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Biomedical subjects

R A Evans

Publications and source records attributed to R A Evans.

At least 37 records · Page 2Linked to original sources
PubMed1997

Human neutrophils do not degrade major basement membrane components during chemotactic migration.

At sites of inflammation, circulating neutrophils (PMNs) migrate through microvessel walls into the subendothelial interstitium. While endothelial passage is mediated by adhesion proteins, including those of the integrin, selectin and immunoglobulin superfamily classes, the mechanisms used to cross the subendothelial basement membrane (BM) are unclear. Studies examining tumour cell invasion and lymphocyte extravasation suggest several possible mechanisms, including proteolysis. Different cells, however, may use different mechanisms to effect passage. To examine neutrophil-basement membrane interactions in more detail, human PMNs were embedded within reconstituted BM (Matrigel) and used in migration assays. The integrity of the gel following migration was assessed by assaying for the release of incorporated radiolabelled products and by-immunoblotting for specific matrix molecule epitopes. PMNs migrated through Matrigel in response to the chemotactic peptide FMLP. Degradation products of laminin, heparan sulphate proteoglycan or of gelatin, however, were not detected. In contrast, phorbol ester, which triggers activation without migration, released approximately 40% of incorporated HSPG, 30% of gelatin and 20% of laminin as intact molecules or degraded fragments. Electron microscopy of migrating cells demonstrated pseudopodia associated with channels within the Matrigel. Although the serine proteinase inhibitor DFP, plasma and a specific anti-neutrophil elastase IgG blocked degradation, these agents failed to inhibit migration. Migration was inhibited, however, when the Matrigel concentration was increased to 10 mg/ml. Thus, although PMNs will degrade matrix components they do not do so during migration, and proteolytic remodelling of the BM is not a pre-requisite for neutrophil passage.

Basement Membrane↗
PubMed1996

The tumor burden of locally recurrent breast cancer is a neglected prognostic factor.

BACKGROUND: Local recurrence following breast-sparing surgery for breast cancer is no longer considered to be an ominous sign. Why this should be the case is not understood, and it poses a dilemma for the surgical oncologist. When does local recurrence represent an independent threat to survival? DATA SOURCES: I reviewed the few studies that have considered the size or tumor burden of locally persistent breast cancer, and the results of the Guy's Hospital Trials. CONCLUSIONS: Locally persistent breast cancer is seldom a risk to patient survival. The surgical literature is seriously deficient in its consideration of the tumor volume of locally persistent cancer. All available evidence suggests that a recurrent tumor is a risk only if its volume exceeds that of the original tumor. Patients appear to have a stable level of host defense against metastasizing tumor cells. Those who survive one breast cancer without developing distant disease can be expected to survive the local persistence of a similar volume of tumor. Investigators should compare the size of each persistent lesion to the size of the patient's primary cancer. Excess deaths will occur only among patients whose persistent disease exceeds the volume of the primary.

Breast↗
PubMed1996

Flexor tenosynovectomy and tenolysis in longstanding rheumatoid arthritis.

A total of 43 patients (49 hands; 424 flexor tendons), who had rheumatoid arthritis of more than 15 years duration at the time of surgery, were clinically assessed at a mean follow-up of 5.7 years (range, 1.2-12 years). Pain and inability to flex actively despite a good passive range of motion were the main surgical indications. The results suggest that the patients had excellent sustained pain relief (mean score = 0.9) and were highly satisfied with the outcome of the procedure (mean score = 2.2). 81% had adequate pulp-to-pulp and key pinch. Range of finger motion (total active motion, TAM) was excellent to good in 45% and fair in 22%. Thirty-three per cent were graded as poor and these were found to be multifactorial in origin, with associated significant joint disease, preoperative tendon ruptures, extensive digital surgery, readhesions and combinations of operative procedures which adversely affect the rehabilitation programme. Flexor tenosynovectomy with tenolysis is a useful procedure with a low rate of recurrence.

Adult↗
PubMed1995

Monitoring acrylic fiber workers for liver toxicity and exposure to dimethylacetamide. 1. Assessing exposure to dimethylacetamide by air and biological monitoring.

Worker exposure to N,N-dimethylacetamide (DMAC) in an acrylic fiber manufacturing facility was measured, over a 1-year study period, by full-shift (12 hours) personal air monitoring for DMAC and by biological monitoring for levels of DMAC, N-methylacetamide (MMAC), and acetamide in spot urine samples. Ninety-three of 127 male workers in seven job classifications in the solution preparation and spinning departments of the plant were monitored on the second consecutive workday after at least 3 days off for the first 10 months of the study and on both the first and second days during the study's final 2 months. Postshift urinary MMAC levels were significantly correlated (P < .0001, r2 = .54) with DMAC in air levels. An air level of 6.7 ppm 12-hour time-weighted average (TWA) corresponded to a urine MMAC level of 62 mg/g creatinine in a postshift spot urine sample obtained after the second consecutive workday. To minimize exposure misclassification due to variability in the regression relationship, a level of 35 mg MMAC/g creatinine in a postshift spot urine sample was recommended as a biomonitoring index. Postshift urine MMAC levels did not appear to plateau at higher air levels, nor did it appear that the DMAC demethylation metabolic mechanisms became saturated at threshold limit value (TLV)-level air-exposure levels. Urine MMAC levels in postshift samples obtained the second workday appeared to be greater than levels in postshift first-day samples, but the number of days until this postshift level would plateau could not be determined from this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetamides↗
PubMed1995

Monitoring acrylic fiber workers for liver toxicity and exposure to dimethylacetamide. 2. Serum clinical chemistry results of dimethylacetamide-exposed workers.

Worker exposure to N,N-dimethylacetamide (DMAC) in an acrylic fiber manufacturing facility was measured, over a 1-year study period, by full-shift (12 hours) personal air monitoring for DMAC and biological monitoring for levels of DMAC, N-methylacetamide (MMAC) and acetamide in post-shift spot urine samples. Evidence of liver toxicity was assessed by serum clinical chemistry tests (serum levels of total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptase) at least once during the study period for all 127 male workers in the two study departments and for 217 male in-plant controls with no previous or current exposure to DMAC. If a worker's biomonitoring results exceeded one of two "trigger" values established for the study (60 mg MMAC/g creatinine or 136 mg DMAC equivalent/g creatinine), additional serum clinical chemistry tests were conducted at weekly intervals for 3 weeks. DMAC-exposed workers were classified as either high exposure, if one or more biomonitoring result exceeded one of the trigger values, or unspecified exposure if none of them did. Control-group employees were classified as no-exposure. Mean DMAC in air levels for the high- and unspecified-exposure groups appeared to differ (geometric mean DMAC in air levels of 1.9 and 1.3 ppm 12-hour time-weighted average, respectively). No significant DMAC exposure-related trends in hepatic serum clinical chemistry results were detected. Neither transient increases in serum analyte levels after a "high" biomonitoring result (one that exceeded a trigger value) nor an elevated mean level over the study period when compared with in-plant controls were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗