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Biomedical subjects

M Fleming

Publications and source records attributed to M Fleming.

At least 37 records · Page 2Linked to original sources

Risk perceptions of offshore workers on UK oil and gas platforms.

Knowledge of the workforce's risk perceptions and attitudes to safety is necessary for the development of a safety culture, where each person accepts responsibility for working safely. The ACSNI Human Factors report stresses the importance of assessing workforce perceptions of risk to achieve a proper safety culture. Risk perception research has been criticized for insufficient analysis of the causal relationships between risk factors and perceived risk. The present study reports some of the factors which predicted risk perception in a sample of 622 employees from six UKCS offshore oil installations who completed a 15-section questionnaire. This paper focuses on the accuracy of workers' risk perceptions and what underlying factors predict the perception of personal risk from both major and minor hazards.

Accidents, Occupational↗

Prenatal diagnosis of Machado-Joseph disease by direct mutation analysis.

MJD is the most frequent dominant ataxia and an incapacitating disorder. Onset is most frequently during the reproductive years, and genetic counseling is its only means of prevention. The causative mutation--an expansion of a (CAG)n on chromosome 14q32.1--can now be directly detected. We now report the first two cases of prenatal diagnosis (PND). The first presented as a simultaneous request for predictive testing and PND at 14 weeks of pregnancy. Owing to time constraints, we performed a full protocol of counseling with shorter inter between sessions, while psycho-social evaluation of the other parent obstetric consults were also begun. We ensured that the couple wished termination if the fetus was a carrier, to avoid a presymptomatic test for the unborn child. We were thus able to deliver test results two weeks before PND. As the fetus carried an expanded allele (77 CAGs) inherited from his father, termination was performed and the couple received counselling, psychological and social support. The second case was the fetus of a carrier-mother that was diagnosed as non-carrier, also after amniocentesis.

Adult↗

Colon cancer with metastasis to the ovary at time of initial diagnosis.

Colon cancer with a synchronous ovarian metastasis is occasionally diagnosed at the time of laparotomy for a pelvic mass. The purpose of this retrospective study is to evaluate the clinical presentation as well as the impact of the type of metastatic spread and surgical intervention on overall survival. We reviewed charts of 23 patients treated between 1980 and 1995. Pain was the initial symptom in 14 patients (61%), with only four patients (17%) complaining of rectal bleeding, but with five patients (22%) complaining of uterine bleeding. At the time of laparotomy, the ovarian capsule was intact in 12 patients. Metastatic disease to the peritoneum was seen in seven patients and to the liver in six patients. On pathological evaluation, the median ovarian tumor size was 10 cm, significantly larger than the median colon tumor size of 4.5 cm. Surgical treatment consisted of colon resection in all but one patient, bilateral or unilateral salpingo-oophorectomy in 22 patients, and hysterectomy in nine patients. Only one patient survived 5 years. Sixteen patients died of colon cancer. The median survival time was 17.8 months, ranging from 1 to 86 months. Tumor size was of no prognostic importance. Median survival time of patients with peritoneal disease (10.8 months) was significantly shorter compared to patients without peritoneal disease (25.2 months). In the presence of liver metastasis, the median survival time was, likewise, significantly reduced from 20.1 months to 8.1 months. In conclusion, macroscopic metastatic disease to the ovary is a poor prognostic factor in colon cancer. In selected patients who can be rendered disease-free by surgery, prolonged survival is possible and an aggressive approach is recommended. Survival of patients with peritoneal disease or liver metastasis is short and a mainly palliative approach is recommended.

Adult↗

Phasic arousal in response to auditory warnings after traumatic brain injury.

Traumatic brain injury (TBI) is believed to have adverse effects on attention, but because of the multifaceted nature of the arousal and attentional network, the precise impact of TBI on various subcomponents of this network remains controversial. As part of a larger program of research on attention in TBI, we studied the effects of auditory warning signals on accuracy, reaction time, and response bias, as indices of phasic arousal in a visual go/no-go task. Warnings were presented randomly at various pre-stimulus intervals to a sample of recently injured patients and control subjects. For each subject and performance index, we examined the time interval required to reach maximal phasic arousal, the degree of performance change occurring at this maximal point, and the ability to maintain this state of increased arousal over longer warning intervals. After adjustment for baseline differences, there were no significant differences between patients and controls in any aspect of performance. Examination of effect sizes suggested that this was not due to limited statistical power, but that any differences between groups, if present, must have been small. In contrast, in our prior research on sustained attention and observable behaviors related to attention, large group differences have been found. These data suggest that mechanisms responsible for auditorily-induced phasic arousal responses are largely preserved in severe TBI.

Adult↗

The potential role of BAX and BCL-2 expression in diffuse alveolar damage.

Apoptosis of type II pneumocytes has been identified in diffuse alveolar damage (DAD), is associated with p53 and WAF1 expression, and may be of pathogenetic importance. BAX, a homologue of BCL-2, is induced by p53 and is a promoter of apoptosis. The proapoptotic effect of BAX is negatively regulated by its binding with BCL-2. In this study, we sought to investigate that role of BAX and BCL-2 in DAD. We hypothesized that alterations in BAX and BCL-2 expression may be important in determining the susceptibility of type II pneumocytes and interstitial cells to apoptosis. Twenty-eight cases of DAD and 16 control cases (i.e., lung tissues adjacent to resected tumors) were retrieved from the files of the University of Utah and the Armed Forces Institute of Pathology. Immunohistochemical stains were performed with antigen retrieval by microwave using antibodies recognizing BAX and BCL-2. The percentage of positively staining pneumocytes and interstitial cells was estimated in each case to the nearest 10%. BAX expression was markedly increased in pneumocytes and interstitial cells in DAD compared with control lung tissues. In DAD, BAX was identified on an average of 80% of alveolar pneumocytes (range 30 to 100%) and 70% of interstitial cells (range 20 to 90%). In control lungs, BAX was identified on an average of 10% of pneumocytes (range 0 to 20%) but not in interstitial cells. Focal BCL-2 staining was identified in interstitial myofibroblasts in 7 of 25 cases of DAD but was only identified in bronchiolar epithelium of control lungs. These results suggest that the induction of BAX in DAD may enhance the susceptibility of alveolar epithelial cells to apoptosis, whereas BCL-2 expression may contribute to the absence of apoptosis in interstitial myofibroblasts. Expression of BCL-2 in interstitial myofibroblasts may contribute to the development of pulmonary fibrosis in some patients.

Adult↗

Methicillin-resistant Staphylococcus aureus: investigation of a hospital outbreak using a case-control study.

A retrospective case-control study of 50 MRSA-positive patients was carried out during an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) at an acute general hospital in London. Controls were randomly selected from MRSA-negative patients admitted during the outbreak period. Risk factors investigated included length of admission prior to screening, number of ward changes, main diagnosis, extent of staff contact, pressure sores, surgical and other invasive procedures and antibiotic treatment. Outcome variables examined were rates of infection (versus colonization) with MRSA and mortality. Patients with MRSA were in hospital longer before microbiological specimens were taken and moved wards more often than controls. In a logistic regression analysis, length of stay in hospital, pressure sores, physiotherapy and surgical procedures were associated with a significantly increased risk of acquiring MRSA. Odds ratios (and 95% confidence intervals) for having acquired MRSA were: 8.3 (1.02-71.43) if a patient had pressure sores; 3.7 (1.10-12.5) if they received physiotherapy; and 3.2 (1.82-10.0) if they underwent surgical procedures. The rate of clinical infection amongst patients with this strain of MRSA was 26% and included life-threatening infections such as septicaemia, underlining the potential virulence of MRSA. Surgery and physiotherapy may have been markers of debility. Physiotherapy was probably a marker of increased rates of contact with all hospital staff, and high standards of hand hygiene should be promoted amongst all staff as the most important factor in controlling an outbreak of MRSA. Good bed management is essential for hospital infection control.

Aged↗

Inattentive behavior after traumatic brain injury.

Clinicians and families report that traumatic brain injury results in a variety of attention deficits. Numerous laboratory studies have documented slowing of information processing, alteration in event-related potentials, or difficulty attending to specific relevant task dimensions in the presence of redundant information. However, little is known about how these information processing abnormalities relate to observable behaviors in daily living or work environments, which presumably form the basis for clinicians' and families' reports. We developed a quantitative assessment of behavioral inattentiveness in both quiet and distracting environments, and demonstrated excellent interrater reliability. Using this assessment, we have studied 20 patients with recent traumatic brain injury and 20 demographically comparable control subjects. We have confirmed marked differences in behavioral attentiveness between patients and controls in both distracting and nondistracting environments.

Activities of Daily Living↗

Prevention and treatment of alcohol-related problems: an international medical education model.

Alcohol abuse and alcoholism are among the world's most pressing public health concerns. Research has shown that while primary care physicians are in a good position to screen for alcohol-use disorders and to aid in treating these problems, they tend to identify only a small percentage of patients with such disorders and they rarely intervene with these persons. This situation is probably attributable to the fact that medical students worldwide are taught very little about alcohol-related problems. Clearly there is an urgent need to educate the world's doctors about preventing, diagnosing, and treating alcohol abuse and addiction. In this paper, the authors describe a model international program for educating physicians about alcohol-related problems that was developed by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in cooperation with the Center for Addiction Research and Education (CARE) at the University of Wisconsin-Madison. They describe the components of the initiative's "trainer-development" approach and critical issues in implementing the program in other countries. Finally, they discuss how the program was successfully implemented in Poland and describe the NIAAA's plans for introducing the model in several other countries.

Alcoholism↗

Association of p53 and WAF1 expression with apoptosis in diffuse alveolar damage.

Little is known about alterations in cell cycle regulatory proteins such as p53 and WAF1 in diffuse alveolar damage (DAD). We hypothesized that up-regulation of p53 and WAF1 in type II pneumocytes in DAD is associated with underlying DNA damage and apoptosis. Twenty cases of DAD and twenty control specimens of lung adjacent to resected tumors were studied. Immunohistochemical stains with antibodies recognizing p53 and WAF1 were performed, and apoptosis was assessed in sixteen cases by the nick end-labeling method. We identified p53 expression and apoptosis in all cases of DAD but not in any of the control lungs. We detected WAF1 expression in nineteen of twenty cases of DAD and in sixteen of twenty control lungs. In general, the distribution and intensity of WAF1 staining were greater in DAD than in control lungs. Staining for both p53 and WAF1 and labeling of apoptotic cells in DAD were usually focal ( < 10% of cells) and predominantly localized in type II pneumocytes. We conclude that increased p53 and WAF1 expression in DAD reflects normal physiological up-regulation in response to cellular and DNA damage and is associated with apoptosis of type II pneumocytes. p53-dependent apoptosis may contribute to the pathogenesis of this disease.

Adolescent↗

Simian virus 40 and pleural mesothelioma in humans.

It has been reported that DNA of SV40, a virus of Asian macaques that is tumorigenic for rodents and can transform human cells in vitro, is present in pleural mesotheliomas and in several other cancers. To verify these observations, we tested paraffin sections from mesothelioma tissues of 50 patients for SV40 DNA using PCR with two separate sets of primers. The analytic sensitivity for detection of SV40 DNA was 1-10 genome copies. We also tested the specimens for beta-globin by PCR to assess the suitability of the specimen DNAs for amplification. beta-Globin amplification was detected in 48 of the 50 specimens, but SV40 DNA was not detected in any tumors, with either of two SV40 primer sets. Furthermore, sera from 34 additional patients with mesothelioma, 33 patients with osteosarcoma (another cancer reported to be SV40-related) and 35 controls were tested for SV40 antibodies by a plaque neutralization assay. The serological data, like the DNA results, did not support an association of SV40 with mesothelioma or with osteosarcoma; antibodies to SV40 were detected in three mesothelioma patients, in one osteosarcoma patient, and in one control. These findings call into question the association of SV40 with mesothelioma.

Adult↗

Sustained arousal and attention after traumatic brain injury.

Clinicians report that patients with traumatic brain injury (TBI) often have difficulty with tasks requiring sustained attention, and there are neuroanatomical and neurophysiological reasons to expect such deficits. Nevertheless, laboratory measures of sustained attention or vigilance in TBI have produced conflicting results. These inconsistencies may be due to patient heterogeneity as well as the fact that vigilance performance is dependent on highly specific features of the task design. We developed a visual vigilance task in which the influence of non-attentional factors was minimized and task difficulty for patients and controls made comparable. Performance was characterized with respect to vigilance level as well as vigilance decrement, using measures of perceptual discrimination, response bias, reaction time and reaction time variability. Twenty-six patients with recent TBI and 18 control subjects were tested on this task. A MANOVA of ranked scores revealed significantly different patient and control performance overall. Initial level of performance (vigilance level) was slower and more variable for patients than controls, and patients showed more conservative response biases. Deterioration over time (vigilance decrement) was steeper for patients than controls for reaction time, reaction time variability, and response bias. Deterioration in accuracy (D') did not differ significantly between patients and controls. Performance was not related to available measures of injury severity. Hypotheses relating arousal mechanisms to vigilance performance are discussed.

Adolescent↗

Characterisation of African isolates of rinderpest virus.

Isolates of rinderpest virus (RPV) recovered from outbreaks of the disease in Kenya and Southern Sudan between 1986 and 1993 were compared to each other and to earlier isolates from East and West Africa. The recent isolates were mildly pathogenic for susceptible cattle and thus resembled other mild strains of RPV recovered from cattle and wildlife in East Africa more than 30 years ago. Monoclonal antibody analysis using a panel of 12 anti-RPV haemagglutinin protein-specific antibodies (mAbs) revealed that individual isolates were distinguishable. However, the panel of mAbs could not be used to relate the isolates on the basis of their pathogenicity or geographic origin. Immunoprecipitation of the virus-induced proteins from infected Vero cells, followed by SDS-polyacrylamide gel electrophoresis, showed that the recent mild RPV isolates from eastern Africa were closely related to each other and to their contemporary isolates from Nigeria and Egypt, but they were distinct from another mild isolate recovered from the region three decades ago. Two distinct lineages of African RPV isolates were identified by sequencing a region of the genome around the proteolytic enzyme cleavage site of the fusion protein from the old and new isolates. One lineage, which included virus isolates recovered from East and West Africa during the 1960s, showed a closer phylogenetic relationship to Asian and Middle Eastern RPV isolates. The other lineage consisted mainly of isolates recovered from East, West and North Africa between 1983 and 1993. The results showed that there was co-circulation of two different lineages of RPV in Nigeria during the epizootics of the 1980s.

Africa↗

Characterisation of morbilliviruses isolated from Lake Baikal seals (Phoca sibirica).

Sequence analysis of the haemagglutinin protein (H) gene of the morbillivirus (PDV-2) isolated from a Siberian seal (Phoca sibirica) during the 1987/1988 epizootic in Lake Baikal revealed that it was most closely related to two recent isolates of canine distemper virus (CDV) from Germany and different from CDV vaccines currently in use in that region. The virus continued to circulate in seals in Lake Baikal after the 1987/1988 epizootic since sera collected from culled seals in the spring of 1992 were positive in morbillivirus ELISA tests, reacting most strongly with the CDV antigen.

Amino Acid Sequence↗

Recombinant capripoxvirus expressing the hemagglutinin protein gene of rinderpest virus: protection of cattle against rinderpest and lumpy skin disease viruses.

A cDNA clone containing the complete coding sequence of the hemagglutinin (H) protein gene of the RBOK vaccine strain of rinderpest virus, under the control of the vaccinia late promoter p11, was inserted by homologous recombination into the thymidine kinase gene of the KS-1 strain of capripoxvirus. The recombinant virus produced authentic H protein as judged by its electrophoretic mobility, transport to the cell surface of infected lamb testis cells, and reactivity with monoclonal antibodies specific for the H protein of rinderpest virus. The recombinant virus induced significant levels of rinderpest virus neutralizing antibodies in vaccinated cattle and protected them from clinical rinderpest after challenge with a lethal dose of a highly virulent heterologous strain of the virus. Protection was achieved using vaccine doses lower than those used with a similar recombinant expressing the fusion protein gene of rinderpest. The parental KS-1 virus is widely used as a vaccine against capripox viruses and so the rinderpest recombinant acts as a dual vaccine to protect cattle against both rinderpest and lumpy skin disease.

Animals↗

Medical education about substance abuse: changes in curriculum and faculty between 1976 and 1992.

PURPOSE: To examine changes in substance abuse education in U.S. medical schools between 1976 and 1992. METHODS: In 1991-92 the authors conducted a 16-year follow-up survey of six clinical departments in each of the 126 U.S. medical schools. Two previous surveys by scholars and surveys conducted by the Liaison Committee on Medical Education, Association of American Medical Colleges, and the National Center for Medical Fellowships in the Addictions provided baseline data for comparison. The statistical methods used in the comparisons were paired t-tests, one-way analyses of variance, and tests of differences between proportions. RESULTS: Significant increases were found in the numbers of required and elective curriculum units for medical students between 1986-87 and 1991-92. The number of medical schools requiring courses in substance abuse treatment increased from five to eight between 1986-87 and 1991-92. For residents, there were significant increases in the numbers of curriculum units for residents in family medicine and pediatrics. The average number of faculty in the 116 medical schools that reported units on substance abuse was 4.1. There were 45 fellowships in addiction medicine identified in 1991-92, with a total of 61 fellows in training. CONCLUSION: While the findings confirm positive changes, the amount of curricula time and the number of faculty having expertise in substance abuse education do not compare well with the amounts of time and numbers of faculty involved in clinical problems of similar prevalence, such as cancer and heart disease.

Curriculum↗

Implementing supported housing in state and local mental health systems.

The Ohio Department of Mental Health has aggressively promoted the development of supported housing--affordable, permanent community housing along with a system of needed support services--for adults with serious mental illness. The authors outline the development of supported housing programs by the state and by Franklin County, Ohio, beginning in the mid-1980s. The county's program, implemented mainly through the county authority for substance abuse and mental health services and a separate nonprofit housing corporation, was assisted by a major grant and loan from the Robert Wood Johnson Foundation Program on Chronic Mental Illness, federal Section 8 housing certificates, and special grants from the Ohio Department of Mental Health. Both the state and the county formulated and followed comprehensive housing development plans. Both entities used creative financing mechanisms, including leveraging, to bring in additional public and private funds, and they worked to involve consumers and families in formulating policies and developing services.

Chronic Disease↗

A national model of faculty development in addiction medicine.

Increasing the number of faculty with expertise in addiction medicine is one of the challenges facing the medical community in the 1990s. To meet this challenge, the Society of Teachers of Family Medicine created a faculty development course to increase the expertise of family practice faculty involved in teaching residents. The authors describe the development, implementation, and consequences of the five-day intensive course that was taught to 165 participants at ten sites in 1990. The participants' self-reporting before and three months after the course showed significant increases in the numbers of participants who taught addiction medicine in eight of 11 clinical situations. The authors conclude that the course represents a model of faculty development in addiction medicine that is applicable to other specialties and health professions.

Evaluation Studies as Topic↗

Different epitope structures select distinct mutant forms of an antibody variable region for expression during the immune response.

Antibody variable (V) regions that initially differ from one another by only single amino acid residues at VH-D and D-JH segment junctions (termed canonical V regions) can be elicited in strain A/J mice by three different haptens. Among such V regions an amino acid substitution due to somatic mutation is recurrently observed at VH CDR2 position 58, regardless of which of these haptens is used for immunization. This substitution confers upon a canonical V region a generic increase in affinity for all the haptens. Conversely, the type of amino acid substitution at VH position 59 resulting from somatic mutation that is recurrently observed among such V regions changes with the eliciting hapten, in a manner that correlates directly with the cognate affinity increases (or decreases) for hapten conferred by the observed substitutions. This small subregion of VH CDR2 therefore plays a major role in determining both affinity and specificity for antigen. The data confirm that affinity for antigen is of pivotal importance in determining the degree of selection of different mutant forms of a V region. Moreover, during an immune response a sufficiently diverse mutant repertoire can be generated from a single canonical V region to allow adaptation to increase affinity for three different epitopes.

Amino Acid Sequence↗