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Biomedical subjects

R Owen

Publications and source records attributed to R Owen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Reconceptualising the outcomes of Continuing Professional Development.

This paper considers the potential outcomes, both positive and negative, of continuing professional development from the perspectives of practitioners and managers. Following a consideration of the literature it draws upon data collected during a 3-year evaluation of the English National Board Framework and Higher Award to highlight divergent views and tensions within Continuing Professional Development (CPD). Considerable discrepancies between practitioners and managers emerge which raise a number of searching questions about the value each group accords to continuing professional development. Based on the data a new framework for conceptualizing the outcomes of CPD is presented which fundamentally undermines a quasi-market approach.

Attitude of Health Personnel↗
PubMed2000

Cellular radiosensitivity and complication risk after curative radiotherapy.

PURPOSE: To test for an association between in vitro fibroblast radiosensitivity and complication risk in a case-control study of breast cancer patients treated under standard conditions in a clinical trial of radiotherapy dose fractionation. PATIENTS AND METHODS: A cohort of patients participating in a randomised clinical trial of radiotherapy dose fractionation was selected on the basis of treatment-induced changes in the breast several years later. Thirty-nine cases with marked normal tissue changes were matched on several variables with 65 controls with no changes attributable to radiotherapy. Dermal fibroblast strains were established from duplicate skin biopsies, and clonogenic cell survival assays performed in triplicate after both high ( approximately 1.6 Gy/min) and low ( approximately 1 cGy/min) dose-rate irradiation. Laboratory studies were blind to patient identity, treatment outcome and radiotherapy schedule. RESULTS: Analysis of 1128 clonogenic survival curves confirmed significant inter-patient variation in fibroblast radiosensitivity as measured by clonogenic survival. However, no association between fibroblast radiosensitivity and the development of late radiotherapy normal tissue effects was detected. CONCLUSIONS: Inter-individual variation in cellular radiosensitivity may not be the main determinant of complication risk in patients undergoing radiotherapy for breast cancer. Other biological and technical factors may be more important in explaining the marked inter-patient differences in normal tissue damage evident several years after curative radiotherapy.

Case-Control Studies↗
PubMed2000

The role of partial laryngeal resection in current management of laryngeal cancer: a collective review.

A spectrum of treatment plans and surgical procedures is available for management of early and moderately advanced laryngeal cancer. While the approach of chemotherapy and irradiation, or irradiation alone, followed by total laryngectomy for failure is often employed in practice by present day clinicians, the options of conventional conservation surgery (CCS), transoral endoscopic laser surgery (TLS) and supracricoid partial laryngectomy (SCPL) provide a wide choice of treatments that may help attain the goal of cure with preservation of laryngeal function and integrity of the airway. While CCS has been supplanted for many early-stage lesions by TLS and for more advanced stages by SCPL, centres throughout the world have reported favourable results with CCS, which is often modified to include resection of more extensive tumours than was previously possible. During the past decade a number of extended CCS procedures have been developed for management of glottic tumours involving both vocal cords and the anterior commissure, the paraglottic space and with vocal cord fixation, and for supraglottic tumours involving the glottis or hypopharynx. TLS has proved an effective, minimally invasive and functionally satisfactory procedure for management of suitable T1 and T2 glottic cancers, and stage I-III supraglottic cancers. The procedure may be effectively employed in combination with neck dissection and postoperative radiotherapy when necessary, particularly for moderately advanced supraglottic carcinomas. SCPL has proven effective in management of glottic and supraglottic cancers of all stages, even with involvement of paraglottic space and thyroid cartilage, provided at least one arytenoid unit can be preserved with clear margins. Invasion of cricoid cartilage is the most significant limitation for this procedure. All three surgical approaches have been employed for irradiation failure, but with greatly increased failure and complication rates compared with the results of treatment of non-irradiated patients. Thus a decision to treat laryngeal cancer initially with irradiation may preclude a satisfactory result from partial laryngectomy should radiation fail. The treatment of laryngeal cancer should be individualized according to the size and extent of the tumour, the age and physical condition of the patient, and the skill and experience of the surgeon with various treatment modalities and surgical procedures.

Combined Modality Therapy↗
PubMed2000

Beneficial effects of viscous dietary fiber from Konjac-mannan in subjects with the insulin resistance syndrome: results of a controlled metabolic trial.

OBJECTIVE: Dietary fiber has recently received recognition for reducing the risk of developing diabetes and heart disease. The implication is that it may have therapeutic benefit in prediabetic metabolic conditions. To test this hypothesis, we investigated the effect of supplementing a high-carbohydrate diet with fiber from Konjac-mannan (KJM) on metabolic control in subjects with the insulin resistance syndrome. RESEARCH DESIGN AND METHODS: We screened 278 free-living subjects between the ages of 45 and 65 years from the Canadian-Maltese Diabetes Study. A total of 11 (age 55+/-4 years, BMI 28+/-1.5 kg/m2) were recruited who satisfied the inclusion criteria: impaired glucose tolerance, reduced HDL cholesterol, elevated serum triglycerides, and moderate hypertension. After an 8-week baseline, they were randomly assigned to take either KJM fiber-enriched test biscuits (0.5 g of glucomannan per 100 kcal of dietary intake or 8-13 g/day) or wheat bran fiber (WB) control biscuits for two 3-week treatment periods separated by a 2-week washout. The diets were isoenergetic, metabolically controlled, and conformed to National Cholesterol Education Program Step 2 guidelines. Serum lipids, glycemic control, and blood pressure were the outcome measures. RESULTS: Decreases in serum cholesterol (total, 12.4+/-3.1%, P<0.004; LDL, 22+/-3.9%, P<0.002; total/HDL ratio, 15.2+/-3.4%, P<0.003; and LDL/HDL ratio, 22.2+/-4.1%, P< 0.002), apolipoprotein (apo) B (15.1+/-4.3%, P<0.0004), apo B/A-1 ratio (13.1+/-3.4%, P< 0.0003), and serum fructosamine (5.2+/-1.4%, P<0.002) were observed during KJM treatment compared with WB-control. Fasting blood glucose, insulin, triglycerides, HDL cholesterol, and body weight remained unchanged. CONCLUSIONS: A diet rich in high-viscosity KJM improves glycemic control and lipid profile, suggesting a therapeutic potential in the treatment of the insulin resistance syndrome.

Aged↗
PubMed2000

Extraprostatic biopsy improves the staging of localized prostate cancer.

OBJECTIVE: To evaluate the role and safety of biopsy of the seminal vesicles and neurovascular bundles in determining the pathologic stage of prostatic carcinoma. METHODS: Eighty-one consecutive patients were enrolled in a comprehensive cryosurgical biopsy protocol that included sextant intraprostatic plus extraprostatic biopsy. The pathologic stage, determined after biopsy, was compared with the clinical stage, determined by digital rectal examination (DRE) and transrectal ultrasonographic (TRUS) evaluation. As well, complication rates for these patients were compared with rates for a separate group that underwent sextant intraprostatic biopsy alone. RESULTS: Of the 81 patients, 61 (75%) were confirmed to have cancer by biopsy. None of these patients was considered to have extraprostatic extension by clinical evaluation (DRE and TRUS), but 16 of 61 (26%) were identified to have extraprostatic cancer in the seminal vesicles (8 of 61, 13%) or in the neurovascular bundles (8 of 61, 13%) by extraprostatic biopsy. There was no significant difference in the complication rates between sextant intraprostatic biopsy and sextant intraprostatic plus extraprostatic biopsy (p>0.97). CONCLUSIONS: Extraprostatic biopsy identifies extension of carcinoma in a large proportion of patients in whom clinical evaluation by DRE and TRUS indicates organ-confined disease. Extraprostatic biopsy is therefore warranted as routine evaluation before surgery in order to correctly stage prostatic carcinoma and select appropriate therapy.

Adult↗
PubMed1999

Impact of travel distance on the disposition of patients presenting for emergency psychiatric care.

For veterans presenting for emergency psychiatric care, this research tested the hypothesis that patients with poor geographic accessibility to ambulatory mental health services would be more likely to be hospitalized. Logistic regression results indicated that distant patients (> 60 miles) were 4.8 times more likely (p < .05) to be admitted for acute psychiatric treatment than were proximal patients (< 60 miles), controlling for clinical and demographic case-mix factors. This finding suggests that the Department of Veterans Affairs might be less effective in its effort to substitute intensive outpatient care in place of expensive inpatient treatment for rural veterans with emergent mental health problems.

Adult↗
PubMed1999

Glycogen synthase kinase 3beta phosphorylation of microtubule-associated protein 1B regulates the stability of microtubules in growth cones.

We have recently shown that glycogen synthase kinase 3beta (GSK3beta) phosphorylates the microtubule-associated protein (MAP) 1B in an in vitro kinase assay and in cultured cerebellar granule cells. Mapping studies identified a region of MAP1B high in serine-proline motifs that is phosphorylated by GSK3beta. Here we show that COS cells, transiently transfected with both MAP1B and GSK3beta, express high levels of the phosphorylated isoform of MAP1B (MAP1B-P) generated by GSK3beta. To investigate effects of MAP1B-P on microtubule dynamics, double transfected cells were labelled with antibodies to tyrosinated and detyrosinated tubulin markers for stable and unstable microtubules. This showed that high levels of MAP1B-P expression are associated with the loss of a population of detyrosinated microtubules in these cells. Transfection with MAP1B protected microtubules in COS cells against nocodazole depolymerisation, confirming previous studies. However, this protective effect was greatly reduced in cells containing high levels of MAP1B-P following transfection with both MAP1B and GSK3beta. Since we also found that MAP1B binds to tyrosinated, but not to detyrosinated, microtubules in transfected cells, we propose that MAP1B-P prevents tubulin detyrosination and subsequent conversion of unstable to stable microtubules and that this involves binding of MAP1B-P to unstable microtubules. The highest levels of MAP1B-P are found in neuronal growth cones and therefore our findings suggest that a primary role of MAP1B-P in growing axons may be to maintain growth cone microtubules in a dynamically unstable state, a known requirement of growth cone microtubules during pathfinding. To test this prediction, we reduced the levels of MAP1B-P in neuronal growth cones of dorsal root ganglion cells in culture by inhibiting GSK3beta with lithium. In confirmation of the proposed role of MAP1B-P in maintaining microtubule dynamics we found that lithium treatment dramatically increased the numbers of stable (detyrosinated) microtubules in the growth cones of these neurons.

Animals↗
PubMed1999

Konjac-mannan (glucomannan) improves glycemia and other associated risk factors for coronary heart disease in type 2 diabetes. A randomized controlled metabolic trial.

OBJECTIVE: To examine whether Konjac-mannan (KJM) fiber improves metabolic control as measured by glycemia, lipidemia, and blood pressure in high-risk type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 11 hyperlipidemic and hypertensive type 2 diabetic patients treated conventionally by a low-fat diet and drug therapy participated. After an 8-week baseline, all were randomly assigned to take either KJM fiber-enriched test biscuits (0.7 g/412 kJ [100 kcal] of glucomannan) or matched placebo wheat bran fiber biscuits during two 3-week treatment phases separated by a 2-week washout period. The diet in either case was metabolically controlled and conformed to National Cholesterol Education Program Step 2 guidelines, while medications were maintained constant. Efficacy measures included serum fructosamine, lipid profiles, apolipoproteins, blood pressure, body weight, and nutritional analysis. RESULTS: Compared with placebo, KJM significantly reduced the metabolic control primary end points: serum fructosamine (5.7%, P = 0.007, adjusted alpha = 0.0167), total:HDL cholesterol ratio (10%, P = 0.03, adjusted alpha = 0.05), and systolic blood pressure (sBP) (6.9%, P = 0.02, adjusted alpha = 0.025). Secondary end points, including body weight, total, LDL, and HDL cholesterol, triglycerides, apolipoproteins A-1, B, and their ratio, glucose, insulin, and diastolic blood pressure, were not significant after adjustment by the Bonferroni-Hochberg procedure. CONCLUSIONS: KJM fiber added to conventional treatment may ameliorate glycemic control, blood lipid profile, and sBP in high-risk diabetic individuals, possibly improving the effectiveness of conventional treatment in type 2 diabetes.

Apolipoproteins↗
PubMed1998

A comparison between colour duplex ultrasonography and arteriography for imaging infrapopliteal arterial lesions.

OBJECTIVE: To investigate the agreement between colour duplex ultrasonography and digital subtraction arteriography of the infrapopliteal arteries. DESIGN: Retrospective, blinded study. SETTING: Vascular laboratory and Radiology Department, University Hospital. METHODS: The infrapopliteal vasculature was examined in a total of 51 limbs by both colour duplex ultrasound and digital subtraction angiography. By examining all arteries from the distal popliteal to the pedal arteries, a total of 204 individual arterial segments were available for analysis. Each segment was graded as 0-49%, 50-99% diameter reduced or occluded by both modalities. Using ultrasound, classification of stenoses was achieved by observing peak systolic velocity ratios; a doubling of peak systolic velocity indicating a > or = 50% diameter reducing stenosis. Where no Doppler signal could be obtained, the vessel was assumed to be occluded. From angiographic studies, two radiologists separately and blindly assessed the extent of disease for each infrapopliteal artery noting areas of > or = 50% diameter reduction and occlusion. The Kappa statistic was used to examine the level of agreement between angiography and ultrasound as well as between both radiologists. RESULTS: The Kappa level (95% confidence interval) of agreement between ultrasound and angiographic assessments for distinguishing patent from occluded segments was 0.61 (0.49-0.74) for all segments. The equivalent agreement between radiologists was 0.80 (0.70-0.89). Poorest agreement was observed from ultrasound assessments of the peroneal and tibioperoneal trunk arterial segments. CONCLUSION: Since agreement between colour duplex scanning and angiography never fell significantly below levels achieved between two radiologists, we conclude that colour duplex ultrasound can be used to assess infrapopliteal artery patency.

Aged↗
PubMed1998

Heterozygosity for mutations in the ataxia telangiectasia gene is not a major cause of radiotherapy complications in breast cancer patients.

Of patients being treated by radiotherapy for cancer, a small proportion develop marked long-term radiation damage. It is believed that this is due, at least in part, to intrinsic individual differences in radiosensitivity, but the underlying mechanism is unknown. Individuals affected by the recessive disease ataxia telangiectasia (AT) exhibit extreme sensitivity to ionizing radiation. Cells from such individuals are also radiosensitive in in vitro assays, and cells from AT heterozygotes are reported to show in vitro radiosensitivity at an intermediate level between homozygotes and control subjects. In order to examine the possibility that a defect in the ATM gene may account for a proportion of radiotherapy complications, 41 breast cancer patients developing marked changes in breast appearance after radiotherapy and 39 control subjects who showed no clinically detectable reaction after radiotherapy were screened for mutations in the ATM gene. One out of 41 cases showing adverse reactions was heterozygous for a mutation (insertion A at NT 898) that is predicted to generate a truncated protein of 251 amino acids. No truncating mutations were detected in the control subjects. On the basis of this result, the estimated percentage (95% confidence interval) of AT heterozygous patients in radiosensitive cases was 2.4% (0.1-12.9%) and in control subjects (0-9.0%). We conclude that ATM gene defects are not the major cause of radiotherapy complications in women with breast cancer.

Ataxia Telangiectasia↗
PubMed1996

Determination of CYP2C19 phenotype in black Americans with omeprazole: correlation with genotype.

BACKGROUND: Our objective was to study omeprazole as a single-dose oral probe in the determination of CYP2C19 phenotype in black subjects and to determine the correlation between phenotype and genotype. METHODS: This single-dose, open-label outpatient study was conducted at a community-based, university-affiliated teaching hospital outpatient clinic. Study subjects were 100 healthy, unrelated black adults (age range, 18 to 50 years) who were receiving no medications. Baseline omeprazole and 2-hour postingestion omeprazole and 5'-hydroxyomeprazole concentrations were measured for phenotype determination. Identification of CYP2C19m1 genotypes were performed with use of the polymerase chain reaction. RESULTS: Results were obtained for 28 men and 72 women. Ninety-eight subjects were found to be phenotypically extensive metabolizers and two to be poor metabolizers (one man; one smoker). Genotype determination revealed that the two poor metabolizers of omeprazole were homozygous for a single base pair mutation (m1/m1) in exon 5 of CYP2C19. Twenty-eight of the extensive metabolizers were heterozygous (m1/wt) and the remaining 70 were homozygous (wt/wt). No side effects were reported. CONCLUSIONS: The 2% prevalence rate of poor CYP2C19 metabolizers in this healthy black population residing in the Midwestern United States is similar to that reported in white subjects and in the Shona population of Zimbabwe but much less than in Asian subjects. Omeprazole is a safe and specific probe of the CYP2C19 enzyme system that correlates well with genotype.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

A new dietary model to study colorectal carcinogenesis: experimental design, food preparation, and experimental findings.

Experimental dietary studies of human colorectal carcinogenesis are usually based on the AIN-76A diet, which is dissimilar to human food in source, preparation, and content. The aims of this study were to examine the feasibility of preparing and feeding rats the diet of a specific human population at risk for colorectal neoplasia and to determine whether changes in the colonic morphology and metabolic contents would differ from those resulting from a standard rat diet. The mean daily food intake composition of a previously evaluated adenoma patient case-control study was used for the "human adenoma" (HA) experimental diet. Foods were prepared as for usual human consumption and processed by dehydration to the physical characteristics of an animal diet. Sixty-four female Sprague-Dawley rats were randomized and fed ad libitum the HA or the AIN-76A diet. Every eight weeks, eight rats from each group were sacrificed, and the colons and contents were examined. Analysis of the prepared food showed no significant deleterious changes; food intake and weight gain were similar in both groups. Compared with the controls, the colonic contents of rats fed the HA diet contained significantly less calcium, concentrations of neutral sterols, total lipids, and cholic and deoxycholic acids were increased, and there were no colonic histological changes other than significant epithelial hyperproliferation. This initial study demonstrated that the HA diet can be successfully processed for feeding to experimental animals and is acceptable and adequate for growth but induces significant metabolic and hyperproliferative changes in the rat colon. This dietary model may be useful for studies of human food, narrowing the gap between animal experimentation and human nutritional research.

Adenoma↗
PubMed1996

Head injury.

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Brain Injuries↗