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Biomedical subjects

M White

Publications and source records attributed to M White.

At least 55 records · Page 3Linked to original sources
PubMed2001

Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression.

BACKGROUND: The recently identified RASSF1 locus is located within a 120-kilobase region of chromosome 3p21.3 that frequently undergoes allele loss in lung and breast cancers. We explored the hypothesis that RASSF1 encodes a tumor suppressor gene for lung and breast cancers. METHODS: We assessed expression of two RASSF1 gene products, RASSF1A and RASSF1C, and the methylation status of their respective promoters in 27 non-small-cell lung cancer (NSCLC) cell lines, in 107 resected NSCLCs, in 47 small-cell lung cancer (SCLC) cell lines, in 22 breast cancer cell lines, in 39 resected breast cancers, in 104 nonmalignant lung samples, and in three breast and lung epithelial cultures. We also transfected a lung cancer cell line that lacks RASSF1A expression with vectors containing RASSF1A complementary DNA to determine whether exogenous expression of RASSF1A would affect in vitro growth and in vivo tumorigenicity of this cell line. All statistical tests were two-sided. RESULTS: RASSF1A messenger RNA was expressed in nonmalignant epithelial cultures but not in 100% of the SCLC, in 65% of the NSCLC, or in 60% of the breast cancer lines. By contrast, RASSF1C was expressed in all nonmalignant cell cultures and in nearly all cancer cell lines. RASSF1A promoter hypermethylation was detected in 100% of SCLC, in 63% of NSCLC, in 64% of breast cancer lines, in 30% of primary NSCLCs, and in 49% of primary breast tumors but in none of the nonmalignant lung tissues. RASSF1A promoter hypermethylation in resected NSCLCs was associated with impaired patient survival (P =.046). Exogenous expression of RASSF1A in a cell line lacking expression decreased in vitro colony formation and in vivo tumorigenicity. CONCLUSION: RASSF1A is a potential tumor suppressor gene that undergoes epigenetic inactivation in lung and breast cancers through hypermethylation of its promoter region.

Adult↗
PubMed2001

Sternal wound infection after heart transplantation: incidence and results with aggressive surgical treatment.

BACKGROUND: Sternal wound infection remains a significant complication. We reviewed the incidence and the treatment of sternal wound infection after heart transplantation. METHODS: Of 226 patients who had a heart transplantation, 20 (8.8%) underwent postoperative wound debridement for superficial or deep sternal wound infection. The incidence and the survival of patients with sternal wound infection were analyzed. RESULTS: The incidence of sternal wound infection was similar among patients treated with four protocols of immunosuppressive drugs: cyclosporine and prednisone (0 of 22; 0%); cyclosporine, prednisone, and azathioprine (2 of 24; 8.3%); cyclosporine, prednisone, azathioprine, and antithymocyte globulin (15 of 139; 10.8%); and cyclosporine, prednisone, mycophenolate mofetil, and antithymocyte globulin (3 of 41; 7.3%) (p = 0.4). Six-month and 5-year survival of patients with sternal wound infection averaged 85% +/- 8% and 74% +/- 10% compared with 92% +/- 2% and 82% +/- 3% in patients without wound infection (p = 0.15). Patients with deep sternal wound infection, debridement, and reconstruction had a 5-year survival averaging 80% +/- 10%. CONCLUSIONS: The incidence of sternal wound infection remains similar between patients treated with the triple drug therapy. Surgical debridement and reconstruction can result in long-term survival after heart transplantation.

Acute Disease↗
PubMed2001

Delays in rod-mediated dark adaptation in early age-related maculopathy.

OBJECTIVE: To determine whether there are disturbances in the rod-mediated kinetics of dark adaptation in early age-related maculopathy (ARM). DESIGN: Comparative, observational case series. PARTICIPANTS: Twenty older adults with early ARM as defined by one or more large (> 63 microm) drusen, focal hyperpigmentation, or both, but no choroidal neovascularization or geographic atrophy, and 16 adults in the same age range with none of these fundus features. All participants had 20/25 visual acuity or better in the tested eye. METHODS: Dark adaptation functions were measured using a modified Humphrey Field Analyzer (Zeiss Humphrey Systems, Dublin, CA) to assess the rate of rod-mediated sensitivity recovery at 12 degrees on the vertical meridian in the inferior visual field after exposure to the equivalent of a 98% bleach. Baseline (prebleach) scotopic sensitivity, visual acuity, contrast sensitivity, and photopic sensitivity were also measured. MAIN OUTCOME MEASURES: Rod-cone break; second and third components of rod-mediated dark adaptation; time to baseline sensitivity; and baseline (prebleach) scotopic sensitivity. RESULTS: Although their visual acuity was at least 20/25, patients with early ARM on average exhibited deficits in almost all rod-mediated parameters of dark adaptation as compared with age-similar healthy participants. For example, the rod-cone break was delayed approximately 10 minutes in early ARM patients as compared with healthy participants. Age-related maculopathy patients were more likely to fall outside the normal reference range for variables representing dark adaptation kinetics than for steady-state visual functions such as scotopic sensitivity. For example, 85% of ARM patients fell outside the normal reference range in at least one dark adaptation kinetic parameter, whereas only 25% of ARM patients fell outside the normal reference range for steady-state scotopic sensitivity. CONCLUSIONS: Rod-mediated kinetic parameters of dark adaptation, which reflect the sensitivity recovery of the visual cycle, are disrupted early in ARM pathogenesis.

Aged↗
PubMed2001

Randomised controlled trial evaluating the effectiveness of behavioural interventions to modify cardiovascular risk factors in men and women with impaired glucose tolerance: outcomes at 6 months.

AIMS: To evaluate the efficacy of interventions to promote a healthy diet and physical activity in people with impaired glucose tolerance (IGT). METHODS: A randomised controlled trial in Newcastle upon Tyne, UK, 1995-98. Participants included 67 adults (38 men; 29 women) aged 24-75 years with IGT. The intervention consisted of regular diet and physical activity counselling based on the stages of change model. Main outcome measures were changes between baseline and 6 months in nutrient intake; physical activity; anthropometric and physiological measurements including serum lipids; glucose tolerance; insulin sensitivity. RESULTS: The difference in change in total fat consumption was significant between intervention and control groups (difference -21.8 (95% confidence interval (CI) -37.8 to -5.8) g/day, P=0.008). A significantly larger proportion of intervention participants reported taking up vigorous activity than controls (difference 30.1, (95% CI 4.3--52.7)%, P=0.021). The change in body mass index was significantly different between groups (difference -0.95 (95% CI -1.5 to -0.4) kg/m(2), P=0.001). There was no significant difference in change in mean 2-h plasma glucose between groups (difference -0.19 (95% CI -1.1 to 0.71) mmol/l, NS) or in serum cholesterol (difference 0.02 (95% CI -0.26 to 0.31) mmol/l, NS). The difference in change in fasting serum insulin between groups was significant (difference -3.4 (95% CI -5.8 to -1.1) mU/l, P=0.005). CONCLUSIONS: After 6 months of intensive lifestyle intervention in participants with IGT, there were changes in diet and physical activity, some cardiovascular risk factors and insulin sensitivity, but not glucose tolerance. Further follow-up is in progress to investigate whether these changes are sustained or augmented over 2 years.

Adult↗
PubMed2001

Smoking and alcohol consumption in a UK Chinese population.

Little research has been conducted on health in Chinese communities in the UK and there are few representative data on smoking, alcohol consumption or other aspects of lifestyle. We undertook a cross sectional population-based study of 380 Chinese and 625 European men and women aged 25 to 64 y, using self-completion and interview questionnaires in Newcastle upon Tyne, UK between 1991 and 1995. We measured self-reported prevalence of cigarette smoking, number of cigarettes smoked per week and age at starting smoking; self-reported prevalence of alcohol consumption and units of alcohol consumed per week. In age-adjusted comparisons smoking was less common in Chinese (24%) than European men (35%) (P=0.00002) and among Chinese (1%) compared with European women (33%) (P<0.00001). Number of cigarettes smoked was similar among Chinese and European male smokers. Median age at starting smoking was higher among Chinese (18.5 y) compared with European men (15 y) (P=0.00001). Smoking was commonest in older Chinese and in younger Europeans. The prevalence of alcohol consumption was lower among Chinese (63%) than European men (93%) (P<0.00001) and among Chinese (29%) compared to European women (89%) (P<0.00001). Median alcohol consumption was significantly lower among Chinese (2 units/week) than European men (16 units/week) (P<0.00001), and among Chinese (1 unit/week) compared to European women (6 units/week) (P<0.00001). Among those who drank alcohol, Chinese men were less likely to drink above recommended limits than European men (1% vs 39%; P<0.00001). Chinese men and women currently have relatively favourable patterns of smoking compared to European adults in Newcastle. Average alcohol consumption among Chinese who drink is lower than among Europeans, and a substantial proportion of the Chinese population in Newcastle drink no alcohol. Patterns of health related behaviour should be tracked over time in ethnic minority populations to identify changes that pose risk to health and which deserve appropriate intervention.

Adult↗
PubMed2001

The incidence of hydroxyethyl starch-associated pruritus.

BACKGROUND: Pruritus due to hydroxyethyl starch (HES) is reported with a very variable frequency but appears to be relatively uncommon in the U.K. compared with other European countries. OBJECTIVES: To determine the frequency of HES-related pruritus in patients discharged from intensive care units (ICUs) in two U.K. hospitals. METHODS: A questionnaire survey was given to 253 patients after discharge from ICU. Questions were designed to exclude pre-existing skin disease and other causes of pruritus. RESULTS: One hundred and fifty-nine completed questionnaires were suitable for analysis. Seventeen of 135 (12.6%) subjects who had received HES reported itch, as did one of 24 who had not received HES. There was no apparent relationship between the occurrence of HES-related pruritus and either the surgical indication or the brand or volume of HES infused. CONCLUSIONS: HES-related pruritus is a problem that dermatologists need to recognize; however, its frequency in the U.K., when other causes of itch are excluded, appears to be lower than suggested in some previous reported studies.

Drug Eruptions↗
PubMed2001

Use of a journal club and letter-writing exercise to teach critical appraisal to medical undergraduates.

INTRODUCTION: There is growing interest in methods of teaching critical appraisal skills at undergraduate and postgraduate levels. We describe an approach using a journal club and subsequent letter writing to teach critical appraisal and writing skills to medical undergraduates. METHODS: The exercise occurs during a 3-week public health medicine attachment in the third year of the undergraduate curriculum. Students work in small groups to appraise a recently published research paper, present their findings to their peers in a journal club, and draft a letter to the journal editor. Evaluation took place through: informal and formal feedback from students; number of letters written, submitted and published, and a comparison of marks obtained by students submitting a literature review assignment with and without critical appraisal teaching during the public health attachment. RESULTS: Feedback from students was overwhelmingly positive. In the first 3(1/2) years, 26 letters have been published or accepted for publication, and 58 letters published on the Internet. There were no significant differences in overall marks or marks for the critical appraisal component of the literature review assignments between the two student groups. DISCUSSION: We believe our approach is an innovative and enjoyable method for teaching critical appraisal and writing skills to medical students. Lack of difference in marks in the literature review between the student groups may reflect its insensitivity as an outcome measure, contamination by other critical appraisal teaching, or true ineffectiveness.

Communication↗
PubMed2001

Cholelithiasis and hyperthyroidism in a cat.

A 14-year-old domestic short-hair cat presented with a history of intermittent malaise and increased drinking. A diagnosis of hyperthyroidism and cholelithiasis was made by a combination of blood testing, radiography and ultrasonography. After medical management of hyperthyroidism, thyroidectomy and cholecystectomy were successfully performed. Removed choleliths were comprised of calcium carbonate and bilirubinate. Histopathological analysis of tissue suggested low grade pancreatic and hepatobiliary disease, as well as hyperthyroidism, might have contributed to stone formation.

Animals↗
PubMed2001

Changes in vasoconstrictive hormones, natriuretic peptides, and left ventricular remodeling soon after anterior myocardial infarction.

OBJECTIVE: Our purpose was to study the changes in vasoconstrictive neurohormones, N-terminal proatrial natriuretic peptide (Nt-proANP), and brain natriuretic peptide (BNP) and their relationship with left ventricular (LV) remodeling soon after anterior myocardial infarction (MI). BACKGROUND: The Healing and Afterload Reducing Therapy (HEART) trial has shown that early use of ramipril improves left ventricular ejection fraction (LVEF) and attenuates LV remodeling when initiated soon after MI. This neurohumoral substudy of HEART investigates the changes in vasoconstrictive and natriuretic peptides and their relationship with LV remodeling. METHODS: One hundred twenty-two patients had blood drawn for the measurement of catecholamines, endothelin-I, angiotensin II, Nt-proANP and BNP, and prostacyclins within 24 hours of an MI, and at 3, 14, and 90 days after the MI. Quantitative echocardiograms were performed at baseline and at 14 days. RESULTS: All neurohormones except angiotensin II (P =.12) and prostaglandins were significantly elevated at baseline. Vasoconstrictive neurohormones decreased significantly over time but remained elevated at 14 days. Both Nt-proANP and BNP were elevated within the first 14 days. BNP decreased significantly by 90 days, whereas Nt-proANP exhibited no change between 14 and 90 days. Ramipril decreased plasma levels of angiotensin II at 3 days but had no effect on the other neurohormones. CONCLUSIONS: Neurohumoral activation occurs and persists in patients with anterior MI and overall preserved LV function. Ramipril had only a modest impact on neurohormones despite its significant benefits on LV remodeling soon after MI.

Angiotensin II↗
PubMed2001

The treatment of moderate to severe psoriasis with a new anti-CD11a monoclonal antibody.

BACKGROUND: Anti-CD11a (hu1124) is a humanized monoclonal antibody directed against the CD11a subunit of LFA-1. This study investigated whether treatment with anti-CD11a antibody provides clinical benefit to patients with moderate to severe plaque psoriasis. METHODS: This was a double-blind, placebo-controlled, phase II, multicenter study. In total, 145 patients with minimum Psoriasis Area and Severity Index scores of 12 and affected body surface area of 10% or more were sequentially enrolled into low-dose (0.1 mg/kg, n = 22) or high-dose (0.3 mg/kg, n = 75) groups. Within groups, patients were randomized to treatment or placebo (n = 48) in a 2:1 ratio. Drug was administered intravenously at weekly intervals for 8 weeks. RESULTS: The percentage of subjects achieving more than 50% improvement in physician's global assessment at day 56 (1 week after final dose) was 15% and 48% for placebo and 0.3 mg/kg of drug, respectively (P =.002). A physician's global assessment of excellent (>75% improvement) was greater in the 0.3 mg/kg group versus placebo (25% vs 2%, P =.0003). Average Psoriasis Area and Severity Index scores at day 56 were 13.9 +/- 7.5 (placebo) and 10.9 +/- 8.4 (0.3 mg/kg) (P <.0001). Epidermal thickness was reduced in the 0.3 mg/kg group compared with the placebo group (37% vs 19%, P =.004). Treatment was well tolerated; mild to moderate flu-like complaints were the most common adverse events. White blood cell counts and lymphocyte counts transiently increased. Depletion of circulating lymphocytes did not occur. CONCLUSIONS: Anti-CD11a antibody administered intravenously in 8 weekly doses of 0.3 mg/kg was well tolerated and induced clinical and histologic improvements in psoriasis.

Adult↗
PubMed2001

Effect of photographic negation on matching the expressions and identities of faces.

In four experiments, participants made speeded same-different responses to pairs of face photographs showing the same woman or different women with the same expression or different expressions. Compared with responses to positive pairs, negative pairs were matched more slowly on identity than on expression. A secondary finding showed that face expressions (same, different) influenced identity responses, and identities influenced expression responses, equally for positive and negative pairs. The independence of this irrelevant-dimension effect from the contrast effect supports the conclusion required by the main finding that negation slows perceptual encoding of surface-based information used for identification more than it does encoding of edge-based information used for expression recognition.

Adolescent↗
PubMed2001

Receiving social support online: implications for health education.

Online support groups are expanding as the general public becomes more comfortable using computer-mediated communication technology. These support groups have certain benefits for users who may not be able to or do not have the desire to attend face-to-face sessions. Online support groups also present challenges when compared to traditional face-to-face group communication. Communication difficulties may arise resulting from lack of visual and aural cues found in traditional face-to-face communication. Online support groups have emerged within health care as a result of the need individuals have to know more about health conditions they are confronting. The proliferation of these online communities may provide an opportunity for health educators to reach target populations with specific messages. This paper reviews the development of health-related online support groups, examines research conducted within these communities, compares their utility with traditional support groups and discusses the implications of these groups for health education.

Attitude to Computers↗
PubMed2001

The performance of the Rose angina questionnaire in South Asian and European origin populations: a comparative study in Newcastle, UK.

BACKGROUND: The Rose angina questionnaire has been extensively used in different cultural settings, but may not perform consistently in different ethnic groups. We set out to assess the performance of the Rose angina questionnaire in UK South Asians compared with Europeans. METHODS: Data on major ECG abnormalities, possible or definite Rose questionnaire angina and diagnosed angina were collected from an age- and sex-stratified random sample of 1509 adults from European, Indian, Pakistani and Bangladeshi ethnic groups. RESULTS: The ECG abnormalities were commoner in South Asians than Europeans (6% versus 2% in men). The prevalence in both South Asian and European men of possible Rose angina and diagnosed angina was 18% and 8%, respectively, but definite Rose angina was less common in South Asians (3% versus 6%). Definite Rose angina showed lower sensitivity for other measures in South Asians than in Europeans: sensitivity for a doctor's diagnosis was 21% in South Asian and 37% in European men. For possible Rose angina, the corresponding figures were 81% and 84%. Similar patterns were seen in women. CONCLUSIONS: The performance of the Rose angina questionnaire was sufficiently inconsistent to warrant further work to achieve greater cross-cultural validity. Possible Rose angina performed more consistently across ethnic groups than definite Rose angina and pending further validation studies may be the most appropriate form to use.

Angina Pectoris↗
PubMed2001

Air pollution and exacerbation of asthma in African-American children in Los Angeles.

Significant increases in asthma morbidity and mortality in the United States have occurred since the 1970s, particularly among African-Americans. Exposure to various environmental factors, including air pollutants and allergens, has been suggested as a partial explanation of these trends. To examine relations between several air pollutants and asthma exacerbation in African-Americans, we recruited a panel of 138 children in central Los Angeles. We recorded daily data on respiratory symptoms and medication use for 13 weeks and examined these data in conjunction with data on ozone (O3) nitrogen dioxide (NO2), particulate matter (PM10 and PM2.5), meteorological variables, pollens, and molds. Using generalized estimating equations, we found associations between respiratory symptom occurrence and several environmental factors. For example, new episodes of cough were associated with exposure to PM10 (OR = 1.25; 95% CI = 1.12-1.39; interquartile range [IQR] = 17 microg/m3, 24-hour average), PM2.5 (OR = 1.10; 95% CI = 1.03-1.18; IQR = 30 microg/m3, 12-hour average), NO2, and the molds Cladosporium and Alternaria, but not with exposure to O3 or pollen. The factors PM10 and O3 were associated with the use of extra asthma medication. For this population several bioaerosols and air pollutants had effects that may be clinically significant.

Adolescent↗
PubMed2001

Therapeutic potential of angiotensin II receptor antagonists.

The circulating renin-angiotensin system plays an important role in cardiovascular homeostasis. More importantly, the local tissue renin angiotensin plays a pivotal role in cell growth and remodelling of cardiomyocytes and on the peripheral arterial vasculature. In addition, the renin angiotensin system is related to apoptosis, control of baroreflex and autonomic responses, vascular remodelling and regulation of coagulation, inflammation and oxidation. The cardioprotective and vascular protective effects of the angiotensin receptive blockade appears to be related to selective blockade of the angiotensin II (A-II) Type I (AT(1)) receptors. However, there is now growing evidence showing that some of the effects of AT-II receptor blockers (ARBs) are related to the activation of the kinin pathways. This paper will review some of the recent mechanisms related to the cardiovascular effects of angiotensin and more specifically of ARBs. This paper will present the novel data on the role of ARB in the development of atherosclerosis, vascular remodelling, coagulation balance and autonomic regulation. Finally, the role of ARBs, used alone or in combination with ACE inhibitor in patients with heart failure, will be discussed.

Angiotensin II↗