Protective effects of anaesthetics in reversible and irreversible ischaemia-reperfusion injury.
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Biomedical subjects
Publications and source records attributed to S Ross.
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Fifteen centers for orthopaedic treatment of the foot and ankle participated in a prospective randomized trial to compare several nonoperative treatments for proximal plantar fasciitis (heel pain syndrome). Included were 236 patients (160 women and 76 men) who were 16 years of age or older. Most reported duration of symptoms of 6 months or less. Patients with systemic disease, significant musculoskeletal complaints, sciatica, or local nerve entrapment were excluded. We randomized patients prospectively into five different treatment groups. All groups performed Achilles tendon- and plantar fascia-stretching in a similar manner. One group was treated with stretching only. The other four groups stretched and used one of four different shoe inserts, including a silicone heel pad, a felt pad, a rubber heel cup, or a custom-made polypropylene orthotic device. Patients were reevaluated after 8 weeks of treatment. The percentages improved in each group were: (1) silicone insert, 95%; (2) rubber insert, 88%; (3) felt insert, 81%; (4)stretching only, 72%; and (5) custom orthosis, 68%. Combining all the patients who used a prefabricated insert, we found that their improvement rates were higher than those assigned to stretching only (P = 0.022) and those who stretched and used a custom orthosis (P = 0.0074). We conclude that, when used in conjunction with a stretching program, a prefabricated shoe insert is more likely to produce improvement in symptoms as part of the initial treatment of proximal plantar fasciitis than a custom polypropylene orthotic device.
An increase in prevalence of wheezing illness in the UK has coincided with a reduction in the consumption of natural antioxidants, which may modulate the lung's response to oxidant stress, limiting the expression of airway inflammation and respiratory symptoms. The hypothesis that intakes and plasma levels of natural antioxidants would be determinants of adult-onset wheezing illness was tested. A nested case-control study was conducted in 94 cases with adult-onset wheeze and 203 controls aged 39-45 yrs identified in a 30-yr follow-up survey. Antioxidant intake was measured by a food frequency questionnaire, and plasma and red cell measurements of antioxidant status were obtained. Outcome measures were onset of wheeze since age 15 yrs (ever wheeze) and wheeze occurring in the past 12 months (current wheeze). After adjusting for the effects of smoking, socioeconomic status, atopy, family history of atopic disease and total energy intake, intakes of vitamin E (odds ratio (OR) = 4.02 for low compared to high tertile of intake) and plasma levels of ascorbate (OR = 0.98 per unit) and alpha-tocopherol:triglyceride ratio (OR = 0.34 per log(e) unit) were inversely related to adult-onset wheeze. In analyses stratified by social class and smoking, intakes of vitamin C and E and plasma levels of ascorbate and alpha-tocopherol:triglyceride ratio were inversely related to current wheeze in the manual social class and among current smokers. No independent associations of vitamin A, beta-carotene or total plasma antioxidant capacity were found. The results support the hypothesis that deficiencies of vitamins C and E are associated with wheezing symptoms. Smokers in the manual social class are particularly susceptible to these effects.
In vertebrates, the hedgehog family of cell signaling proteins and associated downstream network components play an essential role in mediating tissue interactions during development and organogenesis. Loss-of-function or misexpression mutation of hedgehog network components can cause birth defects, skin cancer and other tumors. The mammary gland is a specialized skin derivative requiring epithelial-epithelial and epithelial-stromal tissue interactions similar to those required for development of other organs, where these interactions are often controlled by hedgehog signaling. We have investigated the role of the Patched-1 (Ptc1) hedgehog receptor gene in mammary development and neoplasia. Haploinsufficiency at the Ptc1 locus results in severe histological defects in ductal structure, and minor morphological changes in terminal end buds in heterozygous postpubescent virgin animals. Defects are mainly ductal hyperplasias and dysplasias characterized by multilayered ductal walls and dissociated cells impacting ductal lumens. This phenotype is 100% penetrant. Remarkably, defects are reverted during late pregnancy and lactation but return upon involution and gland remodeling. Whole mammary gland transplants into athymic mice demonstrates that the observed dysplasias reflect an intrisic developmental defect within the gland. However, Ptc1-induced epithelial dysplasias are not stable upon transplantation into a wild-type epithelium-free fat pad, suggesting stromal (or epithelial and stromal) function of Ptc1. Mammary expression of Ptc1 mRNA is both epithelial and stromal and is developmentally regulated. Phenotypic reversion correlates with developmentally regulated and enhanced expression of Indian hedgehog (Ihh) during pregnancy and lactation. Data demonstrate a critical mammary role for at least one component of the hedgehog signaling network and suggest that Ihh is the primary hedgehog gene active in the gland.
OBJECTIVE: To compare human ultralente (UL) insulin with human NPH insulin as basal insulin replacement in patients who use insulin lispro before meals. RESEARCH DESIGN AND METHODS: There were 178 patients with type 1 diabetes who were randomized to receive either human NPH or UL insulin once daily at bedtime in a 1-year double-blind clinical study. Eight-point blood glucose profiles were collected once monthly in the first 4 months, then every 2 months for the remainder of the study. Patients were also asked to perform premeal blood glucose measurements every day throughout the study. If before-supper blood glucose levels consistently exceeded 8 mmol/l despite optimal postprandial control with the lunch dose of insulin lispro, a second dose of basal insulin before breakfast was administered. RESULTS: For the group as a whole, insulin doses before meals and basal insulin doses were similar at baseline. At study's end, meal doses remained the same (30 +/- 1 U/day for UL., 29 +/- 1 U/day for NPH), while basal requirements were somewhat higher for the UL group than the NPH group: 30 +/- 1 U/day vs. 26 +/- 1 U/day, respectively (P < 0.05). The rates of severe hypoglycemia were similar for patients on NPH (0.05 +/- 0.03 per patient every 30 days) and for UL (0.07 +/- 0.04 per patient every 30 days) insulin. There was no significant difference for glycemic control between the NPH and UL groups overall (HbAlc at the end of the study: 7.6 +/- 0.1 vs. 7.7 +/- 0.1%, respectively), and by study's end a similar number of patients in the NPH and the UL groups needed to be switched to twice daily basal insulin (21 and 24%, respectively). Patients requiring twice-daily injections of basal insulin had a longer duration of diabetes (17.8 +/- 1.5 vs. 14.0 +/- 0.8 years, P < 0.05) and a highest baseline HbAlc (8.6 +/- 0.1 vs. 8.0 +/- 0.1%, P < 0.002) and were significantly older (38 +/- 2 vs. 34 +/- 1 years, P < 0.007). Patients who were switched to twice-daily NPH insulin had lower HbAlc levels at study's end compared with those switched to twice-daily UL insulin (7.7 +/- 0.2 vs. 8.2 +/- 0.3%), but this difference was not statistically significant. Distribution of hypoglycemia across the day was also similar in both groups. CONCLUSIONS: UL or NPH insulin, when used as the basal insulin for multiple injection regimens, results in similar glycemic control in patients using insulin lispro before meals. However, in patients who require a second injection of basal insulin, NPH insulin appears to provide lower prebreakfast and prelunch glucose levels compared with UL insulin.
Various reports and surveys since 1988 have highlighted differences in gradings and diversity of roles and responsibilities of nurses in genitourinary medicine (GUM). In addition there was no method of defining how many nurses work in the speciality. Therefore the Genito-Urinary Nurses Association (GUNA) undertook a survey last year to establish how many nurses, of what grade, undertaking what roles are working in GUM clinics. Over half the clinics in the UK responded, from full-time busy London clinics to small part-time rural clinics. The results suggest approximately 2000 nurses working in GUM nationally, with a wide diversity of grades, roles and responsibilities still apparent 10 years after the Monks Report. Further analysis of the data obtained by the survey is given in the report.
BACKGROUND: The management and detection of depression varies widely, and the causes of variation are incompletely understood. AIMS: To describe and explain general practitioners' (GPs') current practice in the recognition and management of depression in young adults, their attitudes towards depression, and to investigate associations of GP characteristics and patient sex with management. METHOD: All GP principals in the Greater Glasgow Health Board were randomized to receive questionnaires with vignettes describing increasingly severe symptoms of depression in either male or female patients, and asked to indicate which clinical options they would be likely to take. The Depression Attitude Questionnaire was used to elicit GP attitudes. RESULTS: As the severity of vignette symptoms increased, GPs responded by changing their prescribing and referral patterns. For the most severe vignette, the majority of GPs would prescribe drugs (76.4%) and refer the patient for further help (73.7%). Male and female patients were treated differently: GPs were less likely to ask female patients than male patients to attend a follow-up consultation (odds ratio [OR] = 0.55), and female GPs were less likely to refer female patients (OR = 0.33). GPs with a pessimistic view of depression, measured using the 'inevitable course of depression' attitude scale, were less willing to be actively involved in its treatment, being less likely to discuss a non-physical cause of symptoms (OR = 0.77) or to explore social factors in moderately severe cases (OR = 0.68). CONCLUSIONS: Accepting the limitations of the method, GPs appear to respond appropriately to increasingly severe symptoms of depression, although variation in management exists. Educational programmes should be developed with the aim of enhancing GP attitudes towards depression, and the effects on detection and management of depression should be rigorously evaluated.
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Improving pain management practices can decrease adverse complications and improve patient outcomes. This in turn will result in the more efficient use of health care resources. Clinicians who are constantly challenged to improve delivery of care are interested in the perceptions of patients. They often rely on their patients' reported levels of satisfaction as an outcome measure for success of a program. Most often, informal methods are used to gather information on satisfaction with care.
OBJECTIVES: To investigate the differences between the characteristics and career intentions of GP registrars in urban and rural areas, and to make recommendations to reduce a potential work force crisis in rural practice. DESIGN: Postal survey. SETTING: All general practices in Scotland. SUBJECTS: In February 1996, 40/196 (20%) of urban and 45/150 (30%) of rural GP registrar places available in Scotland, were vacant (chi 2 = 4.22, df = 1, p = 0.02). Postal questionnaires were sent to all 261 GP registrars in post. RESULTS: Of 235 respondents (90%), the majority wished to remain in general practice (63% of urban and 53% of rural registrars), but only 22% of urban and 18% of rural registrars intended to apply for principal posts immediately after training. Fewer urban (8%) than rural registrars (21%) stated an intention to go abroad to work after training. Rural registrars tended to want to work in rural areas, and vice versa. Part-time and job-sharing were attractive employment options for both groups, and more flexible career structures were favoured by over 80%. CONCLUSIONS: Though much more attention has been paid to recruitment in inner cities, the findings from this study suggest that in Scotland difficulties in finding principals may occur first in rural areas. As general practitioners have an extended role in rural areas, including that of emergency care, shortages could have a serious impact on patient care.
Out of hours care in the UK has undergone radical changes in the past five years, with a rapid increase in the number of general practitioner co-operatives operating from primary care centres. Patients wishing to see a general practitioner outwith normal surgery hours can now be asked to attend a centre, be given telephone advice or may still receive a home visit if required. This overview examines the current literature evaluating these changes. While there are now a number of studies examining general practitioner co-operatives and centres in both England and Scotland, there is little or no work on other forms of out of hours care. In particular, little is known about the continuing role of the single handed general practitioner or about out of hours care in small towns and in rural areas. The need for these issues to be addressed is discussed and the aims of the current Scottish study comparing different models of out of hours care outlined.
The aim of the present study was to use a combination of the reverse transcription-polymerase chain reaction and a new diagnostic test for antibodies against the viral envelope protein E2 to assess the prevalence of hepatitis G virus (GBV-C/HGV) infection in sera of Hungarian children on hemodialysis (HD) or peritoneal dialysis (CAPD), as well as in sera of renal transplant patients (RTx). The GBV-C/HGV RNA prevalence was significantly higher in the whole group of children with renal failure (18.5%) than in the control group (children with urinary tract infection, 2.5%). The difference between the GBV-C/HGV RNA prevalence in the RTx group (33.3%) and in the control group (2.5%) was significant (P = 0.007). Anti-E2, which is considered an indicator of a past GBV-C/ HGV infection, was detected in 10% (1/10) of HD patients, in 33.3% (4/12) of RTx patients, but in none of the children on CAPD. These differences were not significant. Children receiving a renal graft are at an increased risk of developing GBV-C/HGV infection, which may be attributed to the immunosuppressive drugs necessary to maintain the grafts.
A postal survey was undertaken to describe the management of leg ulcers in a sample of primary care settings in Scotland. The management of leg ulcers caused a considerable workload for all three groups of professionals, although general practitioners (GPs) reported seeing fewer patients. Initial assessment of leg ulcers was often carried out by nurses in collaboration with GPs; however, 48% of district nurses reported assessing patients alone. Choice of treatment depended on clinical criteria and frequency of visits to change dressings. Compression bandages were used routinely by 64% of nurses. Practice protocols were unusual, with only 12% of nurses reporting their use. The management of leg ulcers was not always optimum, and the findings indicate that evidence-based guidelines should be more widely adopted for the management of leg ulcers in general practice.
As in other higher eukaryotes, DNA methylation in plants is predominantly found at deoxycytosine residues, while deoxyadenosine residues are not methylated at significant levels. 6mdA methylation has been successfully introduced into yeast and Drosophila via expression of a heterologous methyltransferase, but similar attempts in tobacco had, up until now, proved unsuccessful despite the correct expression of a methyltransferase construct. It was unclear whether this result reflected the failure of heterologous methyltransferases to enter the nucleus, or whether 6mdA methylation, which has been shown to interfere with promoter activity, was toxic for plants. Here we show that 6mdA methylation can be successfully introduced into transgenic tobacco plants via expression of the bacterial dam enzyme. The efficiency of 6mdA methylation was directly proportional to expression levels of the dam construct, and methylation of all GATC sites was observed in a highly expressing line. Increasing expression levels of the enzyme in different plants correlated with increasingly abnormal phenotypes affecting leaf pigmentation, apical dominance, and leaf and floral structure. Whilst introduction of dam-specific methylation does not cause any developmental abnormalities in yeast or Drosophila, our data suggest that methylation of deoxyadenine residues in plants interferes with the expression of genes involved in leaf and floral development.
Nicorandil, a new KATP channel opener, is used in clinical practice for anti-anginal therapy. It exhibits vasodilator properties as does the halogenated anaesthetic isoflurane. We have examined the cardiovascular effects of increasing concentrations of isoflurane after administration of nicorandil in 10 adult beagle dogs anaesthetized with thiopental and whose lungs were ventilated mechanically. During surgery, anaesthesia was maintained with 1.0-1.5% isoflurane. A left thoracotomy was performed and the heart suspended in a pericardial cradle. Monitoring included: ECG; aortic, left ventricular, arterial, central venous and pulmonary artery pressures; cardiac output; coronary flow; and segmental length in the apical region. After surgery, isoflurane anaesthesia was set at an end-tidal concentration of 1.05% (1 MAC) and measurements obtained; these were repeated with 1.4%, 1.75%, 2.1% and 1.05% isoflurane concentrations after appropriate stabilization periods. Nicorandil (100 micrograms kg-1 bolus, 25 micrograms kg-1 min-1 infusion) was begun and a second dose-response study of isoflurane was obtained as before. Blood samples were obtained for measurement of concentrations of nicorandil. Systolic ventricular function was assessed by systolic shortening (%SS) and preload recruitable stroke work (PRSW). Increasing isoflurane concentration produced decreases in heart rate, systolic pressure, cardiac output, %SS and PRSW. Nicorandil produced a slight decrease in systolic arterial pressure (10 and 15 mm Hg after 1.05% and 2.05% isoflurane) and a slight increase in heart rate (10 and 5 beat min-1 after 1.05% and 2.05% isoflurane). Preload, assessed by end-diastolic length, decreased. Coronary blood flow increased with infusion of nicorandil. Left ventricular function was not affected by infusion of nicorandil. We conclude that nicorandil has only minor vaso/venodilatory effects in the presence of isoflurane. Ventricular function was not altered by infusion of nicorandil.
BACKGROUND: The intravenous anaesthetic propofol has been shown to possess free radical scavenging activity and calcium channel blocking effects in a number of in vitro models. We decided to compare the effects of propofol with those of fentanyl on myocardial contractility during and after ischaemia to determine whether propofol could protect the heart and improve recovery of ventricular contractile function in open-chested dogs. METHODS: Twenty adult beagles were acutely instrumented, under halothane anaesthesia, to measure ECG; aortic, left ventricular pressures; cardiac output; coronary flow; and segmental lengths in the regions perfused by the left anterior and left circumflex coronary arteries. After surgery and a stabilisation period halothane anaesthesia was terminated and fentanyl (100 microg x kg[-1] bolus followed by 2 microg x kg[-1] x min[-1] infusion; n=10) or propofol (5 mg x kg[-1] bolus followed by 0.3 mg x kg[-1] x min[-1] infusion; n=10) anaesthesia commenced. After a stabilisation period the LAD coronary artery was occluded for 10 min and then reperfused for 3 h. Measurements were taken throughout the protocol. RESULTS: We found no significant difference in recovery of contractile function between propofol and fentanyl as assessed by normalised preload recruitable work area (50+/-10 vs 47+/-16%), normalised systolic shortening (36+/-12 vs 48+/-14%) and peak left ventricular dP/dt (1665+/-276 vs 1846+/-151 mmHg x s[-1]) at the end of reperfusion. CONCLUSION: We conclude that at the concentration used in this study propofol shows no improvement in contractility during "stunning" when compared to fentanyl.
Risk factors associated with adult onset wheeze were examined in a case control study of subjects aged 39-45 yr derived from a community cohort of 2,056 asymptomatic children originally studied in 1964. Participants included 102 cases with adult onset wheeze (since age 15) and 217 controls with no wheeze. Logistic regression analysis was used to determine independent risk factors for wheeze among all cases and three subgroups: doctor diagnosed asthma (n = 24), wheeze with chronic cough and phlegm (n = 31), and other wheeze (n = 47). The risk of adult onset wheeze among all cases increased with low socioeconomic status (relative risk [RR] 2.36), current smoking (RR 2.01), positive atopic status (RR 3.28), and positive family history of atopic disease (RR 5.49). Gender was not related to the risk of wheezing. The pattern of significant independent risk factors differed between the subgroups of cases. Socioeconomic status was associated with cough and phlegm and other wheeze. Smoking habit was only related to cough and phlegm. Atopy was associated with doctor diagnosed asthma and cough and phlegm. Family history of atopic disease was related to all subgroups, suggesting that despite apparent heterogeneity in diagnostic labeling, concurrent symptoms, and other risk factors, the different forms of adult onset wheeze may share a common allergic basis.