Reawakening the telomeres.
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Cell Division↗
Biomedical subjects
N Johnson
Publications and source records attributed to N Johnson.
Occupational hierarchy, economic sector, and mortality from cardiovascular disease among men and women. Findings from the National Longitudinal Mortality Study.
PURPOSE: Although socioeconomic position has been identified as a determinant of cardiovascular disease among employed men and women in the U.S., the role of economic sector in shaping this relationship has yet to be examined. We sought to estimate the combined effects of economic sector-one of the three major sectors of the economy: finance, government and production-and socioeconomic position on cardiovascular mortality among employed men and women. METHODS: Approximately 375,000 men and women 25 years of age or more were identified from selected Current Population Surveys between 1979 and 1985. These persons were followed for cardiovascular mortality through use of the National Death Index for the years 1979 through 1989. RESULTS: In men, the lowest cardiovascular mortality was found for professionals in the finance sector (76/100,000 person/years). The highest cardiovascular mortality was found among male non-professional workers in the production sector (192/100,000 person years). A different pattern was observed among women. Professional women in the finance sector had the highest rates of cardiovascular mortality (133/100,000 person years). For both men and women, the professional/non-professional gap in cardiovascular mortality was lower in the government sector than in the production and finance sectors. These associations were strong even after adjustment for age, race and income. CONCLUSIONS: Characteristics of government, finance and production work differentially influence the risk of cardiovascular disease mortality. Men, women, professionals and non-professionals experience this risk differently.
Adult↗
The General Medical Council's Performance Procedures: peer review of performance in the workplace.
The General Medical Council procedures to assess the performance of doctors who may be seriously deficient include peer review of the doctor's practice at the workplace and tests of competence and skills. Peer reviews are conducted by three trained assessors, two from the same speciality as the doctor being assessed, with one lay assessor. The doctor completes a portfolio to describe his/her training, experience, the circumstances of practice and self rate his/her competence and familiarity in dealing with the common problems of his/her own discipline. The assessment includes a review of the doctor's medical records; discussion of cases selected from these records; observation of consultations for clinicians, or of relevant activities in non-clinicians; a tour of the doctor's workplace; interviews with at least 12 third parties (five nominated by the doctor); and structured interviews with the doctor. The content and structure of the peer review are designed to assess the doctor against the standards defined in Good Medical Practice, as applied to the doctor's speciality. The assessment methods are based on validated instruments and gather 700-1000 judgements on each doctor. Early experience of the peer review visits has confirmed their feasibility and effectiveness.
Clinical Competence↗
Depressive cognition: a test of depressive realism versus negativity using general knowledge questions.
This research is an examination of whether cognition in depressed individuals incorporates a realistic view of the world or a general tendency toward negativity. Participants provided two types of probability judgments of the likelihood that they correctly answered general knowledge questions: the probability that they correctly answered each of the individual questions and an aggregate judgment, after completing the questionnaire, of the percentage of all the questions they thought they had correctly answered. These tasks generally elicit overconfidence and accuracy in nondepressives. In accord with theories of both depressive realism and general negativity, in their item-by-item assessments of their answers to the individual questions, depressed participants demonstrated less overconfidence than nondepressed participants. In accord with the theory of general negativity but not with the theory of depressive realism, however, depressed participants demonstrated underconfidence in their aggregate judgments. The implications of these findings on theories of depressive cognition are discussed.
Cognition↗
Effectiveness of a formal post-baccalaureate pre-medicine program for underrepresented minority students.
PURPOSE: To address the effectiveness of a formal postbaccalaureate (PB) experience for underrepresented minority (URM) students before medical school. The program provided an intense year-long experience of course work, research, and personal development. METHOD: There were 516 participants from one medical school: 15 URM medical students had completed the formal PB program, 58 students had done independent PB work before matriculation, and 443 students were traditional matriculants. Cognitive and academic indicators [college science and non-science grade-point averages (GPAs); biology, physics, and verbal MCAT scores; and percentage scores from first-year medical school courses] were compared for the three groups. RESULTS: Both groups of students with PB experience demonstrated competency in the first year of medical school consistent with traditional students even though the students who had completed the formal PB program had lower MCAT scores and lower college GPAs than did the traditional students. Traditional predictors of academic performance during the first year of medical school did not significantly contribute to actual academic performances of students from the formal PB program. CONCLUSION: The results support the use of a formal PB program to provide academic readiness and support for URM students prior to medical school. Such a program may also improve retention. Noncognitive variables, however, may be important to understanding the success of such students in medical school.
Adult↗
N-Acetyltransferases, sulfotransferases and heterocyclic amine activation in the breast.
Heterocyclic amines are mammary carcinogens in rats and their N-hydroxy metabolites are substrates for subsequent metabolic activation by N-acetyltransferases (NAT) and sulfotransferases (SULT) in man. We investigated the expression of these enzymes in human breast tissue and the relationship between NAT genotype and NAT mRNA expression or enzyme activity. Immunohistochemical staining of sections of breast tissue identified expression of NAT1 and NAT2 protein in human mammary epithelial cells, but not in the stroma. We also measured the formation of DNA adducts of the heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in calf thymus DNA after incubation of their promutagenic N-hydroxy metabolites with mammary cytosols prepared from reduction mammoplasty tissue. Experimental observations gained from use of enzyme cofactors and NAT and/or SULT inhibitors on cytosolic enzyme activity, recombinant NAT1 activity and heterocyclic amine-DNA adduct formation suggest that both NAT1 and SULT1A enzymes contribute significantly to the activation of N-hydroxylated heterocyclic amines in mammary tissue. NAT1 mRNA transcript levels were found to be two- to three-fold higher than mRNA transcripts of the NAT2 gene in reduction mammoplasty tissue and mammary epithelial cells. NAT1-specific p-aminobenzoic acid acetylation activity, but not NAT2-specific sulfamethazine acetylation activity, was detectable in mammary cytosols. There was no association apparent between NAT genotype and the levels of NAT mRNA or NAT enzyme activity, or between NAT1 genotype and IQ-DNA adduct formation mediated by mammary cytosols. Western blot analysis of mammary cytosolic protein showed detectable levels of SULT1A1 and SULT1A3.
Amines↗
The management of menorrhagia--SMART study (Satisfaction with Mirena and Ablation: a Randomised Trial).
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Catheter Ablation↗
The impact of ethnicity on the presentation of polycystic ovarian syndrome.
The effect of ethnicity on the prevalence and presentation of polycystic ovarian syndrome (PCOS) was examined in a cross-sectional study of women with clinical - and ultrasound - diagnosed PCOS. European, Maori and Pacific Island women were seen in proportion to the general population, whereas Indian women were over-represented and Chinese women under-represented. European and Maori women were more likely to present with hirsutism than other ethnic groups (43% versus 25%, p < 0.05), while European women were less likely to present with infertility (46% versus 68%, p < 0.01). The Pacific Island women had little or no acne but other signs of PCOS were similar among ethnic groups. Although less than 10% of patients were referred with obesity, the majority of PCOS women were overweight on examination. Maori and Pacific Island women were more obese and had the highest rates of insulin resistance and lipid abnormalities. The adverse metabolic profile of many of these women, particularly the Maori and Pacific Islanders, is very likely to predispose them to early cardiovascular disease.
Adolescent↗
Cognitive function in the oldest old: Women perform better than men.
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Aged↗
Training of junior doctors: the responsibility of consultants and trainers.
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Education, Medical, Graduate↗
Congressional outlook: nursing shortages.
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Age Factors↗
Tobacco use and oral cancer: a global perspective.
For both genders, cancer of the mouth and pharynx ranks sixth overall in the world; it is also the third most common site among males in developing countries. In industrialized countries, men are affected two to three times as often as women, largely due to higher use of alcohol and tobacco. Ethnicity strongly influences prevalence due to social and cultural practices, as well as socioeconomic differences. In population terms, survival rates around the world show little improvement. In terms of etiology, the effects of tobacco use, heavy alcohol consumption, and poor diet together explain over 90 percent of cases of head and neck cancer. All forms of tobacco represent risk factors for oral cancer, but on present evidence, snuff habits as they exist in Scandinavia and probably in the United States carry lower risks of serious health hazards, including oral cancer. Alcohol synergizes with tobacco as a risk factor for all upper aerodigestive tract SCC: this is super-multiplicative for the mouth, additive for the larynx, and between additive and multiplicative for the esophagus. The increase in oral cancer in the Western world has been related to rising alcohol use.
Alcohol Drinking↗
The assessment of poorly performing doctors: the development of the assessment programmes for the General Medical Council's Performance Procedures.
BACKGROUND: Modernization of medical regulation has included the introduction of the Professional Performance Procedures by the UK General Medical Council in 1995. The Council now has the power to assess any registered practitioner whose performance may be seriously deficient, thus calling registration (licensure) into question. Problems arising from ill health or conduct are dealt with under separate programmes. METHODS: This paper describes the development of the assessment programmes within the overall policy framework determined by the Council. Peer review of performance in the workplace (Phase 1) is followed by tests of competence (Phase 2) to reflect the relationship between clinical competence and performance. The theoretical and research basis for the approach are presented, and the relationship between the qualitative methods in Phase 1 and the quantitative methods in Phase 2 explored. CONCLUSIONS: The approach is feasible, has been implemented and has stood legal challenge. The assessors judge and report all the evidence they collect and may not select from it. All their judgements are included and the voice of the lay assessor is preserved. Taken together, the output from both phases forms an important basis for remediation and training should it be required.
Clinical Competence↗
Placental arylamine N-acetyltransferase type 1: potential contributory source of urinary folate catabolite p-acetamidobenzoylglutamate during pregnancy.
Human arylamine N-acetyltransferase type 1 (NAT1), better known as a drug-metabolising enzyme, has been proposed to acetylate the folate catabolite p-aminobenzoylglutamate (p-abaglu) to N-acetamidobenzoylglutamate (ap-abaglu) which is a major urinary folate catabolite. Using mass spectroscopic analysis, we demonstrate the formation of ap-abaglu by recombinant human NAT1 and human placental homogenates. Using density gradient centrifugation the placental enzymic activity which acetylates p-aba and the placental enzymic activity acetylating p-abaglu both have an S(20,w) value of 3.25 S. This is the expected value for a monomer of human NAT1 (33 kDa). The specific NAT1 inhibitor 5-iodosalicylate inhibits acetylation of both p-aba and p-abaglu catalysed by either recombinant human NAT1 or placental samples as the source of enzyme. These data demonstrate that NAT1 is the major placental enzyme involved in acetylating p-abaglu.
4-Aminobenzoic Acid↗
Expression of arylamine N-acetyltransferases in pre-term placentas and in human pre-implantation embryos.
Arylamine N -acetyltransferases (NATs) catalyse the acetylation from acetyl-CoA of arylamines and hydrazines. There are two human isoenzymes which show polymorphism, and both enzymes are involved in the activation and detoxification of environmental carcinogens and teratogens. The two human isoenzymes NAT1 and NAT2 show different tissue distribution, with human NAT2 being found in liver and intestine whilst human NAT1 is expressed in many tissues including erythrocytes, bladder, lymphocytes and neural tissue, as well as liver and intestine. It has been proposed that NAT1 has an endogenous role in the acetylation of the folate catabolite p -aminobenzoyl-L-glutamate (pABGlu) to produce the major urinary product, N -acetyl-pABGlu. The murine homologue of human NAT1 is known to be concentrated in the neural tube during development. We show here that human NAT1 but not human NAT2 is expressed in pre-implantation embryos at the blastocyst stage and show that NAT1 is also expressed in early human placenta at the earliest available stage, 5.5 weeks. We demonstrate that there is inter-individual variation in NAT1 expression. In view of the role of folate in protecting against neural tube defects, we propose that NAT1 is a candidate risk factor for susceptibility to neural tube defects.
Acetylation↗
p53 and P-glycoprotein expression are significant prognostic markers in advanced head and neck cancer treated with chemo/radiotherapy.
The development of biological markers of response to chemo- and radiotherapy to judge benefit to risk ratios for toxic treatments is still at an experimental stage. Tumour cell death is largely by apoptosis and the p53 gene has a major influence on this. P-glycoprotein (P-gp) accumulation has been correlated with treatment failure in several types of cancer. p53 and P-gp expression were studied in 111 advanced head and neck cancers treated with radiotherapy and up to four courses of synchronous or sequential chemotherapy. The probability of survival at 5 years for patients in the trial as a whole was 27.7%, while the cohort used for this marker project was 29.4%. Among the subjects used for the marker study at the time of analysis, 13 remained disease-free and 18 were alive. Immunohistochemistry was used to assess p53 and P-gp expression; 27/111 (24%) head and neck cancers demonstrated p53/P-gp expression and 33/111 (30%) were both p53- and P-gp- negative. In univariate analysis, both p53 and P-gp expression were associated with reduced disease-free and overall survival. Multivariate analysis revealed tumour size, p53, and P-gp expression as the most powerful pretreatment prognosticators in the study cohort. Long-term follow-up results suggest that p53 and P-gp co-expression predicts the biological behaviour or the outcome following chemo/radiotherapy in advanced head and neck cancer.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Expression of p53 in oral squamous cell carcinoma is associated with the presence of IgG and IgA p53 autoantibodies in sera and saliva of the patients.
Around 50% of head and neck cancers are known to have aberrations of the p53 gene. Overexpression of the mutant p53 protein can induce a specific humoral response in cancer patients. Matched saliva, serum, and tissue samples from 26 patients with histologically confirmed oral squamous and verrucous carcinoma were investigated. p53 protein expression was evaluated by immunohistochemistry and antibodies specific for 53 protein were analysed in sera and whole mouth saliva by ELISA, immunoprecipitation, and competition assays; 16/25 (64%) samples demonstrated the stabilized p53 protein in tissues and 7/26 (27%) had a high level of p53 antibody in serum. In samples where matching saliva was available, p53 antibody was also present in saliva. In some tumours, only IgA-type p53 antibody was detected. p53 antibodies were found only in the serum and saliva of patients who showed p53 overexpression in their tumour tissues. These results demonstrate that detection of p53 antibodies can offer a specific and non-invasive method for the detection of a subset of tumours with p53 aberrations.
Autoantibodies↗
How to effectively use consultants.
Apart from a few pioneering medical centers, most medical organizations lack the internal knowledge and technical expertise to develop a comprehensive digital imaging business plan, create medical imaging architectures, select vendor(s), and implement picture archiving and communication systems (PACS) and other information systems. Many of these processes are only done once (eg, vendor selection and initial implementation) and developing such one-time expertise in-house is wasteful and inefficient. It is highly unlikely that an inexperienced hospital-based group undertaking their first and only PACS project will be able to match the experience and depth of a well-organized consulting group with prior experience. Organizations therefore are looking to consulting groups to fill their internal resource gaps. This report presents the benefits of engaging consultants, guidelines for selecting a consulting group, and insight on effectively using the consultants. The presentation is based on actual experiences using consultants for planning, selecting, and implementing a PACS at Children's Hospital Medical Center, Cincinnati.
Consultants↗