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Biomedical subjects

A Ward

Publications and source records attributed to A Ward.

At least 55 records · Page 3Linked to original sources
PubMed2000

IGF-II ameliorates the dystrophic phenotype and coordinately down-regulates programmed cell death.

Duchenne muscular dystrophy (DMD) is a fatal and crippling disease of skeletal muscle which displays increased fibre turnover and elevated levels of programmed cell death (PCD) in muscle stem cells. Previously we showed that this cell death is inhibited by the growth factor IGF-II. To determine the functional significance of PCD to the dystrophic phenotype, we used a transgene to over-express IGF-II in the mdx mouse. We found that ectopic expression of IGF-II inhibited the elevated PCD observed in skeletal muscles in the absence of functional dystrophin and significantly ameliorates the early gross histopathological changes in skeletal muscles characteristic of the dystrophic phenotype. Replacement of the dystrophin gene abolished abnormal skeletal muscle cell PCD levels in vivo in a dose-dependent manner and in dystrophic SMS cell lines cultured in vitro. Thus elevation of stem cell PCD in dystrophic skeletal muscle is a direct consequence of the loss of functional dystrophin. Together these data demonstrate that elevated skeletal muscle cell PCD is a critical component of dystrophic pathology and is inversely correlated with both dystrophin gene dosage and with muscle fibre pathology. Targeting PCD in dystrophic muscles reduces both PCD and the classical features of dystrophic pathology in the mdx mouse suggesting that IGF-II is a strong candidate for therapeutic intervention in the dystrophinopathies.

Animals↗
PubMed2000

Alternative Curricular Options in Rural Networks (ACORNS): impact of early rural clinical exposure in the University of West Australia medical course.

The aim of this study was to assess the impact of a 4-day rural placement in Western Australia on the interest of fourth year medical students in a career in rural general practice. Students undertaking their Alternative Curricular Options in Rural Networks attachment (ACORNS) completed pre- and post-questionnaires examining their expectations, experiences of, and attitudes to rural general practice. Of the 103 students who participated, 81% expressed an interest in a rural career after the placement, whereas prior to this experience only 48% had been interested. The students also recorded a wide range of learning experiences, both clinical and procedural, and expressed positive attitudes to the variety of experiences and the role of the rural GP. The study concluded that early exposure to rural general practice enhances students' interest in a potential rural practice career and provides them with a broad range of experiences. The role of rural practitioners as role models for students needs to be acknowledged and reinforced.

Attitude of Health Personnel↗
PubMed2000

Lobular carcinoma in situ of the breast is not caused by constitutional mutations in the E-cadherin gene.

Lobular carcinoma in situ (LCIS) is an unusual histological pattern of non-invasive neoplastic disease of the breast occurring predominantly in women aged between 40 and 50 years. LCIS is frequently multicentric and bilateral, and there is evidence that it is associated with an elevated familial risk of breast cancer. Although women with LCIS suffer an increased risk of invasive breast disease, this risk is moderate suggesting that LCIS may result from mutation of a gene or genes conferring a high risk of LCIS, but a lower risk of invasive breast cancer. The high frequency of somatic mutations in E-cadherin in LCIS, coupled with recent reports that germline mutations in this gene can predispose to diffuse gastric cancer, raised the possibility that constitutional E-cadherin mutations may confer susceptibility to LCIS. In order to explore this possibility we have examined a series of 65 LCIS patients for germline E-cadherin mutations. Four polymorphisms were detected but no pathogenic mutations were identified. The results indicate that E-cadherin is unlikely to act as a susceptibility gene for LCIS.

Adult↗
PubMed2000

Developmental and behavioural outcome in obstetric brachial plexus palsy.

Forty-four children with obstetric brachial plexus palsy were assessed for both developmental attainment and behavioural problems. Analysis of the resulting data revealed developmental and behavioural problems previously not identified, particularly in those with more severe injuries. These effects were independent of the general condition of the child at birth, as indicated by their Apgar scores. Further studies are required to provide clarification of these children's difficulties, the mechanisms by which they occur and effective strategies to address them.

Brachial Plexus↗
PubMed2000

Attachment research in eating disorders.

AIM: In a recent review, disturbances in attachment have been linked with eating disorder symptomatology. However, because of the limitations of study design, few inferences could be drawn about these processes in the aetiology and maintenance of eating disorder. Since that review, there has been further development in the instruments used and the publication of several further studies of attachment processes in eating disorders. We reviewed the field, expecting that greater clarity may have emerged in the 3 years since the previous review. METHOD: A review of the literature was carried out, using the computer search PsychLIT, Medline, Embase and The Cochrane Library. RESULTS: There have been more studies published in this area in the last 3 years than in the entire period up until then. These can broadly be divided into those carried out in clinical and non-clinical populations, with greater weight ascribed to the former. The vast majority of studies found that attachment processes, by whatever method measured, are abnormal in eating disordered populations. Attachment style (dismissing versus preoccupied) may be linked with eating disorder diagnostic subgroup. CONCLUSIONS: Insecure attachment is common in eating disordered populations, with implications for therapy. Further work with refined instruments may clarify whether or not there is a specific association between attachment style and eating disorder subgroup. However, such an association is likely to be complicated and it may be more fruitful to study specific aspects of attachment, rather than global attachment style, in relation to eating disorder behaviour. The transgenerational transmission of attachment is a fruitful area for further investigation in eating disordered populations.

Feeding and Eating Disorders↗
PubMed2000

Expression, purification and properties of multidrug efflux proteins.

A general strategy is described for the amplified expression, purification and characterization in Escherichia coli of multidrug efflux proteins from Staphylococcus aureus, Bacillus subtilis, Methanococcus janaschii and E. coli. They all catalyse drug/H(+) antiport of substrates such as quinolones and ethidium and exemplify a family of putatively 12-helix membrane proteins. The gene for each protein was cloned downstream of the tac promoter in plasmid pTTQ18; an oligonucleotide encoding six histidine residues was added, in frame, to the C-terminus to facilitate purification. Growth conditions were optimized in 1-25-litre cultures of E. coli host strains to amplify the expression of each protein; the retention of activity was confirmed by assays of antibiotic resistance in vivo and/or assays of energized transport activity in vitro with synthetic substrates. Proteins were solubilized in dodecylmaltoside and purified to more than 90% homogeneity with Ni(2+)-nitrilotriacetate-affinity column chromography, yielding 5-25 mg per 25 litres of original culture. All the transport proteins migrated anomalously in SDS/PAGE at apparent molecular masses below those predicted from the gene sequence; identity and integrity were therefore confirmed by N-terminal amino acid sequencing and Western blotting for the C-terminal hexahistidine tag. Examination of the secondary structure of detergent-solubilized proteins by CD or Fourier-transform infrared spectroscopy following purification indicated a high content of alpha-helix (more than 75%). Matrix-assisted laser desorption ionization MS confirmed the high degree of purity and the true molecular mass. The formation of three-dimensional crystals is being attempted but crystals have yet to be grown that diffract X-rays. The growth of two-dimensional protein arrays has been more successful, with diffraction of electrons at low resolution. Proteins have been fused to green fluorescent protein or maltose-binding protein to facilitate these structural analyses. In addition, ligands for efflux proteins labelled with (13)C or (15)N have been synthesized to implement solid-state NMR studies of the ligand-binding site.

Bacillus subtilis↗
PubMed1999

An inpatient treatment model for adults with mild intellectual disability and challenging behaviour.

Following the closure of the large mental handicap hospitals in the UK, the majority of people with intellectual disability (ID) are currently living in the community. However, people with ID who also exhibit challenging behaviour (CB) have been the most difficult-to-place group and use a large amount of service resources. A variety of service options have been proposed for the assessment and treatment of CBs, but there is little information on the effectiveness of these alternatives. The Mental Impairment Evaluation and Treatment Service (MIETS) is one of these service options and the aim of the present study is to describe and evaluate this service. The present authors studied the first 64 patients admitted to MIETS following its opening. A within-subject comparison research design was used. Demographic and clinical data were obtained from case records and the effectiveness of MIETS interventions was evaluated by comparing the number of incidents of challenging behaviour, the use of seclusion, and the place of residence before and after the MIETS intervention. Only 10 (17.5%) of the patients had been admitted from community facilities, but 48 (84.2%) of the patients were discharged to community placements (P < 0.000 I1). The MIETS also significantly reduced the frequency and severity of challenging behaviours (P < 0.0001). It is concluded that the MIETS is an effective treatment model for people with ID and CB, and that there is no place for therapeutic nihilism in this difficult-to-place group of patients.

Adolescent↗
PubMed1999

Monocular and binocular depth discrimination thresholds.

BACKGROUND: Measurement of stereoacuity at varying distances, by real or simulated depth stereoacuity tests, is helpful in the evaluation of patients with binocular imbalance or strabismus. Although the cue of binocular disparity underpins stereoacuity tests, there may be variable amounts of other binocular and monocular cues inherent in a stereoacuity test. In such circumstances, a combined monocular and binocular threshold of depth discrimination may be measured--stereoacuity conventionally referring to the situation where binocular disparity giving rise to retinal disparity is the only cue present. A child-friendly variable distance stereoacuity test (VDS) was developed, with a method for determining the binocular depth threshold from the combined monocular and binocular threshold of depth of discrimination (CT). METHODS: Subjects with normal binocular function, reduced binocular function, and apparently absent binocularity were included. To measure the threshold of depth discrimination, subjects were required by means of a hand control to align two electronically controlled spheres at viewing distances of 1, 3, and 6m. Stereoacuity was also measured using the TNO, Frisby, and Titmus stereoacuity tests. BTs were calculated according to the function BT= arctan (1/tan alphaC - 1/tan alphaM)(-1), where alphaC and alphaM are the angles subtended at the nodal points by objects situated at the monocular threshold (alphaM) and the combined monocular-binocular threshold (alphaC) of discrimination. RESULTS: In subjects with good binocularity, BTs were similar to their combined thresholds, whereas subjects with reduced and apparently absent binocularity had binocular thresholds 4 and 10 times higher than their combined thresholds (CT). The VDS binocular thresholds showed significantly higher correlation and agreement with the TNO test and the binocular thresholds of the Frisby and Titmus tests, than the corresponding combined thresholds (p = 0.0019). CONCLUSION: The VDS was found to be an easy to use real depth (distance) stereoacuity test. The method described for calculating the BT provides one simple nonlinear solution for determining the respective contributions of binocular and monocular (MT) depth discrimination to the combined depth threshold.

Adolescent↗
PubMed1999

Race, presenting signs and symptoms, use of carotid artery imaging, and appropriateness of carotid endarterectomy.

BACKGROUND AND PURPOSE: We sought to determine whether there are racial differences in use of carotid artery imaging after controlling for clinical factors and to ascertain racial differences in presenting signs and symptoms and overall appropriateness for carotid endarterectomy (CE). METHODS: We performed a retrospective cohort study of 803 patients older than 45 years, hospitalized between 1991 and 1994 at any of 4 Veterans Affairs Medical Centers, with a discharge diagnosis of transient ischemic attack or ischemic stroke. Clinical data were abstracted from the medical record, including presenting symptoms, diagnostic test results, and use of surgical procedures. Appropriateness for CE was determined according to RAND criteria. RESULTS: Black patients were more likely than white patients to present with stroke (78% versus 55%) but less likely to present with transient ischemic attack (22% versus 45%; P=0.001). There was no racial difference in medical comorbidity or preoperative risk. Black patients were less likely to have an imaging study of their carotid arteries (67% versus 79%; P=0.001). Race remained an independent predictor of imaging after adjustment for clinical factors (odds ratio=1.50; 95% CI, 1.06 to 2.13). Because of higher prevalence of significant carotid artery stenosis, whites were significantly more likely than blacks to be assessed as appropriate candidates for surgery with the use of RAND criteria (18% versus 4%; P=0.001). CONCLUSIONS: Use of carotid artery imaging, a critical step in determining eligibility for CE, is influenced by the patient's race after controlling for clinical presentation. Adjustment for appropriateness of CE reduces but does not eliminate the importance of race.

Black or African American↗
PubMed1999

Compulsory treatment in anorexia nervosa. Short-term benefits and long-term mortality.

BACKGROUND: Anorexia nervosa is a mental disorder with a high long-term mortality. Patients are ambivalent about treatment and often avoid it. Of necessity, compulsory treatment sometimes must be considered. A report from the Mental Health Act Commission has helped to reduce previous confusion. AIMS: To identify the premorbid and clinical features that predisposed to compulsory admissions, the short-term benefits of the treatment and the long-term mortality rates (derived from the National Register). METHOD: Eighty-one compulsory patients were compared with 81 voluntary patients. RESULTS: Predisposing factors to a compulsory admission were a history of childhood sexual or physical abuse or previous self-harm. Detained patients had more previous admissions. Detained patients gained as much weight during admission as voluntary patients, but took longer. More deaths among compulsory than voluntary patients (10/79 v. 2/78) were found 5.7 years (mean) after admission. CONCLUSIONS: Compulsory treatment is effective in the short term. The higher long-term mortality in the detained patients is due to selection factors associated with an intractable illness.

Adult↗
PubMed1998

Human growth-differentiation factor 3 (hGDF3): developmental regulation in human teratocarcinoma cell lines and expression in primary testicular germ cell tumours.

We describe the cloning and initial characterization of a novel cDNA from human embryonal carcinoma (EC) cells. This cDNA, which we named human growth differentiation factor 3 (hGDF3), encodes the homologue of mouse GDF3, a TGFbeta superfamily member belonging to the Growth/Differentiation Factors. We have analysed the expression of hGDF3 in human embryonal carcinoma cell lines and in primary testicular germ cell tumours of adolescents and adults (TGCTs). Expression of hGDF3 in human EC cell lines is stem cell-specific, is down-regulated upon RA-mediated differentiation and is increased upon culture of the cells in the presence of activin A. In TGCTs, hGDF3 expression is low in seminomas, while expression in non-seminomas is readily detectable and appears to be associated with the EC and yolk sac components in the tumours. We have also mapped the hGDF3 locus to the short arm of human chromosome 12, a region consistently overrepresented in human testicular germ cell tumours. Thus, hGDF3 represents an embryonal carcinoma stem cell-associated marker both in vitro and in vivo.

Activins↗
PubMed1998

Regulation of the Wilms' tumour suppressor (WT1) gene by an antisense RNA: a link with genomic imprinting?

Antisense transcripts are typically associated with the down-regulation of gene expression. In this issue, Moorwood et al. present evidence that an antisense RNA can enhance expression of the Wilms' tumour suppressor locus WT1. We suggest that the unusual function of the WT1 antisense RNA might relate to the recent discovery of an antisense transcript that is involved in regulating imprinted expression of the murine Igf2r gene, particularly since there is some evidence that the WT1 gene is regulated by genomic imprinting in humans.

Animals↗
PubMed1998

Epidemiological and surgical aspects of urogenital fistulae: a review of 25 years' experience in southeast Nigeria.

The aim of the study was to determine the epidemiological background, clinical details and surgical outcome of patients presenting with urogenital fistulae to St Luke's Hospital, Uyo, and the associated VVF Unit at Mbribit Itam, Akwa Ibom State, Nigeria, between January 1970 and December 1994. A retrospective review of hospital operating theater records and case notes was carried out. Clinical details and outcome were assessed for the total cohort of 2484 patients. Epidemiological data were extracted from the case notes of 715 patients presenting between January 1990 and December 1994. Of these 92.2% were of obstetric etiology, 80.3% following neglected obstructed labor, 6.9% following cesarean section, and 5.0% followed ruptured uterus; 4.4% followed pelvic surgery and the remaining 3.4% of miscellaneous causes included malignancy, coital injury, infection and trauma; 8% had a coexisting rectovaginal fistula or third-degree perineal tear. Only 37.3% of patients were aware of their age; the median age of this group was 28 years. Literacy was difficult to judge reliably, although 29% were able to sign their name. Parity ranged from 0 to 17, and only 31.4% of fistulae related to first pregnancies. Although 73.1% were delivered in hospital, in 97.1% labor was initially managed at home, with a traditional birth attendant, in a maternity home, or in church; 34.1% were delivered by cesarean section, although the live-birth rate was only 10.3% in the causative pregnancy. For a variety of reasons 124 women were not operated upon: 1954 underwent only one operation, giving a presumptive cure rate at first operation of 81.2%; 247 underwent two, 116 three, 32 four, and 11 five operations during the study period. The ultimate closure rate was 97.7%, with only 0.6% undergoing urinary diversion. The type and distribution of fistulae recorded in this series is consistent with previous series of largely obstetric fistulae from the developing world. Surgical cure rates are also comparable. The epidemiological background is at variance with previous reports in several respects; this may reflect biosocial differences in the population studied.

Adult↗
PubMed1998

Periurethral injection of autologous fat for the treatment of post-fistula repair stress incontinence: a preliminary report.

The aim of the study was to assess the effectiveness of periurethral injection of autologous fat for the treatment of stress incontinence caused by inherent sphincter weakness in women following the repair of obstetric urogenital fistulae. Ten patients with symptomatic stress incontinence following repair of vesicovaginal or urethrovaginal fistula of obstetric origin were assessed clinically, by cystourethroscopy, and by Valsalva leak-point pressure (VLPP). Four showed some degree of bladder neck mobility and were treated by bladder neck suspension procedures. Six appeared to have pure sphincter weakness and were treated by periurethral injection of autologous fat. For logistic reasons, the initial follow-up was undertaken 2 weeks postoperatively, including clinical assessment and VLPP. Two patients were subjectively cured, 2 improved and 2 perceived no change in their symptoms following the procedure. The symptomatic changes correlated with the operative appearance, and with the subsequent changes in VLPP. Although numbers are small and follow-up short, we feel that these preliminary results justify further investigation of the technique in this most difficult group of patients.

Adipose Tissue↗
PubMed1998

New directions in perioperative management for pediatric solid organ transplantation.

Advances in pediatric solid organ transplantation have furthered the understanding of end-organ failures and refined the strategies for perioperative management of these otherwise lethal diseases. As the donor pool expands, the number of transplantations increases and long-term survival continues to improve, more complete knowledge of the immunologic and pathologic processes will be gained. A thorough understanding of the principles of transplantation medicine remains essential for physicians to provide optimal perioperative care of pediatric organ transplant patients.

Child↗