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Biomedical subjects

K Hunt

Publications and source records attributed to K Hunt.

At least 19 recordsLinked to original sources

Prevalence and risk factors for joint pain among men and women in the West of Scotland Twenty-07 study.

OBJECTIVE: To examine the association between three modifiable risk factors (obesity, smoking, and alcohol consumption) and reported joint pain. METHODS: Cross sectional data were collected on 858 people aged 58 years living in the West of Scotland and on the same individuals four years later, aged 62 years. RESULTS: There was a positive relation between obesity and reported pain in the hips, knees, ankles, and feet. The strongest relation was with knee pain (odds ratio = 2.42 (95% confidence interval, 1.65 to 3.56)). There were no strong consistent associations between smoking habits and pain in any joint after adjusting for sex, alcohol consumption, body mass index, social class, and occupational exposures. Similarly, alcohol was not consistently related to pain in any joint in the fully adjusted models. CONCLUSIONS: Obesity had consistent and readily explained associations with lower limb joint pain. The data suggest that smoking behaviour and alcohol consumption are not consistently associated with joint pain across the body.

Arthralgia↗

Gastrointestinal stromal tumors: overview of pathologic features, molecular biology, and therapy with imatinib mesylate.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. These tumors develop at any site but are most commonly reported in the stomach. They originate from the neoplastic transformation of the intestinal pacemaker cell, the interstitial cell of Cajal. GISTs strongly express the receptor tyrosine kinase KIT and have mutations in the KIT gene, most frequently in exon 11 encoding the intracellular juxtamembranous region. Expression of KIT is seen in almost all GISTs, regardless of the site of origin, histologic appearance, or biologic behavior, and is therefore regarded as one of the key diagnostic markers. Distinction from smooth muscle tumors, such as leiomyosarcomas, and other mesenchymal tumors is very important because of prognostic differences and therapeutic strategies. Predicting the biologic behavior of GISTs is often difficult by conventional pathologic examination; tumor size and mitotic rate are the most important prognostic indicators. The prognostic significance of KIT mutations is controversial and thus far has not been clearly linked with biologic behavior. KIT mutations are associated with tumor development, and cytogenetic aberrations are associated with tumor progression. The pathogenesis of GISTs involves a gain-of-function mutation in the KIT proto-oncogene, leading to ligand-independent constitutive activation of the KIT receptor. KIT-wild-type GISTs have shown mutually exclusive platelet-derived growth factor receptor (PDGFR) mutation and activation. The use of imatinib mesylate (also known as Gleevec or STI-571) has greatly increased the therapeutic efficacy for this otherwise chemotherapy-resistant tumor. GISTs with very low levels of KIT expression may respond to imatinib mesylate therapy if the receptors are activated by specific mechanisms. KIT-activating mutations fall into two groups: the regulatory type and the enzymatic site type. The regulatory type of mutation is conserved at the imatinib binding site, whereas the enzymatic site mutation has a structurally changed drug-binding site, resulting in drug resistance. Resistance to the drug is the major cause of treatment failure in cancer therapy, emphasizing the need for researchers to understand KIT signaling pathways so as to identify new therapeutic targets. This review summarizes the pathologic features of GISTs, recent advances in understanding their molecular and biologic features, and therapy with imatinib mesylate.

Antineoplastic Agents↗

Control of posture with FES systems.

One of the major obstacles in restoration of functional FES supported standing in paraplegia is the lack of knowledge of a suitable control strategy. The main issue is how to integrate the purposeful actions of the non-paralysed upper body when interacting with the environment while standing, and the actions of the artificial FES control system supporting the paralyzed lower extremities. In this paper we provide a review of our approach to solving this question, which focuses on three inter-related areas: investigations of the basic mechanisms of functional postural responses in neurologically intact subjects; re-training of the residual sensory-motor activities of the upper body in paralyzed individuals; and development of closed-loop FES control systems for support of the paralyzed joints.

Algorithms↗

Paclitaxel in the multimodality treatment for inflammatory breast carcinoma.

BACKGROUND: Inflammatory breast carcinoma (IBC) is a rare but aggressive form of breast carcinoma. Anthracycline-based regimens represent the standard of treatment for IBC. Reports of significant clinical activity of paclitaxel in metastatic breast carcinoma led the authors to investigate the role of this drug in the management of IBC. METHODS: Forty-four patients with IBC were enrolled between February 1994 and January 1998. The treatment plan consisted of induction chemotherapy (IC), mastectomy, adjuvant chemotherapy, and radiotherapy. Forty-two patients received IC with four cycles of fluorouracil, doxorubicin, and cyclophosphamide. If the clinical response was less than partial, patients were "crossed over" to paclitaxel before mastectomy. All patients received adjuvant paclitaxel. Patients unresectable after paclitaxel were offered high-dose chemotherapy with autologous peripheral blood progenitor cell support. RESULTS: Thirty-four patients (81%) achieved an objective clinical remission; 3 patients (7%) achieved a clinical complete remission, 31 (74%) a partial remission. Six patients (14%) achieved pathologic complete remission. Sixteen patients were treated with paclitaxel, 7 of them (44%) were able to undergo mastectomy. Median time to progression (TTP) was 22 months. Median overall survival (OS) was 46 months. Concordance between clinical and pathologic response was documented in only 8 patients (24%). No differences in TTP and OS compared with a historical group of 178 IBC patients treated with anthracycline-based regimens. CONCLUSIONS: Paclitaxel improves tumor resectability in anthracycline-refractory IBC. The impact of paclitaxel on the prognosis of IBC needs to be better evaluated in future trials using more dose-intensive schedules of administration. New imaging modalities may contribute to improve assessment of response to IC.

Adenocarcinoma↗

A decision analytical cost analysis of offering ECV in a UK district general hospital.

OBJECTIVE: To determine the care pathways and implications of offering mothers the choice of external cephalic version (ECV) at term for singleton babies who present with an uncomplicated breech pregnancy versus assisted breech delivery or elective caesarean. DESIGN: A prospective observational audit to construct a decision analysis of uncomplicated full term breech presentations. SETTING: The North Staffordshire NHS Trust. SUBJECTS: All women (n = 176) who presented at full term with a breech baby without complications during July 1995 and June 1997. MAIN OUTCOME MEASURES: The study determined to compare the outcome in terms of the costs and cost consequences for the care pathways that resulted from whether a women chose to accept the offer of ECV or not. All the associated events were then mapped for the two possible pathways. The costs were considered only within the hospital setting, from the perspective of the health care provider up to the point of delivery. RESULTS: The additional costs for ECV, assisted breech delivery and elective caesarean over and above a normal birth were 186.70 pounds sterling, 425.36 pounds sterling and 1,955.22 pounds sterling respectively. The total expected cost of the respective care pathways for "ECV accepted" and "ECV not accepted" (including the probability of adverse events) were 1,452 pounds sterling and 1,828 pounds sterling respectively, that is the cost of delivery through the ECV care pathways is less costly than the non ECV delivery care pathway. CONCLUSIONS: Implementing an ECV service may yield cost savings in secondary care over and above the traditional delivery methods for breech birth of assisted delivery or caesarean section. The scale of these expected cost savings are in the range of 248 pounds sterling to 376 pounds sterling per patient. This converts to a total expected cost saving of between 43,616 pounds sterling and 44,544 pounds sterling for the patient cohort considered in this study.

Adult↗

Lay constructions of a family history of heart disease: potential for misunderstandings in the clinical encounter?

BACKGROUND: Family history is recognised as a risk factor for coronary heart disease (CHD) by epidemiologists, health professionals, and the public, and could act either as a spur or barrier to changing health behaviour. However, there has been no systematic investigation of which factors affect whether people regard themselves as having a family history of CHDor not. METHODS: We used purposive sampling to select 61 men and women who were middle class or working class from a large cross-sectional survey. Half the respondents had indicated in this previous survey that they had heart disease in their family. The range of understanding of the meaning of having a family history was explored in detailed qualitative semistructured interviews. FINDINGS: Perception of a family history of heart disease depended on knowledge of the health of family members, the number and closeness of relatives with heart conditions, the age of affected relatives, and the respondent's sex and social class. Men, particularly working-class men, required a greater number of close relatives to be affected to perceive that they had a family history. Even when respondents judged that heart disease ran in their family, they did not always perceive themselves as at increased risk because they felt different in crucial ways from affected relatives. INTERPRETATION: The factors that people and epidemiologists judge as relevant to establish presence of a family history can differ. We suggest that these differences could lead to misunderstandings between doctor and patient, which could undermine advice on CHD risks and associated behavioural changes.

Adult↗

The effects of rigid collar placement on intracranial and cerebral perfusion pressures.

Rigid collars are routinely used to immobilise the cervical spine during early management of trauma victims until spinal injury is excluded. Spinal injuries commonly coexist in patients with severe head injury, and there is still uncertainty as to whether application of a rigid collar may adversely affect intracranial pressure. The aim of this study was to examine this effect by applying rigid collars to patients with traumatic head injury. The results showed a significant rise from the baseline intracranial pressure when the collars were applied (mean rise = 4.6 mmHg, p < 0.0001). The mean rise in intracranial pressure was greater in those patients with a baseline intracranial pressure > 15 mmHg compared to those with a baseline intracranial pressure < 15 mmHg (p < 0.05). Since there was no significant change in cardiorespiratory parameters during this time, venous compression in the neck seems a likely explanation for the effect observed. These findings suggest that in head-injured patients, rigid collars should be removed as soon as cervical spine injury has been excluded or, if this is delayed, an alternative method of spinal stabilisation considered.

Adolescent↗

A cross-sectional study of IGF-I determinants in women.

Evidence is accumulating that elevated circulating insulin-like growth factor I (IGF-I) is related to increased cancer risk. The identification of hormonal, reproductive and lifestyle characteristics influencing its synthesis and bioavailability is of particular interest. Data from 400 women, who served as controls in two case-control studies nested within the same prospective cohort study, were combined. IGF-I, IGF-binding proteins 1, 2 and 3 (IGFBP-1, -2, -3) and insulin were measured in serum samples from all subjects and cotinine in 186 samples. Age appears to be the most important determinant of total IGF-I levels in women. Anthropometric measures, such as body mass index (BMI) or waist-to-hip ratio (WHR) do not seem to influence total IGF-I concentrations in peripheral blood, but may modulate IGF-I bioavailability through insulin-dependent changes in IGFBP-1 and -2 concentrations. Age at menarche, phase of the menstrual cycle at blood draw, parity, menopause, past oral contraceptive or hormone replacement therapy use, and tobacco smoking do not appear to exert an independent effect on IGF-I and its binding proteins. There was some suggestion that regular physical activity may increase total IGF-I and that women with positive family history of breast cancer might have higher IGF-I levels than those without such diagnosis in their relatives.

Age Factors↗

Locoregional irradiation for inflammatory breast cancer: effectiveness of dose escalation in decreasing recurrence.

PURPOSE: To evaluate the effect of radiation dose escalation on locoregional control, overall survival, and long-term complication in patients with inflammatory breast cancer. PATIENTS AND METHODS: From September 1977 to December 1993, 115 patients with nonmetastatic inflammatory breast cancer were treated with curative intent at The University of Texas M. D. Anderson Cancer Center. The usual sequence of multimodal treatment consisted of induction FAC or FACVP chemotherapy, mastectomy (if the tumor was operable), further chemotherapy, and radiation therapy to the chest wall and draining lymphatics. Sixty-one patients treated from September 1977 to September 1985 received a maximal radiation dose of 60 Gy to the chest wall and 45-50 Gy to the regional lymph nodes, 22 treated once a day at 2 Gy per fraction, and 35 were treated b.i.d. (32 after mastectomy and all chemotherapy was completed, and 2 immediately after mastectomy; one patient had distant metastases discovered during b.i.d. irradiation, and treatment was stopped). Four additional patients received preoperative radiation with standard fractionation. Based on the analysis of the failure patterns of the patients, the dose was increased for the b.i.d. patients in the new series, with 51 Gy delivered to the chest wall and regional nodes, followed by a 15-Gy boost to the chest wall with electrons. From January 1986 to December 1993, 39 patients were treated b.i.d. to this higher dose after mastectomy and all the chemotherapy was completed; and 8 additional patients received preoperative irradiation with b.i.d. fractionation to 51 Gy. During this period, another 7 patients were treated using standard daily doses of 2 Gy per fraction to a total of 60 Gy, either because they had a complete response or minimal residual disease at mastectomy or because their work schedule did not permit the b.i.d. regimen. Comparison was made between the groups for locoregional control, disease-free and overall survival, and complication rates. RESULTS: The median follow-up time was 5.7 years (range, 1.8-17.6 years). For the entire patient group, the 5- and 10-year local control rates were 73.2% and 67.1%, respectively. The 5- and 10-year disease-free survival rates were 32.0% and 28.8%, respectively, and the overall survival rates for the entire group were 40.5% and 31.3%, respectively. To evaluate the effectiveness of dose escalation, a specific comparison of patients who received b.i.d. radiation after mastectomy and completion of adjuvant chemotherapy was performed. There were 32 patients treated b.i.d. to 60 Gy in the old series versus 39 patients treated b.i.d. to 66 Gy in the new series. There was an significant improvement in the rate of locoregional control for the b.i.d. patients for the old vs. new series, from 57.8% to 84.3% and from 57.8% to 77.0% (p = 0.028) at 5 and 10 years, respectively. Chemotherapy regimens did not change significantly during this time period.Long-term complications of radiation, such as arm edema more than 3 cm (7 patients), rib fracture (10 patients), severe chest wall fibrosis (4 patients), and symptomatic pneumonitis (5 patients), were comparable in the two groups, indicating that the dose escalation did not result in increased morbidity. Significant differences in the rates of locoregional control (p = 0.03) and overall survival (p = 0.03), and a trend of better disease-free survival (p = 0.06) were also observed that favored the recently treated patients receiving the higher doses of irradiation. CONCLUSION: Twice-daily postmastectomy radiation to a total of 66 Gy for patients with inflammatory breast cancer resulted in improved locoregional control, disease free survival, and overall survival, and was well tolerated.

Adult↗

Irish descent, religion and food consumption in the west of Scotland.

Mortality and morbidity of people of Irish descent in Britain is high, including from cardiovascular causes potentially linked with diet. The west of Scotland has long had a pattern of Irish migration, where migrants were poorer than the host population, and their different religious background gave rise to prolonged discrimination. This paper uses data collected in 1987/88 from the west of Scotland Twenty-07 study to test whether dietary differences due to poverty or to other factors have persisted among the descendents of these migrants. Being born of Catholic parents was the index of Irish descent used, these respondents consumed less of a factor represented by fruit, yoghurt and vegetables, and more of one represented by snacks and processed foods than the rest of the sample. The picture for those reporting current Catholic affiliation in adulthood was similar. Differences are largely associated with social class and mediated not by low income but by educational disadvantage. The findings suggest the continuation of a diet affected by limited opportunities for social mobility, and thus by obstacles to sustained educational advancement, among the descendants of Irish migrants even after several generations.

Adolescent↗

Social class, sex, and age differences in mucosal immunity in a large community sample.

There have been very few reports addressing levels and distribution of commonly used PNI measures in large community samples. In this study, we report such data for secretion rates of secretory immunoglobulin A (sIgA), as determined from saliva samples taken from 1971 subjects interviewed as part of the West of Scotland Twenty-07 survey of health in West Central Scotland. Univariate analyses of demographic variables found lower sIgA and salivary flow to be significantly related to poorer social class, increased age, and being female. Smokers also had lower sIgA but not lower salivary flow. Multivariate analysis showed that demographic variables were significant predictors of sIgA independently of each other and assay variation. Adding smoking status to the equation confirmed it as an independent predictor and also indicated that social class differences in sIgA are partly explicable in terms of smoking status. In view of reported associations between sIgA levels and stress, its role as a first line of mucosal defense, and its relevance to health, these first results from a large survey are of interest. Further work is now needed to explore which factors, including psychosocial ones, may be contributing to subgroup differences.

Adolescent↗

Variation of recruitment nonlinearity and dynamic response of ankle plantarflexors.

The ankle plantarflexor muscles of paraplegics may be trained to provide balance without support from the hands (in the laboratory environment) with the controller based on a two-block Hammerstein muscle model. This paper presents data on the variations of the recruitment curve block and linear dynamics block with electrode position, among various individuals and with fatigue. The tests were conducted in six groups: 'a' tests of a neurologically-intact subject were repeated on one day several times to record the effect of muscle fatigue; 'b' the same individual kept electrodes attached for a week and the muscle was identified every day; 'c' the same subject attached electrodes at marked positions every day for a week prior to identification; 'd' another normal attached electrodes at notionally the same positions over a period of one week; 'e' three normals and 'f' two paraplegics. Measurements were made with the Wobbler apparatus, in which the subject is supported upright in a standing posture. When comparing tests of fresh muscle every day, little difference was found between the nonlinear recruitment curves and linear dynamics of groups 'b' and 'c'. In fatigued muscle the dynamics were slower. When the electrode position was not carefully reproduced, and over a longer period, significant differences in nonlinearity appear in the curve shapes (group 'd') and a similar amount of variation occurs between normals, between paraplegics, and from normals to paraplegics. The paraplegic curves show wider deadbands. The effect of prolonged stimulation on normals is slight but on paraplegics it is significant.

Adult↗

Are perceptions of a family history of heart disease related to health-related attitudes and behaviour?

It has been argued that perceptions of familial tendencies to disease are common and important in decisions about health-related behaviours. Indeed, it has been suggested that the increased 'geneticization' of society may lead to an increased fatalism about health, which could undermine initiatives aimed at reducing coronary-prone behaviour. To date, much of the research on lay perceptions of inheritance has been based on people at high risk of particular genetic disorders or on qualitative research with small general population samples. Here we investigate perceptions of a family history of heart disease, using quantitative techniques, to test hypotheses about the relationship between a perceived family history (pFH), coronary 'candidacy' and adherence to health promotion advice which were raised by earlier anthropological work. We find that reported perceptions of a family history of heart disease are common, particularly amongst women in middle-age. In isolation a pFH is not related to current smoking; however, the odds of smoking are lower for those with a pFH of heart disease when account is also taken of other attitudinal factors (the 'salience' of heart disease and the strength of adherence to conventional coronary health promotion.

Adolescent↗