Biomedical subjects

D Sykes

Publications and source records attributed to D Sykes.

At least 19 recordsLinked to original sources

PubMed2006

Characterization of patients with an inadequate clinical outcome from osteoporosis therapy: the Observational Study of Severe Osteoporosis (OSSO).

BACKGROUND: Osteoporotic fractures remain a major public health problem. Currently available osteoporosis therapies significantly reduce the risk of fractures, but up to 50% of patients have an inadequate clinical outcome to therapy. AIM: To describe the clinical and quality of life (QOL) of a study population meeting a proposed definition of inadequate clinical outcome to osteoporosis therapy, recruited for the Observational Study of Severe Osteoporosis (OSSO). DESIGN: Cross-sectional, observational study. METHODS: Post-menopausal women with osteoporosis (n = 2314) were divided into Group 1 (those who had previously experienced a fragility fracture despite osteoporosis drug therapy for at least 12 months) (n = 1309, 57%), or Group 2 (those who had previously discontinued osteoporosis drug therapy due to non-compliance or side-effects) (n = 1005; 43%). Baseline clinical characteristics, quality of life (QOL) and osteoporosis/falls risk factors were analysed. RESULTS: The overall population had low BMD (mean +/- SD T-score at lumbar spine -3.1 +/- 1.1), and risk factors for fracture such as previous fractures (67.8%), family history (15.1%), and prolonged glucocorticoid use (17.5%). QOL was poor: total QUALEFFO and EQ-5D scores were 46.8 +/- 18.7, and 0.50 +/- 0.33, respectively. Patients in Group 1 had higher age and body mass index, fewer hours of exercise, more previous fragility fractures and falls, and poorer QOL scores. DISCUSSION: Our definition of inadequate clinical outcome from osteoporosis drug therapy identifies a severe osteoporosis cohort with poor QOL and increased fracture risk. Using such a definition may lead to earlier recognition of inadequate clinical outcome to osteoporosis therapy, and improved interventions and results.

Absorptiometry, Photon↗

PubMed2005

Economic evaluation of parathyroid hormone (PTH) in the treatment of osteoporosis in postmenopausal women.

Parathyroid hormone (PTH) is a new treatment for osteoporosis and has been shown to reduce the risks of vertebral and non-vertebral fractures in postmenopausal women in clinical trials. The objective of this study was to estimate the cost-effectiveness of teriparatide in addition to calcium and vitamin D, using a simulation model. The base case analysis was conducted for a cohort of 69-year-old women in Sweden who had at least one previous vertebral fracture and low bone mineral density. The model simulated the course of events in 6-month cycles in individual patients until death or 100 years of age. During each cycle the patients were at risk of experiencing clinical vertebral, hip or wrist fractures, or death. Total accumulated life-time costs and quality-adjusted life years (QALYs) were estimated. Swedish data on fracture costs, utility reductions after fracture, fracture risks and mortality rates were used. The model incorporated new epidemiological evidence that indicates fracture risks and mortality rates are higher in the subsequent years post-fracture. The results showed that the cost-effectiveness of the treatment is highly dependant on the risk profile of the treated patients and the timing of starting treatment relative to previous fractures. The cost per QALY gained for treatment of a population of 69-year-olds with a T-score at the femoral neck of -3 was in the base case estimated to be between EUR (euro) 20,000 and 64,000 for patients with a recent or historic vertebral fracture respectively. The study provides further evidence of the benefit and cost-effectiveness of starting osteoporotic treatments early in patients with a new fracture, and also that teriparatide may provide valuable clinical benefits for these patients and may be considered a cost-effective intervention when targeted to the appropriate patients.

Aged↗

PubMed2004

Help-seeking behaviour and associated factors among women with urinary incontinence in France, Germany, Spain and the United Kingdom.

OBJECTIVES: To assess the proportion of women who consult their doctor about urinary incontinence (UI), and explore factors associated with help-seeking in France, Germany, Spain and the UK. METHODS: A representative sample of 29,500 women received a 13 item postal questionnaire to identify those with UI. A randomly selected sub-sample of 2953 women with UI received a more detailed follow-up questionnaire. RESULTS: There was a response rate of 58% in the initial survey and 53% in the second. Thirty-one percent of all women had consulted a doctor about their UI symptoms with more women consulting in France and Germany than in the UK and Spain. A number of factors relating to general health care, UI and women's attitudes were found to be associated with help-seeking after adjusting for women's age, UI duration and frequency, and 'bothersomeness' of UI; factors traditionally associated with help-seeking. After adjusting for these factors, willingness to take long-term medication and having spoken to others about UI were found to be strong predictors of help-seeking in all four countries.

Female↗

PubMed2004

Cost-effectiveness of raloxifene in the UK: an economic evaluation based on the MORE study.

Raloxifene treatment has been shown to reduce the risk of vertebral fractures and breast cancer in postmenopausal women. The long-term economic implications of treatment with raloxifene have not yet been investigated. The aim of this study was to assess the cost-effectiveness of treating postmenopausal women in the UK with raloxifene. A previously developed computer simulation model was used to estimate the cost-effectiveness of osteoporotic treatments with extra skeletal benefits. The model was populated with epidemiological data and cost data relevant for a UK female population. Data on the effect of treatment were taken from the Multiple Outcomes of Raloxifene (MORE) study, which recruited women with low bone mineral density or with a prior vertebral fracture. Cost-effectiveness was estimated using Quality Adjusted Life Years (QALYs) and life years gained as primary outcome measures. The cost per QALY gained of treating postmenopausal women without prior vertebral fractures was 18,000 pounds, 23,000 pounds , 18,000 pounds and 21,000 pounds at 50, 60, 70 and 80 years of age. Corresponding estimates for women with prior vertebral fractures were 10,000 pounds, 24,000 pounds, 18,000 pounds and 20,000 pounds. In relation to threshold values that are recommended in the UK, the analysis suggests that raloxifene is cost-effective in the treatment of postmenopausal women at an increased risk of vertebral fractures.

Adult↗

PubMed2004

The prevalence of urinary incontinence in women in four European countries.

OBJECTIVE: To determine the prevalence, type and treatment behaviour of women with urinary incontinence in four European countries. SUBJECTS AND METHODS: Data were collected using a postal survey which was sent to 29,500 community-dwelling women aged > or = 18 years in France, Germany, Spain and the UK. Subjects were asked about the type of urinary incontinence they had experienced and their treatment behaviour. RESULTS: Of the women who responded, 35% reported involuntary loss of urine in the preceding 30 days; stress urinary incontinence was the most prevalent type. The lowest prevalence was in Spain (23%), while the prevalence was 44%, 41% and 42% for France, Germany and the UK, respectively. About a quarter of women with urinary incontinence in Spain (24%) and the UK (25%) had consulted a doctor about it; in France (33%) and Germany (40%) the percentages were higher. Overall, <5% of the women had ever undergone surgery for their condition. While pads were used by half of the women, there were some differences among the countries. CONCLUSIONS: Millions of women in Europe have urinary incontinence; the consultation and treatment rates were low in the European countries included in this study.

Adolescent↗

PubMed2004

Pharmaceutical treatment of symptomatic vertebral fractures in primary care.

BACKGROUND: Vertebral fractures are associated with a reduction in quality of life and are an important predictor of other non-spine fractures. Previous work has shown that up to 60% of patients with a vertebral fracture identified in primary care remain untreated. OBJECTIVE: To examine the prevalence of pharmaceutical treatment and predictors of treatment in a primary care setting. METHODS: Case-control study using the general practice research database (GPRD). All women aged 50 years and over with a first diagnosis of a vertebral fracture since 1990 were identified and matched with a control by age and practice. Appropriate use of a pharmaceutical agent was defined as a prescription occurring within 30 days of the diagnosis being recorded. RESULTS: We identified 2719 women with the same number of controls. Within 30 days of diagnosis 61% of women were prescribed treatment, compared with only 3% of the controls. Bisphosphonate was the single most important treatment prescribed. Predictors of any drug treatment included: year of fracture (most recent year increased the likelihood of treatment); age (younger patients were more likely to receive treatment); history of back pain; low body weight; history of steroid use. CONCLUSIONS: Treatment of diagnosed vertebral fractures is becoming more common. Treated patients tend to be younger but to have a higher prevalence of clinical risk factors than untreated patients. There remain significant numbers of patients who are not offered treatment.

Age Factors↗

PubMed2001

The cost-effectiveness of IVF in the UK: a comparison of three gonadotrophin treatments.

BACKGROUND: The objective of this study was to evaluate the cost-effectiveness of women undergoing IVF treatment with recombinant FSH (rFSH) in comparison with highly purified urinary FSH (uFSH-HP) and human menopausal gonadotrophins (HMG). METHODS: A decision-analytic model was used to estimate cost-effectiveness ratios for 'the average cost per ongoing pregnancy' and 'incremental cost per additional pregnancy' for women entering into IVF treatment for a maximum of three cycles. The model was constructed based on a previously published large prospective randomized clinical trial comparing rFSH and uFSH-HP. Where necessary, these data were augmented with a combination of expert opinion, evidence from the literature and observational data relating to the management and cost of IVF treatment in the UK. The cost of rFSH, uFSH-HP and HMG were obtained from National Health Service list prices in the UK. RESULTS: The model predicted a cumulative pregnancy rate after three cycles of 57.1% for rFSH and 44.4% for both uFSH-HP and HMG. The cost of IVF treatment was 5135 pounds sterling for rFSH, 4806 pounds sterling for uFSH-HP and 4202 pounds sterling for HMG. When assessed in association with outcomes, the average cost per ongoing pregnancy was more favourable with rFSH (8992 pounds sterling) than with either uFSH-HP (10 834 pounds sterling) or HMG (9472 pounds sterling). The incremental cost per additional pregnancy was 2583 pounds sterling using rFSH instead of uFSH-HP and 7321 pounds sterling using rFSH instead of HMG. These results were robust to changes in the baseline assumptions of the model. CONCLUSION: rFSH is a cost-effective treatment strategy in ovulation induction prior to IVF.

Cost-Benefit Analysis↗

PubMed2000

Medico-legal aspect of dental implants.

The practising environment in health care is ever changing in both clinical and management areas. Within dentistry, two major changes have occurred with the development of implantology into a sound treatment approach and a burgeoning of dental litigation. There are medico-legal issues that relate to dental implant treatment with which clinicians must become familiar and there are medico-legal implications that impact on risk management by Medical Indemnity Organizations (MDOs) and the indemnity premiums they set for their members. The aim of this paper is to discuss these issues and highlight those areas of significance to clinicians.

Dental Implantation, Endosseous↗

PubMed1999

Helicobacter pylori infection rates in duodenal ulcer patients in the United States may be lower than previously estimated.

OBJECTIVE: Published studies have estimated the rate of Helicobacter pylori (H. pylori) infection in patients with duodenal ulcer disease to be as high as 95%; the majority of remaining duodenal ulcers have been attributed to the use of ulcerogenic drugs such as nonsteroidal antiinflammatory drugs (NSAIDs). We aimed to assess the H. pylori prevalence rates of U.S. duodenal ulcer patients in large, well-controlled studies. METHODS: More than 2900 patients with endoscopically diagnosed non-NSAID duodenal ulcers were enrolled in a series of six placebo-controlled, double-blind studies conducted in the United States that assessed H. pylori using a combination of tests. Patients were considered infected with H. pylori only if culture growth was observed, or both histological and CLOtest results were positive. Patients were considered uninfected if the results of at least two tests were negative. Patients with missing test results, results of only a single test, or conflicting test results were not evaluable for H. pylori assessment. RESULTS: Of the 2394 endoscopically diagnosed evaluable duodenal ulcer patients, 73% (1737) were confirmed infected with H. pylori at study entry. CONCLUSIONS: The results of six carefully designed and controlled studies suggest that an assumed H. pylori infection rate of approximately 95% may overestimate the actual rate of H. pylori infection in duodenal ulcer patients in the United States. Although H. pylori infection is an important factor in the etiology of noniatrogenic duodenal ulcer disease, other factors may predominate in some patients and should not be overlooked in determining an appropriate course of treatment. The empiric use of antibiotic therapy for ulcer patients without confirmation of the presence of H. pylori cannot be recommended.

Adolescent↗

PubMed1999

Thromboembolic disease susceptibility related to red cell membrane fluidity in patients with polycythemia vera and effect of phlebotomies.

Thromboembolic disorders are frequent complications in polycythemia vera. In addition to thrombocytosis with hyperaggregability, leukocytosis, and high hematocrit, hyperviscosity syndrome, a new component, is described in the pathophysiology of this phenomenon. There is decreased red cell membrane fluidity with decreased deformability which increases the susceptibility to microvascular occlusion and also increases the chance of disseminated intravascular coagulation (DIC). Periodic phlebotomies improved the hematologic picture in these patients and results in the removal of the "stiff" red cells with an increased production of young red cells, greater membrane fluidity, deformability and less chance of microvascular occlusion.

Aged↗

PubMed1998

Low density lipoproteins and Lovastatin modulate the organ-specific transendothelial migration of primary and metastatic human colon adenocarcinoma cell lines in vitro.

Tumor cell arrest and tumor migration are two of the critical steps in the metastatic cascade. We hypothesized that these steps may be facilitated by the low density lipoprotein (LDL)-induced activation of microvessel endothelial cells (MVEC). The purpose of our study was to investigate the biological effects of an LDL-enriched milieu and the effects of the anticholesterol drug Lovastatin on metastatic behavior. The SW480 and SW620 are primary and metastatic human colonic adenocarcinoma cell lines derived from the same patient. We investigated the effect of LDL on adhesion and migration of the two tumor cell lines across human brain, lung, liver and dermal endothelial monolayers. Adhesion and migration assays were done before and after pretreatment of the MVEC or tumor cells with LDL (100 microg/ml) for 24 h. Although metastatic SW620 cells were more adherent to MVEC compared with primary SW480 cells, LDL pretreatment of SW480 and SW620 cells did not affect tumor cell adhesion to MVEC. In contrast, tumor cell migration was significantly increased across endothelial monolayers when MVEC were pretreated with LDL. Transendothelial cell migration was not significantly affected by pretreatment of the tumor cells with LDL. Lovastatin is an inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. It has been shown to have anti-tumor activity in vitro. We investigated the effect of Lovastatin on tumor cell kinetics and tumor cell migration across MVEC. Growth curves and migration assays were done before and after pretreatment of the tumor cells with Lovastatin (30 microg/ml). Migration assays were also done after treatment of unstimulated or LDL-stimulated MVEC (100 microg/ml) for 24 h with Lovastatin. Lovastatin inhibited the in vitro growth of the metastatic SW620 cell line to a greater extent than the invasive SW480E cell line. On the other hand, pretreatment of tumor cells with Lovastatin (30 microg/ml) did not suppress transendothelial tumor cell migration of tumor cells. Finally, Lovastatin given to mice effectively suppressed the number of MCA-26 tumor colonies in the liver of Balb/c mice compared with untreated mice.

Adenocarcinoma↗

PubMed1998

Aqua-Reslin droplet analysis.

Aerosol droplets were collected, counted, and sorted using a laser system, the Army Insecticide Measuring System, Teflon-coated slides, and magnesium oxide-coated slides. All droplets, for each method and replication, were generated by a London Aire 1820 or a Leco Model 1600. These data indicate that the Army Insecticide Measuring System or Teflon-coated slides are so closely similar to the laser that they could effectively be used in the field without an overwhelming loss in precision.

Aerosols↗

PubMed1993

Inhibition of binding of basic fibroblast growth factor to low and high affinity receptors by carrageenans.

The effect of carrageenans, a family of polysulphated polysaccharides, on the binding of basic fibroblast growth factor (bFGF) to low affinity (heparin-like) receptors and high affinity receptors on baby hamster kidney cells was investigated. kappa-, iota-, and lambda-carrageenans all inhibited binding of bFGF to both types of receptors with iota-carrageenan being the most potent inhibitor (IC50 values of approx. 0.7 and 4 micrograms/mL for inhibition of binding to low and high affinity receptors respectively). Heparin reduced the inhibition of bFGF binding to high affinity receptors caused by iota-carrageenan. Heparin and iota-carrageenan were comparable in their activities at displacing pre-bound bFGF from both low affinity receptors and high affinity receptors. These results indicate that iota-carrageenan binds to the heparin-binding domain on bFGF and that this may be sufficient to reduce the ability of bFGF to bind to high affinity receptors.

Animals↗

PubMed1992

Changes in transcripts of basement components during rat liver development: increase in laminin messenger RNAs in the neonatal period.

The expression of laminin and type IV collagen messenger RNA in rat liver was investigated in relation to liver development. Levels of messenger RNA for laminin chains A, B1 and B2, and alpha 1 and alpha 2 chains of type IV collagen were studied by Northern-blot and dot-blot analysis. Although the expression of messenger RNAs for laminin B1 and B2 chains was higher in 19-day gestational fetal liver when compared with the adult, the highest level was detected in 15-day newborns. This finding coincides with the final establishment of the mature liver. Laminin A messenger RNA was not detected in the 19-day gestational fetus or in the neonatal period. In contrast, alpha 1-(IV) and alpha 2-(IV) collagen messenger RNAs maintained high levels in the early neonate and then decreased gradually after 15 days. Our findings suggest that during late stages of liver ontogeny the main components of liver basement membrane proteins undergo a significant alteration in their synthesis. The data further suggest that laminin may play a role in the final stages of hepatic differentiation.

Animals↗

PubMed1992

Glycosylated haemoglobin in the diagnosis of diabetes mellitus in elderly people.

An oral glucose tolerance test (OGTT, 75 g WHO criteria) was applied to healthy elderly subjects (mean age 76 years) within a week of measurement of random blood glucose and glycosylated haemoglobin (HbA1). The 'Corning' method was used to assay HbA1 (established normal range for our laboratory 5-8%). Sixty-five subjects (38 women) of whom 54 were not diabetic on WHO criteria for OGTT participated in the study. Five of the 54 patients with non-diabetic OGTT results had abnormal HbA1 (greater than 8%). These five subjects had no evidence of impaired glucose tolerance. Eleven subjects had diabetic OGTT results of whom only four had raised HbA1 assay results. Seven subjects had normal HbA1 in spite of diabetic OGTT. The mean HbA1 in the group of subjects with normal OGTT (n = 52) was 6.7% (SD 1.05, range 4.6-8.7%). It appears from our study that the normal range of HbA1 in elderly subjects is not markedly different from established normal values. The poor sensitivity (36%) and predictive value (44%) of abnormal HbA1 in detecting diabetes, as shown in our study, would not permit its use for screening purposes nor as a confirmatory test for diabetes in elderly subjects.

Aged↗

PubMed1992

The effect of hemiplegia on blood pressure measurement in the elderly.

The blood pressure in both arms of 103 unselected hemiplegic patients was measured using a random-zero sphygmomanometer. Although for the whole sample the mean blood pressure in the paretic and unaffected arm was similar, a significant difference was found when the patients were subdivided according to the tone of the arm. The blood pressure was higher in paretic arms of patients with a spastic stroke and lower in the affected arm if the tone was flaccid. No other characteristics were associated with significant blood pressure differences, so that the findings appear to be directly related to changes in muscle tone. After a stroke the blood pressure should always be measured in the unaffected arm because changes in tone make measurements unreliable.

Aged↗

PubMed1991

The truncated glucocorticoid receptor in the P1798 mouse lymphosarcoma is associated with resistance to glucocorticoid lysis but not to other glucocorticoid-induced functions.

Glucocorticoid receptors in lines of the P1798 mouse lymphosarcoma either sensitive or resistant to glucocorticoid-induced lysis have been characterized and their functional significance determined. The glucocorticoid receptor from the cortisol-sensitive tumor is an Mr approximately 98,000 protein with a Stokes radius of 7.4 nm in the oligomeric, non-DNA-binding state and 5.6 nm in the transformed, DNA-binding state. This receptor binds glucocorticoid and reacts with the BUGR-2 monoclonal antibody. In contrast, two abnormal receptor species were identified in the cortisol-resistant tumor. One is an Mr approximately 98,000 non-steroid-binding but immunologically reactive protein. The other is an Mr approximately 45,000 species which contains both steroid- and DNA-binding sites but exhibits little or no reactivity with BUGR-2, suggesting that its NH2 terminus is truncated in a region within or adjacent to the BUGR epitope. This species had Stokes radii of 5.8 and 3.5 nm in nontransformed and transformed states, respectively. In both tumor lines, glucocorticoids stimulated the activities of glutamine synthetase and 5'-nucleotidase and the synthesis of glucocortin. However, glucocorticoid-induced tumor regression occurred only in the cortisol-sensitive tumor. Additionally, the glucocorticoid inducibility of a specific protein in the sensitive, but not in the resistant, tumor was demonstrated, as well as the presence of a protein specific to the resistant line. Taken together, these results suggest that the truncated glucocorticoid receptor in the P1798 lymphosarcoma is functional, although possibly in a more restricted gene-specific manner, and that the lysis defect, while possibly resulting from a truncated receptor, may also result from the inability of glucocorticoids to induce a critical protein in the pathway of programmed cell death and/or from the presence of a protein which inhibits the lytic response.

5'-Nucleotidase↗

PubMed1991

Opportunistic screening of visual acuity of elderly patients attending outpatient clinics.

A standard Snellen letter chart was used to screen the visual acuities of 202 elderly patients while they attended outpatients clinics. Patients overestimated the adequacy of their vision: only 34 patients reported inadequate vision while 72 had significant measured visual impairment. Of these, 30 patients had refractive errors and 42 primarily non-refractive problems. Thirty patients were examined by an ophthalmologist, of whom 24 had previously undiagnosed conditions. Eighteen patients had treatable conditions, predominantly cataracts and glaucoma. Ten patients with untreatable conditions had the benefit of a definitive diagnosis, most commonly of age-related macular degeneration, and an assessment of eligibility for registration of blindness. The routine assessment of elderly patients should include objective screening of their visual acuity.

Aged↗