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Biomedical subjects

S Farrow

Publications and source records attributed to S Farrow.

At least 19 recordsLinked to original sources
PubMed2002

Increased mortality in women with cataract: a population based follow up of the North London Eye Study.

BACKGROUND/AIMS: In diabetics, cataract is associated with higher risk of death. In non-diabetics the data are conflicting, but some indicate an association between one type of cataract (nuclear) and increased mortality. The aim of this study was to estimate and compare age and sex specific mortality for elderly people with and without cataract in a population based cohort. METHODS: A random sample drawn from a defined population of elderly people (age 65 and older) registered with 17 general practice groups in north London formed the study cohort and were followed up for 4 years. The age and sex specific mortality from various causes was estimated and compared in those with and without cataract. RESULTS: In non-diabetics (n=1318), cataract (lens opacity at baseline) was significantly associated with higher mortality in women. The age standardised death rate per 1000 was 39.8 and 24.8 in women with and without cataract, respectively (age adjusted hazard ratio 1.7, confidence limits 1.1 to 2.7, p=0.032). This was not the case in non-diabetic men (hazard ratio 0.9, confidence limits 0.6 to 1.5, p=0.782). The excess mortality in women with cataract was consistent for cardiovascular, respiratory, and other non-cancer causes of death. There was no association between cataract and mortality from cancer. CONCLUSIONS: This study has shown, for the first time, that cataract is associated with higher mortality in women but not in men, among the non-diabetic population. This sex effect suggests that women may be exposed to risk factors that increase both the risk of cataract and mortality, and that men may have little or no exposure to these "sex specific" factors. Possible risk factors that warrant further investigation may be those associated with some pregnancy and childbearing experience.

Age Distribution↗
PubMed2000

The deficit in cataract surgery in England and Wales and the escalating problem of visual impairment: epidemiological modelling of the population dynamics of cataract.

BACKGROUND: The pool of old cases of cataract, the expected new cases, and the shortfall in cataract surgery and consequently the numbers dying with poor vision without the benefit of cataract surgery are regarded as escalating problems worldwide. Successive governments and the professional ophthalmic bodies have not had the wherewithal to estimate the magnitude or interaction of these elements in the population of the UK. This study has collected and applied the best available epidemiological data on cataract prevalence, incidence and service utilisation, and demography to address the problem of control of the cataract pool in the population of England and Wales. METHODS: Data from recent surveys undertaken by the authors, both on prevalence of vision impairing cataract and on patterns of cataract surgery, were used together with demographic and service utilisation information obtained from government departments. These were integrated within a holistic model, which was run under varied assumed levels and patterns of service provision. RESULTS: The study shows that there is a serious pool of unoperated vision impairing cataract in the population aged 65 and older, reflecting a shortfall in cataract surgery. Continuing with the present level and pattern of service provision, the pool will increase to over 2.5 million by the year 2001. In addition, more than 700 000 will die with unoperated impaired vision. CONCLUSIONS: Targeting of existing or new additional operations to those below the visual acuity of 6/12 will have relatively little effect on numbers dying without surgery, but should have a substantial controlling effect on the pool of vision impairing cataract in the population.

Age Factors↗
PubMed2000

Exploration of a group model in fieldwork education.

OBJECTIVE: Organizational changes, such as program management and managed care, and fluctuations in resources present challenges to the effective provision of fieldwork placements. This study compared an innovative group model with a traditional 1:1 supervision model to determine their effect on students and supervisors. METHOD: The two models were implemented at an urban clinical facility in several areas of practice over a 2 year period. Questionnaires were used to assess student skill development, student and supervising therapist satisfaction, and impact on supervising therapists' use of time. Focus groups were used to explore the advantages and disadvantages of each model. RESULTS: There were few statistically significant differences in students' (n = 26) and supervising therapists' (n = 28) ratings when the two models were compared. The qualitative findings suggest that the advantages of one model often relate to the disadvantages of the other model. In addition, supervising therapists and students offered several suggestions for how to improve implementation of the group model. CONCLUSION: When the results of the study are compared to the objectives established for the group model, it appears that many of the objectives outlined for the model were partially achieved. Several issues, such as the student-supervisor relationship and the evaluation process, need to be addressed with participants to ensure successful implementation of the group model.

Data Collection↗
PubMed1999

Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK signalling complex.

Colorectal cancer is a major cause of cancer deaths in Western countries, but epidemiological data suggest that dietary modification might reduce these by as much as 90%. Cyclo-oxygenase 2 (COX2), an inducible isoform of prostaglandin H synthase, which mediates prostaglandin synthesis during inflammation, and which is selectively overexpressed in colon tumours, is thought to play an important role in colon carcinogenesis. Curcumin, a constituent of turmeric, possesses potent anti-inflammatory activity and prevents colon cancer in animal models. However, its mechanism of action is not fully understood. We found that in human colon epithelial cells, curcumin inhibits COX2 induction by the colon tumour promoters, tumour necrosis factor alpha or fecapentaene-12. Induction of COX2 by inflammatory cytokines or hypoxia-induced oxidative stress can be mediated by nuclear factor kappa B (NF-kappaB). Since curcumin inhibits NF-kappaB activation, we examined whether its chemopreventive activity is related to modulation of the signalling pathway which regulates the stability of the NF-kappaB-sequestering protein, IkappaB. Recently components of this pathway, NF-kappaB-inducing kinase and IkappaB kinases, IKKalpha and beta, which phosphorylate IkappaB to release NF-kappaB, have been characterised. Curcumin prevents phosphorylation of IkappaB by inhibiting the activity of the IKKs. This property, together with a long history of consumption without adverse health effects, makes curcumin an important candidate for consideration in colon cancer prevention.

Antineoplastic Agents↗
PubMed1998

Prevalence of serious eye disease and visual impairment in a north London population: population based, cross sectional study.

OBJECTIVE: To estimate the magnitude of serious eye disorders and of visual impairment in a defined elderly population of a typical metropolitan area in England, and to assess the frequency they were in touch with, or known to, the eye care services. DESIGN: Cross sectional survey using two stage cluster random sampling. SETTING: General practices in north London. SUBJECTS: Random sample of people aged 65 and older, drawn from a defined population of elderly people registered with 17 general practice groups. MAIN OUTCOME MEASURES: Proportions and population prevalence estimates were determined for visual acuity, assessed with the person's own spectacles (if any), classified into four categories: prevalence of cataract, age related macular degeneration, and refractive error causing visual impairment and of definite primary open angle glaucoma; and status of contact with eye services. RESULTS: 1547 of 1840 (84%) eligible people were examined. The population prevalence of bilateral visual impairment (visual acuity <6/12) was 30%, of which 72% was potentially remediable. 92 of these 448 cases (21%) had visual acuity <6/60 ("blindness") in one or both eyes. Prevalence of cataract causing visual impairment was 30%; 88% of these people were not in touch with the eye services. The prevalence of vision impairing, age related macular degeneration was 8% and of glaucoma (definite cases) was 3%. Three quarters of the people with definite glaucoma were not known to the eye services. CONCLUSIONS: Untreated visual impairment and eye disorders affect a substantial proportion of people aged 65 years and older. These findings should contribute to the setting up of future strategies for preservation of sight and eye health services in general.

Age Distribution↗
PubMed1998

Group therapy and organ transplantation.

Group therapy for organ transplantation patients is in its infancy but has a promising future. Overextended transplantation service providers are interested in its potential for cost-efficient and effective forms of psychosocial intervention. This article summarizes the biomedical and psychosocial aspects of solid organ transplantation, one institution's group therapy program, common group themes, and specific demands on the group therapist working with this population.

Adaptation, Psychological↗
PubMed1997

Induction of the E-selectin promoter by interleukin 1 and tumour necrosis factor alpha, and inhibition by glucocorticoids.

Cytokine-induced expression of the endothelial cell surface adhesion molecule E-selectin is inhibited by glucocorticoids (GCs). To investigate possible mechanisms for steroid inhibition, a reporter gene (ESAP) was constructed, comprising the cytokine responsive region of the E-selectin gene (nt -383 to +81) coupled to alkaline phosphatase (AP). In A549 cells stably transfected with the ESAP gene, AP production was highly responsive to the cytokines interleukin 1beta (IL-1beta) and tumour necrosis factor alpha, with ED50 values of 3 pM and 1000 pM respectively. Furthermore the cytokine-induced AP responses were inhibited by GCs, indicating that both transcriptional activation and GC suppression of the E-selectin gene were mediated via regulatory elements within the same region of the promoter. The relative potencies of GC drugs as inhibitors of IL-1beta (10 pM)-stimulated ESAP-gene activation were fluticasone> beclomethasone>dexamethasone, with IC50 values of 0.13, 1.1 and 2.7 nM respectively. Inhibition by fluticasone was blocked by the GC receptor (GR) antagonist drug mifepristone (Ru486), which is consistent with the suppressive effects of GCs being mediated via the GR. However, because the E-selectin promoter lacks a consensus glucocorticoid responsive element, mechanisms for inhibition independent of GR-DNA binding were investigated. Evidence that GCs also inhibited cytokine activation of a synthetic nuclear factor kappaB (NFkappaB)-driven reporter gene transiently transfected into A549 cells suggested that interference with the activation and/or function of this transcription factor was important for GC inhibition of ESAP. However, in A549-ESAP cells, fluticasone (100 nM) did not affect IL-1beta (10 pM)-induced IkBalpha degradation, NFkappaB-p65 nuclear translocation or the DNA-binding capacity of nuclear NFkappaB complexes, over a period during which cytokine-induced ESAP-gene activation was inhibited. Finally, there was no evidence to suggest that GC enhancement of IkBalpha gene expression contributed to the suppression of the cytokine response. We conclude that interference by GR with the transcriptional activation potential of DNA-bound NFkappaB complexes might contribute to mechanisms underlying the anti-inflammatory effects of GCs.

Androstadienes↗
PubMed1996

Alpha 2-adrenergic agonists increase cellular lactate efflux.

We reported previously that genetic polymorphisms of the alpha 2-adrenergic receptor are associated with hyperinsulinemia, diabetes mellitus, and hypertension in blacks. The evolutionary driving force for maintaining such deleterious mutations in the black population is unknown. Recognizing that vascular alpha 2-adrenergic receptors mediate cold-induced vasoconstriction and that temperature maintenance is a primary thrust of cellular metabolism, we postulated that vascular alpha 2-adrenergic receptors contribute significantly to metabolic heat generation in homeotherms such as humans. Using aerobic lactate production as an indicator of thermogenesis, we measured metabolic heat production in HT29 cells that expressed the gene encoding human vascular alpha 2-adrenergic receptors. Epinephrine, an alpha 2-adrenergic receptor agonist, increased net lactate efflux from 226 +/- 20 to 280 +/- 20 nmol/min (mean +/- SE) (P = .06). Clonidine, a more specific alpha 2-adrenergic agonist, increased lactate efflux from 110 +/- 6 to 156 +/- 8 nmol/min (P < .01). Similarly, in the presence of physiological concentrations of glucose (5.5 mmol/L), insulin increased lactate production from 123 +/- 6 to 175 +/- 10 nmol/min (P < .01). Because differences in aerobic glycolysis may also explain the heat intolerance and abnormal fuel homeostasis found in genetically hypertensive rats, we also measured lactate production in cultured vascular smooth muscle cells isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive control Wistar-Kyoto rats (WKY). Vascular smooth muscle cells from SHRSP had significantly greater lactate efflux compared with cells from normotensive WKY (296 +/- 4 versus 172 +/- 2 nmol/min, P < .001). These differences were not due to abnormalities in glucose uptake, as lactate efflux was greater in SHRSP cells compared with WKY cells when dextrose was replaced with equimolar concentrations of fructose (230 +/- 6 versus 138 +/- 2 nmol/min, P < .001). alpha 2-Adrenergic agonists increase lactate efflux in HT29 cells, and abnormalities in vascular smooth muscle lactate metabolism in genetically hypertensive rats is independent of altered glucose uptake. These data provide support for our hypothesis that balanced polymorphisms of the alpha 2-adrenergic receptor could offer protection against cold stress by increasing the thermogenic response associated with aerobic lactate production.

Adrenergic alpha-Agonists↗
PubMed1996

Intra-operative parathyroid hormone assay for simplified localization of parathyroid adenomas.

Lack of success in parathyroid surgery is usually due to failure to identify the abnormal parathyroid gland correctly at operation. The surgeon may be helped by rapid parathyroid hormone (PTH) assay in peripheral blood after removal of a suspected adenoma, and by frozen section histology, but these are not true localization techniques. We have adapted a non-isotopic immunoassay for rapid measurement of PTH in samples from the upper, middle and lower thyroid veins taken at operation, before exploration begins. Fifteen patients with primary hyperparathyroidism were operated on. In 10 the parathyroid adenoma was located easily, and was associated with high local venous PTH levels. In four patients the abnormal parathyroid was not immediately apparent but the assay indicated its location, which was confirmed after further exploration. In one patient there was no difference in PTH levels in the six venous samples. An ectopic adenomatous gland was successfully identified behind the thymus. The operation was successful in all patients as shown by a fall in the plasma calcium to the normal range. We conclude that intra-operative selective venous sampling and rapid PTH assay facilitates operative localization of parathyroid adenomas.

Adenoma↗
PubMed1996

Metoclopramide does not inhibit atrial natriuretic factor-stimulated diuresis in man.

BACKGROUND: An understanding of the reflex hormonal responses that occur with a redistribution of the blood volume upon exposure to microgravity or during water immersion is operationally relevant. Further, dopamine receptor antagonists, which are used in the treatment of the motion sickness induced by microgravity, or at sea, may affect fluid metabolism. Atrial natriuretic factor (ANF) is a potent diuretic and natriuretic hormone that is released following central blood volume expansion in man. ANF is also a potent inhibitor of angiotensin- and potassium-stimulated aldosterone release. HYPOTHESIS: Since ANF-induced diuresis may be mediated by dopamine, we sought to determine whether inhibition of dopamine receptors blocks ANF-induced natriuresis and diuresis. Also, since ANF has been shown to inhibit aldosterone secretion induced by adrenocorticotropic hormone (ACTH) in vitro, we investigated whether ANF decreases aldosterone in man infused with exogenous ACTH. METHODS AND RESULTS: In six healthy, sodium-replete men, infusion of synthetic ANF (0.01 microgram.kg.min, Anaritide, Wyeth Laboratories) significantly increased urine flow from 7.1 +/- 0.7 to 11.7 +/- 1.8 ml.min-1 (p < 0.05) and decreased aldosterone from 74.7 +/- 9.0 to 55.8 +/- 6.5 pg.ml-1 (p = N.S.). Metoclopramide (Met), a dopaminergic antagonist, increased plasma aldosterone from 104.5 +/- 8.9 to 163 +/- 12.5 pg.ml-1 (p < 0.05). ANF-induced diuresis was not inhibited by Met, but ANF significantly inhibited Met-stimulated increases in plasma aldosterone. ANF did not attenuate ACTH-stimulated increases in plasma aldosterone. Also, ANF-induced diuresis and natriuresis were not affected by concomitant infusions of ACTH, but the ANF-induced kaliuresis was significantly attenuated by ACTH. CONCLUSION: These studies suggest: a) Synthetic ANF induces a diuresis, natriuresis and kaliuresis; b) the D2 receptor antagonist Met increases plasma aldosterone; c) ANF-induced diuresis is not subject to dopaminergic blockade with Met, but Met-induced increases in plasma aldosterone are inhibited by ANF; and d) ANF does not attenuate ACTH-stimulated increases in mineralocorticoid production. These studies have operational significance, as they demonstrate that D2 dopaminergic blockade by the antinausea agent metoclopramide does not prevent the effects of increased ANF in response to central volume expansion such as occurs during exposure to microgravity or following water immersion.

Adrenocorticotropic Hormone↗
PubMed1995

Alpha 2-adrenergic receptor gene polymorphism and hypertension in blacks.

alpha 2-Adrenergic receptors are found on presynaptic neurons of the central and peripheral nervous systems, on blood vessels, on platelets, on adipocytes, and in the kidney and pancreas. Activation of these ubiquitous adrenoreceptors results in decreased neuronal norepinephrine release, vasodilation, a fall in blood pressure, platelet aggregation, increased sodium excretion, and decreased insulin release. We hypothesized that defects in alpha 2-adrenergic receptors, or postreceptor defects, could explain the increased prevalence of hypertension in blacks. To test our hypothesis, we first determined whether or not a polymorphism of the alpha 2-adrenergic receptor gene was associated with pathologic elevations in blood pressure in American blacks. Dra-I identified a restriction fragment-length polymorphism (RFLP) of 6.3 and 6.7 kb of the alpha 2-adrenergic receptor gene on chromosome 10 in humans. Of 227 patients studied, 13/107 hypertensive subjects were homozygous for the 6.3-kb allele, whereas only 3/120 normotensive volunteers were homozygotes (P = .008). When analyzed by race, 13/82 black hypertensive subjects were homozygous for the 6.3-kb allele, whereas only 2/59 normotensive blacks were homozygous for the 6.3-kb alleles (P = .02). However, only 1/61 white normotensive and 0/25 white hypertensive subjects were homozygous for the 6.3-kb allele (P = 1.00). Ethnic variation among blacks may explain our findings. Alternatively, a genetic polymorphism in, or near, the alpha 2-adrenergic receptor on chromosome 10 can contribute to the development of hypertension in blacks.

Alleles↗
PubMed1995

Genetic polymorphism of the alpha 2-adrenergic receptor is associated with increased platelet aggregation, baroreceptor sensitivity, and salt excretion in normotensive humans.

It is likely that a number of independent heritable traits, each encoded by a singular gene, contribute to pathologic elevations in blood pressure in humans. Genetic polymorphisms of individual genes may result in intermediate phenotypes which, by themselves, do not raise blood pressure, but, coupled with environmental or epistatic forces, contribute to the prevalence of human hypertension. The gene for the alpha 2-adrenergic receptor encoded by chromosome 10 (C10 A2AR) is polymorphic, and Southern blotting with a cDNA probe following restriction enzyme digest of this gene results in fragments of either 6.3 kb or 6.7 kb in size. We reported an association between homozygosity for the 6.3 kb allele and hypertension in blacks. Blacks with hypertension also have an increased risk for thrombotic stroke, increased baroreceptor sensitivity, and decreased sodium excretion. We noted that the C10 A2AR, which modulates norepinephrine release in blood-pressure-regulating regions of the brain, is also expressed on platelets and in the kidney. We postulated that functional changes associated with the C10 A2AR gene polymorphism could be responsible for increased baroreceptor sensitivity, epinephrine-mediated platelet aggregation, and decreased sodium excretion in some individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1995

Access, expectations and communication: Japanese mothers' interaction with GPs in a pilot study in North London.

The objectives of this study were: (i) to assess access to British GPs among Japanese mothers in Barnet: (ii) to describe what Japanese mothers expect from a consultation with a GP and; (iii) to understand what the barriers are for Japanese mothers in communicating with GPs. Semi-structured interviews were conducted with eighteen Japanese mothers residing in Barnet, North London, England. The interviews were recorded and their content subsequently transcribed and translated into English. First, gaining quick access to GPs was found to be much more difficult than communicating with GPs. The receptionist and appointment systems were sometimes seen as impediments to early consultation. Second, language was regarded as the biggest barrier in face-to-face communication. In particular the Japanese mothers found it difficult to understand colloquial expressions which were sometimes favoured by GPs. Third, GPs were unfamiliar with the Japanese mothers' expectations and experiences within their own health care system. These findings in relation to access, expectations and communication have provided us with some pointers as to the nature of the current difficulties experienced by one ethnic group.

Adult↗