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Biomedical subjects

M Osborne

Publications and source records attributed to M Osborne.

At least 19 recordsLinked to original sources
PubMed2005

The reliability of lymph-node staging in rectal cancer after preoperative chemoradiotherapy.

AIMS: To determine the prognostic significance of the nodal stage and number of nodes recovered in the surgical specimen after preoperative synchronous chemoradiation (SCRT) and surgery for locally advanced or unresectable rectal cancer. MATERIALS AND METHODS: One hundred and eighty-two consecutive patients with locally advanced or unresectable (T3/T4) rectal carcinomas were entered on a prospective database and treated in this department with preoperative chemoradiation, followed 6-12 weeks later by surgical resection. Most patients received chemotherapy in the form of low-dose folinic acid and 5-fluorouracil (5-FU) 350 mg/m2 via a 60-min infusion on days 1-5 and 29-33 of a course of pelvic radiotherapy delivered at a dose of 45 Gy in 25 fractions over 33 days to a planned volume. After resection, patients with a positive circumferential margin (< or = 1 mm), extranodal deposits or Dukes' C histology received adjuvant 5-FU-based-chemotherapy (n = 40). RESULTS: After SCRT, 161 patients underwent resection. Twenty-one patients remained unresectable or refused an exenterative operation. Median follow-up is 36 months. Down-staging was achieved in most patients, with 19 having a complete pathological response (pT0). The median number of lymph nodes recovered for all patients was five (range 0-21). The 3-year survival rate for node-positive patients is 47%, for node-negative patients with less than three lymph nodes recovered is 62% and for node-negative patients with three or more lymph nodes recovered is 70%. Compared with node-positive patients, simple regression models revealed a reduced hazard ratio (HR) of 0.72 (0.36-1.43) for node-negative patients with less than three nodes recovered and 0.48 (0.26-0.89) for node-negative patients with three or more lymph nodes recovered. In a multivariate model, including nodal status, excision status, age and sex only positive excision margins significantly predicted a poor outcome: HR = 3.05 (1.55-5.97). CONCLUSIONS: The number of nodes found after preoperative chemoradiation is a significant prognostic factor by univariate analysis. In this study, patients with node-negative histology, and at least three nodes recovered, had better long-term survival than patients in whom two or less nodes were recovered or with positive nodes. This effect was attenuated by the inclusion of excision status in multivariate models.

Adenocarcinoma↗
PubMed2005

Genetic and ecological dynamics of species replacement in an arid-land river system.

Museum records indicate that Hybognathus placitus was introduced into the Pecos River, New Mexico during the early 1960s. Approximately 10 years later, a congener, Hybognathus amarus, was extirpated from the system. We used microsatellite and mtDNA data, ecological data and modelling, and a computer simulation approach to reconstruct the history of invasion and species replacement. To identify the potential role of hybridization and introgression, we genetically screened H. amarus (n = 389) from the Rio Grande, New Mexico, and H. placitus (n = 424) from the Pecos River, New Mexico using four nuclear microsatellites and a partial fragment of the mtDNA ND4 gene. Assignment tests excluded hybridization as a primary factor in species replacement and suggested a role for interspecific competition. Genetic analyses showed that H. placitus were introduced into the Pecos River from at least two genetically distinct source populations in the Canadian and Red rivers, Oklahoma. Lotka-Volterra models of interspecific competition indicated that the number of founding individuals could have been as few as 20 for H. placitus to have competitively displaced H. amarus in the Pecos River in 10 to 15 generations. Observed differences of allele frequencies between source and founder populations indicated that between 32 and 115 H. placitus individuals founded the Pecos River. Genetic and ecological data suggest that interspecific competition could have led to species replacement in this arid-land river system.

Animals↗
PubMed2005

Topiramate ameliorates hyperglycaemia and improves glucose-stimulated insulin release in ZDF rats and db/db mice.

Topiramate (TPM) is a novel neurotherapeutic agent. Clinical studies reported that TPM treatment reduced body weight and decreased fasting blood glucose levels in obese patients with or without type 2 diabetes. It is unclear whether the blood glucose-normalizing phenomenon observed during TPM treatment is a primary effect or the consequence of reduced food intake and weight loss. In the present studies, we chronically treated female Zucker diabetic fatty (ZDF) rats (fed with a diabetogenic diet) and db/db mice with TPM (30-300 mg/kg/day) to examine the effect of TPM on hyperglycaemia and its relationship with food intake and body weight gain. Our data showed that TPM treatment markedly reduced blood glucose levels in both ZDF rats and db/db mice without a significant reduction in body weight gain. Pair-fed db/db mice treated with the vehicle alone did not exhibit a significant decrease in blood glucose levels compared with mice fed ad libitum. TPM treatment increased glucose-stimulated insulin release by 2-3-fold during an oral glucose tolerance test in both ZDF rats and db/db mice. We also observed a 1.4-fold increase of pancreatic insulin content and heightened insulin immunostaining in pancreatic beta cells in db/db mice treated with TPM. Our data suggest that the antidiabetic effect of TPM is independent of the changes in body weight gain and food intake. Improved glucose-induced insulin release may, in part, underlie the mechanisms by which TPM ameliorates the hyperglycaemia.

Abdomen↗
PubMed2003

Harvesting the radial artery: does it affect early postoperative hand function?

BACKGROUND: The radial artery (RA) is increasingly being used as a conduit for coronary artery bypass grafting. Previous studies have demonstrated that there is no significant deterioration in hand function in the long term. The aim of this study was to assess whether removal of the RA caused any alteration in the function or power of the hand 5 days postoperatively that would affect the patient's ability for self care on returning home. METHODS: A consecutive series of 37 patients undergoing RA harvesting was assessed over a period of 12 months from August 2000 to July 2001 as part of a prospective controlled trial. Grip power and fine motor skills in the operated hand were assessed preoperatively with an elasticated grip strength tester and an 18-hole peg board. This test was repeated 5 days postoperatively. The results were analyzed with a paired-sample t test to assess whether there was a significant difference between preoperative and postoperative hand function. RESULTS: The analysis showed that there was no statistically significant difference in fine motor function or grip power following surgery to harvest the RA. CONCLUSION: This study provides evidence to suggest that the RA can be safely harvested for use as a conduit in coronary artery bypass grafting, with no significant short-term deterioration in hand function.

Aged↗
PubMed2001

Recurrence rates in patients with central or retroareolar breast cancers treated with mastectomy or lumpectomy.

BACKGROUND: Although breast conservation with lumpectomy and radiation treatment has become a commonly used treatment for breast cancer, there are little data to support the use of lumpectomy for central and retroareolar breast cancers. In this study, we investigate the local and distant recurrence rates of patients with central or retroareolar breast cancers treated with lumpectomy compared with mastectomy. METHODS: This study provides a retrospective analysis of 99 patients, from 1981 to 2000, with central or retroareolar breast cancers treated with mastectomy or lumpectomy to determine the frequency of local and distant recurrence. The mastectomy and lumpectomy patients were compared with respect to recurrence and other prognostic factors including: tumor location, tumor size, axillary nodal status, and final surgical margins. RESULTS: The overall frequency of local recurrence was 5 of 99 (5.0%) in the entire group, 3 of 67 (4.5%) and 2 of 32 (6.3%) of patients who underwent mastectomy and lumpectomy, respectively (P >0.99). Overall, 3 patients experienced a distant recurrence as a first event, with 2 patients (3.0%) in the mastectomy group and 1 patient (3.1%) in the lumpectomy group (P >0.99). The type of surgical management was not statistically significant related to either local or distant disease recurrence, with median time to local recurrence of 3.0 years for the mastectomy patients and 5.0 years for lumpectomy patients. Of the patients with central tumors who underwent mastectomy 2 of 42 (4.8%) developed local recurrences compared with those who had a lumpectomy, 1 of 21 (4.8%). Similarly for retroareolar tumors, the local recurrence rate was 1 of 25 (4.0%) for patients undergoing mastectomy and 1 of 11 (9.1%) for those undergoing lumpectomy (P >0.99). CONCLUSIONS: In this study there was no significant difference in local or distant failure rates of those patients with central or retroareolar tumors treated with mastectomy versus lumpectomy. We conclude lumpectomy to be a reasonable treatment option for selected patients with central or retroareolar breast cancers.

Adult↗
PubMed2001

Field studies on equine influenza vaccination regimes in thoroughbred foals and yearlings.

SUMMARY: The purpose of these studies was to examine the response of Thoroughbred foals and yearlings to different influenza vaccines and vaccination regimes. The horses' antibody levels against haemagglutinin, an established correlate of protection were measured by haemagglutination inhibition. The first study investigated the extent to which maternal antibodies interfered with the humoral response to a subunit vaccine. The findings suggest that repeat vaccination in the face of maternal antibodies may induce tolerance as defined by serological testing. The second study compared the immune response elicited by a subunit immune stimulating complex (ISCOM) vaccine, an inactivated whole virus vaccine and the same product containing equine herpesviruses and equine reoviruses in addition to equine influenza virus. The monovalent vaccine induced a significantly better response than the ISCOM or the multivalent vaccine. The final study demonstrated that the inclusion of an additional booster vaccination, between the second and third vaccination recommended by the vaccine manufacturers and required under the rules of racing in certain countries, is of benefit to young horses. Since these studies were performed, several of the vaccines have been updated with more recent virus strains in line with WHO/OIE recommendations. However, the general principles investigated in the studies remain relevant to these vaccines.

Animals↗
PubMed2000

Bone marrow micrometastases in breast cancer patients.

BACKGROUND: The status of the axillary nodes has historically been the most important indicator of prognosis in breast cancer patients. However, approximately one third of node-negative patients recur with systemic disease. The detection of bone marrow micrometastases (BMM) may represent additional information in predicting distant recurrence and survival. METHODS: Bone marrow aspiration is obtained from the patient's anterior iliac crest at the time of breast cancer surgery. Cytospins are prepared from this aspirate and stained for polymerase chain reaction (PCR) analysis. RESULTS: Multiple studies have evaluated the clinical implications of BMM. The majority of studies have found a significant correlation between the presence of BMM and decreased survival. The information of bone marrow status may serve as a complement to axillary lymph node status in assessing the prognosis of breast cancer patients. CONCLUSIONS: There is a strong correlation between the presence of bone marrow micrometastases and poorer survival. These results may have an impact upon therapeutic recommendations in breast cancer patients.

Biopsy, Needle↗
PubMed2000

Value of a contrast agent in equivocal carotid ultrasound studies: pictorial essay.

The aim of the present study was to assess the use of an echo-enhancing agent (Levovist; Schering AG) in equivocal carotid bifurcation ultrasound studies and compare the information obtained with digital subtraction angiography (DSA). Contrast-enhanced carotid ultrasound studies were performed on 30 carotid bifurcations in 28 patients. The standard carotid ultrasound examinations were considered equivocal for two reasons: apparent acute internal carotid artery occlusions (n = 10), and possibly patent but critically stenosed internal carotid arteries with the residual flow lumen being incompletely visualized (n = 20). All patients underwent subsequent carotid digital subtraction angiography. All patients with apparent acute carotid occlusions (n = 10) were correctly characterized on contrast-enhanced ultrasound when compared with DSA. The majority were complete occlusions (n = 8) although in two cases there were critical carotid stenoses requiring surgical endarterectomy. In the 'incompletely visualized lumen' group (n = 20), the majority (n = 16) were correctly characterized on contrast enhanced ultrasound: 13 cases of critically stenotic but patent internal carotid arteries, two cases without a haemodynamically significant stenosis and one case of a carotid occlusion with patent vasa vasorum. One of the critical carotid stenoses was prospectively reported as occluded on the 'gold standard' angiography. In three cases the flow lumen was still incompletely visualized due to calcified plaque despite an echo-enhancing agent; angiography revealed no significant stenosis in all cases. There was one false negative for internal carotid occlusion. This occurred early in the series and could be considered to be a technical error. Importantly, there were no false positives for carotid occlusion. Contrast-enhanced carotid ultrasound significantly improves diagnostic confidence in equivocal carotid ultrasound studies. In appropriate clinical settings this may reduce the need for subsequent carotid angiography.

Acute Disease↗
PubMed1999

Pre-operative chemo-radiotherapy in locally advanced rectal cancer: is this the way of future management?

The purpose of the present paper was to update a prospective analysis (H Elsaleh et al. unpubl. data, 1997) investigating the effectiveness and toxicity of pre-operative pelvic radiotherapy with modest dose 5-fluorouracil (5-FU) in locally advanced rectal cancer (T3-T4). A total of 31 patients were assessed (28 T3 and three T4 tumours). Pre-operative pelvic radiotherapy was delivered in four fields, 45 Gy to the International Commission on Radiation Units and Measurements (ICRU) point in 25 fractions over 5 weeks. A radiosensitizing dose of 5-FU was delivered at 500 mg/m2 on days 1, 2 and 3, and days 22, 23 and 24. Mesorectal excision of the rectal tumour either by anterior or abdomino-perineal resection was planned at 4-6 weeks from completion of pre-operative treatment. Response to therapy was assessed by fresh macroscopic measurement of the surgical specimen. Patients had a low toxicity profile; an estimated 50% or greater response was seen in 24 out of 31 (two complete responses). There were no surgical difficulties achieving resection. No late complications were documented, although follow-up was short. In locally advanced rectal cancer, pre-operative chemo-radiotherapy had a low toxicity profile. Appropriately fractionated pre-operative chemo-radiotherapy is a reasonable option in this disease and should be further evaluated. The optimal method of delivery of the radiosensitizing agent (5-FU) is the subject of further investigation.

Adult↗
PubMed1999

Clinical experiences of medical students in Oregon with dying patients.

BACKGROUND: In Oregon only 31% of patients now die in acute care hospitals. This transformation carries profound implications for undergraduate medical education. METHODS: Students graduating from Oregon Health Sciences University between 1996 and 1998 were surveyed regarding their direct clinical involvement in the care of dying patients. RESULTS: Students had cared for substantial numbers of dying patients, and nearly all had participated in important advance planning discussions. However, student involvement had diminished markedly towards the latter stages of dying. Forty-five percent of the students had cared for two or fewer patients who died while still in the hospital. Even when patients died in the hospital, the students had rarely been present at the bedside at the time of patient death. Forty-two percent of the students had graduated having never witnessed a patient death. CONCLUSIONS: The findings highlight the need to create opportunities for students to care for dying patients in settings outside the acute care hospital.

Adult↗
PubMed1998

High throughput analysis of differential gene expression.

Elucidation of the changes in gene expression associated with biological processes is a central problem in biology. Advances in molecular and computational biology have led to the development of powerful, high-throughput methods for the analysis of differential gene expression. These tools have opened up new opportunities in disciplines ranging from cell and developmental biology to drug development and pharmacogenomics. In this review, the attributes of five commonly used differential gene expression methods are discussed: expressed sequence tag (EST) sequencing, cDNA microarray hybridization, subtractive cloning, differential display, and serial analysis of gene expression (SAGE). The application of EST sequencing and microarray hybridization is illustrated by the discovery of novel genes associated with osteoblast differentiation. The application of subtractive cloning is presented as a tool to identify genes regulated in vivo by the transcription factor pax-6. These and other examples illustrate the power of genomics for discovering novel genes that are important in biology and which also represent new targets for drug development. The central theme of the review is that each of the approaches to identifying differentially expressed genes is useful, and that the experimental context and subsequent evaluation of differentially expressed genes are the critical features that determine success.

Animals↗
PubMed1997

Predictors of intrusive thoughts and avoidance in women with family histories of breast cancer.

Having a family history of cancer is an important predictor of lifetime cancer risk. Individuals with family histories of cancer have been reported to experience symptoms of general distress and to have frequent intrusive thoughts and avoidance regarding cancer. To date, little is known about predictors of such distress. A relation between perception of cancer risk and distress has been suggested, but the possibility that prior cancer-related events may contribute to distress in these women has received little attention. The major aim of the study was to examine the contribution of the past experience of the death of a parent from cancer to distress in women at familiar risk for breast cancer. Women with family histories of breast cancer (Risk Group, N = 46) were assessed on the day of their yearly mammography screening and four to eight weeks after normal result notification in order to confirm the generalizability of their distress. Their levels of intrusive thoughts, avoidance, and perceived lifetime risk for breast cancer were significantly higher than those of women with no family histories of cancer who were not undergoing mammography (Comparison Group, N = 43), and this was true on both assessment days. Among the women in the Risk Group, those whose parent(s) had died of cancer had the highest levels of intrusive thoughts, avoidance, and perceived risk. Results suggested that perceived risk mediated the effect of this event on intrusive thoughts and avoidance regarding breast cancer. The findings are discussed in terms of theories of cognitive responses to traumatic and stressful life events. Implications for future research and interventions are discussed.

Adult↗
PubMed1997

Cancer prevention.

Explore the source record for details and available documents.

Anticarcinogenic Agents↗
PubMed1997

Prevalence of recurring BRCA mutations among Ashkenazi Jewish women with breast cancer.

The BRCA1 mutations 185delAG and 5382insC and the BRCA2 mutation 6174delT have been detected in a significant proportion of Ashkenazi Jewish women with early-onset breast cancer. A group of 236 Jewish women with breast cancer was screened for the presence of these alterations. Mutations were detected in 25.0% (59/236). Among women with breast cancer diagnosed at or before the age of 45, the prevalence of these mutations was 29.1% (42/144). Among women diagnosed with breast cancer after age 45, mutations were noted in 18.5% (17/92). Among women with a family history of breast or ovarian cancer, the likelihood of detecting a mutation was 32.1% (53/165). BRCA1 185delAG was the most common mutation overall (40/236, 16.9%). The ratio of BRCA1 185delAG to BRCA2 6174delT was 4.0 in women with early-onset breast cancer and 1.3 in women with breast cancer diagnosed after age 45. Clinical features such as age at diagnosis, family history of breast or ovarian cancer, bilateral breast cancer, and personal history of breast and ovarian cancer increase the likelihood of detecting mutations among Ashkenazi women with breast cancer. The yield of testing is low in the absence of any of these features.

Adult↗