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Biomedical subjects

R Ash

Publications and source records attributed to R Ash.

At least 19 recordsLinked to original sources
PubMed2006

Assessing the prognostic significance of transrectal ultrasound extracapsular extension in prostate cancer.

AIMS: To determine the prognostic value of transrectal ultrasound (TRUS)-detected extraprostatic disease for prostate cancer in patients receiving radical external-beam radiation therapy (EBRT). MATERIALS AND METHODS: A chart review of 181 patients treated with radical EBRT for prostate cancer was conducted. All patients underwent TRUS assessment by one radiologist. The median radiation dose delivered to the prostate was 66 Gy (range 53-70 Gy) in 33 fractions (range 20-39 fractions). Median follow-up time for all patients was 6.5 years. Sixty-four (35%) out of 181 patients were found to have extracapsular disease on TRUS. Clinical relapse was defined as the first occurrence of either salvage hormonal therapy administration by the treating oncologist or clinical, radiological, and/or pathologic evidence of recurrent or progressive disease. In terms of biochemical failure, two prognostic variable analyses were carried out using both the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus guidelines and the Houston definition of biochemical failure. The primary end point for the prognostic variable analyses was time to first clinical or biochemical failure (CBF). RESULTS: For time to CBF using the ASTRO consensus guidelines for biochemical failure, univariable analysis revealed that the prostate-specific antigen (PSA) (P = 0.018), clinical T stage (P = 0.002), Gleason score (P = 0.021), adjuvant hormonal therapy (P = 0.032) and TRUS T staging (P = 0.0001) were statistically significant prognostic factors. On multivariable analysis, clinical T stage (P = 0.051) was of borderline statistical significance, whereas PSA (P = 0.036), TRUS T stage (P = 0.0002) and adjuvant hormonal therapy (P = 0.015) were found to be independent prognostic factors. For time to CBF using the Houston definition of biochemical failure, univariable analysis revealed that PSA (P = 0.001), Gleason score (P = 0.026) and prostate volume (P = 0.013) were statistically significant prognostic factors. On multivariable analysis, PSA (P = 0.002), Gleason score (P = 0.012), and adjuvant hormonal therapy (P = 0.041) were found to be independent prognostic factors. TRUS T staging was not found to be independently significant. CONCLUSIONS: A clear role for TRUS staging as an independent prognostic factor, in the setting of other more established variables, such as Gleason grade, PSA, and digital rectal examination (DRE) T stage, was not confirmed in this study, population.

Aged↗
PubMed1998

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Communication↗
PubMed1996

Phenobarbital induction of CYP1A1 gene expression in a primary culture of rainbow trout hepatocytes.

In mammals, phenobarbital (PB) is an in vivo inducer of the cytochrome P4502B (CYP2B) family, whereas in teleosts PB induction of cytochrome P450 is unclear. We show that teleost cytochrome P4502K1 (CYP2K1) protein levels and 7-pentoxyresorufin-O-deethylase activity were not induced by exposure of primary cultures of rainbow trout hepatocytes to PB. Instead, cytochrome P4501A1 (CYP1A1) gene expression was strongly induced by PB, based upon observations of marked increases in CYP1A1 mRNA, CYP1A1 protein, and 7-ethoxyresorufin-O-deethylase activity. In accordance with these data we provide a temporal study employing antibodies for the aromatic hydrocarbon (Ah) receptor that showed an increase in Ah receptor in nuclear extracts prepared from cells exposed to PB. Employment of the electrophoretic mobility shift assay (EMSA) showed PB to cause activation or "transformation" of the Ah receptor in nuclear extracts. Studies employing actinomycin D and cycloheximide indicated that PB induction of CYP1A1 was regulated at both the transcriptional and post-transcriptional levels. Nuclear run-off experiments confirm that PB causes an increase in CYP1A1 transcription. Inhibition of protein synthesis led to the superinduction of CYP1A1 mRNA, suggesting the regulation of teleost CYP1A1 may involve a labile repressor protein. These findings suggest that PB induction of the CYP1A1 gene involves the Ah receptor and is via transcriptional activation.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1996

Postoperative care of the lung transplant recipient.

This article reviews the nursing care of the patient who receives a lung transplant, starting with preparation for admission to the ICU. Issues of oxygenation, airway clearance, hemodynamic and fluid assessment, infection control, incisional assessment, and pain are addressed throughout the hospitalization. Emotional support, discharge and medication teaching, and changes in lifestyle are all important aspects of the rehabilitation phase before discharge.

Humans↗
PubMed1995

Picrotoxin is a CYP1A1 inducer in rainbow trout hepatocytes.

Picrotoxin is a CYP2B inducer in mammals (1). However, in primary cultures of rainbow trout hepatocytes we showed CYP1A1 gene expression to be strongly induced as characterized by 7-ethoxyresorufin-O-deethylase activity, immunoblots of CYP1A1 protein, and Northern blots of CYP1A1 mRNA. Induction of CYP1A1 in these cells appeared to be via the aromatic hydrocarbon (Ah) receptor as indicated by increased levels of Ah receptor in the nuclear extracts of picrotoxin-treated cells. Picrotoxin induction of CYP1A1 was blocked by actinomycin D. Superinduction of CYP1A1 mRNA occurred in cells treated with cycloheximide. Co-incubation of hepatocytes with picrotoxin and a saturating concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in synergistic increases in CYP1A1 gene expression. These results suggest that picrotoxin induction of CYP1A1 is regulated at the level of transcription and may involve an alternative mechanism(s) to that of TCDD.

Animals↗
PubMed1995

Phase III randomized, double-blind placebo-controlled trial of rhGM-CSF following allogeneic bone marrow transplantation.

Preliminary studies in allogeneic BMT suggest that recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is well tolerated. This is a prospective, multicenter, randomized, double-blind, placebo-controlled trial. Yeast-derived rhGM-CSF 250 micrograms/m2/day or placebo was administered by 4-hour i.v. infusion starting on the day of marrow infusion (day 0) to day 20. All patients received HLA-identical sibling marrow and cyclosporine and prednisone for GVHD prophylaxis. Fifty three patients received rhGM-CSF and 56 received placebo. Comparison of demographics revealed no differences. The time to achieve an absolute neutrophil count of > 0.5 x 10(9) cells/l was shortened in rhGM-CSF treated patients (day 13 vs. 17, P = 0.0001). The incidences of grade III-IV mucositis and infection were significantly reduced (P = 0.005, P = 0.001, respectively) and duration of hospitalization was modestly shortened by 1 day (P = 0.02) in rhGM-CSF treated patients. No differences in platelet recovery, erythrocyte recovery, incidence of veno-occlusive disease, GVHD severity, relapse or survival were observed. In conclusion, rhGM-CSF is well tolerated and reduces post-transplant morbidity in patients undergoing HLA-identical allogeneic BMT.

Adult↗
PubMed1995

Selective T cell depletion with CD8-conjugated magnetic beads in the prevention of graft-versus-host disease after allogeneic bone marrow transplantation.

The effects of a new immunomagnetic method of selectively depleting CD8+ lymphocytes from donor bone marrow were studied in 29 patients undergoing transplantation from HLA-identical sibling (n = 20) or alternative (n = 9) donors. The direct immunomagnetic depletion method consistently removed > 95% of CD8+ cells and the non-specific loss of other cell subsets was only about 15%. Recovery of CFU-GM and BFU-e was on average > 100%. The final graft contained 0.9 +/- 0.6 x 10(8)/kg nucleated cells and 1.4 +/- 2.7 x 10(5)/kg CD8+ cells. Patients also received cyclosporine starting day -1. Engraftment occurred in 28 patients (97%), including three patients who received a non-TBI conditioning regimen. One patient receiving an unrelated transplant failed to engraft. Median time to ANC > 500 x 10(6)/L was 17 (12-23) days. Four of 20 patients receiving grafts from HLA-identical siblings (20%) developed acute GVHD grade > or = II. However, five of eight patients with grafts from alternative donors (63%) had grade > or = II GVHD. Nearly all patients developed fever around day 7, accompanied by fluid overload, mild skin rash and shortness of breath. This syndrome necessitated treatment with steroids. Immunomagnetic CD8 depletion is a simple and reproducible method of selective T cell depletion. In combination with cyclosporine it appears to be effective in the prevention of severe acute GVHD in HLA-identical sibling transplants, but not in transplants from less perfectly matched donors.

Adult↗