Implementing findings of research revisited.
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Evidence-Based Medicine↗
Biomedical subjects
R Jones
Publications and source records attributed to R Jones.
Lipid dynamics in the plasma membrane of fresh and cryopreserved human spermatozoa.
Preserving the integrity of the plasma membrane of spermatozoa is crucial for retention of their fertilizing capacity, especially after stressful procedures such as freezing and storage. In this investigation we have measured lipid diffusion in different regions of the plasma membrane of fresh and cryopreserved human spermatozoa using a sensitive, high resolution fluorescence photobleaching technique (FRAP) with 5-(N-octadecanyl)aminofluorescein as reporter probe. Results show that diffusion was significantly faster on the plasma membrane overlying the acrosome and decreased progressively in the postacrosome, midpiece and principal piece. The midpiece plasma contains a higher proportion of immobile lipids than other regions. In cryopreserved spermatozoa, lipid diffusion in the plasma membrane was significantly reduced on the acrosome, postacrosome and midpiece relative to fresh spermatozoa. Diffusion, however, could be restored to normal levels by washing spermatozoa in a medium containing 0.4% polyvinylpyrrolidine but not in medium alone or in medium containing 0.4% albumin. These results suggest that (i) lipid dynamics in the plasma membrane of human spermatozoa varies significantly between surface regions; (ii) in-plane diffusion is adversely affected by cryopreservation; and (iii) washing frozen spermatozoa in 0.4% polyvinylpyrrolidine restores membrane lipid fluidity to normal levels. The latter finding has important implications for improving the fertility of human spermatozoa following cryopreservation.
Adult↗
Health surveys in the workplace: comparison of postal, email and World Wide Web methods.
Health surveys in the workplace are an important part of epidemiology, needs assessment and health promotion. Since the workplace is changing rapidly with the use of computer networks, we examined the feasibility, validity and cost of health surveys using e-mail and the World Wide Web (WWW). Five hundred systematically sampled university staff in a convenience sample of 10 English universities were surveyed using either e-mail alone, e-mail plus a WWW form or postal questionnaire. Response rates, speed of response, validity and costs were examined. The postal survey obtained the best response rate: 72% as compared with 34% for e-mail alone and 19% for the WWW, but it was also the most expensive at 92p per reply, with 35p for e-mail, and 41p for the WWW. Most of the electronic responses were made within five days. In 1997, the increased response rate justified the higher cost of postal questionnaires. e-mail and WWW surveys are easy, quick and inexpensive to administer, and despite low response rates may be useful for pilot studies. The rapid changes in the spread and use of information technology means we have to keep reassessing the methods we use for health surveys in the workplace.
Feasibility Studies↗
The novel epididymal secretory protein ESP13.2 in Macaca fascicularis.
Newly synthesized mammalian spermatozoa undergo critical modifications as they pass along the epididymis. The modifications endow spermatozoa with fertilizing ability and occur largely as a consequence of epididymal gene expression. With this in mind, we here employed a cDNA cloning strategy designed to identify key epididymal gene products. We describe a novel cynomolgus monkey (Macaca fascicularis) epididymal transcript designated cy-ESP13.2, of 690 nucleotides. The putative human ortholog was cloned and is highly conserved. Both cDNA sequences predict small, secretory proteins with a disulfide-stabilized core. Anti-peptide polyclonal antibodies were raised to a predicted cy-ESP13.2 surface loop. Western blotting with these antibodies revealed high-level, epididymis-specific expression of cy-ESP13.2, consistent with the pattern of cy-ESP13.2 mRNA expression assessed by Northern blotting. cy-ESP13.2 protein was of 30 kDa and was readily detectable in epithelial cells lining the efferent ductules, initial segment, and cauda regions of the epididymis, but not on spermatozoa. Similarities to members of the four-disulfide-core family suggest clues to ESP13.2 function.
Amino Acid Sequence↗
Tissue distribution of tramadol and metabolites in an overdose fatality.
Tramadol (Ultram) is a centrally acting, synthetic analgesic agent. Although it has some affinity for the opiate receptors, tramadol is believed to exert its analgesic effect by inhibiting the re-uptake of norepinephrine and serotonin. There are several published cases of tramadol's involvement in drug-related deaths and impairment. Reports of deaths involving tramadol alone with associated tissue concentrations are rare. This report documents a case in which tramadol overdose was identified as the cause of death. The following tramadol concentrations were found in various tissues: blood, 20 mg/L; urine, 110.2 mg/L; liver, 68.9 mg/kg; and kidney, 37.5 mg/kg. Tissue distributions of the two primary metabolites, N-desmethyl and O-desmethyl tramadol, are also reported. In each tissue or fluid except urine, the tramadol concentration was greater than either metabolite, consistent with other reports of drug-impaired drivers and postmortem cases. The O-desmethyl metabolite concentration was greater than the N-desmethyl metabolite concentration in all tissues; this is in contrast to other postmortem reports, in which the majority of cases report concentrations of O-desmethyl as less than those of N-desmethyl. This may be useful as an indicator of time lapse between ingestion and death.
Adult↗
Tau pathology in a family with dementia and a P301L mutation in tau.
Familial forms of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) have recently been associated with coding region and intronic mutations in the tau gene. Here we report our findings on 2 affected siblings from a family with early-onset dementia, characterized by extensive tau pathology and a Pro to Leu mutation at codon 301 of tau. The proband, a 55-year-old woman, and her 63-year-old brother died after a progressive dementing illness clinically diagnosed as Alzheimer disease. Their mother, 2 sisters, maternal aunt and uncle, and several cousins were also affected. Autopsy in both cases revealed frontotemporal atrophy and degeneration of basal ganglia and substantia nigra. Sequencing of exon 10 of the tau gene revealed a C to T transition at codon 301, resulting in a Pro to Leu substitution. Widespread neuronal and glial inclusions, neuropil threads, and astrocytic plaques similar to those seen in corticobasal degeneration were labeled with a battery of antibodies to phosphorylation-dependent and phosphorylation-independent epitopes spanning the entire tau sequence. Isolated tau filaments had the morphology of narrow twisted ribbons. Sarkosyl-insoluble tau exhibited 2 major bands of 64 and 68 kDa and a minor 72 kDa band, similar to the pattern seen in a familial tauopathy associated with an intronic tau mutation. These pathological tau bands predominantly contained the subset of tau isoforms with 4 microtubule-binding repeats selectively affected by the P301L missense mutation. Our findings emphasize the phenotypic and genetic heterogeneity of tauopathies and highlight intriguing links between FTDP-17 and other neurodegenerative diseases.
Atrophy↗
Granulomatous 'foreign body reactions' contribute to exaggerated in-stent restenosis.
BACKGROUND: Results of previous studies with stents coated with 'biocompatible' polymers showed that severe inflammatory reaction and subsequent in-stent restenosis may occur. OBJECTIVE: To evaluate the contribution of granulomatous reaction from uncoated stents to formation of in-stent neointimal hyperplasia. METHODS: Uncoated stainless-steel stents were implanted into 21 porcine coronary arteries without oversizing and harvested after 2 months (n = 6) or 6 months (n = 7). We compared the stents with granulomatous reaction with those without foreign-body reaction. RESULTS: Granulomatous reactions occurred in five 21 stents and resulted in there being significantly greater in-stent neointimal hyperplasia than there was with stents without foreign-body reaction (angiographic diameter stenosis 45 +/- 36 versus 16 +/- 16%, area of neointimal 3.30 +/- 1.4 versus 1.22 +/- 0.4 mm2, thickness of neointima 0.46 +/- 0.29 versus 0.11 +/- 0.09 mm, stenosed area 56 +/- 24 versus 20 +/- 7%, P < 0.01 for each comparison). This increase in amount of neointima was accompanied by significantly greater proliferating cell nuclear antibody staining (15 +/- 5 versus 3 +/- 2%, P < 0.05) in the presence of a granuloma near the stent struts. CONCLUSIONS: A localized granulomatous reaction is associated with a significant increase in amount of stent neointima and proliferation of cells. Thus, permanent stent implants may provoke granulomatous vascular reactions that may affect late-healing responses and clinical outcomes.
Animals↗
Helicobacter pylori and dyspepsia: trick or treat?
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Dyspepsia↗
Perceptions of good medical practice in the NHS: a survey of senior health professionals.
OBJECTIVES: To categorize senior health professionals' experience with poor medical practice in hospitals and in general practice, to describe perceptions which senior NHS staff have of good medical practice, and to describe how problems of poor medical practice are currently managed. DESIGN: A postal questionnaire survey. The questionnaire sought perceptions of good medical practice, asked participants to characterise deviations from good practice, and to describe experience with managing poor performance at the time of the introduction of the General Medical Council (GMC) performance procedures. SETTING: A range of NHS settings in the UK: hospital trusts, health authorities/boards, local medical committees, community health councils. SUBJECTS: Senior health professionals involved in the management of medical professional performance. MAIN MEASURES: Perceptions of what constitutes good medical practice. RESULTS: Most respondents considered that persistent problems related to clinical practice (diagnosis, management, and outcome and prescribing) would require local management and, possibly, referral to the GMC performance procedures. Informal mechanisms, including informal discussion, education, training, and work shifting, were the most usual means of handling a doctor whose performance was poor. Many took a less serious view of deficiencies in performance on manner and attitude and communication, although consultation skills rather than technical skills comprised the greatest number of complaints about doctors. CONCLUSIONS: Senior NHS professionals seem reluctant to consider persistently poor consultation skills in the same critical light as they do persistently poor technical practice. These attitudes may need to change with the implementation of clinical governance and updated guidance from the GMC on what constitutes good medical practice.
Quality Assurance, Health Care↗
Surgical resection rate in lung cancer.
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Carcinoma, Small Cell↗
Selection of the T cell repertoire.
Advances in gene technology have allowed the manipulation of molecular interactions that shape the T cell repertoire. Although recognized as fundamental aspects of T lymphocyte development, only recently have the mechanisms governing positive and negative selection been examined at a molecular level. Positive selection refers to the active process of rescuing MHC-restricted thymocytes from programmed cell death. Negative selection refers to the deletion or inactivation of potentially autoreactive thymocytes. This review focuses on interactions during thymocyte maturation that define the T cell repertoire, with an emphasis placed on current literature within this field.
Animals↗
alpha-smooth-muscle actin and microvascular precursor smooth-muscle cells in pulmonary hypertension.
Little is known of the molecular basis of smooth-muscle cell development in the microvessels of the adult lung in pulmonary hypertension (PH). Using quantitative and immunogold electron microscopy techniques we report the development of microvascular precursor smooth-muscle cells (PSMCs) expressing alpha-smooth-muscle actin (alphaSMA), a first marker of smooth-muscle cell differentiation, in rats with hyperoxic PH. Increase in the frequency of distal (alveolar wall) vessels with alphaSMA cells preceded (Pchi2 < 0.02, Day 4) the increase in proximal (alveolar duct) vessels (Pchi2 < 0.02, Day 14). The smallest vessel with cells expressing alphaSMA (< 50 micrometer in diameter) increased most with time (Pchi2 < 0.001). Immunopositive PSMCs were rare in normal lung and frequent in hyperoxia. Well-developed filament arrays decorated with alphaSMA were detected in intermediate cells early in hyperoxia (Day 4). Similar filament networks were detected later in fibroblasts recruited to vessel walls (Days 7 to 14). By Day 28, cells derived from fibroblasts formed several layers in the vessel wall and expressed dense alphaSMA filament arrays, in either a central domain or mesh. Thus, intermediate cells are the source of cells expressing alphaSMA early in the microvessels in hyperoxic pulmonary hypertension and fibroblasts of cells in the late stage-the time of intense neomuscularization of the microvessels.
Actins↗
Primary care and the US health care system.
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Continuity of Patient Care↗
Prognostic and predictive factors for patients with metastatic breast cancer undergoing aggressive induction therapy followed by high-dose chemotherapy with autologous stem-cell support.
PURPOSE: We performed a retrospective review to determine predictive and prognostic factors in patients with metastatic breast cancer who received induction therapy, and, if they responded to treatment, high-dose chemotherapy. PATIENTS AND METHODS: Patients with metastatic breast cancer received induction therapy with doxorubicin, fluorouracil, and methotrexate (AFM). Partial responders then received immediate high-dose chemotherapy, whereas those who achieved complete remission were randomized to immediate or delayed high-dose chemotherapy with hematopoietic stem-cell support. We performed a retrospective review of data from these patients and used Cox proportional hazards regression models for analyses. RESULTS: The overall response rate for the 425 patients enrolled was 74% (95% confidence interval, 70% to 78%). Multivariate analysis of data from all 425 patients revealed that positive estrogen receptor status (P =.0041), smaller metastatic foci (</= 2 v > 2 cm) (P =. 0165), a longer disease-free interval from initial diagnosis to diagnosis of metastases (</= 2 v > 2 years) (P =.0051), and prior treatment with tamoxifen (P =.0152) were good prognostic signs for overall survival. Patients who had received prior adjuvant therapy (P =.0001) and those who developed liver metastases (P =.0001) had decreased long-term survival. In the subgroup of responders to AFM induction, multivariate analysis showed that those with visceral metastases did less well (P =.0006), as did patients who had received prior adjuvant therapy (P =.0023). However, those who had received tamoxifen therapy in the adjuvant setting did better (P =. 0143). CONCLUSION: The chance for long-term remission with induction therapy with AFM and high-dose chemotherapy is increased for hormone receptor positive-patients with nonvisceral metastases who have not received prior adjuvant chemotherapy and have long disease-free intervals.
Adult↗
The legal and risk management conundrum of telemedicine.
A store-and-forward teledermatology service was established between two general practices and the department of plastic surgery at Derriford Hospital in Plymouth. An academic lawyer and an expert in risk management made an assessment of the service. They looked at the following issues: medicolegal problems; security; confidentiality; and risk. None of them was considered insoluble and there is no reason why such issues should prevent the National Health Service from developing telemedicine services. All organizations considering telemedicine need to ensure that the proposed telemedicine service satisfies the issues raised in this study.
Computer Security↗
A nursing-centered treatment team in inpatient medical psychiatry.
1. Nurses have the most extensive direct contact with their patients, yet in the traditional physician-centered model, they are often excluded from decision making. We have developed a new model of patient care with the nurse as the primary therapist and contact person, as well as the individual who cares for each patient's physical needs. 2. Out team approach improves efficiency, integration of care, and staff unity, which can be especially helpful for patients with personality disorders. 3. Patients appreciate the approach and are better able to increase focus on treatment when the physicians are not present in the ward.
Humans↗
Publish or perish. The debate from a global perspective.
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Authorship↗
Maternal serum activin A and follistatin levels in pregnancies with Down syndrome.
Inhibin A is now an established second-trimester maternal serum marker of Down syndrome. Since activin A has a common beta-subunit to inhibin A we evaluated this substance and its binding protein, follistatin, as potential markers. We studied 30 affected and 199 unaffected pregnancies at 13-16 weeks' gestation. There was a statistically significant increase in activin A level among the cases with 8 (27 per cent) exceeding the 90th centile in the controls, and 6 (20 per cent) above the 95th centile. However, the extent of overlap was too great to be of value in screening. There was a small decrease in follistatin levels among cases but it did not reach statistical significance.
Activins↗