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Biomedical subjects

S Holmes

Publications and source records attributed to S Holmes.

At least 73 records · Page 4Linked to original sources

A systematic approach to erectile dysfunction in the cardiovascular patient: a consensus statement.

Sexual activity is no more stressful to the heart when compared with a number of other natural daily activities, e.g. walking one mile on the level in 20 minutes. The cardiac risk of sexual activity in patients diagnosed with cardiovascular disease is minimal in properly assessed and advised patients. Erectile dysfunction (ED) is common, affecting 10% of men aged 40-70 years and increases in frequency with age. ED and cardiovascular disease share many of the same risk factors and often coexist. ED in the diagnosed cardiovascular patient should be identified by routine questioning in general practice. Modern therapies can restore a sexual relationship in the majority of patients with ED and can lead to a substantial improvement in quality of life. The majority of patients assessed to be at low or intermediate cardiac risk, as defined later in this paper (Table 4), can be effectively managed in primary care. Primary care treatment for ED in patients defined as high risk can be initiated following a specialist opinion and/or confirmation that the patient's cardiovascular condition is stabilised. There is no evidence that currently licensed treatments for ED add to the overall cardiovascular risk in patients with or without diagnosed cardiovascular disease.

Adult↗

Processing of the Alzheimer's disease amyloid precursor protein in Pichia pastoris: immunodetection of alpha-, beta-, and gamma-secretase products.

betaA4 (Abeta) amyloid peptide, a major component of Alzheimer's disease (AD) plaques, is a proteolytic product of the amyloid precursor protein (APP). Endoproteases, termed beta- and gamma-secretase, release respectively the N- and C-termini of the peptide. APP default secretion involves cleavage within the betaA4 domain by alpha-secretase. To study the conservation of APP processing in lower eukaryotes, the yeast Pichia pastoris was transfected with human APP695 cDNA. In addition to the full-length integral transmembrane protein found in the cell lysate, soluble/secreted APP (sAPP) was detected in the culture medium. Most sAPP comprised the N-terminal moiety of betaA4 and corresponds to sAPPalpha, the product of alpha-secretase. The culture medium also contained minor secreted forms detected by a monoclonal antibody specific for sAPPbeta (the ectodomain released by beta-secretase cleavage). Analysis of the cell lysates with specific antibodies also detected membrane-associated C-terminal fragments corresponding to the products of alpha and beta cleavages. Moreover, immunoprecipitation of the culture medium with three antibodies directed at distinct epitopes of the betaA4 domain yielded a 4 kDa product with the same electrophoretic mobility as betaA4 synthetic peptide. These results suggest that the alpha-, beta-, and gamma-secretase cleavages are conserved in yeast and that P. pastoris may offer an alternative to mammalian cells to identify the proteases involved in the generation of AD betaA4 amyloid.

Alzheimer Disease↗

Antibodies to TR2 (herpesvirus entry mediator), a new member of the TNF receptor superfamily, block T cell proliferation, expression of activation markers, and production of cytokines.

TR2 (TNFR-related 2) is a recently identified member of the TNFR family with homology to TNFRII. We have demonstrated previously that TR2 mRNA is expressed in resting and activated human T cells and that TR2-Ig partially inhibits an allogeneic mixed leukocyte proliferation response. We now characterize TR2 further by the use of specific mAbs. Flow-cytometry analysis using TR2 mAbs confirmed that resting PBL express high levels of cell surface TR2, and that TR2 is widely expressed on all freshly isolated lymphocyte subpopulations. However, stimulation of purified T cells with either PHA or PHA plus PMA resulted in decreased surface expression within 48 h of activation before returning to resting levels at 72 h. TR2 mAbs inhibited CD4+ T cell proliferation in response to stimulation by immobilized CD3 or CD3 plus CD28 mAbs. Assay of culture supernatants by ELISA showed inhibition of TNF-alpha, IFN-gamma, IL-2, and IL-4 production, which, for IL-2 and TNF-alpha was also confirmed by intracellular cytokine staining. Furthermore, expression of activation markers on CD4+ T cells, including CD25, CD30, CD69, CD71, and OX40 (CD134), was inhibited. TR2 mAbs inhibited proliferation in a three-way MLR, and a response to soluble recall Ag, tetanus toxoid. In conclusion, these results suggest that TR2 is involved in the activation cascade of T cell responses and TR2 mAbs prevent optimal T cell proliferation, cytokine production, and expression of activation markers.

Animals↗

Analysis of the Saccharomyces spindle pole by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry.

A highly enriched spindle pole preparation was prepared from budding yeast and fractionated by SDS gel electrophoresis. Forty-five of the gel bands that appeared enriched in this fraction were analyzed by high-mass accuracy matrix-assisted laser desorption/ ionization (MALDI) peptide mass mapping combined with sequence database searching. This identified twelve of the known spindle pole components and an additional eleven gene products that had not previously been localized to the spindle pole. Immunoelectron microscopy localized eight of these components to different parts of the spindle. One of the gene products, Ndc80p, shows homology to human HEC protein (Chen, Y., D.J. Riley, P-L. Chen, and W-H. Lee. 1997. Mol. Cell Biol. 17:6049-6056) and temperature-sensitive mutants show defects in chromosome segregation. This is the first report of the identification of the components of a large cellular organelle by MALDI peptide mapping alone.

Amino Acid Sequence↗

Xerostomia: aetiology and management in cancer patients.

Although oral complications are common sequelae of cancer/cancer treatment, only sporadic research is published in the literature. It is clear that 'routine' oral hygiene measures are inadequate; a little time and effort may, however, reduce oral discomfort. This is particularly true in the case of xerostomia, which is often thought to be a relatively minor symptom with few deleterious effects. Many patients, however, find xerostomia a significant cause of distress, and for this reason alone, health care professionals require knowledge and appreciation of the pathology and aetiology of the condition and approaches to its management. This paper reviews the physiology of salivation and the aetiology of xerostomia and considers the ways in which the condition can be managed.

Antineoplastic Agents↗

Analysis of uroliths from cats and dogs in New Zealand, 1993-96.

AIMS: Canine and feline uroliths were analysed to determine the prevalence of particular types of urolith and the dog breeds at risk. METHODS: Three hundred and sixty-nine uroliths recovered from 316 dogs and 53 cats between November 1993 and December 1996 were analysed by X-ray diffraction, and by infrared spectrometry where X-ray diffraction alone was non-diagnostic. RESULTS: Bitches of small breeds especially Welsh corgi and Bichon frise, were most frequently affected. Struvite was the most common urolith (204 dogs). Oxalate (60 dogs) was the second most prevalent urolith identified, followed by cystine (24 dogs). The breeds producing cystine calculi were: Dalmatian, Bassett hound, Borzoi, Newfoundland, Shetland sheepdog, Labrador, Chihuahua, Fox terrier, English bulldog, Bichon frise, Doberman pinscher, Border collie. Silica uroliths were identified for the first time in New Zealand. All feline uroliths were struvite. CONCLUSION: The results are useful in determining the prevalence of specific types of urolith in New Zealand and the breeds at risk of forming them.

Journal Article↗

Promoting oral health in institutionalised older adults: a nursing perspective.

Current demographic trends necessitate that increased attention be paid to problems arising in the older population. One such area relates to the oral cavity, which may be affected by both the effects of aging and the effects of disease and illness. Yet the evidence shows a significant lack of adequate oral care, which may create major problems for affected individuals, causing oral and dental problems that may, in turn, predispose to nutritional deficiencies, communication difficulties and devastating dental disease (Ogle, 1982). This paper reviews the literature pertaining to this complex subject, concluding that although nurses have an important role in providing effective oral care for the institutionalised patient, it is difficult to identify appropriate techniques, agents and tools with which to provide such care. Further research in this field is undoubtedly needed.

Aged↗

The aetiology of malnutrition in hospital.

Malnutrition is a largely unrecognised problem in hospitals. Older people, people with cancer, respiratory disease and gastrointestinal problems are particularly vulnerable.

Hospitalization↗

Risk of chronic arthropathy among women after rubella vaccination. Vaccine Safety Datalink Team.

CONTEXT: A review by the Institute of Medicine found a possible relationship between rubella vaccination and chronic arthritis among women. OBJECTIVE: To evaluate the risk of persistent joint and neurologic symptoms in rubella seronegative women subsequently vaccinated with RA 27/3 rubella vaccine. DESIGN: Retrospective cohort study based on computerized laboratory data and medical record review. Records were reviewed for symptoms occurring within 2 years before and after the date of serological testing and to identify vaccinees. Possible cases were evaluated by a rheumatologist blinded to serological findings and vaccination status. SETTING: Large health maintenance organization in northern California. PATIENTS: Women aged 15 to 59 years serotested for rubella during 1990 with continuous health plan membership for 2 years before and after the date of their serological test. Seronegative women immunized within 1 year of serotesting (n=971) were defined as exposed. Primary comparison groups included all unvaccinated, seronegative women (n=924) and randomly selected seropositive, unvaccinated women (n=2421) matched to exposed subjects on serological test date and age (+/-3 years). MAIN OUTCOME MEASURES: Prevalence and incidence of chronic joint and neurologic symptoms during 1-year follow-up period stratified by age and serological findings, immunization, and postpartum status. RESULTS: No significantly increased risk was associated with receipt of rubella vaccine for any outcome except for prevalence of carpal tunnel syndrome in vaccinated women at least 30 years old compared with seropositive, unvaccinated women (2.9% vs 1.4%; P=.03). A total of 34 women had onset of conditions within the 1-year follow-up period; 9 of these were in the group of seronegative, immunized women, of whom 6 had onset of symptoms within 6 weeks of vaccination. Among these 6 women, symptoms included transient arthritis or arthralgias (<6 weeks duration) in 4 women, arthralgia of indeterminate chronicity in 1 woman, and carpal tunnel syndrome in 1 woman. Postpartum women across all groups were less likely to be seen for nontraumatic arthropathies than nonpostpartum women (4.5% vs 7.2%, P=.08 in vaccinated women; 4.8% vs 8.1%, P=.09 in seronegative controls; and 4.8% vs 10.0%, P=.01 in seropositive controls). CONCLUSIONS: In this large retrospective cohort analysis there was no evidence of any increased risk of new onset chronic arthropathies or neurologic conditions in women receiving the RA 27/3 rubella vaccine. These data support the continued vaccination of rubella-susceptible women to reduce the risk of congenital rubella syndrome.

Adolescent↗

Hirsutism.

Explore the source record for details and available documents.

Female↗

Case-control study of stroke and the quality of hypertension control in north west England.

OBJECTIVE: To examine the risk of stroke in relation to quality of hypertension control in routine general practice across an entire health district. DESIGN: Population based matched case-control study. SETTING: East Lancashire Health District with a participating population of 388,821 aged < or = 80. SUBJECTS: Cases were patients under 80 with their first stroke identified from a population based stroke register between 1 July 1994 and 30 June 1995. For each case two controls matched with the case for age and sex were selected from the same practice register. Hypertension was defined as systolic blood pressure > or = 160 mm Hg or diastolic blood pressure > or = 95 mm Hg, or both, on at least two occasions within any three month period or any history of treatment with antihypertensive drugs. MAIN OUTCOME MEASURES: Prevalence of hypertension and quality of control of hypertension assessed by using the mean blood pressure recorded before stroke) and odds ratios of stroke (derived from conditional logistic regression). RESULTS: Records of 267 cases and 534 controls were examined; 61% and 42% of these subjects respectively were hypertensive. Compared with non-hypertensive subjects hypertensive patients receiving treatment whose average pre-event systolic blood pressure was controlled to < 140 mm Hg had an adjusted odds ratio for stroke of 1.3 (95% confidence interval 0.6 to 2.7). Those fairly well controlled (140-149 mm Hg), moderately controlled (150-159 mm Hg), or poorly controlled (> or = 160 mm Hg) or untreated had progressively raised odds ratios of 1.6, 2.2, 3.2, and 3.5 respectively. Results for diastolic pressure were similar; both were independent of initial pressures before treatment. Around 21% of strokes were thus attributable to inadequate control with treatment, or 46 first events yearly per 100,000 population aged 40-79. CONCLUSIONS: Risk of stroke was clearly related to quality of control of blood pressure with treatment. In routine practice consistent control of blood pressure to below 150/90 mm Hg seems to be required for optimal stroke prevention.

Adult↗

A community based stroke register in a high risk area for stroke in north west England.

STUDY OBJECTIVE: To develop a community based stroke register to assess the magnitude of the problem of stroke in an entire health district in a high risk area for stroke. DESIGN: Community based stroke register from general practice data. SETTING: East Lancashire Health Authority with a 1995 population of 534,287. PATIENTS: The stroke register was developed and maintained for one calendar year in East Lancashire between 1 July 1994 and 30 June 1995. Efforts were made to include all patients who had a stroke during this period from participating general practices, using several sources of referral. MAIN RESULTS: Of the district's 118 general practices, 93 (79%) participated fully, covering a population of 405,272. A total of 932 strokes, including 642 first ever cases, were cross checked and confirmed, with only 50% from any single source, mainly the practices. The total stroke incidence rate was 1.60 per 1000 per year, adjusted for the England and Wales 1991 census population. The rate increased considerably with age from 0.88/1000 for ages 50-54 to 20.56/1000 for ages 85-89 years. From 50-74 years, the age specific incidence was higher in men, but overall it was higher in women (1.87; 95% confidence interval 1.67, 2.04 per 1000) than in men (1.31; 1.15, 1.47 per 1000), and slightly lower than in Oxford a decade earlier. The rate also varied in different localities, with higher rates in the central towns of Hyndburn (2.05/ 1000), Blackburn (1.63/1000), and Burnley (1.80/1000) and lowest values in rural areas (1.18/1000 in Pendle). Case fatality from stroke at 28 days was 34% and the hospital admission rate was high at 70%. CONCLUSIONS: The multiple source registration method is required for a stroke register. Stroke incidence in this area was still high and there was considerable variation across the district. Case fatality rates were similar to those in previous studies.

Adult↗