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Biomedical subjects

A Clarke

Publications and source records attributed to A Clarke.

At least 37 records · Page 2Linked to original sources

The rheological properties of self-emulsifying systems, water and microcrystalline cellulose.

The rheological properties of mixtures of equal parts of a range of ratios of a self-emulsifying system (MP) and water (W) added to microcrystalline cellulose (MCC), have been measured by an extrusion capillary rheometer. These measurements allow assessment of both the shear and tension components of flow plus the elastic behaviour of the wet powder masses, although the results for the estimation of shear stress require careful interpretation due to the limitation of the measuring system and the assumptions made in their derivation. The results indicate that there are three regions of behaviour of the systems, which are all significantly different from the mixtures containing only W and MCC. At low MP contents (1.5--23%), the masses increase in their resistance to shear and elongational flow and have lower elasticity. These similarities in behaviour occur in spite of considerable increase in the viscosity of the MPW mixtures and a change to non-Newtonian flow of the fluid. The behaviour of the 46% MP system is intermediate between these systems and the high MP concentrations (69, 80 and 92%). These latter systems show less resistance to shear and elongational flow than the first group of concentrations, but show considerably higher levels of elasticity. As the resistance to shear decreases, so does the impairment of the surface of the extrudate. There is clear evidence of a systematic change in behaviour of the wet powder masses as the values for the angle of entry of the wet mass into the die when plotted against the ratio of the resistance to die entry (upstream pressure loss) to the shear stress within the die, is linear on a log/log scale. Also, the values of compliance of the systems as a function of shear stress fall on a common curve. Changes in the ratio of the MPW to MCC for a system for a single level of MP (46%) resulted in a change in the values of the rheological parameters but not the type of behaviour. As all these wet powder masses had been shown previously to form pellets by the process of extrusion/spheronization, it is clear that systems with a wide range of rheological characteristics can be processed and no single rheological parameter can be used to provide complete characterisation of the processability of such systems.

Cellulose↗

Self-reported bladder function five years post-hysterectomy.

We have examined the contribution of hysterectomy, compared with less invasive surgery, for dysfunctional uterine bleeding (DUB) on the prevalence of bladder problems five years after surgery. We report a prospective cohort study of over 25,000 women treated for benign cause menorrhagia by three types of surgery - transcervical endometrial resection/ablation and hysterectomy with or without bilateral oophorectomy. Postal questionnaires were sent five years after surgery investigating satisfaction with surgery and bladder function. When adjusted for confounders the odds of severe urinary incontinence (OR = 1.59, CI 95%, 1.35 - 1.87), urinary frequency (1.23 (1.04 - 1.45)), and nocturia (1.19, (1.03 - 1.38)) - were increased for women who had a hysterectomy compared with endometrial ablation. Hysterectomy with bilateral oophorectomy was not as strongly associated with severe bladder problems. Women who had the LAVH were most likely to report severe urinary incontinence (2.02, CI 95% 1.32 - 3.07), but not severe frequency or nocturia.

Adult↗

Non-Hodgkin's lymphoma in systemic lupus erythematosus.

BACKGROUND: Recent evidence supports an association between systemic lupus erythematosus (SLE) and non-Hodgkin's lymphoma (NHL). OBJECTIVES: To describe demographic factors, subtypes, and survival of patients with SLE who develop NHL. METHODS: A multi-site cohort of 9547 subjects with definite SLE was assembled. Subjects at each centre were linked to regional tumour registries to determine cancer cases occurring after SLE diagnosis. For the NHL cases ascertained, descriptive statistics were calculated, and NHL subtype frequency and median survival time of patients determined. RESULTS: 42 cases of NHL occurred in the patients with SLE during the 76,948 patient-years of observation. The median age of patients at NHL diagnosis was 57 years. Thirty six (86%) of the 42 patients developing NHL were women, reflecting the female predominance of the cohort. In the patients, aggressive histological subtypes appeared to predominate, with the most commonly identified NHL subtype being diffuse large B cell (11 out of 21 cases for which histological subtype was available). Twenty two of the patients had died a median of 1.2 years after lymphoma diagnosis. CONCLUSIONS: These data suggest aggressive disease in patients with SLE who develop NHL. Continuing work should provide further insight into the patterns of presentation, prognosis, and aetiology of NHL in SLE.

Adult↗

Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome.

BACKGROUND: Sotos syndrome is characterised by learning difficulties, overgrowth, and a typical facial appearance. Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos. In contrast, a recurrent approximately 2 Mb microdeletion has been reported as responsible for approximately 50% of Japanese cases of Sotos. METHODS: We screened 471 cases for NSD1 mutations and deletions and identified 23 with 5q35 microdeletions. We investigated the deletion size, parent of origin, and mechanism of generation in these and a further 10 cases identified from published reports. We used "in silico" analyses to investigate whether repetitive elements that could generate microdeletions flank NSD1. RESULTS: Three repetitive elements flanking NSD1, designated REPcen, REPmid, and REPtel, were identified. Up to 18 cases may have the same sized deletion, but at least eight unique deletion sizes were identified, ranging from 0.4 to 5 Mb. In most instances, the microdeletion arose through interchromosomal rearrangements of the paternally inherited chromosome. CONCLUSIONS: Frequency, size, and mechanism of generation of 5q35 microdeletions differ between Japanese and non-Japanese cases of Sotos. Our microdeletions were identified from a large case series with a broad range of phenotypes, suggesting that sample selection variability is unlikely as a sole explanation for these differences and that variation in genomic architecture might be a contributory factor. Non-allelic homologous recombination between REPcen and REPtel may have generated up to 18 microdeletion cases in our series. However, at least 15 cannot be mediated by these repeats, including at least seven deletions of different sizes, implicating multiple mechanisms in the generation of 5q35 microdeletions.

Abnormalities, Multiple↗

Readmission to hospital 5 years after hysterectomy or endometrial resection in a national cohort study.

OBJECTIVES: To investigate the readmission experience of a large national prospective cohort of women up to 5 years after undergoing either transcervical resection of the endometrium (TCRE) or hysterectomy to assess reasons for readmission and whether TCRE can be viewed as a definitive substitute for hysterectomy. DESIGN AND PARTICIPANTS: Data are from the VALUE/MISTLETOE prospective national cohort studies of hysterectomy and TCRE respectively. 5294 women who underwent hysterectomy for dysfunctional uterine bleeding in 1994/5 and 4032 women who underwent TCRE in 1993/4 and who responded to postal questionnaires were included. Surgeons gathered operative details. Women completed postal follow up questionnaires at 3 and 5 years after surgery asking about readmission to hospital and reasons for readmission. Adjusted proportional hazard ratios were calculated for likelihood of readmission in each category comparing types of surgery. RESULTS: 41.7% of women undergoing hysterectomy and 44.6% of women undergoing TCRE experienced one or more readmissions to hospital overall within 5 years (adjusted hazard ratio for all readmissions (AHR) 0.87 (95% confidence interval (CI) 0.80 to 0.95)). 12.6% of hysterectomy patients and 30.3% of TCRE patients were readmitted for gynaecological reasons (AHR 0.40 (95% CI 0.33 to 0.48)). Rates of readmission for gynaecological reasons were similar up to 6 months but were markedly reduced for hysterectomy compared with TCRE patients towards the end of the follow up period (AHR for readmission at 3-5 years 0.28 (95% CI 0.20 to 0.39)). CONCLUSIONS: There are differences in the pattern of readmission to hospital after hysterectomy and TCRE for dysfunctional uterine bleeding. Women undergoing a hysterectomy are less likely to be readmitted to hospital up to 5 years after their operation overall, and are significantly less likely to be readmitted for reasons related to their operation, particularly for gynaecological reasons. Hysterectomy appears to be a more definitive operation. The different options for surgery for dysfunctional uterine bleeding are not interchangeable; they represent different patterns of care. Information should be available to women and practitioners to inform choices between these options.

Adult↗

Facial transplantation: adding to the reconstructive options after severe facial injury and disease.

The ability to reconstruct complex facial injuries is still a considerable challenge despite the development of microsurgical techniques. The reconstructive options for conditions such as panfacial burns are severely limited. The result after multiple surgical procedures in this group is often poor in terms of function and cosmesis. Facial transplantation provides a potential solution, but opinion is currently divided about the extent to which the potential benefits to the quality of life can be justified when weighed against the technical, psychological and immunological risks. This paper reviews the current status of the debate and argues that a rigorous research strategy is the only logical basis for countering the ethical objections to a procedure that offers considerable benefits over existing reconstructive options.

Face↗

Improving the referral process for familial breast cancer genetic counselling: findings of three randomised controlled trials of two interventions.

OBJECTIVES: To evaluate the effectiveness and cost-effectiveness of two complementary interventions, using familial breast cancer as a model condition. The primary care intervention consisted of providing computerised referral guidelines and related education to GPs. The nurse counsellor intervention evaluated genetic nurses as substitutes for specialist geneticists in the initial assessment and management of referred patients. DESIGN: The computerised referral guidelines study was a pragmatic, cluster randomised controlled trial (RCT) with general practices randomised to intervention or control groups. The nurse counsellor intervention was tested in two concurrent RCTs conducted in separate UK health service locations, using predetermined definitions of equivalence. SETTING: The computerised referral guidelines trial took place in general practices in Scotland from November 2000 to June 2001. The nurse counsellor intervention took place in a regional genetics clinic in Scotland, and in two health authorities in Wales served by a single genetics service during 2001. PARTICIPANTS: The computerised referral guidelines study involved GPs and referred patients. Both nurse counsellor intervention trials included women referred for the first time, aged 18 years or over and whose main concern was family history of breast cancer. INTERVENTIONS: The software system was developed with GPs, presenting cancer genetic referral guidelines in a checklist approach. Intervention GPs were invited to postgraduate update education sessions, and both intervention and control practices received paper-based guidelines. The intervention period was November 2000 to June 2001. For the nurse counsellor trial, trial 1 ran outpatient sessions with the same appointment length as the standard service offered by geneticists, but the nurse counsellor saw new patients at the first appointment and referred back to the GP or on to a clinical geneticist according to locally developed protocol, under the supervision of a consultant geneticist. The control intervention was the current service, which comprised an initial and a follow-up appointment with a clinical geneticist. In trial 2, a nurse counsellor ran outpatient sessions with the same appointment length as the new consultant-based cancer genetics service and new patients were seen at the first appointment and referred as in trial 1. The control intervention was a new service, and comprised collection of family history by telephone followed by a consultation with a clinical assistant or a specialist registrar, supervised by a consultant. The intervention was implemented between 1998 and 2001. MAIN OUTCOME MEASURES: In the software system trial, the primary outcome was GPs' confidence in their management of patients with concerns about family history of breast cancer. For the nurse counsellor trial, the primary outcome was patient anxiety, measured using standard scales. RESULTS: In the software system trial, 57 practices (230 GPs) were randomised to the intervention group and 29 (116 GPs) to the control group. No statistically significant differences were detected in GPs' confidence or any other outcomes. Fewer than half of the intervention GPs were aware of the software, and only 22 reported using it in practice. The estimated total cost was GBP3.12 per CD-ROM distributed (2001 prices). For the two arms of the nurse counsellor trial, 289 patients (193 intervention, 96 control) and 297 patients (197 intervention and 100 control) consented, were randomised, returned a baseline questionnaire and attended the clinic for trials 1 and 2 respectively. The analysis in both cases suggested equivalence in all anxiety scores, and no statistically significant differences were detected in other outcomes in either trial. A cost-minimisation analysis suggested that the cost per counselling episode was GBP10.23 lower in intervention arm than in the control arm and GBP10.89 higher in the intervention arm than in the control arm (2001 prices) for trials 1 and 2, respectively. Taking the trials together, the costs were sensitive to the grades of doctors and the time spent in consultant supervision of the nurse counsellor, but they were only slightly affected by the grade of nurse counsellor, the selected discount rate and the lifespan of equipment. CONCLUSIONS: Computer-based systems in the primary care intervention cannot be recommended for widespread use without further evaluation and testing in real practice settings. Genetic nurse counsellors may be a cost-effective alternative to assessment by doctors. This trial does not provide definitive evidence that the general policy of employing genetics nurse counsellors is sound, as it was based on only three individuals. Future evaluations of computer-based decision support systems for primary care must first address their efficacy under ideal conditions, identify barriers to the use of such systems in practice, and provide evidence of the impact of the policy of such systems in routine practice. The nurse counsellor trial should be replicated in other settings to provide reassurance of the generalisability of the intervention and other models of nurse-based assessment, such as in outreach clinics, should be developed and evaluated. The design of future evaluations of professional substitution should also address issues such as the effect of different levels of training and experience of nurse counsellors, and learning effects.

Breast Neoplasms↗

The provision of dental care for patients with natural rubber latex allergy: are patients able to obtain safe care?

BACKGROUND: The number of people with allergy to natural rubber latex (NRL) has increased significantly in recent years. AIM: To assess the experiences of latex-allergic patients in accessing appropriate dental care, and also the willingness and ability of general dental practitioners to provide care for these patients. METHOD: Two self completing postal questionnaires, one to patients and one to general dental practitioners. RESULTS: The majority of latex-allergic patients are able to obtain dental treatment. Some do experience adverse reactions, which may be severe, in spite of precautions being taken. Although many general dental practitioners are willing to accept such patients for treatment, few appear to be fully aware of all the necessary precautions required. Most do not have policies for the management of sensitised patients and staff, and a number are still using powdered natural rubber latex gloves in spite of the risk to patients and staff. CONCLUSION: Latex-allergic patients can usually obtain safe treatment in general dental practice, but more education of dentists about the risks associated with natural rubber latex is required. Information about the latex content of equipment would be advantageous.

Adolescent↗

Factors associated with abnormal Pap results in systemic lupus erythematosus.

OBJECTIVE: Previous studies have suggested that women with systemic lupus erythematosus (SLE) are at greater risk for cervical dysplasia than are women in the general population. However, the factors associated with abnormal Pap test results in SLE have not been well studied. We therefore aimed to determine the factors associated with lifetime occurrence of an abnormal Pap test in women with SLE, and the influence of immunosuppressive exposure on the odds of abnormal Pap test results occurring after diagnosis of SLE. METHODS: Data were pooled from SLE cohorts from three centres. Self-report data were available on smoking, reproductive history, use of oral contraceptives (OC), history of sexually transmitted diseases (STDs) and whether the subjects had had cervical dysplasia on Pap testing. Logistic regression was used to examine the effect of these variables on the lifetime odds of cervical dysplasia. We then generated the adjusted odds ratio (OR) for the effect of immunosuppressive exposure on cervical dysplasia occurring after diagnosis of SLE. RESULTS: History of STDs and use of OCs were positively associated with reports of cervical dysplasia in adjusted analyses. The ORs for the effect of immunosuppressives on abnormal Pap test occurrence (adjusted for race, age, smoking, nulliparity, OC use and history of STDs) after diagnosis of SLE was 1.6 (95% CI 1.0, 2.7). CONCLUSIONS: A history of STDs and use of OCs were associated with abnormal Pap reports in this SLE sample. Immunosuppressive exposure may confer further risk to women with SLE.

Adult↗

Hormonal exposures and breast cancer in a sample of women with systemic lupus erythematosus.

OBJECTIVES: To determine if breast cancer risk in women with SLE is modified by a history of exposure to hormone replacement therapy (HRT) or oral contraceptives (OC), after adjusting for other risk factors. METHODS: Data were pooled from SLE cohorts at three centres. For each female cohort member (n = 871), the probability of developing breast cancer was estimated from factors (age, parity, age at first live birth, age of menarche, personal history of benign breast disease, family history) in the Gail model, an established tool for predicting breast cancer risk. From these probabilities, the expected number of breast cancers for the cohort was estimated. Actual occurrence of cases was determined by linkage with regional cancer registries. Standardized incidence ratios (SIRs; ratio of cancers observed to expected) were calculated, with subgroup analyses according to HRT and OC exposure. RESULTS: In the cohort, 15 breast cancers occurred vs 7.2 predicted [SIR 2.1, 95% confidence interval (CI) 1.1, 3.5]. When controlling for Gail model risk factors, estimates were similar for women never exposed to HRT vs those exposed to HRT. Adjusted SIR estimates appeared similar also for women exposed or not exposed to OC. CONCLUSIONS: Although not definitive, the data suggest that the breast cancer experience in this sample is not completely explained by factors such as reproductive and family history, or by exogenous hormonal exposures. Other determinants, including medication exposures or genetic factors (possibly related to oestrogen receptors or metabolism) may be important. Variations in these factors might explain why an elevated risk of breast cancer has not been apparent in all SLE populations.

Adult↗

Severe complications of hysterectomy: the VALUE study.

OBJECTIVES: To model the determinants of serious operative and post-operative complications of hysterectomy and their potential risk factors. DESIGN: A prospective cohort of women undergoing hysterectomies for benign indications in 1994/1995, with a six-week postsurgery follow up. POPULATION AND SETTING: A total of 37,512 women from 276 NHS and 145 private hospitals in England, Wales and Northern Ireland, originally recruited to compare the outcomes of endometrial destruction with those of hysterectomy. METHODS: Gynaecologists reported hysterectomies for non-malignant indications carried out during a 12-month period beginning in October 1994 and follow up data were obtained at outpatient follow up six weeks postsurgery. Odds ratios of severe complications by indication and method, adjusting for measured intrinsic risk factors, were calculated. MAIN OUTCOME MEASURES: Severe operative and post-operative complications. RESULTS: Severe operative complications occurred in 3%. The risk decreased with age and increased with greater parity and history of serious illness. Women with symptomatic fibroids (4.4%, 95% CI 3.9-4.9) experienced more complications than women with dysfunctional uterine bleeding (3.6%, 3.2-3.8), adjusted odds ratio (OR) = 1.3 (95% CI 1.1-1.6). Laparoscopic procedures (6.1%) doubled the risk of operative complications of abdominal hysterectomy (3.6%) (adjusted OR = 1.9, 1.5-2.5). Post-operative complications occurred in around 1% of women, with a slight decrease with increasing age, and the strongest risk factor was a history of operative complications. Relative to dysfunctional uterine bleeding (1.0%), a higher risk for fibroids (1.2%) persisted after adjustments (RR = 1.5, 1.1-2.0). Both vaginal (1.2%) and laparoscopic (1.7%) techniques had significantly higher adjusted risks than abdominal operations (0.9%), RR = 1.4 (1.0-1.9) and RR = 1.6 (1.0-2.7). There were no operative deaths; 14 women died within the six-week postsurgery (a crude mortality rate of 3.8/1000, 2.5-6.4). CONCLUSIONS: Hysterectomy is a common, routine surgery with comparatively rare serious complications. However, younger women, women with more vascular pelvis, who undergo hysterectomy, especially laparoscopically assisted vaginal surgery for symptomatic fibroids, are at most risk of experiencing severe complications both operatively and post-operatively. Therefore, a less invasive alternative treatment for symptomatic fibroids could particularly benefit this group of women, while less invasive treatments for dysfunctional uterine bleeding, such as various methods of endometrial ablations or resections, would need to meet the current low levels of clinical complications in order to replace hysterectomy.

Adolescent↗

An evaluation of differences in hip external rotation strength and range of motion between female dancers and non-dancers.

OBJECTIVES: To evaluate the differences in hip external rotation (ER) strength and inner, outer, and total hip ER range of motion (ROM) between dancers and non-dancers and between left and right sides in each group. METHODS: Seventy one subjects (34 dancers and 37 non-dancers) volunteered for this study. The strength (truncated range average torque (TRAT), work, and angle specific torque (AST)) of the hip external rotator muscle group, through the full available active hip ER ROM, was evaluated using concentric isokinetic (30 degrees /s) testing on a KinCom dynamometer. Adjustment for lean body mass (LBM) was made for comparison of strength between groups. A two way repeated analysis of covariance was used to compare strength between groups. A two way repeated analysis of variance was used to compare strength between sides and ROM between groups and sides. Bonferroni correction was made for multiple analyses, and significance was accepted at p<or=0.05. RESULTS: AST at 0 degrees , 20 degrees , 30 degrees , and 40 degrees of hip ER was greater in the dancers than the non-dancers (p<or=0.022). TRAT, work, AST(0 degrees ), AST(20 degrees ), and AST(30 degrees ) of hip ER were all greater on the right side than the left (p = 0.007) in both groups. Dancers had greater inner ER ROM (p = 0.013) and less outer ER ROM than non-dancers (p<or=0.001). There was no difference in total ER ROM between groups (p = 0.133). The right side had greater inner ER (p<or=0.001) and total ER ROM (p<or=0.001) than the left in both groups. CONCLUSIONS: Ballet dancers have greater inner range, angle specific strength and inner range ER ROM, demonstrated by a shift in the dancers' strength curves. This shift in the strength curve towards the inner range of hip ER may be an adaptive training response.

Adolescent↗