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J Young

Publications and source records attributed to J Young.

At least 181 records · Page 10Linked to original sources
PubMed1999

Autoantibodies interacting with purified native thyrotropin receptor.

Native thyrotropin receptor (TSHR) was purified by immunoaffinity chromatography from membrane extracts of stably transfected L cells. An ELISA test was devised to study anti-TSHR autoantibodies directly. Comparison of native TSHR with bacterially expressed, denatured TSHR showed that the latter was not recognized by the autoantibodies, suggesting that they bind to conformational epitopes only present on the native receptor. The use of deglycosylated TSHR and of purified receptor ectodomain (alpha-subunit) showed that the autoantibodies recognized only the protein backbone moiety of the receptor and that their epitopes were localized entirely in its ectodomain. Autoantibodies were detected in 45 of 48 subjects with untreated Graves' disease and in 26 of 47 healthy volunteers. The affinity for the receptor was similar in the two groups (Kd = 0.25-1 x 10-10 M) and the autoantibodies belonged to the IgG class in all cases. Although the concentration of autoantibodies was higher in Graves' disease patients (3.50 +/- 0.36 mg.L-1) than in control subjects (1.76 +/- 0.21) (mean +/- SEM), there was an overlap between the groups. Receptor-stimulating autoantibodies (TSAb) were studied by measuring cAMP synthesis in stably transfected HEK 293 cells. Their characteristics (recognition of alpha-subunit, of deglycosylated TSHR, nonrecognition of bacterially expressed denatured receptor) were similar to those of the antibodies detected by the ELISA test. TSAb were only found in individuals with Graves' disease. The ELISA test measures total anti-TSHR antibodies, whereas the test using adenylate cyclase stimulation measures antibodies that recognize specific epitopes involved in receptor activation. Our observations thus disprove the hypothesis according to which Graves' disease is related to the appearance of anti-TSHR antibodies not present in normal subjects. Actually, anti-TSHR antibodies exist in many euthyroid subjects, in some cases even at concentrations higher than those found in patients with Graves' disease. What distinguishes the latter from normal subjects is the existence of subpopulation(s) of antibodies directed against specific epitope(s) of the receptor involved in its activation.

Animals↗
PubMed1999

Patient satisfaction with nursing care: a measurement conundrum.

Patient satisfaction is a major indicator of quality care. There are several theories on the types of concepts that should be measured concerning patient satisfaction with nursing care. Given the different theories of patient satisfaction, the issue of accurate measurement of this concept presents nurse researchers, clinicians and leaders with a challenge. This paper will discuss the findings of a patient satisfaction survey that was conducted in two acute care surgical wards, using the revised 28-item La Monica-Oberst patient satisfaction scale and telephone interviews. Data were analysed using descriptive statistics. Textual data were managed using NUD*IST and analysed for common emerging themes and categories. The findings of the quantitative and qualitative data were compared in order to determine similarities and differences. The survey results revealed very high levels of patient satisfaction; however, the qualitative data revealed some anomalies. Specifically, due to the numbers of nurses involved in the care, some patients had difficulties answering the questionnaire. Moreover, they were unable to discriminate nursing care from the rest of their overall patient experience. Within this study, it seemed that patients' perceptions of nurses influenced the way patients rated quality nursing care. Based on this information, the authors question the accuracy of the measurement of patient satisfaction and raise issues that need to be considered in order to further clarify the measurement of this concept.

Adult↗
PubMed1999

Detection of telomerase activity in biopsy samples of colorectal cancer.

BACKGROUND: Telomerase is a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends. The expression of telomerase is thought to be required for cellular immortality and oncogenesis. METHODS: To investigate the role of telomerase in the pathogenesis of colorectal cancer, we analysed telomerase activity in biopsy samples of colorectal cancer and colonic adenomas. Using a polymerase chain reaction-based assay, we examined telomerase activity in 52 samples of colorectal cancer, 12 colonic adenomas and 30 normal colonic mucosa samples obtained by endoscopic biopsy. RESULTS: Telomerase activity was detectable in 88.5% (46/52) of colorectal carcinomas, in 50% (6/12) of colonic adenomas but not in normal colorectal mucosa. There was no correlation between telomerase activity and tumour location, type, size and differentiation (P > 0.05). CONCLUSIONS: It was concluded that telomerase activation plays a role in the evolution of colorectal cancer, and that measurement of telomerase activity in biopsied colorectal mucosa samples may provide information both as a diagnostic marker to detect small numbers of cancer cells, and as a screening method for patients at high risk for colorectal carcinoma.

Adenoma↗
PubMed1999

No evidence of increased risk of colorectal cancer in individuals heterozygous for the Cys282Tyr haemochromatosis mutation.

BACKGROUND AND AIMS: Previous studies have suggested that increased body iron stores and heterozygosity for haemochromatosis are associated with an increased risk of colorectal carcinoma. The aim of this study is to determine if there is an association between (i) colorectal carcinoma and heterozygosity for the Cys282Tyr mutation of the haemochromatosis gene (HFE) and (ii) this mutation and tumour site or stage. METHODS: Two hundred and twenty-nine unselected patients (127 males, 102 females, mean age 68.0 years) with sporadic colorectal carcinoma and 228 controls (145 males, 83 females, mean age 69.7 years) were studied. DNA was tested for the presence of the Cys282Tyr mutation by digestion with Rsa1 and fragments separated by electrophoresis. RESULTS: Twenty-one patients with colorectal cancer and 23 control subjects were heterozygous for the Cys282Tyr mutation of HFE (relative risk 0.90). There was no association between heterozygosity of the Cys282Tyr mutation and tumour site or stage. CONCLUSIONS: Heterozygosity for the Cys282Tyr mutation of HFE does not appear to be a risk factor for colorectal carcinoma.

Aged↗
PubMed1999

Effects of a physiotherapist-led stroke training programme for nurses.

AIM: to assess the effects of a physiotherapist-led stroke training programme for nurses working in a rehabilitation ward on clinical practice and patient outcome. METHOD: before and after group comparison with outcome assessment by observational and quantitative methods. Non-participant observation before and after the 5-month training programme recorded patient position, transfers and contact with nursing staff. Quantitative assessments of disability, satisfaction and mood were made at baseline, discharge and 4 months after stroke onset. We also noted selected stroke complications, rehabilitation ward length of stay and discharge destination. RESULTS: there was a significant improvement in the number of observed 'good' transfers of patients undertaken by nurses (chi2 = 9.13, df = 1, P = 0.003) but the training programme had no impact on the time the patients spent in 'poor' positions. There was no significant difference between the two groups for Barthel index scores at discharge and at 4 months. Neither was there any significant difference in the Hospital Anxiety and Depression scale, occurrence of secondary complications, length of stay or the Patient and Carer Satisfaction Questionnaires. CONCLUSION: within the limitations of the research design adopted, some improvements in clinical practice were reported but there were no significant differences in patient outcome. The training programme required no additional resources and should be replicable in most district general hospitals.

Aged↗
PubMed1999

Specialist gynaecologists and survival outcome in ovarian cancer: a Scottish national study of 1866 patients.

OBJECTIVE: To determine whether specialist gynaecological surgeons improved survival in women with ovarian cancer when compared with general gynaecologists. DESIGN: Retrospective case note review. POPULATION: All women diagnosed with ovarian cancer in Scotland in 1987, 1992, 1993 and 1994. METHODS: Data on prognostic factors and surgical and post-operative management was extracted from case notes. Surgeons were classified as specialist gynaecologists, general gynaecologists or general surgeons by an independent committee with no knowledge of an individual's outcome. Cox's proportional hazards model was used to determine the relative risk of a patient dying, if managed by specialist and general gynaecologists, after adjustment for age, histology, tumour differentiation, presence of ascites and socio-economic status. Analysis was performed separately for each FIGO stage. MAIN OUTCOME MEASURES: Relative hazard ratios for survival up to three years. RESULTS: Survival benefit for specialists varied according to the stage of the disease. The greatest benefit was observed among women with Stage III disease (44% of women presented at this stage) where there was a 25% (relative hazard ratio = 0.75, P = 0.005) reduction in the rate of dying for women operated on by specialist gynaecologists, compared with women operated on by general gynaecologists. Differential use of platinum chemotherapy did not explain this survival advantage. Specialist gynaecologists more often debulked tumour to < 2 cm than general gynaecologists in Stage III cases (36.3% vs 28.7%, P = 0.07). In women with Stage III carcinoma with > 2 cm remaining, survival was significantly improved for women treated by specialist gynaecologists (relative hazard ratio = 0.71, P = 0.007). No significant differences were observed for patients with Stages I, II and IV disease, although there were fewer deaths in women with early stage disease. CONCLUSIONS: Specialist gynaecologists improve survival for some women with ovarian cancer.

Aged↗
PubMed1999

Prospective study of outcome in antenatally diagnosed renal pelvis dilatation.

AIMS: To ascertain the outcome associated with antenatal renal pelvis dilatation; to recommend guidelines for postnatal investigation and determine an upper limit of normal for the anterioposterior dimensions of the fetal renal pelvis. METHODS: Infants whose antenatal ultrasound scan showed a fetal renal pelvis of 5 mm or greater were investigated using postnatal renal tract ultrasound and a micturating cystogram. Isotope studies were also performed, where appropriate. RESULTS: Vesicoureteric reflux (VUR), the most common diagnosis, was evident in 23/104 (22%). In 14 infants with VUR the postnatal ultrasound scan was normal. There was no evidence of renal scarring or dysplasia in any of the refluxing kidneys. Other diagnoses were pelviureteric junction obstruction, renal dysplasia, and idiopathic dilatation. Antenatal counselling and parental information facilitated postnatal assessment. CONCLUSIONS: Infants with antenatal renal pelvis measurements of 5 mm or greater should be investigated postnatally, as a significant percentage will have VUR. A normal postnatal ultrasound scan does not preclude the presence of VUR.

Female↗
PubMed1999

Screening SMAD1, SMAD2, SMAD3, and SMAD5 for germline mutations in juvenile polyposis syndrome.

BACKGROUND AND AIMS: Juvenile polyps occur in several Mendelian disorders, whether in association with gastrointestinal cancer alone (juvenile polyposis syndrome, JPS) or as part of known syndromes (Cowden, Gorlin, and Bannayan-Zonana) in association with developmental abnormalities, dysmorphic features, or extraintestinal tumours. Recently, some JPS families were shown to harbour germline mutations in the SMAD4 (DPC4) gene, providing further evidence for the importance of the TGFbeta signalling pathway in colorectal cancer. There remains, however, considerable, unexplained genetic heterogeneity in JPS. Other members of the SMAD family are excellent candidates for JPS, especially SMAD2 (which, like SMAD4, is mutated somatically in colorectal cancers), SMAD3 (which causes colorectal cancer when "knocked out" in mice), SMAD5, and SMAD1. METHODS: SMAD1, SMAD2, SMAD3, and SMAD5 were screened for germline mutations in 30 patients with JPS and without SMAD4 mutations. RESULTS: No mutations were found in any of these genes. A G-A C89Y polymorphism with possible effects on protein function was found in SMAD3, but the frequencies of the G and A alleles did not differ between patients with JPS and controls. CONCLUSIONS: It remains to be determined whether or not this polymorphism is involved in a minor predisposition to colorectal or other carcinomas. SMAD4 may be the only member of the SMAD family which causes JPS when mutant in the germline. The other genes underlying JPS remain to be identified.

Adenomatous Polyposis Coli↗
PubMed1999

DNA microsatellite instability in hyperplastic polyps, serrated adenomas, and mixed polyps: a mild mutator pathway for colorectal cancer?

AIM: To investigate the distribution of DNA microsatellite instability (MSI) in a series of hyperplastic polyps, serrated adenomas, and mixed polyps of the colorectum. METHODS: DNA was extracted from samples of 73 colorectal polyps comprising tubular adenomas (23), hyperplastic polyps (21), serrated adenomas (17), and mixed polyps (12). The presence of MSI was investigated at six loci: MYCL, D2S123, F13B, BAT-40, BAT-26, and c-myb T22, using polymerase chain reaction based methodology. MSI cases were classified as MSI-Low (MSI-L) and MSI-High (MSI-H), based on the number of affected loci. RESULTS: The frequency of MSI increased in tubular adenomas (13%), hyperplastic polyps (29%), serrated adenomas (53%), and mixed polyps (83%) (Wilcoxon rank sum statistic, p < 0.001). Hyperplastic epithelium was present in nine of 12 mixed polyps and showed MSI in eight of these. MSI was mostly MSI-L. MSI-H occurred in two serrated adenomas and three mixed polyps. Clonal relations were demonstrated between hyperplastic and dysplastic epithelium in four of eight informative mixed polyps. CONCLUSIONS: The findings support the view that hyperplastic polyps may be fundamentally neoplastic rather than hyperplastic. A proportion of hyperplastic polyps may serve as a precursor of a subset (10%) of colorectal cancers showing the MSI-L phenotype, albeit through the intermediate step of serrated dysplasia. This represents a novel and distinct morphogenetic pathway for colorectal cancer.

Adenoma↗
PubMed1999

Characterisation of a subtype of colorectal cancer combining features of the suppressor and mild mutator pathways.

BACKGROUND: 10% of sporadic colorectal cancers are characterised by a low level of microsatellite instability (MSI-L). These are not thought to differ substantially from microsatelite-stable (MSS) cancers, but MSI-L and MSS cancers are distinguished clinicopathologically and in their spectrum of genetic alterations from cancers showing high level microsatellite instability (MSI-H). AIMS: To study the distribution of molecular alterations in a series of colorectal cancers stratified by DNA microsatellite instability. METHODS: A subset of an unselected series of colorectal cancers was grouped by the finding of DNA MSI at 0 loci (MSS) (n = 51), 1-2 loci (MSI-L) (n = 38) and 3-6 loci (MSI-H) (n = 25). The frequency of K-ras mutation, loss of heterozygosity (LOH) at 5q, 17p and 18q, and patterns of p53 and beta catenin immunohistochemistry was determined in the three groups. RESULTS: MSI-H cancers had a low frequency of K-ras mutation (7%), LOH on chromosomes 5q (0%), 17p (0%) and 18q (12.5%), and a normal pattern of immunostaining for p53 and beta catenin. MSI-L cancers differed from MSS cancers in terms of a higher frequency of K-ras mutation (54% v 27%) (p = 0.01) and lower frequency of 5q LOH (23% v 48%) (p = 0.047). Whereas aberrant beta catenin expression and 5q LOH were concordant (both present or both absent) in 57% of MSS cancers, concordance was observed in only 20% of MSI-L cancers (p = 0.01). CONCLUSIONS: MSI-L colorectal cancers are distinct from both MSI-H and MSS cancers. This subset combines features of the suppressor and mutator pathways, may be more dependent on K-ras than on the APC gene in the early stages of neoplastic evolution, and a proportion may be related histogenetically to the serrated (hyperplastic) polyp.

Adenoma↗
PubMed1999

Infrequent loss of heterozygosity of APC/MCC and DCC genes in gastric cancer showing DNA microsatellite instability.

AIM: To investigate the role of DNA microsatellite instability (MSI) in gastric carcinogenesis by studying associations between MSI status, clinicopathological features, and loss of genetic loci. METHODS: Six microsatellite loci and loss of heterozygosity at APC, DCC, and MCC were analysed by polymerase chain reaction based methods in 53 cases of advanced gastric cancer. RESULTS: MSI was observed in 32.1% of gastric carcinomas (17/53) and 20% of foci of intestinal metaplasia (3/15). Seven gastric carcinomas (13.7%) were MSI-high (MSI-H) (three loci or more) and 10 (18.9%) were MSI-low (MSI-L) (one or two loci). The frequency of MSI-H was higher in intestinal (25.0%) than in diffuse carcinomas (3.7%) (p < 0.05). None of the MSI-H tumours showed loss of heterozygosity at APC, MCC, or DCC loci. CONCLUSIONS: MSI may have an important and early role in a subset of gastric cancers, particularly the intestinal type. The MSI-H subset of gastric cancer has features in common with its colorectal counterpart, whereas MSI-L and microsatellite stable cancers appear to develop through the loss of heterozygosity pathway.

Adult↗
PubMed1999

Improving the repeat prescribing process in a busy general practice. A study using continuous quality improvement methodology.

PROBLEM: A need to improve service to patients by reducing the time wasted by reception staff so that the 48 hour target for processing repeat prescription requests for patient collection could be achieved. DESIGN: An interprofessional team was established within the practice to tackle the area of repeat prescribing which had been identified as a priority by practice reception staff. The team met four times in three months and used continuous quality improvement (CQI) methodology (including the Plan-Do-Study-Act cycle) with the assistance of an external facilitator. BACKGROUND AND SETTING: A seven partner practice serving the 14,000 patients on the northern outskirts of Bournemouth including a large council estate and a substantial student population from Bournemouth University. The repeat prescribing process is computerised. KEY MEASURES FOR IMPROVEMENT: Reducing turn around times for repeat prescription requests. Reducing numbers of requests which need medical records to be checked to issue the script. Feedback to staff about the working of the process. STRATEGIES FOR CHANGE: Using a Plan-Do-Study-Act cycle for guidance, the team decided to (a) coincide repeat medications and to record on the computer drugs prescribed during visits; (b) give signing of prescriptions a higher priority and bring them to doctors' desks at an agreed time; and (c) move the site for printing prescriptions to the reception desk so as to facilitate face to face queries. EFFECTS OF CHANGE: Prescription turnaround within 48 hours increased from 95% to 99% with reduced variability case to case and at a reduced cost. The number of prescriptions needing records to be looked at was reduced from 18% to 8.6%. This saved at least one working day of receptionist time each month. Feedback from all staff within the practice indicated greatly increased satisfaction with the newly designed process. LESSONS LEARNT: The team's experience suggests that a combination of audit and improvement methodology offers a powerful way to learn about, and improve, practice. The interventions used by the team not only produced measurable and sustainable improvements but also helped the team to learn about the cost of achieving the results and provided them with tools to accomplish the aims. The importance of feedback to all staff about CQI measures was also recognised.

Accounts Payable and Receivable↗
PubMed1999

Lung volume reduction surgery (LVRS) for chronic obstructive pulmonary disease (COPD) with underlying severe emphysema.

BACKGROUND: Lung volume reduction surgery (LVRS) has recently re-emerged as a surgical option for the treatment of end stage chronic obstructive pulmonary disease (COPD) due to underlying severe emphysema. Advocates of LVRS claim that it represents a significant breakthrough in the management of this challenging group of patients while sceptics point to uncertainty about the effectiveness of the operation. METHODS: A systematic review was conducted of the evidence on the effects of LVRS in patients with end stage COPD secondary to severe emphysema. RESULTS: The most rigorous evidence on the effectiveness of LVRS came from case series. Seventy five potentially relevant studies were identified and 19 individual series met the methodological criteria for inclusion. The pattern of results was consistent across individual studies despite a significant degree of clinical heterogeneity. Significant short term benefits occurred across a range of outcomes which appeared to continue into the longer term. Physiological improvements were matched by functional and subjective improvements. Early mortality rates were low and late mortality rates compared favourably with those of the general COPD population. However, the entire research base for the intervention is subject to the limitations of study designs without parallel control groups. CONCLUSIONS: LVRS appears to represent a promising option in the management of patients with severe end stage emphysema. However, until the results of ongoing clinical trials are available, the considerable uncertainty that exists around the effectiveness and cost effectiveness of the procedure will remain.

Dyspnea↗
PubMed1999

Effect of a physiotherapist-led training programme on attitudes of nurses caring for patients after stroke.

BACKGROUND: A multidisciplinary project team developed a five-month physiotherapist-led training programme designed to enhance nurses' rehabilitation skills. AIMS: Investigation of the effects of the training programme on nurses attitudes to patients with stroke. METHOD: An attitude questionnaire was completed by the participating nurses before and after the training programme. In a complementary qualitative evaluation the nurses' expectations and views of the training programme were explored. RESULTS: Analysis of the attitude questionnaire indicated that the programme was successful in positively influencing the nurses' attitudes (median of the change in score 2, p = 0.005). The qualitative interviews reflected a similar outcome. CONCLUSIONS: Quantitative and qualitative evaluation indicates that the training programme had some effect in changing nurses' attitudes to treating patients after a stroke. Such a training programme could be a useful contribution to post-stroke care.

Attitude of Health Personnel↗
PubMed1999

The antigonadotropic activity of a 19-nor-progesterone derivative is exerted both at the hypothalamic and pituitary levels in women.

We have previously shown in postmenopausal women that a 19-nor-progesterone derivative, nomegestrol acetate (NOMA) had a strong antigonadotropic activity and that this effect was not mediated via the androgen receptor. The aim of the present study was to further assess the action of this progestin on gonadotropin secretion in women. To demonstrate at which level of the hypothalamo-pituitary-ovarian axis the gonadotropin inhibition was exerted, 10 normally cycling (NC) women, 3 women with a gonadotropin-independent ovarian function [McCune-Albright (MCA) syndrome], and 5 women with functional hypothalamic amenorrhea (FHA) participated in the study. NC women were treated orally with 5 mg NOMA for 21 days, after one control cycle. Plasma estradiol (E2) and progesterone, LH, and FSH levels were measured during each cycle. A frequent sampling study (every 10 min for 4 h), followed by a classic GnRH test (100 microg, i.v.), was performed on day 11. Women with MCA were studied before, during NOMA, and after long-acting GnRH agonist administration. In women with FHA, pulsatile GnRH (20 microg s.c., every 90 min) was given for two cycles with or without NOMA (5 mg for 21 days). In all NC women, ovulation was suppressed by NOMA. Mean plasma LH levels, LH pulse frequency, and the LH response to exogenous GnRH were significantly decreased. In MCA, neither NOMA nor GnRH agonist modified multiple ovarian cysts on ultrasound or plasma E2, levels which remained elevated, ruling out a direct ovarian effect. In FHA, pulsatile GnRH administration recreated a normal ovulatory menstrual cycle. Addition of NOMA prevented the increase of plasma E2, decreased the amplitude of LH pulses, and prevented ovulation. In view of this unexpected action of NOMA at the pituitary level, seven samples of normal human female pituitaries were tested for the presence of progesterone receptor (PR) using a double labeling immunocytochemical technique. The presence of PR was detected in the seven human pituitary tissues. In addition, PR was found to be expressed only in gonadotroph cells. In conclusion, NOMA, a 19-nor-P derivative, has a potent antigonadotropic activity exerted at the hypothalamic level, inhibiting ovulation in NC women. In women with FHA, NOMA decreased the gonadotropin stimulation induced by pulsatile GnRH administration. According to the presence of PR in gonadotroph cells of normal human pituitaries, 19-nor-progesterone derivatives may also act on the gonadotropin secretion at the pituitary level.

Adolescent↗