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Biomedical subjects

G Marsh

Publications and source records attributed to G Marsh.

At least 19 recordsLinked to original sources

Influenza vaccination of healthcare workers: a literature review of attitudes and beliefs.

BACKGROUND: Influenza vaccination coverage among healthcare workers (HCW) is insufficient despite health authority recommendations in many countries. Numerous vaccination campaigns encouraging HCW to be vaccinated have met with resistance. We reviewed published influenza vaccination programs in healthcare settings to understand the reasons for their success and failure, as well as the attitudes and beliefs of HCW. METHODS: Relevant articles published up to June 2004 were identified in the MEDLINE/Pubmed database. RESULTS: Thirty-two studies performed between 1985 and 2002 reported vaccination rates of 2.1-82%. Vaccination campaigns including easy access to free vaccine and an educational program tended to obtain the highest uptake, particularly in the USA. Yet, even this type of campaign was not always successful. Two main barriers to satisfactory vaccine uptake were consistently reported: (1) misperception of influenza, its risks, the role of HCW in its transmission to patients, and the importance and risks of vaccination (2) lack of (or perceived lack of) conveniently available vaccine. CONCLUSION: To overcome these barriers and increase uptake, vaccination campaigns must be carefully designed and implemented taking account of the specific needs at each healthcare institution.

Attitude to Health↗

Lymphohaematopoietic cancer risk among chemical workers exposed to benzene.

AIMS: To determine cause specific mortality in a cohort of 2266 chemical workers exposed to benzene in various manufacturing processes after 1935. METHODS: The cohort has accumulated over 80 000 person-years of observation; about 70% of the workers were followed for more than 30 years since first exposure. RESULTS: Mortality from non-malignant diseases of the blood was increased (SMR 2.17, 95% CI 0.87 to 4.48), and correlated with duration of benzene exposure, although risk had decreased from the previous investigation of this cohort. The risk for leukaemia was slightly above background (SMR 1.14, obs 12, 95% CI 0.59 to 1.99) but has also decreased since the earlier study of this cohort. SMRs for acute non-lymphocytic leukaemia (ANLL), chronic lymphatic leukaemia, and non-Hodgkin's lymphoma were 1.11, 0.42, and 1.06 respectively. There was evidence of a weak trend of increasing SMRs for leukaemia and possibly ANLL with increasing low-level cumulative exposure but not with other measures. CONCLUSION: Leukaemia and ANLL results were consistent with the mildly increased risk estimates from lower exposure subgroups of the Pliofilm cohort.

Adult↗

In vitro estrogenicity of polybrominated diphenyl ethers, hydroxylated PDBEs, and polybrominated bisphenol A compounds.

Polybrominated diphenyl ethers (PBDEs) are used in large quantities as additive flame retardants in plastics and textile materials. PBDEs are persistent compounds and have been detected in wildlife and in human adipose tissue and plasma samples. In this study, we investigated the (anti)estrogenic potencies of several PBDE congeners, three hydroxylated PBDEs (HO-PBDEs), and differently brominated bisphenol A compounds in three different cell line assays based on estrogen receptor (ER)-dependent luciferase reporter gene expression. In human T47D breast cancer cells stably transfected with an estrogen-responsive luciferase reporter gene construct (pEREtata-Luc), 11 PBDEs showed estrogenic potencies, with concentrations leading to 50% induction (EC(50)) varying from 2.5 to 7.3 microM. The luciferase induction of the most potent HO-PBDE [2-bromo-4-(2,4,6-tribromophenoxy)phenol] exceeded that of estradiol (E(2)), though at concentrations 50,000 times higher. As expected, brominated bisphenol A compounds with the lowest degree of bromination showed highest estrogenic potencies (EC(50) values of 0.5 microM for 3-monobromobisphenol A). In an ER alpha-specific, stably transfected human embryonic kidney cell line (293-ER alpha-Luc), the HO-PBDE 4-(2,4,6-tribromophenoxy)phenol was a highly potent estrogen with an EC(50) < 0.1 microM and a maximum 35- to 40-fold induction, which was similar to E(2). In an analogous ER beta-specific 293-ER betas-Luc cell line, the agonistic potency of the 4-(2,4,6-tribromophenoxy)phenol was much lower (maximum 50% induction compared to E(2)), but EC(50) values were comparable. These results indicate that several pure PBDE congeners, but especially HO-PBDEs and brominated bisphenol A-analogs, are agonists of both ER alpha and ER beta receptors, thus stimulating ER-mediated luciferase induction in vitro. These data also suggest that in vivo metabolism of PBDEs may produce more potent pseudoestrogens.

Air Pollutants, Occupational↗

Internal fixation versus hemiarthroplasty versus total hip arthroplasty for displaced subcapital fractures of femur--13 year results of a prospective randomised study.

In this prospective randomised trial we compare the mortality, morbidity and functional results of patients following each of the three principal methods of treatment for displaced subcapital fractures of the femur. Two hundred and ninety patients over the age of 65 years were included and randomly allocated to undergo closed reduction and internal fixation with a sliding compression screw plate or uncemented Austin Moore hemiarthroplasty or cemented Howse II total hip arthroplasty (THA). Nineteen patients were subsequently excluded. The 13 year results show that there was no statistical difference in the mortality between the three groups (81, 85 and 91% respectively). Internal fixation and hemiarthroplasty groups fared poorly with a revision rate of 33 and 24%, respectively, compared with 6.75% in the THA group. The dislocation rate was 13% following hemiarthroplasty and 20% following THA. Average Harris hip scores were 62, 55 and 80, respectively, for the internal fixation, hemiarthroplasty and THA groups. In the long term, both internal fixation and hemiarthroplasty resulted in a poor outcome with respect to pain and mobility. Despite high early complications, THA resulted in least pain and most mobility both in the short and long-term and was encouraging with a revision rate of only 6.25%. THA should be seriously considered in physiologically active patients with a displaced subcapital fracture of the femur.

Aged↗

Towards the nonstick egg: designing fluorous proteins.

Anyone who has made scrambled eggs will have had cause to praise the properties of Teflon. Teflon's highly chemically inert and nonstick nature derives from the perfluorinated polymer polytetrafluoroethylene. Perfluorocarbons have unique and valuable physical properties not found in nature. By incorporating fluorine into proteins, it might be possible to produce biological molecules with novel and useful properties.

Fluorine Compounds↗

Microinvasive cervical carcinoma: a retrospective study of cases presenting to the Oxford Colposcopy Unit between 1989 and 1996.

This a retrospective analysis of 65 cases of microinvasive disease and 5-8 years of follow-up (mean 6.2 years), evaluating the effectiveness of cytology and colposcopy in the diagnosis of microinvasive disease and the role of conservative surgery in its management. Cervical cytology reports indicated disease more severe than CIN III in 23% of cases. A further 7% at colposcopy were thought to have possible invasive disease despite no indication from the smear report, this impression correlated with increasing depth of invasion (>1.40 mm).

Journal Article↗

Potent competitive interactions of some brominated flame retardants and related compounds with human transthyretin in vitro.

Brominated flame retardants such as polybrominated diphenyl ethers (PBDEs), pentabromophenol (PBP), and tetrabromobisphenol A (TBBPA) are produced in large quantities for use in electronic equipment, plastics, and building materials. Because these compounds have some structural resemblance to the thyroid hormone thyroxine (T(4)), it was suggested that they may interfere with thyroid hormone metabolism and transport, e.g., by competition with T(4) on transthyretin (TTR). In the present study, we investigated the possible interaction of several brominated flame retardants with T(4) binding to TTR in an in vitro competitive binding assay, using human TTR and 125 I-T(4) as the displaceable radioligand. Compounds were tested in at least eight different concentrations ranging from 1.95 to 500 nM. In addition, we investigated the structural requirements of these and related ligands for competitive binding to TTR. We were able to show very potent competition binding for TBBPA and PBP (10.6- and 7.1-fold stronger than the natural ligand T(4), respectively). PBDEs were able to compete with T(4)-TTR binding only after metabolic conversion by induced rat liver microsomes, suggesting an important role for hydroxylation. Brominated bisphenols with a high degree of bromination appeared to be more efficient competitors, whereas chlorinated bisphenols were less potent compared to their brominated analogues. These results indicate that brominated flame retardants, especially the brominated phenols and tetrabromobisphenol A, are very potent competitors for T(4) binding to human transthyretin in vitro and may have effects on thyroid hormone homeostasis in vivo comparable to the thyroid-disrupting effects of PCBs.

Animals↗

Comparative incidence of de novo nonlymphoid malignancies after liver transplantation under tacrolimus using surveillance epidemiologic end result data.

BACKGROUND: An increased incidence of de novo nonlymphoid malignancies has been shown in immunocompromised patients. However, the true risk over time compared to the general population has not been determined. METHODS: One thousand consecutive patients were carefully followed for an average of 77.8+/-11.1 (range, 56.3-96.3) months after primary liver transplantation at a single center. All de novo nonlymphoid malignancies were recorded. Each malignancy was compared with a standard Occupational Cohort Mortality Analysis Program population matched for age, sex, and length of follow-up using modified life table technique and surveillance epidemiology end result (SEER) data. RESULTS: Fifty-seven patients accounted for de novo malignancies and contributed 4795.3 total person years, a mean+/-SD of 36+/-21 (median, 36; range, 6-74) months after liver transplantation. Twenty-two of these malignancies were skin malignancies including two melanomas. Oropharyngeal cancers (n=7) were found to be 7.6 times higher (P<0.05) and respiratory malignancies (n=8) were 1.7 times higher (P>0.05) compared to the SEER incidence rate. Female reproductive system malignancies including breast cancer (n=3) were 1.9 times lower (P>0.05) and genitourinary malignancies were (n=5) 1.5 times lower (P>0.05) than their matched cohorts. No differences was observed in gastrointestinal malignancies (n=5). There was a significant difference in survival of the patients after diagnosis of malignancy depending on the type of cancer. There were two Kaposi's sarcomas, two metastatic unknown primaries, one thyroid, one brain, and one ophthalmic malignancies in the series. Mortality for Kaposi's and metastatic disease of unknown primary was 100% within 5 months, while the 1-year mortality for oropharyngeal cancer was 57.1% and that for lung cancers was 62.5%. Long-term survival for skin cancer was highest: 86.4% at 3 years (P=0.015 by log-rank test). CONCLUSION: An increased incidence of de novo cancers in the chronically immunocompromised patient demands careful long-term screening protocols which will help to facilitate the diagnosis at an early stage of the disease. This is particularly true for oropharyngeal cancers where the risk is more than 7 times higher compared to SEER incidence data matched for age, sex, and length of follow-up.

Adult↗

Patient choice in diabetes education curriculum. Nutritional versus standard content for type 2 diabetes.

OBJECTIVE: To examine the effects of patient choice between two education curriculums that emphasized either the standard or nutritional management of type 2 diabetes on class attendance and other outcomes among a mostly Hispanic patient population. RESEARCH DESIGN AND METHODS: A total of 596 patients with type 2 diabetes were randomly assigned to either a choice or no choice condition. Patients in the choice condition were allowed to choose their curriculum, while patients in the no choice condition were randomly assigned to one of the two curriculums. Outcomes were assessed at baseline and at a 6-month follow-up. RESULTS: When given a choice, patients chose the nutrition curriculum almost four times more frequently than the standard curriculum. Contrary to our hypothesis, however, patients who had a choice did not significantly increase their attendance rates or demonstrate improvements in other diabetes outcomes compared with patients who were randomly assigned to the two curriculums. Patients in the nutrition curriculum had significantly lower serum cholesterol at a 6-month follow-up, whereas patients in the standard curriculum had significant improvements in glycemic control. Of the randomized patients, 30% never attended any classes; the most frequently cited reasons for nonattendance were socioeconomic. Hispanic patients, however, were just as likely as non-Hispanic patients to attend classes and participate at the follow-up. Patients who attended all five classes of either curriculum significantly increased their diabetes knowledge, gained less weight, and reported improved physical functioning compared with patients who did not attend any classes. CONCLUSIONS: Although providing patients with a choice in curriculums at the introductory level did not improve outcomes, differential improvements were noted between patients who attended curriculums with different content emphasis. We suggest that diabetes education programs should provide the opportunity for long-term, repetitive contacts to expand on the modest gains achieved at the introductory level, as well as provide more options to match individual needs and interests and to address socioeconomic barriers to participation.

Adult↗

Electrophysiological correlates of higher states of consciousness during sleep in long-term practitioners of the Transcendental Meditation program.

Standard ambulatory night sleep electroencephalograph (EEG) of 11 long-term practitioners of the Transcendental Meditation (TM) program reporting "higher states of consciousness" during sleep (the experimental group) was compared to that of nine short-term practitioners and 11 non-practitioners. EEG tracings during stages 3 and 4 sleep showed the experimental group to have: 1) theta-alpha activity simultaneously with delta activity and 2) decreased chin electromyograph (EMG) during deep sleep (p = 0.002) compared to short-term practitioners. Spectral analysis fast Fourier transform (FFT) data of the first three cycles showed that: 3) the experimental subjects had significantly greater theta 2 (6-8 Hz)-alpha 1 (8-10 Hz) relative power during stages 3 and 4 than the combined control groups [t(30) = 5.5, p = 0.0000008] with no difference in time in delta; 4) there was a graded difference across groups during stages 3 and 4 in theta 2-alpha 1 power, with experimentals having greater power than short-term practitioners, who in turn had greater power than non-practitioners [t(30) = 5.08, p = 0.00002]; and 5) experimentals also had increased rapid eye movement (REM) density during REM periods compared to short-term practitioners (p = 0.04). Previous studies have found increased theta-alpha EEG activity during reported periods of "transcendental consciousness" during the TM technique. In the Vedic tradition, as described by Maharishi Mahesh Yogi, transcendental consciousness is the first of a sequence of higher states. The maintenance of transcendental consciousness along with deep sleep is said to be a distinctive criterion of further, stabilized higher states of consciousness. The findings of this study are interpreted as physiological support for this model.

Adult↗

Telomerase activity in human gynaecological malignancies.

AIM: To evaluate whether increased telomerase activity can be clinically useful for detecting malignant cells in a variety of gynaecological specimens. METHODS: Telomerase activity was examined in frozen tissue samples of histologically confirmed lesions of the endometrium, ovary, and cervix. It was also assessed in exfoliated cells in cervical smears from patients with premalignant and malignant lesions and in ascitic fluid obtained from cases with malignant or non-malignant ovarian tumours. RESULTS: Solid tissues from carcinomas were telomerase positive in all specimens of endometrial (6/6) and cervical (6/6) origin, and in almost all from the ovary (12/13). Normal tissues from the cervix (0/5) and the ovary (0/5) were telomerase negative, but samples from normal endometrium were found to show telomerase activity, possibly due to the cyclical regenerative nature of this tissue. Conversely, dissociated cells in cervical smears from preneoplastic and frankly neoplastic lesions rarely showed detectable telomerase activity. Thus smears from patients with malignant tumours were only positive in one of two patients, whereas those from CIN-2 (0/5) and CIN-3 (1/17) lesions and from normal (0/10) samples were almost all negative. Telomerase activity was also scarcely detectable in cells obtained from ascitic fluid from patients with ovarian tumours. CONCLUSIONS: As in many other organs, telomerase activity is increased in solid tissue specimens from malignant tumours of the female reproductive tract, but it is not yet a reliable indicator of the presence of exfoliated cancerous or precancerous cells in clinical specimens from such lesions. Interpretation should be guarded until more extensive studies have been conducted. The data on solid tissues presented here confirm that activation of this enzyme is a major hallmark of the neoplastic process.

Ascites↗

Operations improvement and reengineering at Ohio State University Medical Center.

Rising costs and increasing competition have forced hospitals to respond to the needs of their customers. At Ohio State University Medical Center, operations improvement and reengineering are being used to redesign processes and to position the medical center competitively in today's changing environment. An operations improvement team identified business processes with the greatest opportunity for positive impact based on the goals of the medical center. Next, these areas were prioritized and teams appointed to begin the reengineering process. Reengineering methods focused on specific outcomes, including improved patient satisfaction, reduced cost, and improved clinical and service quality. Throughout the process, the goals and successes of reengineering were communicated to the organization and community.

Academic Medical Centers↗

Large loop excision of the transformation zone (LLETZ) as an alternative to both local ablative and cone biopsy treatment: a series of 1000 patients.

One thousand patients, referred to the Oxford Colposcopy Clinic, were treated with either large loop excision of the transformation zone (LLETZ, 891 cases) or LLETZ cone (109 cases). Forty-five LLETZ cones were performed empirically, 64 under microcolposcopic guidance. Over 98% of patients were managed as outpatients under local anaesthesia, and 87% of new patients treated with LLETZ had treatment at their first visit. Ninety percent of patients had at least cervical intraepithelial neoplasia grade one (CIN I) and 73% had CIN II or worse. Seventeen cases of invasive or possibly invasive disease were detected, 6 of them unsuspected. The overall rate of complete excision of CIN or worse was 72%. Follow-up was cytologic with or without colposcopy depending on lesion severity. Ninety-one percent of 967 treated patients were free of dyskaryosis at a mean follow-up of 23 months, with complete excision of CIN or worse at LLETZ a significant predictive factor. No cases of invasive carcinoma have developed following treatment. Major morbidity was uncommon, with 3.8% severe hemorrhage. Stenosis was noted in 3.8% cases, mostly after LLETZ cone. One patient (0.1%) has reduced fertility possibly attributable to LLETZ. Questionnaire assessment revealed a very high degree of acceptability of the treatment to patients. LLETZ and LLETZ cone have proved highly acceptable and effective outpatient diagnostic and treatment alternatives to both local ablation and cone biopsy in the Oxford Colposcopy Clinic.

Adolescent↗

A third instance of the high oxygen affinity variant, Hb Heathrow [beta 103(G5)Phe- greater than Leu]: identification of the mutation by mass spectrometry and by DNA analysis.

Hb. Heathrow [beta 103(G5)Phe- greater than Leu] was identified in an Englishman with a life-long history of polycythemia, his father had been similarly affected. A hemoglobin variant was suspected from the high oxygen affinity of the patient's blood. The Hb Heathrow abnormal beta chain was resolved from the normal beta chain by high performance liquid chromatography, and the abnormal peptide and the amino acid replacement were identified by mass spectrometry. The corresponding base change (C- greater than G at codon 103) was demonstrated by sequence analysis of the polymerase chain reaction amplified exon 2 of the genomic beta-globin gene. This is only the third known instance of Hb Heathrow.

Aged↗

Two decades of increasing mortality from Parkinson's disease among the US elderly.

To examine the possible role of environmental factors in the cause of Parkinson's disease (PD), we reviewed mortality trends for PD in the United States from 1962 through 1984. We found that age-specific mortality for PD in all demographic groups had changed notably during this 23-year interval. Among whites of both sexes, substantial declines were observed among the middle-aged, while notable increases were seen in the geriatric age groups. Similar changes were found in nonwhites; among nonwhites in the geriatric age range, increases of 22% to 553% were observed among women. Men generally had a 100% higher risk of death due to PD than did women. Whites were at three times the risk of nonwhites. The observed temporal changes appear to reflect improved treatment, better case ascertainment, and a true rise in the incidence of PD, particularly among the elderly. This rise may be due to preventable environmental causes and will require further investigation.

Aged↗

Mortality of workers potentially exposed to epichlorohydrin.

An epidemiological study was undertaken to determine whether the animal carcinogen, epichlorohydrin (ECH), produces cancer in man. A total of 863 workers with probable exposure to ECH at two chemical plants during 1948-65 were followed up for deaths up to 1983. Twenty years or more after first exposure the all cancer SMR was 112.2 (22 deaths) and the SMR for leukaemia was 500.0 (three deaths), which is statistically significant. All cancer, leukaemia, and most other causes of death were related to estimated levels of exposure to ECH, except violence. The most consistent (both plants) relation was between exposure level and heart disease. Overall, the heart disease SMR 20 years or more after first exposure was 39.2 (five deaths) for low exposure and 105.4 (17 deaths) for high exposure. Limited evidence of a cardiovascular disease relation to ECH production in one other epidemiological study is supported by this study. Allyl chloride used in the production of ECH may play a part. The relation of heart disease and exposure does not appear to be an artifact, although the fact that many other causes of death were also related to exposure argues against a causal relation.

Cardiovascular Diseases↗

Parkinsonism death rates by race, sex and geography: a 1980s update.

To evaluate temporal changes in the geographic distribution of Parkinson's disease (PD) mortality in the United States, we reviewed death rates for PD in the nine regions of the United States for 1980-1984. Age-adjusted mortality for all ages and for the elderly (65 years of age and older) was analyzed. Variation in PD mortality was observed among the regions for all demographic groups. The patterns were different from those reported during 1959-1961. Changing geographic patterns in mortality provide evidence for an environmental etiology for PD.

Cause of Death↗