titers than control animals at 3 weeks (pre-AChR booster, p < 0.01). At 6 weeks (post-AChR booster), only ARTS-treated animals had significantly lower titers than controls (p < 0.01). ARTS-treated animals developed sterile abscesses at injection sites, which were minimal in the ARTG-treated group. ARTS and ARTG prevent EAMG.

Animals↗

Inhalation exposure to a hepatocarcinogenic concentration of methylene chloride does not induce sustained replicative DNA synthesis in hepatocytes of female B6C3F1 mice.

We have used methylene chloride as a model to study cellular and molecular processes responsible for liver tumor induction by chlorinated hydrocarbons. Because of current interest in the role of enhanced cell proliferation in tumor induction, measurement of S-phase hepatocytes was incorporated into recently conducted toxicity and carcinogenicity studies. In prechronic studies, female B6C3F1 mice were exposed to 0, 1000, 2000 or 8000 p.p.m. methylene chloride by inhalation, 5 days per week, for up to 4 weeks followed by a 1 and 2 week recovery period. Mice exposed to concentrations of 2000, 4000 or 8000 p.p.m. methylene chloride had sustained increased liver weight commencing after 1 week of exposure and returning to normal after the 1 or 2 week recovery period. The increased liver weight was attributed to hepatocellular hypertrophy secondary to intracellular glycogen accumulation. Tritiated thymidine was administered by osmotic minipumps to label S-phase hepatocytes over a 6 day period. At most intervals examined there was decreased hepatocyte labeling in mice exposed to methylene chloride. However, there was a transitory increased number of S-phase hepatocytes observed at the 2 week interval in the 1000, 4000 and 8000 p.p.m. methylene chloride groups. In a chronic study, female mice were exposed to 2000 p.p.m. methylene chloride for up to two years. Following labeling with BRDU using 6 day minipumps, a statistically significant decrease in S-phase hepatocytes was observed after 13 weeks of methylene chloride exposure. A minor increased labeling index (LI) observed at 52 weeks was not considered to be a methylene chloride treatment-related effect. Retrospective immunohistochemical staining for proliferating cell nuclear antigen (PCNA) in liver sections containing foci of cellular alteration allowed demonstration of S-phase hepatocytes in these clonally expanded preneoplastic lesions. While foci frequently had higher LI's than surrounding normal hepatocytes, there was no difference in the mean LI of foci from methylene chloride-treated mice versus foci occurring spontaneously in control mice. The absence of a sustained increase in S-phase hepatocytes in female B6C3F1 mice suggests that enhanced cell proliferation is not a major mechanistic factor associated with the observed hepatocarcinogenicity of methylene chloride.

Administration, Inhalation↗

Pharmacokinetics of interpleural bupivacaine in patients undergoing cholecystectomy.

Arterial and venous plasma concentrations of bupivacaine were measured following interpleural administration of 20 ml of 0.5% solution with adrenaline in patients undergoing cholecystectomy. Mean maximum arterial and venous concentrations in eight of 11 patients were 1.90 (SD 0.36) and 1.65 (0.48) mg litre-1 and occurred at 22 (10) min and 25 (10) min, respectively. An arteriovenous difference for bupivacaine of approximately 20% was noted during the first 45-60 min after administration. Mean systemic venous plasma clearance (0.15 (0.08) litre h-1 kg-1) was less and the mean elimination half-life (6.85 (2.29) h) and mean body residence time (9.99 (3.00) h) were longer than reported previously for interpleural bupivacaine--possibly because of continued slow absorption of the drug from its absorption site.

Adult↗

[Loco-regional recurrence following surgery of breast carcinoma: prognostic factors and therapeutic consequences].

The course following local relapse after mastectomy was studied prospectively in 225 women. Factors significantly influencing the further course were determined. On the whole the prognosis was relatively good, with a projected 5-year relapse-free survival of 47%, a median time interval of 53 months until development of distant metastases, and an estimated death rate of 41% after 5 years. The most important factor influencing the incidence and time interval until appearance of distant metastases is the axillary lymph node status at the time of mastectomy. N0 patients have a much better prognosis than N+ patients in univariate as well as multivariate analysis. Other factors in univariate analysis which play a role in either the incidence of distant metastases or overall survival include estrogen receptor content, site of the local relapse (skin or regional lymph nodes), time interval between mastectomy and the occurrence of the local relapse, and number of tumor nodules in the local relapse. In multivariate analysis virtually the only really independent prognostic factors are primarily the initial axillary lymph node status for survival free of distant metastases and the time interval from mastectomy to local relapse for overall survival.

Breast Neoplasms↗

Idiotypic control of the immune response.

Anti-idiotypic antibodies are antibodies against the antigenic determinants (idiotypes) of an antibody's antigen-binding region. Anti-idiotypes can bind near (Ab2 gamma) or away (Ab2 alpha) from the antigen-combining site or can carry the internal image of the antigen (Ab2 beta). Idiotypes and anti-idiotypes have been described in T- and B-cell systems. They have been used in basic research to purify and characterize receptors and ligands against receptors, to treat tumors, to make vaccines and to diagnose and suppress the immune response. In experimental myasthenia gravis anti-idiotypes protect animals against the disease, block idiotype binding and share idiotypic specificities.

Animals↗

Estrogen receptor levels and survival of breast cancer patients. A study on patients participating in randomized trials of adjuvant therapy.

A series of 1,022 patients taking part in clinical trials to compare postoperative radiation therapy with postoperative CMF chemotherapy, and postoperative tamoxifen with no adjuvant therapy, had their tumors analyzed for estrogen receptor content. Isoelectric focusing of the receptor in polyacrylamide gel was used for receptor assay and the results were related to tumor DNA content. The estrogen receptor content was significantly correlated to prolonged survival both for premenopausal and postmenopausal women. It was confirmed that postmenopausal women have increased median receptor values, and for this group values of more than approximately 0.3 fmol per microgram DNA were correlated to prolonged survival. For premenopausal women, a lower level of more than 0.1 fmol per microgram of DNA defined patients with prolonged survival. Lymph node involvement and receptor level were independent prognostic indicators. Patients randomized to tamoxifen or CMF tended to live longer as compared with control patients but this was not statistically significant. Moreover, there was no tendency for adjuvant tamoxifen to further increase the survival of patients with receptor-containing tumors as compared with control patients with similar receptor values.

Adult↗

A rapid cell culture technique for assessing the toxicity of detergent-based products in vitro as a possible screen for eye irritancy in vivo.

It is generally accepted that the Draize rabbit eye irritation test has several disadvantages and inadequacies when used as an indicator for potential irritancy of detergent-based commercial products. In the search for a possible in vitro screen, it was decided to use mouse LS cells in suspension, taking 50% cell death (CD50) after exposure to the product for 4 h as the endpoint. This result for eleven samples was compared with rabbit eye irritation data ranked on an arbitrary classification of mild, moderate and severe. All samples with a CD50 less than 0.5 mg ml-1 were severe eye irritants while, with one exception, all those with a CD50 greater than 1.0 mg ml-1 were mild irritants. Samples between these two cytotoxicity levels were, in general, moderately irritant to the rabbit eye. It would appear that the present in vitro test is a possible screen for the irritancy of detergent-based products.

Animals↗

Reliability of measuring trunk motions in centimeters.

A method of measuring trunk motion and two related motions using a tape measure and a stepstool was developed by physical therapists at our hospital. The purpose of this study was to assess the reliability of this method. Three repetitions of six motions performed by 24 subjects were each measured by three physical therapist raters on two separate days. The motions were forward bending, backward bending, right side bending, right rotation, right straight leg raising, and right prone knee bending. Reliability, standard deviation, and standard error were calculated for each motion. Only forward bending exhibited good single measurement reliability. Reliability coefficients for all motions were higher for the average of three successive measurements or for the measurement of a motion on successive days by the same rater. Measurements of rotation and straight leg raising, despite the improvement, continued to have low reliability. Analysis of variance was used to determine the significance of the differences between means for each motion across three raters, three repetitions, and two days. By looking at the analysis of variance and reliability estimates together, the authors identified two types of constant error affecting the data.

Adult↗