Exercise-related lower leg pain: vascular.
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Adult↗
Biomedical subjects
C Bradshaw
Publications and source records attributed to C Bradshaw.
Familial dementia caused by polymerization of mutant neuroserpin.
Aberrant protein processing with tissue deposition is associated with many common neurodegenerative disorders; however, the complex interplay of genetic and environmental factors has made it difficult to decipher the sequence of events linking protein aggregation with clinical disease. Substantial progress has been made toward understanding the pathophysiology of prototypical conformational diseases and protein polymerization in the superfamily of serine proteinase inhibitors (serpins). Here we describe a new disease, familial encephalopathy with neuroserpin inclusion bodies, characterized clinically as an autosomal dominantly inherited dementia, histologically by unique neuronal inclusion bodies and biochemically by polymers of the neuron-specific serpin, neuroserpin. We report the cosegregation of point mutations in the neuroserpin gene (PI12) with the disease in two families. The significance of one mutation, S49P, is evident from its homology to a previously described serpin mutations, whereas that of the other, S52R, is predicted by modelling of the serpin template. Our findings provide a molecular mechanism for a familial dementia and imply that inhibitors of protein polymerization may be effective therapies for this disorder and perhaps for other more common neurodegenerative diseases.
Biopolymers↗
Chemotyping of yeast mutants using robotics.
By now, the EUROFAN programme for the functional analysis of genes from the yeast genome has attained its cruising speed. Indeed, several hundreds of yeast mutants with no phenotype as tested by growth on standard media and no significant sequence similarity to proteins of known function are available through the efforts of various laboratories. Based on the methodology initiated during the pilot project on yeast chromosome III (Yeast 13, 1547-1562, 1997) we adapted it to High Throughput Screening (HTS), using robotics. The first 100 different gene deletions from EUROSCARF, constructed in an FY1679 strain background, were run against a collection of about 300 inhibitors. Many of these inhibitors have not been reported until now to interfere in vivo with growth of Saccharomyces cerevisiae. In the present paper we provide a list of novel growth conditions and a compilation of 49 yeast deletants (from chromosomes II, IV, VII, X, XIV, XV) corresponding to 58% of the analysed genes, with at least one clear and stringent phenotype. The majority of these deletants are sensitive to one or two compounds (monotropic phenotype) while a distinct subclass of deletants displays a hyper-pleiotropic phenotype with sensitivities to a dozen or more compounds. Therefore, chemotyping of unknown genes with a large spectrum of drugs opens new vistas for a more in-depth functional analysis and a more precise definition of molecular targets.
Antifungal Agents↗
Familial encephalopathy with neuroserpin inclusion bodies.
We report on a new familial neurodegenerative disease with associated dementia that has presented clinically in the fifth decade, in both genders, and in each of several generations of a large family from New York State-a pattern of inheritance consistent with an autosomal dominant mode of transmission. A key pathological finding is the presence of neuronal inclusion bodies distributed throughout the gray matter of the cerebral cortex and in certain subcortical nuclei. These inclusions are distinct from any described previously and henceforth are identified as Collins bodies. The Collins bodies can be isolated by simple biochemical procedures and have a surprisingly simple composition; neuroserpin (a serine protease inhibitor) is their predominant component. An affinity-purified antibody against neuroserpin specifically labels the Collins bodies, confirming their chemical composition. Therefore, we propose a new disease entity-familial encephalopathy with neuroserpin inclusion bodies (FENIB). The conclusion that FENIB is a previously unrecognized neurodegenerative disease is supported by finding Collins bodies in a small kindred from Oregon with familial dementia who are unrelated to the New York family. The autosomal dominant inheritance strongly suggests that FENIB is caused by mutations in the neuroserpin gene, resulting in intracellular accumulation of the mutant protein.
Amino Acid Sequence↗
Lay carers' satisfaction with community palliative care: results of a postal survey. South Tyneside MAAG Palliative Care Study Group.
This paper reports the substantive findings of a study that examined the feasibility of using postal questionnaires to assess the satisfaction of lay caregivers with the care received in the community by those dying of cancer. The focus of the analysis was the quality of information provided by health professionals, health services used in the final year of the dying person's life and the lay carer's views about the quality of these services. The study was a retrospective survey of lay carers identified from death certificates over a 9-month period. Of the 355 people contacted, 156 completed the questionnaires, a 44% response rate. The results of the survey indicate that information provision was deemed unsatisfactory by a large proportion of respondents, and that dissatisfaction with care received from hospital, the district nursing service and the general practitioner was common. Levels of satisfaction with care were clearly related to a range of service factors. Our survey also highlighted clear differences in the perceived quality of specialist and generic services for those dying of cancer. A comparison of the findings from this postal study with those reported in earlier retrospective interview surveys of lay carers suggests that the use of the postal questionnaire is a valid and cost-effective approach for assessing quality of care. The data provide baseline information against which improvements in the quality of care can be measured.
Caregivers↗
Feasibility of using postal questionnaires to examine carer satisfaction with palliative care: a methodological assessment. South Tyneside MAAG Palliative Care Study Group.
This paper reports on the methodological findings from a project which examined the feasibility of using a postal questionnaire to assess lay carer satisfaction with palliative care. The focus of this paper is the process of questionnaire development and its psychometric evaluation. The questionnaire was derived from an interview schedule used in previous national surveys of care for the dying, and was refined through qualitative work with recently bereaved lay carers. It was then tested in a postal survey of 355 lay carers identified from death registration certificates. Overall response rates were low, but significantly enhanced by the use of a single reminder sent 3 weeks after the initial mailshot. The analysis indicated that in the majority of cases the person targeted to receive the questionnaire was the most appropriate informant. Psychometric evaluation of the questionnaire against five criteria was encouraging, with low item nonresponse and ineligible response, and some evidence of discriminatory power, reliability, and face and content validity. Postal approaches appear to represent an acceptable means of assessing user satisfaction with palliative care, compared with more resource-intensive methods.
Caregivers↗
CD44 and CD44v6 downregulation in clinical prostatic carcinoma: relation to Gleason grade and cytoarchitecture.
BACKGROUND: Altered expression of CD44 has been implicated in tumor progression and metastasis in multiple neoplasms. METHODS: CD44 expression in archival tissues of prostate carcinoma was examined by immunohistochemistry with monoclonal antibodies against core CD44 and the RNA splice variant CD44v6 (v6). RESULTS: Core CD44 expression was reduced in the majority of primary neoplastic foci (n = 94) and loss of expression correlated with increasing Gleason grade. Staining for v6 was absent in most carcinomas and metastases. Expression of core CD44 in pelvic lymph node (n = 27) and bone metastases (n = 21) was significantly reduced. In addition, CD44 expression correlated with cytoarchitecture. Tall columnar tumor cells typically stained positively, yet more rounded cells forming cribiform structures or nests showed reduced expression. All cases of high-grade prostatic intraepithelial neoplasia were positive for core CD44 yet, there was decreased expression in cribiform and micropapillary variants. CONCLUSIONS: The majority of clinically relevant human prostatic carcinomas and metastases downregulate expression of CD44. Additional studies to determine whether CD44 cell surface expression relates to clinical outcome independent of other established clinicopathologic risk factors are warranted.
Alternative Splicing↗
Discriminant validity of the TSC-40 in an outpatient setting.
This study examines the discriminant validity of the Trauma Symptom Checklist (TSC-40) in a clinical sample. The TSC-40 was developed as a research instrument for assessing the impact of a history of sexual victimization. Previous validity studies used nonclinical samples of women (Elliott & Briere, 1992; Gold, Milan, Myall, & Johnson, 1994). In the present study, the TSC-40 was administered to 103 men and 79 women requesting services at two outpatient clinics. Information about sexual victimization was collected from the client during intake and from the therapist after the client had received 6 months of therapy. A history of CSA was associated both with high symptom levels across symptom dimensions, and, specifically, with elevation on the trauma subscale of the TSC-40. The findings support the view that, in a clinical setting, CSA is associated both with generalized distress and with PTSD symptoms.
Adult↗
Obturator nerve entrapment.
PURPOSE: To describe a case of obturator nerve entrapment, a previously unreported cause of chronic groin pain in athletes. CASE SUMMARY: A 23-year-old man, an elite Australian rules footballer, presented with a 2-year history of groin pain. Conservative treatment was unsuccessful. Examination postexercise revealed adductor weakness and medial thigh paraesthesia. Diagnosis of obturator nerve entrapment was confirmed by EMG and nerve block. Surgical neurolysis was performed. The patient returned to sport and has remained symptom free. DISCUSSION: Although intrapelvic obturator nerve entrapment has been reported following surgical trauma, no cases of sport-related entrapment have been described. RELEVANCE: Obturator nerve entrapment should be considered as a potential cause of chronic groin pain in athletes.
Adult↗
Stress fracture of the body of the talus in athletes demonstrated with computer tomography.
PURPOSE: This article describes a series of four previously unreported stress fractures of the body of the talus. CASE SUMMARY: The four patients presented with ankle pain of gradual onset for periods of three weeks to 12 months. Radioisotope scans in all four patients showed identical pictures of markedly increased uptake in the region of the body of the talus. Computed tomographic scan images were also similar showing a distinct fracture line through the posterolateral aspect of the body of the talus extending into the subtalar joint. All four patients were treated differently ranging from rest to surgery, but no treatment appears totally successful. DISCUSSION: A single case of stress fracture of the neck of talus has previously been reported in a runner, but no previous cases of stress fracture of the body of the talus have been reported. The mechanism may be that in the presence of excessive subtalar pronation and plantar-flexion, the lateral process of the calcaneus impinges on the concave posterolateral corner of the talus. No treatment appeared totally successful but the authors would recommend a six week period of non-weight-bearing rest. RELEVANCE: The diagnosis of stress fracture of the body of the talus should be considered in the athlete who presents with gradual onset of ankle pain.
Adult↗
Policy priorities in diabetes care: a Delphi study.
OBJECTIVES: To produce policy priorities for improving care of diabetes based on the findings of original research into patient and professional opinions of diabetes care in South Tyneside. To judge the feasibility of implementing these priorities as policy. DESIGN: A two round Delphi survey with a panel of 28 ¿experts.¿ In the first round each respondent produced a list of recommendations based on the findings of a report of patients' and professionals' opinions of diabetes care. 20 respondents produced a total of 180 recommendations, reviewed by a monitoring panel to produce a summary list of 28 recommendations. In the second round respondents rated each recommendation on two 5 point Likert scales. SETTING: Mainly Tyneside but also other parts of England. SUBJECTS: 28 healthcare professionals, including patients and patients' representatives. MAIN MEASURES: Voting by experts on how important each recommendation was to improving diabetes care service, and how likely the recommendation was to be implemented in the next five years. RESULTS: There was a high degree of consensus among respondents about recommendations considered important and likely to be implemented--namely, those concerned with improving communications between doctors in hospital and in general practice, and improving communications with patients. Respondents were more pessimistic about the prospects of implementing the recommendations than about their importance. Respondents thought that standards were important for improving care, and half would stop payments to general practice diabetic clinics that did not keep to district standards for diabetes care. For two recommendations a mismatch occurred between the importance of the recommendations and likelihood of implementation. This may reflect the practical problems of implementing recommendations. 18 of the 22 respondents thought that the study was useful in generating recommendations. CONCLUSIONS: The Delphi technique is a useful method for determining priorities for diabetes care and in assessing the feasibility of implementing recommendations.
Attitude of Health Personnel↗
Stress fractures: a review of 180 cases.
OBJECTIVE: To review the cases of stress fracture seen over a 2-year period at a sports medicine clinic. DESIGN: One hundred and eighty cases diagnosed as stress fractures on the basis of clinical picture and radiological evidence were reviewed. The following features of each stress fracture were noted: age, sex, site, sport/activity. SETTING: A sports medicine centre in Melbourne, Australia. PATIENTS: The average age was 21.8 years. Seventy eight of these stress fractures were seen in women, 102 in men. RESULTS: The most common sites of stress fractures were the metatarsal bones (n = 42), tibia (n = 36), fibula (n = 30), tarsal navicular (n = 26) and pars interarticularis (n = 17). The most common sport was track (n = 54). Other common sports activities were jogging/distance running (n = 35), dance (n = 32) and Australian football (n = 14). The distribution of sites of stress fractures varied from sport to sport. Among the track athletes (n = 54), navicular (n = 19), tibia (n = 14) and metatarsal (n = 9) were the most common stress fracture sites. The distance runners (n = 35) predominantly sustained tibia (n = 15), and fibula (n = 8) stress fractures, while metatarsal stress fractures (n = 18) were the most common among dancers. The distribution of sports varied with the site of the stress fracture. In the metatarsal stress fractures (n = 42), dance was the most common activity. Distance running (n = 15) and track (n = 14) were the most common sports in the group to have sustained tibia stress fractures (n = 36). Track athletes (n = 14) were particularly prevalent in the navicular stress fracture group (n = 26). CONCLUSION: The distribution of sites of stress fractures in this study shows some differences from previously published studies.
Adult↗
Aspirin in acute myocardial infarction.
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Aspirin↗
Manipulative physiotherapy for spinal problems in primary care: outcomes of care.
Outcome measures for physiotherapy in a primary health care setting should be evaluated before physiotherapy becomes widely available in general practice. The aim of this study was to assess changes in outcome measures in patients with spinal problems treated with bed rest, advice and analgesia ('traditional' treatment) and with manual/manipulative physiotherapy ('active' treatment). A retrospective analysis was carried out of computerized records of patients treated in primary care with manual and manipulative physiotherapy for spinal problems and a group with a similar age/sex/diagnosis profile who were given traditional treatment. Outcome measures in the 12 months following the initial diagnosis were: referrals, recurrences, casualty attendances, X-rays and number of prescribed analgesic and non-steroidal anti-inflammatory agents (NSAIDs). In the active group, there were 231 lumbar and 154 cervical patients, and 82 and 75, respectively, in the traditional group. There was a significant decrease in the recurrence rate [odds ratio (OR) = 0.56, 95% confidence interval (CI) 0.37-0.84] and in the numbers attending casualty (OR = 0.19, 95% CI 0.04-0.76) for 'active' compared with 'traditional' patients. For patients with cervical problems, there was a significant decrease in the active group of NSAIDs prescribed (P < 0.05). Certain outcomes of spinal problems are improved by the provision of manipulative physiotherapy in general practice.
Analgesics↗
Glycated haemoglobin levels in patients with diabetes in one general practice over a 10-year period.
The aim of the study was to evaluate the level of control, as reflected by HbA1c, in patients with diabetes attending one general practice over a 10-year period. The study was based in one general practice in South Tyneside, UK and consisted of an analysis of HbA1c values of all patients with diabetes attending the practice between 1983 and 1992. HbA1c levels were analysed and are presented as multiples of the standard deviation above the mean. In the practice 256 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 76 with insulin-dependent diabetes mellitus (IDDM), attended for a total of 1596 doctor/patient contacts in the diabetic clinic over 10 years. The prevalence of diabetes was 1.9%. Over the course of the clinic, in any one year, 25% of patients with NIDDM and 55% with IDDM had levels of HbA1c above those thought to be associated with increased risk of microvascular complications. Significant reduction in glycated haemoglobin (HbA1c) occurred in the first year after diagnosis (p < 0.01) and after changing treatment from diet alone to diet and oral hypoglycaemic agents (p < 0.001). We conclude that a large proportion of patients within this population had levels of glycaemic control that put them 'at increased risk'.
Biomarkers↗
A midwifery team for high-risk pregnancies.
A midwifery group practice approach has been developed for the care of high-risk mothers at the Chelsea & Westminster Hospital. The team of six midwives working with the professor of obstetrics, the consultant obstetrician and a physician cares for a caseload of 200 high-risk women a year. Midwives are able to acquire and maintain the skills necessary to care for high-risk mothers. Audit of the scheme is essential and will be complemented by a satisfaction survey completed by clients, midwives and doctors.
Female↗
Conformational properties of four peptides corresponding to alpha-helical regions of Rhodospirillum cytochrome c2 and bovine calcium binding protein.
Four peptides corresponding to alpha-helical regions delimited by residues 63-73 and 97-112 of cytochrome c2 (Rhodospirillum) and residues 24-36 and 45-55 of bovine calcium binding protein are predicted to be alpha-helical by a recently developed method [Rooman, M., Kocher, J.P., & Wodak, S.J. (1991) J. Mol. Biol. 221, 961-979], synthesized by solid phase methods, and purified by HPLC, and their solution conformations are determined by NMR and CD. The observed conformational properties of these peptides in solution confirmed prediction results: in water/TFE (60/40, v/v) at room temperature, these peptides adopt an alpha-helical conformation, as shown by an extended pattern of strong, sequential dNN(i,i + 1) NOE cross-peaks, d alpha N(i,i + 1) NOEs of reduced intensity, several medium-range [d alpha N(i,i + 3), d alpha N(i,i + 4), d alpha beta-(i,i + 3)] NOE connectivities, small 3JH alpha N values, and more upfield alpha-proton chemical shifts. CD studies at different TFE concentrations and at room temperature provide further evidence of the propensity of these peptides to adopt an alpha-helical conformation in solution, as determined by the ellipticity values at 222 nm, and by deconvolution of the CD spectra. According to the method used, helicities in the range 34-50% and 55-75% are found for the 63-73 and 97-112 fragments of cytochrome c2, respectively, and in the range 53-80% and 42-65% for the fragments 24-36 and 45-55 of calcium binding protein in water/TFE (60/40, v/v) at 298 K. In addition, the experiments and predictions agree for those residues that are more flexible. Finally, the relevance of our results for the protein folding pathways is discussed.
Algorithms↗