Measurement of protein carbonyls in human brain tissue.
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Biomedical subjects
Publications and source records attributed to P Evans.
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BACKGROUND: Glutaraldehyde and formaldehyde are commonly used sterilizing agents that are known skin sensitizers. There is some controversy, however, regarding their capacity to cause respiratory allergy. The authors have demonstrated previously that topical exposure of mice to chemical contact allergens such as 2,4-dinitrochlorobenzene (DNCB) or respiratory allergens such as trimellitic anhydride (TMA) induces characteristic cytokine secretion profiles consistent with the selective activation of T helper1 (TH1)- and TH2-type cells, respectively. OBJECTIVE: To investigate the quality of immune response provoked following topical exposure of mice to these materials. METHODS: BALB/c strain mice were exposed topically to 50% formaldehyde or to various concentrations of glutaraldehyde in acetone. Control animals were treated concurrently with the reference contact allergen DNCB (1% in acetone:olive oil [AOO]) or with the reference respiratory sensitizer TMA (10% in AOO). Thirteen days after the initiation of exposure, draining lymph node cells (LNCs) were cultured for 12-120h and cytokine content of supernatants analysed by cytokine-specific enzyme-linked immunosorbent assay. RESULTS: DNCB-alpha and formaldehyde-activated LNCs produced high levels of the TH1-type cytokine interferon gamma, but little of the TH2-type products interleukins 4 and 10. TMA- and glutaraldehyde-stimulated LNCs displayed the converse TH2-type pattern of cytokine expression. CONCLUSIONS: These data are consistent with glutaraldehyde, but not formaldehyde, having significant potential to cause allergic sensitization of the respiratory tract.
OBJECTIVE: In rheumatoid arthritis, education programmes successfully impart knowledge but, notwithstanding issues of empowerment, this knowledge has to be translated into behavioural change to have a chance of improving disease outcome. Arguably, behavioural change must also occur early if outcomes are to be improved. For these reasons, we planned a study of patient education in early disease, with radiological damage and quality of life as the main outcome variables. METHODS: We performed a randomized controlled trial in people with rheumatoid arthritis of < 5 yr duration. The main intervention was a 4 week education programme, each weekly session lasting 2 h. Assessments were made at entry, at 4 weeks and at 12 months. The main outcome variables were the modified Larsen radiological score for the hands and the SF-36 quality of life questionnaire. Secondary outcome variables were the Health Assessment Questionnaire (HAQ), Ritchie Articular Index (RAI), Patient Knowledge Questionnaire (PKQ), Compliance Questionnaire (CQ), plasma viscosity (PV), pharmaceutical changes and consulting behaviour. RESULTS: The patient numbers were 34 (10 male, 24 female) for the control group and 43 (16 male, 27 female) for the education group. The groups were matched for age (56.5 yr for control, 55 yr for education), disease duration (3.5 yr vs 3.0 yr) and duration of second-line drug therapy (14 months vs 12 months). We found no significant difference between the groups for Larsen scores at 12 months, although scores for the education group were lower (39.5 vs 43.0, P = 0.13). The 'social functioning' and 'general health perception' subscales of the SF-36 showed a significant improvement in the education group, but no significant differences between groups were seen. No significant differences were found for the HAQ, RAI, PV and CQ, but the education group had more disease-specific knowledge than the control group at 12 months (PKQ scores: 17 vs 21, P = 0.0002). No differences were found for out-patient visits and in-patient admissions, but the education group had slightly more changes in second-line drugs during the study (0.43 changes/person in the control group, 0.51 changes/person in the education group). CONCLUSIONS: We found no significant difference between the groups in our primary outcome measures, but a trend in favour of the education group was found in radiological progression. Further studies of this kind, using larger patient numbers, are required since the difference may result from improved self-care, better compliance with joint protection strategies and, possibly, improved drug compliance.
OBJECTIVE: To develop a curriculum for residents in obstetrics and gynecology that also provides training in family medicine. METHODS: We designed a 5-year curriculum with 36 months of obstetrics and gynecology, 12 of which are as chief resident, with a 4-month rotation through family medicine to meet the primary care requirements, and rotations of 1 month each in geriatrics and emergency medicine. The curriculum includes the 30 months of required rotations mandated by family medicine (three of which are in obstetrics and gynecology), with the 6 months' available elective time allocated to obstetrics and gynecology. RESULTS: The Residency Review Committee for Obstetrics and Gynecology accredited the curriculum, which meets the Accreditation Council for Graduate Medical Education Special Requirements for Family Medicine, in August 1996. CONCLUSION: This 5-year residency curriculum educates physicians in both obstetrics and gynecology, and family medicine, and graduates are eligible to pursue board certification in both specialties.
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The endocoid tribulin has four known bioactivities: monoamine oxidase A and B inhibitory activities (MAO-AI and MAO-BI) and peripheral and central benzodiazepine receptor binding inhibitory activities (PBR-I and CBR-I). Analysis of the four bioactivities in rat tissue reveals regional dissociation. Most notably liver was particularly rich in PBR-I yet contained no detectable MAO-AI. In addition we have succeeded in separating the four activities from human urine. MAO-AI and MAO-BI have greater retention on charcoal than PBR-I and CBR-I when eluted step-wise with aqueous methanol. MAO-AI can be separated from MAO-BI and in addition PBR-I can be separated from CBR-I by step aqueous methanol elution from Amberlite XAD-4. Hence we present two lines of evidence that, contrary to the original view, tribulin is composed of a number of distinct molecular components.
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The level of secretory immunoglobulin A (sIgA) measured in saliva is downregulated during periods of chronic stress. In contrast, the response to an acute stress challenge is a transient increase. The process of awakening is associated with stress neuroendocrine activation characterised by increases in salivary cortisol. We therefore examined if this period of hypothalamic-pituitary-adrenal (HPA) activation was associated with changes in salivary sIgA. Associations of sIgA with the diurnal cortisol cycle were also investigated in a separate study. The awakening cortisol response was measured in 30 healthy day-active young adults. There was a marked elevation from the first awakening level over the succeeding 30 min. SIgA showed the opposite response with a marked fall from the highest first awakening concentration in the same samples over the same period. The cortisol rise was significantly correlated with the sIgA fall (r = 0.42). Salivary sIgA showed a similar diurnal cycle to cortisol in a study on eight healthy young adults. An early morning acrophase was followed by a decline to a stable base some 6 h after awakening. The physiological significance of these relationships and possible implications for vulnerability to infection are discussed.
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BACKGROUND AND OBJECTIVES: Small ethnographic and clinic-based studies indicate that crack-smoking sex workers are at high risk for human immunodeficiency virus (HIV) and sexually transmitted diseases (STD). STUDY GOALS: To examine the prevalence of risky sexual behaviors and HIV and STD in a large sample of street-recruited crack-smoking sex workers. STUDY DESIGN: From 1991 to 1992, 419 crack-smoking sex workers were recruited from urban neighborhoods, interviewed, and serologically tested. RESULTS: Many female and male sex workers reported sex with injectors (30% to 41%) or HIV-infected persons (8% to 19%), past STD (73% to 93%), and inconsistent condom use (> 50% for all types of sex). Sex workers who worked in crack houses or vacant lots, were paid with crack, or injected drugs had the riskiest sex practices. Most sex workers initiated sex work before they first smoked crack. More than 25% were infected with HIV (27.9%), syphilis (37.5%), or herpes simplex virus type 2 (66.8%). CONCLUSIONS: Interventions to prevent HIV/STD transmission among crack-smoking sex workers are urgently needed.
Abdominal tuberculosis (TB) is an uncommon condition in Western societies although Europe and America have noted an increase of this condition in immigrants and AIDS patients. This report documents three diagnosed cases of abdominal TB over a 12-month period in a Melbourne western suburbs teaching hospital which services a large migrant population. We also review the literature on this condition. If migrants present with diffuse abdominal symptoms, the diagnosis of abdominal tuberculosis should always be considered. Laparoscopy should replace diagnostic laparotomy as the definitive diagnostic tool.
BACKGROUND: Chemicals vary considerably in their intrinsic ability to cause allergic contact dermatitis. Presently, there are no experimental methods available for the quantitative assessment of the relative sensitizing potency of chemical allergens. OBJECTIVE: The objective of the investigations described here was to evaluate the use of the local lymph node assay for determining the relative skin sensitizing potential of chemicals. This has been addressed by comparing the sensitizing potency of formaldehyde with glutaraldehyde. METHODS: Dose responses induced by formaldehyde and glutaraldehyde in the local lymph node assay, using either acetone or dimethylformamide (DMF) as the application vehicle, have been measured. Relative skin sensitizing potency was estimated as a function of the amount of chemical required to induce a threefold increase in lymph node cell proliferative activity, a mathematically derived EC3 value (estimated concentration required to induce a stimulation index of 3). RESULTS: In both vehicles, glutaraldehyde induced substantially more vigorous responses in the local lymph node assay (EC3 values of 0.006mol/L in acetone and 0.002mol/L in DMF) than did formaldehyde (EC3 values of 0.18mol/L in acetone and 0.11mol/L in DMF). CONCLUSIONS: These results demonstrate that glutaraldehyde has a considerably greater potential to induce skin sensitization than does formaldehyde; the data are consistent with what is known of the ability of these chemicals to cause allergic contact dermatitis in humans. Using formaldehyde and glutaraldehyde as examples, the results here illustrate the utility of EC3 values derived from local lymph node assay responses for the estimation of the relative potency of skin sensitizing chemicals.
Secretory immunoglobulin A (sIgA) in saliva and cardiovascular reactions to mental arithmetic and cold pressor tasks were recorded in 16 healthy young men on two sessions, 4 weeks apart. Both tasks elicited significant increases in sIgA secretion rate, reflecting increases in both salivary volume and sIgA concentration. Whereas mental arithmetic elicited a mixed pattern of alpha- and beta-adrenergic cardiovascular reactions, the pattern of reactions to cold pressor was predominantly alpha-adrenergic. Task levels of sIgA secretion rate, sIgA concentration, and saliva volume showed moderate to high test-retest reliability (r = .52-.83), although test-retest correlations were less impressive for change scores (r = -.19-.53). The pattern of correlations between change in sIgA secretion rate and cardiovascular reactivity variables was inconsistent.
BACKGROUND: The Royal College of General Practitioners has offered international travel scholarships for the past decade. Each year a number of general practitioners travel from the UK to work or study assisted by the scheme, while others come to this country for similar purposes. AIM: To investigate the value of international scholarships for recipients and others. METHOD: All those receiving awards in 1988-94 were surveyed by postal questionnaire. RESULTS: Fifty-one out of 58 award winners (88%) replied. Almost all cited some of a wide variety of personal benefits from international travel, and some established continuing links with colleagues overseas. Many gave examples of useful results for others, both patients and colleagues. Scholarships appear to have made a significant contribution to careers, especially for those based outside Britain. CONCLUSION: Relatively modest travel scholarships were viewed both favourably in hindsight and produced a wide range of benefits to recipients, colleagues, and patients. International travel should probably be considered more widely in career planning.
Primary duodenal adenocarcinoma not involving the ampullary region is rare. Our aim was to review the outcome of these patients and determine the factors that affect survival. We performed a retrospective review of all patients with primary, nonampullary duodenal adenocarcinoma at the Cleveland Clinic Foundation from January 1986 through December 1996. Twenty-six patients with primary, nonampullary duodenal malignancies were identified. There were 16 adenocarcinomas, 3 gastrinomas, 3 stromal tumors, 3 leiomyosarcomas, and 1 carcinoid tumor. Patients with adenocarcinoma had symptoms present an average of 6.1 months. Tumors were identified by upper gastrointestinal contrast study and esophagogastroduodenoscopy in 90 per cent and 87 per cent of patients, respectively. Twelve of 13 (93%) cancers found in the third or fourth portion of the duodenum were adenocarcinomas. Seven of the 16 adenocarcinomas were resectable on exploration. Those that were contained within the serosa have not recurred (mean, 6 years); one of the two patients with locally invasive adenocarcinoma remains disease free. The average survival for patients with unresectable disease was 6.7 months. The 5-year survival rates were: all adenocarcinoma, 38 per cent; resectable, 86 per cent; and unresectable, 0 per cent. All patients presenting with weight loss or obstructive symptoms died of disease; those with melena survived long term. Patients with tumors other than adenocarcinoma had a 90 per cent 5-year survival. We conclude that patients typically present with a long history of symptoms. Distal duodenal malignancies are most frequently adenocarcinomas. Upper gastrointestinal contrast study or endoscopy is often diagnostic. Patients with weight loss and/or obstructive symptoms had invasive disease and a morbid prognosis. Aggressive surgery is warranted, and most with resectable disease (86%) had long-term survival.
A PCR-based intron jumping strategy has been utilized to investigate the exon/intron structure of the human transferrin receptor gene and determine the sequences of exon/intron junctions. There are 18 exons and introns 5' to a large exon encoding the last translated segment and a sizable 3' untranslated segment. All of the translated segments are encoded by exons 2-19. The tight turn motif, which is critical to the process of endocytosis, is encoded by exon 3. Based on recent studies of human/chicken receptor chimeras, it appears that the residues most likely to be involved in transferrin binding are encoded by exons 17-19. Exon 12 exhibits the greatest degree of homology with the gene for the prostate specific membrane antigen. A polymorphism has been tentatively identified at nucleotide position 519 in exon 4; the presence of either adenine or guanine should result in either serine or glycine, respectively, at position 142 of the amino acid sequence. This analysis of genomic structure will permit further detailed studies of the regulation, expression and evolution of the human transferrin receptor gene.