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Biomedical subjects

S Ross

Publications and source records attributed to S Ross.

At least 55 records · Page 3Linked to original sources

Assessing dissatisfaction with an out of hours service: reasons and remedies.

OBJECTIVE: To identify characteristics associated with dissatisfaction following contact with an out of hours co-operative in Glasgow, and to identify reasons for this dissatisfaction. To make recommendations for good practice in the light of these findings. DESIGN: Survey of attenders during one week of operation of an out of hours co-operative. Analysis of factors associated with dissatisfaction. SETTING: The Glasgow Emergency Medical Service, October 1996. SUBJECTS: Questionnaires were received from 1115 patients or their carers, representing a 69.3% response rate. RESULTS: Dissatisfaction was associated with unmet expectations, particularly among those expecting home visits. Parents of young children, more affluent patients, and those experiencing problems with daytime services also tended to be dissatisfied. Seventy four (7%) respondents indicated that they were very dissatisfied with aspects of the service. A high proportion of this dissatisfaction was related to telephone contact. Transport to out of hours centres caused problems for some patients, particularly for those with young children. Perceptions of dismissive attitudes by medical staff, and of incorrect diagnoses and treatment were causes of strong dissatisfaction. Patients with adverse medical outcomes were also likely to be very dissatisfied. CONCLUSION: Clear reasons for dissatisfaction were found among our sample. In most cases, remedial management action could be taken to reduce the likelihood of major dissatisfaction with the service.

Adolescent↗

Characterization of Alzheimer's beta -secretase protein BACE. A pepsin family member with unusual properties.

The cerebral deposition of amyloid beta-peptide is an early and critical feature of Alzheimer's disease. Amyloid beta-peptide is released from the amyloid precursor protein by the sequential action of two proteases, beta-secretase and gamma-secretase, and these proteases are prime targets for therapeutic intervention. We have recently cloned a novel aspartic protease, BACE, with all the known properties of beta-secretase. Here we demonstrate that BACE is an N-glycosylated integral membrane protein that undergoes constitutive N-terminal processing in the Golgi apparatus. We have used a secreted Fc fusion-form of BACE (BACE-IgG) that contains the entire ectodomain for a detailed analysis of posttranslational modifications. This molecule starts at Glu(46) and contains four N-glycosylation sites (Asn(153), Asn(172), Asn(223), and Asn(354)). The six Cys residues in the ectodomain form three intramolecular disulfide linkages (Cys(216)-Cys(420), Cys(278)-Cys(443), and Cys(330)-Cys(380)). Despite the conservation of the active site residues and the 30-37% amino acid homology with known aspartic proteases, the disulfide motif is fundamentally different from that of other aspartic proteases. This difference may affect the substrate specificity of the enzyme. Taken together, both the presence of a transmembrane domain and the unusual disulfide bond structure lead us to conclude that BACE is an atypical pepsin family member.

Amino Acid Sequence↗

Primary and secondary care management of women with early breast cancer from affluent and deprived areas: retrospective review of hospital and general practice records.

OBJECTIVES: To investigate whether poorer survival of breast cancer among deprived women compared with affluent women is related to their NHS care. DESIGN: Retrospective review of hospital and general practice case records. SETTING: Greater Glasgow Health Board area. SUBJECTS: Women diagnosed with breast cancer in 1992-3 who lived in the most affluent (deprivation categories 1 and 2) and the most deprived areas (deprivation categories 6 and 7) of Glasgow (Carstairs and Morris deprivation index). MAIN OUTCOME MEASURES: Breast cancer treatment, time from general practice consultation to clinic visit and surgery, and details of hospital admissions and follow up in primary and secondary care. RESULTS: The access to care and surgical and oncological treatment of women from affluent and deprived areas were similar. Admissions to hospital for problems not related to breast cancer were more common in those living in deprived areas (number admitted once or more: 51 (24%) v 13 (10%), P=0.001). Consultation patterns in general practice by the second year after diagnosis showed women in deprived areas consulting more frequently than women in affluent areas (median (interquartile range) number of consultations (5 (2-10) v 7 (4-13), P=0.01). CONCLUSION: Women living in affluent areas did not receive better NHS care for breast cancer than women in deprived areas. However, women from deprived areas seem to have greater comorbidity, and poorer outcomes from breast cancer among these women is probably due to factors which result in deprived communities having poorer health outcomes rather than to management of their breast cancer.

Adult↗

Socio-economic deprivation and stage of disease at presentation in women with breast cancer.

BACKGROUND: This study describes and compares the pathological prognostic factors and surgeon assessment of stage of breast cancer of women living in affluent and deprived areas to assess whether clinical stage at presentation may explain the known poorer survival outcomes for deprived women. PATIENTS AND METHODS: A population-based review of the case records of 417 women with breast cancer was carried out. RESULTS: No difference in pathological criteria was found between the 88% of women living in affluent and deprived areas for whom such data were available. Clinical assessment of the remaining 50 cases showed that women living in deprived areas were more likely to present with locally advanced or metastatic disease. CONCLUSION: The poorer survival of women from deprived areas with breast cancer may be explained by more deprived women presenting with advanced cancers.

Breast Neoplasms↗

Reduced risk of persisting cytomegalovirus pp65 antigenemia and cytomegalovirus interstitial pneumonia following allogeneic PBSCT.

In order to evaluate the risk of cytomegalovirus (CMV) associated disease after allogeneic stem cell transplantation (SCT), 158 consecutive patients at risk for infection were analyzed. BMT was performed in 101 patients and peripheral blood stem cell transplantation (PBSCT) in 57 patients. CMV antigenemia was found in 57 cases (56%) after BMT and 27 cases (47%) after PBSCT, respectively. CMV antigenemia resistant to a 14-day course of GCV was found in 26 patients (26%) after BMT but in only four patients (7%) after PBSCT (P < 0.01). Eighteen patients (11%) developed CMV disease, 14 post BMT and four post PBSCT. Lethal CMV-related interstitial pneumonia (CMV-IP) occurred in 13 cases of whom 12 patients were bone marrow recipients (P = 0.04). The subgroup of seronegative patients with a CMV seropositive donor had a significantly lower risk of developing CMV antigenemia, GCV-resistant CMV antigenemia (P < 0.01) and CMV-related disease (P = 0.01). In conclusion, the incidence of persistent CMV antigenemia and CMV-IP was significantly reduced when allogeneic transplantation was performed with peripheral blood stem cells instead of bone marrow. These findings suggest that our previous in vitro data on improved immune reconstitution after allogeneic PBSCT as compared to allogeneic BMT have clinical relevance.

Adolescent↗

Long-term comparison of losartan and enalapril on kidney function in hypertensive type 2 diabetics with early nephropathy.

BACKGROUND: The objectives of this study were to compare the effects of the angiotensin II receptor blocker, losartan, to those of the angiotensin-converting enzyme inhibitor, enalapril, on albuminuria and renal function in relationship to clinic and ambulatory blood pressure (ABP) in hypertensive type 2 diabetic subjects with early nephropathy. The tolerability of these agents and their effect on the metabolic profile were also evaluated. METHODS: The study was a one-year prospective, double-blind trial with losartan and enalapril administered alone or in combination with hydrochlorothiazide and other antihypertensive agents. ABP and renal and biochemical parameters were measured at baseline and after 12, 28, and 52 weeks of active treatment. Ninety-two hypertensive type 2 diabetics with early nephropathy completed the study. RESULTS: Both losartan and enalapril administered alone or in combination with other agents induced significant reductions in sitting clinic (P < 0.05) and ABP (P < 0.002) without a statistical difference between groups. Geometric means for urinary albumin excretion (UAE) decreased significantly (P < 0.001) in patients treated with losartan from 64. 1 to 41.5 microg/min and in those treated with enalapril from 73.9 to 33.5 microg/min after 52 weeks of therapy. A significant relationship (P < 0.05) between changes in systolic and diastolic ABP and the decrease in UAE at 52 weeks was seen in both groups. The decline in glomerular filtration rate (GFR) was stabilized at the end of therapy and was identical in both treatment groups. Treatment with enalapril was associated with a significantly higher incidence of cough (P = 0.006) and a rise in serum uric acid (P = 0.002) compared with losartan. CONCLUSIONS: Our results indicate that a one-year course of antihypertensive therapy with either losartan or enalapril significantly reduces UAE in hypertensive type 2 diabetic patients with early nephropathy. The reduction in UAE with each treatment is similarly related to decrements in ABP. In addition, the rate of decline in GFR is similar in both treatment groups.

Aged↗

Dietary management of feline chronic renal failure: where are we now? In what direction are we headed?

Dietary modification is of primary importance in managing cats with chronic renal failure. Diets designed for cats with chronic renal failure are typically formulated to be pH neutral and contain reduced quantities of protein, phosphorus and sodium and an increased quantity of potassium. These changes in diet formulation are designed to ameliorate clinical signs of renal failure by adapting dietary intakes to meet the limited ability of failing kidneys to adapt to the normal range of dietary intakes. Important recent clinical trials support the therapeutic value of dietary therapy in cats with chronic renal failure.

Acidosis↗

Functional foods: the Food and Drug Administration perspective.

Because the Federal Food, Drug, and Cosmetic Act (FFDCA) does not provide a statutory definition of functional foods, the Food and Drug Administration has no authority to establish a formal regulatory category for such foods. The primary determinant of the regulatory status of a food is its intended use, which is determined largely by the label and labeling information accompanying the product. This information includes nutrient information, nutrient content claims, and various types of health claims. In marketing these foods, manufacturers may come under one of several existing regulatory options. The first decision manufacturers will make that will help determine their product's regulatory status is whether the product is a food or a drug. Thus, manufacturers and retailers have a range of legal and regulatory categories in which their products may be classified. This article describes the definitions provided in the FFDCA for a drug and a food, the safety and labeling requirements of various food categories, and types of possible claims for dietary supplements.

Dietary Supplements↗

Fentanyl protects the heart against ischaemic injury via opioid receptors, adenosine A1 receptors and KATP channel linked mechanisms in rats.

We have investigated if fentanyl protects against myocardial ischaemic injury and if so, if the mechanism of this protection is mediated via opioid and adenosine A1 receptors, and KATP channels. Langendorff rat hearts were subjected to global ischaemia (30 min) and reperfusion (60 min). The drugs were administered before induction of ischaemia and maintained throughout the experiment. Treatment with fentanyl 740 nmol litre-1 improved post-ischaemic mechanical function, assessed as developed pressure, +dP/dtmax and -dP/dtmin, compared with controls after 60 min of reperfusion. These effects were abolished by naloxone 1 mumol litre-1, DPCPX 10 mumol litre-1, a selective adenosine A1 antagonist and sodium 5-hydroxydecanoate 100 mumol litre-1, a K+ATP channel blocker. We conclude that fentanyl protected the heart against post-ischaemic injury by a mechanism which was blocked by an opioid and an adenosine A1 receptor antagonist and also by a KATP channel antagonist.

Adenosine Triphosphate↗

Blunt splenic injury in adults: Multi-institutional Study of the Eastern Association for the Surgery of Trauma.

BACKGROUND: Nonoperative management of blunt injury to the spleen in adults has been applied with increasing frequency. However, the criteria for nonoperative management are controversial. The purpose of this multi-institutional study was to determine which factors predict successful observation of blunt splenic injury in adults. METHODS: A total of 1,488 adults (>15 years of age) with blunt splenic injury from 27 trauma centers in 1997 were studied through the Multi-institutional Trials Committee of the Eastern Association for the Surgery of Trauma. Statistical analysis was performed with analysis of variance and extended chi2 test. Data are expressed as mean +/- SD; a value of p < 0.05 was considered significant. RESULTS: A total of 38.5 % of patients went directly to the operating room (group I); 61.5% of patients were admitted with planned nonoperative management. Of the patients admitted with planned observation, 10.8% failed and required laparotomy; 82.1% of patients with an Injury Severity Score (ISS) < 15 and 46.6% of patients with ISS > 15 were successfully observed. Frequency of immediate operation correlated with American Association for the Surgery of Trauma (AAST) grades of splenic injury: I (23.9%), II (22.4%), III (38.1%), IV (73.7%), and V (94.9%) (p < 0.05). Of patients initially managed nonoperatively, the failure rate increased significantly by AAST grade of splenic injury: I (4.8%), II (9.5%), III (19.6%), IV (33.3%), and V (75.0%) (p < 0.05). A total of 60.9% of the patients failed nonoperative management within 24 hours of admission; 8% failed 9 days or later after injury. Laparotomy was ultimately performed in 19.9% of patients with small hemoperitoneum, 49.4% of patients with moderate hemoperitoneum, and 72.6% of patients with large hemoperitoneum. CONCLUSION: In this multicenter study, 38.5% of adults with blunt splenic injury went directly to laparotomy. Ultimately, 54.8% of patients were successfully managed nonoperatively; the failure rate of planned observation was 10.8%, with 60.9% of failures occurring in the first 24 hours. Successful nonoperative management was associated with higher blood pressure and hematocrit, and less severe injury based on ISS, Glasgow Coma Scale, grade of splenic injury, and quantity of hemoperitoneum.

Adult↗

Coronary risk profiles in men with coronary artery disease: effects of body composition, fat distribution, age and fitness.

BACKGROUND: Few studies have investigated the influence of body composition, abdominal obesity, age and fitness on coronary risk factors in populations of patients with coronary heart disease (CHD). We investigated whether abdominal obesity or generalized adiposity is a better predictor of cardiovascular risk in men with coronary artery disease (CAD), and the effects of exercise training on coronary risk factors in younger and older patients with CAD. METHODS: The study population consisted of 81 male patients aged 33-83 years (mean +/- SD 60.0 +/- 13.3 years) with established CAD. We studied the relationships among body composition, body fat distribution, dietary intake, peak aerobic capacity, lipid concentrations, and plasma glucose and insulin concentrations. We subsequently measured the influence of exercise training on these components. RESULTS: The study population was characterized by a high prevalence of obesity, particularly in younger patients. Body mass index, rather than body fat distribution, was the best anthropometric predictor of plasma triglyceride concentrations (r2 = 0.11, P < 0.05) and cholesterol/high-density lipoprotein cholesterol (HDL-C) ratio (r2 = 0.13, P < 0.01). Body weight, rather than body fat distribution, was the best predictor of plasma HDL-C concentration (r2 = 0.14, P < 0.01) and fasting glucose concentrations (r2 = 0.10, P < 0.05). Fat mass was the best anthropometric predictor of fasting plasma insulin concentrations (r2 = 0.38, P < 0.0001) and for the glucose-insulin ratio (r2 = 0.39, P < 0.0001) in men with CAD. Younger patients tended to have greater improvements in HDL-C concentrations and the cholesterol:HDL-C ratio than did older individuals, as a result of exercise training. CONCLUSION: In men with CAD, general measures of obesity, such as body weight, body mass index, and fat mass are better predictors of coronary risk factors than body fat distribution. Younger and older men with CAD experienced similar improvements in body composition and body fat distribution after an exercise training program.

Adult↗

Prediabetes and perinatal mortality.

OBJECTIVE: The association between gestational diabetes mellitus (GDM) and perinatal outcome is largely based on case series and retrospective studies that found an increased risk of perinatal mortality and stillbirth as the onset of diabetes approached. Our objective was to assess the relationship between latency to diabetes and perinatal outcome of prediabetic pregnancies in a contemporary population of women with adult-onset diabetes. RESEARCH DESIGN AND METHODS: A population of 403 diabetic women from two recruitment sites completed a pretested questionnaire. RESULTS: Details of 1,181 pregnancy outcomes were obtained. This comprised 1,024 live births, 22 stillbirths, and 8 early neonatal deaths. Crude analysis suggested a relationship between time to diabetes (latency) < or =20 years and both perinatal death and stillbirth: odds ratio (95% CI), 2.41 (1.17-4.95) and 2.15 (0.93-4.98). Generalized additive modeling revealed a nonlinear relationship between the variables time to diabetes, and maternal age and perinatal outcome. Final logistic regression analysis was then performed for the outcomes perinatal death and stillbirth, with maternal age as a second-degree polynomial, year of birth as a continuous variable, and time to diabetes dichotomized < or =20 years to diagnosis and >20 years. This final analysis documented a significant association between time to diabetes < or =20 years and both perinatal death (4.06 [1.79-9.36]) and stillbirth (3.35 [1.25-9.05]). CONCLUSIONS: There appeared to be an increased risk of perinatal death and stillbirth in pregnancies occurring in the last 20 years before the diagnosis of diabetes.

Cohort Studies↗

Thrombin causes pseudopod detachment via a pathway involving cytosolic phospholipase A2 and 12/15-lipoxygenase products.

Thrombin causes rapid pseudopod detachment and shortening in Dunning rat prostatic carcinoma (MAT-Lu) cells. As seen by interference reflection microscopy and by immunofluorescence analysis with antibodies to paxillin and talin, the primary event is disassembly of adhesion sites. Biochemically, thrombin is a potent activator of cytosolic phospholipase A2 and increases eicosanoid production in these cells. The pseudopod effects are blocked by lipoxygenase (but not cyclooxygenase) inhibitors. Arachidonic acid and 12(S)-hydroxyeicosatetraenoic acid or 15(S)-hydroxyeicosatetraenoic acid mimic the thrombin effect. We conclude that in certain cancer cells, thrombin is a pseudopod repellent that exerts its effect via a cascade involving cytosolic phospholipase A2, 12/15-lipoxygenase, and 12(S)- and/or 15(S)-hydroxyeicosatetraenoic acid.

Animals↗

A randomized placebo-controlled double-blind trial of lipid-lowering strategies in patients with renal insufficiency: diet modification with or without fenofibrate.

BACKGROUND: Renal insufficiency is characterized by lipoprotein abnormalities including elevated triglyceride levels. PATIENTS AND METHODS: The safety and efficacy of micronized fenofibrate as a treatment for dyslipidemia in patients with progressive renal insufficiency was evaluated in a randomized, placebo-controlled double-blind study comparing fenofibrate and dietary modification to dietary modification alone. Patients were evaluated following a 3-month pre-randomization period of dietary counseling. Twenty-eight patients with moderate renal insufficiency and triglyceride levels 2.3 mmol/l or LDL/HDL ratio 5 were randomized to placebo (n = 12) or fenofibrate (n = 16) therapy. Treatment and dietary counseling continued for 6 months. RESULTS: Ten of 16 patients (63%) treated with fenofibrate achieved a 30% reduction in triglyceride levels or LDL/HDL ratio reduction < 5 compared to 2 of 17% in the placebo group (p = 0.015). Triglyceride levels were significantly reduced in the fenofibrate group (-31%) versus placebo (+1.3%, p = 0.003). In compliant patients (n = 25) there was also a significantly greater increase in HDL cholesterol levels in the fenofibrate group (+19.9%) compared to placebo (-4.7%, p = 0.001). Changes in measured creatinine clearance were not significantly different between the groups and there were no serious adverse effects of treatment. CONCLUSION: Fenofibrate therapy combined with dietary modification effectively reduced triglyceride levels in renal insufficiency patients without serious adverse effects.

Adult↗

Social variation in reasons for contacting general practice out-of-hours: implications for daytime service provision?

BACKGROUND: Contact with general practice out-of-hours services increases with socioeconomic deprivation. The reasons for this association are unclear but may include variations in access to daytime services or differences in morbidity. AIM: To identify the reasons for contact with the Glasgow Emergency Medical Service (GEMS) in relation to patient sociodemographic characteristics and the nature of the presenting problem. METHOD: All contacts with GEMS over a one-week period (n = 3193) in October 1996 were identified and a random 1:2 sample were sent a postal questionnaire investigating their reasons for contacting the service. Sociodemographic data and presenting problems were extracted from the service contact sheet. Data were analysed using correspondence analysis. RESULTS: Correspondence analysis identified two factors characterised as 'perceived problems with daytime services' and 'perceived urgency'. Scores on the former dimension were significantly associated with age (P < 0.0001), gender (P < 0.0001), socioeconomic category (P < 0.0001), and presenting problem (P = 0.015) and scores were higher in adults, in males, among the non-affluent (particularly those resident in deprived areas), and in those presenting with a musculoskeletal problem. Scores on the latter dimension were significantly associated with age (P < 0.0001) and presenting problem (P < 0.0001). Scores tended to increase after childhood and for each of the five most frequent categories of presenting problem relative to other symptoms. CONCLUSIONS: Compared to those from affluent areas, patients from non-affluent areas appear to perceive difficulties accessing their general practitioner during surgery hours and may contact out-of-hours services as an alternative.

Adolescent↗