Modulation of matrix metalloproteinases in trophoblast cell lines.
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Cell Hypoxia↗
Biomedical subjects
M Morgan
Publications and source records attributed to M Morgan.
Sensory perception: supernormal hearing in the blind?
A recent experimental study suggests that blind individuals may compensate for their lack of vision with better-than-normal hearing. This provides support for a view dating back to 18th century philosophers, but the data raise as many problems as they solve.
Auditory Threshold↗
Lack of efficacy of 24-h infusional topotecan in platinum-refractory ovarian cancer: A Gynecologic Oncology Group trial.
BACKGROUND: The aim of this study was to evaluate the efficacy of a more convenient topotecan administration schedule in the second-line treatment of advanced platinum-refractory ovarian cancer. METHODS AND MATERIALS: The Gynecologic Oncology Group conducted a Phase II trial of 24-h infusional topotecan (8.5 mg/m(2)), repeated every 3 weeks in 26 patients with platinum-refractory ovarian cancer (failure to respond to initial platinum-based treatment or development of recurrent disease within 6 months of completion of chemotherapy). RESULTS: Grade 4 neutropenia (85% of patients) and thrombocytopenia (12%) were the major toxicities encountered. Of the 25 patients evaluable for response, only a single patient experienced an objective response (4%). CONCLUSIONS: When employed at this dose and schedule (24-h infusion every 3 weeks), topotecan has minimal second-line activity in platinum-refractory ovarian cancer.
Adult↗
All Wales surveillance of methicillin-resistant Staphylococcus aureus (MRSA): the first year's results.
Over the last five years, hospitals in Wales have experienced difficulties with increasing numbers of isolates of methicillin-resistant Staphylococcus aureus (MRSA). Continuous total population surveillance of MRSA was introduced with the objectives of gaining an understanding of the extent and variation in time and place of its occurrence, the burden of disease and possible risk factors associated with its isolation and resistance to other antibiotics. All first isolates of MRSA from both hospital and community settings and all isolates of methicillin-sensitive Staphylococcus aureus (MSSA) associated with bacteraemia and cerebrospinal fluid (CSF) isolates detected in medical microbiology laboratories in Wales were collected via CoSurv, a set of interconnected data-base modules for communicable disease control. A data set was collected on each isolate and the patient associated with that isolate and compiled centrally at CDSC (Wales) for all-Wales analysis of the MRSA situation. Surveillance started in January 1996 and at the end of the first year, 2700 new isolates of MRSA had been reported from hospital and community settings, giving a rate of 92.43/100,000 population. The incidence of MRSA from bacteraemias and CSF was 5.20/100,000 compared with 12.70/100,000 for MSSA. MRSA from bacteraemia and CSF was significantly more commonly associated with male patients than MSSA. MRSA patients were significantly older. For all MRSA isolates, the highest reporting rate was in men aged 75+ (647.21/100,000). The highest incidence of invasive disease was also in men aged 75+ (45.69/100,000). Isolates from post-surgical patients were more likely to be involved in invasive disease (OR = 2.59), P < 0.001) than strains from other sources. The majority of isolates were resistant to at least two antibiotics in addition to methicillin, most frequently erythromycin and the fluoroquinolones. Very little resistance to fusidic acid, mupirocin or rifampicin was reported. Continuous total population surveillance has provided a minimum incidence of MRSA in Wales and has allowed a simple and intelligible picture of the problem to be determined, which has been fed back to hospitals to assist decisions on control.
Adolescent↗
The information superhijack.
Infection control teams are not alone in their need to manipulate data. How best can such manipulation be achieved and what tools are available to turn information into knowledge. The workshop included discussion and demonstration of some methods currently being used by infection control teams. While the workshop did not aim to produce all the answers, participants were able to question, discuss and learn new ways that they might take their own practice in the future.
Cross Infection↗
Promoting self-care in epilepsy: the views of patients on the advice they had received from specialists, family doctors and an epilepsy nurse.
The aim of the study was to examine patients' satisfaction with information and advice on epilepsy and self-care provided by medical specialists, general practitioners and a special nurse. We interviewed patients following a trial of nurse-run clinics for epilepsy in general practice. 44 patients, two-thirds of whom had at least one epilepsy attack in the prior 6 months were seen in their homes in the south of England. A recurring theme from interview data was that patients perceived the doctors' time as too limited to explain the condition and how to manage it, whilst the nurse had the time and expertise to do so. Overall the nurse trained in epilepsy care was valued highly for providing advice and support, especially in explaining the social aspects of epilepsy. Patients expressed the belief that they would have benefited most by seeing a special nurse at the time when epilepsy was first diagnosed.
Adolescent↗
Attachment tests of Pasteuria penetrans to the cuticle of plant and animal parasitic nematodes, free living nematodes and srf mutants of Caenorhabditis elegans.
Populations of Pasteuria penetrans isolated from root-knot nematodes (Meloidogyne spp.) and cyst nematodes (Heterodera spp.) were tested for their ability to adhere to a limited selection of sheathed and ex-sheathed animal parasitic nematodes, free living nematodes, including Caenorhabditis elegans wild type and several srf mutants, and plant parasitic nematodes. The attachment of spores of Pasteuria was restricted and no spores were observed adhering to any of the animal parasitic nematodes either with or without their sheath or to any of the free living nematodes including C. elegans and the srf mutants. All spore attachment was restricted to plant parasitic nematodes; however, spores isolated from cyst nematodes showed the ability to adhere to other genera of plant parasitic nematodes which was not the case with spores isolated from root-knot nematodes. The results are discussed in relationship to cuticular heterogeneity.
Animals↗
Chemical labyrinthectomy and cochlear implantation for Menière's disease--an effective treatment or a last resort?
The surgical management of Menière's disease presents a difficult and controversial problem and includes various procedures ranging from 'placebo operations' to vestibular nerve section. The situation is even more complex in the case where the only hearing ear is affected. We present a case of severe debilitating vertigo due to Menière's disease that was treated by chemical labyrinthectomy and cochlear implantation. This unique management strategy allowed restoration of useful hearing and relief of vertigo.
Audiometry, Pure-Tone↗
Making holes in the visual world.
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Humans↗
Role of matrix metalloproteinases in normal and disease processes.
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Arteriosclerosis↗
Resistance to methicillin in isolates of Staphylococcus aureus from blood and cerebrospinal fluid in Wales, 1993-1997.
Surveillance data for organisms isolated from blood cultures and cerebrospinal fluid (CSF) specimens has been gathered electronically in Wales since 1993. Over this period the proportion of total reported organisms from blood cultures and CSF represented by methicillin-resistant staphylococci (MRSA) has risen steadily. This has corresponded to a rise in rates of methicillin resistance amongst Staphylococcus aureus isolated from blood cultures and CSF from 4 to 43%. In certain age/gender groups in 1997, more than 50% of isolates of S. aureus were resistant to methicillin, suggesting that a change in empirical treatment may be necessary for suspected staphylococcal sepsis.
Adolescent↗
p53, mdm-2, and p21 waf-1 in the porokeratoses.
The etiology of the porokeratoses is unknown. Overexpression of the p53 tumor suppressor protein and disregulated cell cycle control have been pathogenically implicated. The p53 tumor suppressor gene product is regulated by mdm2 and both gene products influence cell cycle progression through the cyclin-dependent kinase inhibitor p21. Thirty-three cases of the various types of porokeratosis were immunohistochemically studied for p53, mdm2, and p21 proteins. Each of the cases showed increased p53 and decreased mdm2 and p21 expression within keratinocytes underlying cornoid lamella. This study confirms the previous findings of increased p53 staining and expands the potential roles of mdm2 and p21 in the pathogenesis of the porokeratoses.
Cyclin-Dependent Kinase Inhibitor p21↗
The Gal3p-Gal80p-Gal4p transcription switch of yeast: Gal3p destabilizes the Gal80p-Gal4p complex in response to galactose and ATP.
The Gal3, Gal80, and Gal4 proteins of Saccharomyces cerevisiae comprise a signal transducer that governs the galactose-inducible Gal4p-mediated transcription activation of GAL regulon genes. In the absence of galactose, Gal80p binds to Gal4p and prohibits Gal4p from activating transcription, whereas in the presence of galactose, Gal3p binds to Gal80p and relieves its inhibition of Gal4p. We have found that immunoprecipitation of full-length Gal4p from yeast extracts coprecipitates less Gal80p in the presence than in the absence of Gal3p, galactose, and ATP. We have also found that retention of Gal80p by GSTG4AD (amino acids [aa] 768 to 881) is markedly reduced in the presence compared to the absence of Gal3p, galactose, and ATP. Consistent with these in vitro results, an in vivo two-hybrid genetic interaction between Gal80p and Gal4p (aa 768 to 881) was shown to be weaker in the presence than in the absence of Gal3p and galactose. These compiled results indicate that the binding of Gal3p to Gal80p results in destabilization of a Gal80p-Gal4p complex. The destabilization was markedly higher for complexes consisting of G4AD (aa 768 to 881) than for full-length Gal4p, suggesting that Gal80p relocated to a second site on full-length Gal4p. Congruent with the idea of a second site, we discovered a two-hybrid genetic interaction involving Gal80p and the region of Gal4p encompassing aa 225 to 797, a region of Gal4p linearly remote from the previously recognized Gal80p binding peptide within Gal4p aa 768 to 881.
Adenosine Triphosphate↗
Follow up of workers previously exposed to silver solder containing cadmium.
OBJECTIVES: To study longitudinal biological monitoring data on urinary and blood cadmium collected in a small cohort of nine workers who had been brazing for several years with solders containing cadmium. METHODS: Cadmium was measured by neutron activation analysis in livers and kidneys, and estimates of renal function were carried out in 1983 and 1995. During the intervening period exposure to cadmium was dramatically reduced by local exhaust ventilation control and substitution of the solder containing cadmium. RESULTS: From urinary protein measurements there was evidence within the group of increasing renal tubular damage over the 12 year period, even though exposure to cadmium was dramatically reduced over this period and almost eliminated by 1995. There was no evidence from serum creatinine of decreasing glomerular filtration rate, and the renal tubular handling of calcium, phosphate, or urate had not worsened significantly. Blood and urinary cadmium concentrations reduced significantly over the 12 year period but were still substantial in 1995. Blood cadmium concentrations tended to reflect cadmium body burden in 1995 when exposure had been low for several years, and decreased most significantly during 1983-90. By contrast urinary cadmium concentrations only decreased significantly from about 1990 onwards. Urinary cadmium was not significantly correlated with liver or kidney cadmium concentration in either 1983 or 1995. This may be due to the level of tubular dysfunction in the cohort. Calculated cumulative excretion of cadmium over the 12 year period was substantially greater than the loss of cadmium measured in livers and kidneys and the derived loss in body burden. Reasons for this are discussed. It is possible that in cohorts, where renal damage is apparent, urinary concentrations reflect a substantial component of current exposure rather than stored body losses. CONCLUSIONS: The data reinforce the concept that blood cadmium concentrations may not always reflect recent exposure, but may reflect body burden derived from historical exposure depending on the degree of current exposure; and that the decline in urinary and blood cadmium measurements after removal from, or reduction in, exposure will be slow and depend on the historical body burden.
Adult↗
Results of treatment for soft tissue sarcoma in childhood and adolescence: a final report of the German Cooperative Soft Tissue Sarcoma Study CWS-86.
PURPOSE: The goal of the second German Soft Tissue Sarcoma Study CWS-86 (1985 to 1990) was to improve the prognosis in children and adolescents with soft tissue sarcoma by means of a clinical trial comprising intensive chemotherapy and risk-adapted local therapy. PATIENTS AND METHODS: There were 372 eligible patients. A staging system based on the postsurgical extent of disease was used. Chemotherapy consisted of vincristine, dactinomycin, doxorubicin, and ifosfamide. Radiotherapy was administered early at 10 to 13 weeks simultaneously with the second chemotherapy cycle (32 Gy or 54. 4 Gy). The single dose was reduced to 1.6 Gy and given twice daily (accelerated hyperfractionation). RESULTS: The event-free survival (EFS) and overall survival rates at 5 years were 59% +/- 3% and 69% +/- 3%, respectively. The 5-year EFS rate according to stage was as follows: stage I, 83% +/- 5%; stage II, 69% +/- 6%; stage III, 57% +/- 4%; and stage IV, 19% +/- 6%. The outcome for patients with stage III disease who required radiotherapy was much better in the CWS-86 study compared with the CWS-81 study (5-year EFS, 60% +/- 5% v 44% +/- 6%; P =.053). The most common treatment failure was isolated local relapse, with 14% of patients relapsing at the primary tumor site. CONCLUSION: The improved design of the study incorporating risk-adapted radiotherapy allowed treatment to be reduced for selected groups of patients without compromising survival.
Adolescent↗
Altered insulin secretion associated with reduced lipolytic efficiency in aP2-/- mice.
Recent studies have shown that genetic deficiency of the adipocyte fatty acid-binding protein (aP2) results in minor alterations of plasma lipids and adipocyte development but provides significant protection from dietary obesity-induced hyperinsulinemia and insulin resistance. To identify potential mechanisms responsible for this phenotype, we examined lipolysis and insulin secretion in aP2-/- mice. Beta-adrenergic stimulation resulted in a blunted rise of blood glycerol levels in aP2-/- compared with aP2+/+ mice, suggesting diminished lipolysis in aP2-/- adipocytes. Confirming this, primary adipocytes isolated from aP2-/- mice showed attenuated glycerol and free fatty acid (FFA) release in response to dibutyryl cAMP. The decreased lipolytic response seen in the aP2-/- mice was not associated with altered expression levels of hormone-sensitive lipase or perilipin. The acute insulin secretory response to beta-adrenergic stimulation was also profoundly suppressed in aP2-/- mice despite comparable total concentrations and only minor changes in the composition of systemic FFAs. To address whether levels of specific fatty acids are different in aP2-/- mice, the plasma FFA profile after beta-adrenergic stimulation was determined. Significant reduction in both stearic and cis-11-eicoseneic acids and an increase in palmitoleic acid were observed. The response of aP2-/- mice to other insulin secretagogues such as arginine and glyburide was similar to that of aP2+/+ mice, arguing against generally impaired function of pancreatic beta-cells. Finally, no aP2 expression was detected in isolated pancreatic islet cells. These results provide support for the existence of an adipo-pancreatic axis, the proper action of which relies on the presence of aP2. Consequently, aP2's role in the pathogenesis of type 2 diabetes might involve regulation of both hyperinsulinemia and insulin resistance through its impact on both lipolysis and insulin secretion.
Adipocytes↗
Locum doctors in general practice: motivation and experiences.
BACKGROUND: There is evidence of dissatisfaction with locum doctors' performance, but little is known about doctors who work as locums in general practice or about their experiences of this work. AIM: To describe the motivations and experiences of doctors providing locum cover in general practices. METHOD: A postal questionnaire survey distributed to locums through organizations such as locum groups, commercial agencies, and general practices. RESULTS: Questionnaires were returned by 111 doctors currently working as locums in general practice. Four main reasons for working as a locum GP were: as a short-term option while between posts, to gain experience of different practices before commitment to one practice, to balance work and family or other commitments, to continue part-time work after retirement. One-quarter of responders intended to continue working as a locum indefinitely. The drawbacks of locum work included frustration with low status, lack of security, and difficulty accessing structured training and education. CONCLUSION: Locum doctors in general practice are a heterogeneous group that includes those who have chosen this type of work. The doctors who intend to continue as locums indefinitely represent a useful resource in primary care whose ability to provide short-term cover could be maximized. The need to control the quality of 'freelance' doctors should not overshadow the need to control the quality of their working environments.
Attitude of Health Personnel↗
Elderly people's beliefs about influenza vaccination.
BACKGROUND: Influenza is an important cause of death in the elderly. The uptake of influenza vaccination, despite its effectiveness, is low. AIM: To examine beliefs about influenza vaccination in elderly patients at risk from influenza. METHOD: A qualitative study using semi-structured interviews with 50 patients aged over 75 years at risk from influenza, equally divided between vaccinated and non-vaccinated groups. RESULTS: Although they acknowledged their medical diseases, the patients regarded themselves as healthy in the sense of being independent and active. Few in either the vaccinated or non-vaccinated groups believed themselves at risk of dying from influenza even though they recognized it could be fatal for particular groups of people. Decisions to have the vaccination were based on other considerations, including whether it was thought likely to reduce (or increase) the number and severity of colds and influenza-like illnesses. Although the group with negative views towards vaccination placed more emphasis on the 'side-effects' from the vaccination (including colds and influenza), this was also common in the group who were more positive towards vaccination; however, the side-effects were interpreted in different ways. CONCLUSION: Recommendations to vaccinate according to individual risk status are not in keeping with lay beliefs. The policy to include all people aged 75 years and older as a group requiring influenza vaccination is supported by this study. The evidence that vaccination reduces morbidity from influenza and does not cause colds and influenza needs stressing.
Aged↗