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Biomedical subjects

A Hutchings

Publications and source records attributed to A Hutchings.

At least 19 recordsLinked to original sources
PubMed2006

Reporting ethics committee approval and patient consent by study design in five general medical journals.

BACKGROUND: Authors are required to describe in their manuscripts ethical approval from an appropriate committee and how consent was obtained from participants when research involves human participants. OBJECTIVE: To assess the reporting of these protections for several study designs in general medical journals. DESIGN: A consecutive series of research papers published in the Annals of Internal Medicine, BMJ, JAMA, Lancet and The New England Journal of Medicine between February and May 2003 were reviewed for the reporting of ethical approval and patient consent. Ethical approval, name of approving committee, type of consent, data source and whether the study used data collected as part of a study reported elsewhere were recorded. Differences in failure to report approval and consent by study design, journal and vulnerable study population were evaluated using multivariable logistic regression. RESULTS: Ethical approval and consent were not mentioned in 31% and 47% of manuscripts, respectively. 88 (27%) papers failed to report both approval and consent. Failure to mention ethical approval or consent was significantly more likely in all study designs (except case-control and qualitative studies) than in randomised controlled trials (RCTs). Failure to mention approval was most common in the BMJ and was significantly more likely than in The New England Journal of Medicine. Failure to mention consent was most common in the BMJ and was significantly more likely than in all other journals. No significant differences in approval or consent were found when comparing studies of vulnerable and non-vulnerable participants. CONCLUSION: The reporting of ethical approval and consent in RCTs has improved, but journals are less good at reporting this information for other study designs. Journals should publish this information for all research on human participants.

Editorial Policies↗
PubMed2005

An experimental study of determinants of the extent of disagreement within clinical guideline development groups.

OBJECTIVE: To assess the effect of design features and clinical and social cues on the extent of disagreement among participants in a formal consensus development process. METHODS: Factorial design involving 16 groups consisting of 135 general practitioners (GPs) and 42 mental health professionals from England. The groups rated the appropriateness of four mental health interventions for three conditions (chronic back pain, irritable bowel syndrome, and chronic fatigue syndrome) in the context of various clinical and social cues. The groups differed in three design features: provision of a systematic literature review (versus not provided), group composition (mixed versus GP only), and assumptions about the healthcare resources available (realistic versus idealistic). Disagreement was measured using the mean absolute deviation from a group's median rating for a scenario. RESULTS: None of the design features significantly affected the extent of disagreement within groups (all p>0.3). Disagreement did differ between treatments (closer consensus for cognitive behavioural therapy and behavioural therapy than for brief psychodynamic intervention therapy and antidepressants) and cues (closer consensus for depressed patients and patients willing to try any treatment). CONCLUSION: In terms of the extent of disagreement in the groups in this study, formal consensus development was a robust technique in that the results were not dependent on the way it was conducted.

Adult↗
PubMed2005

Increased risk of tuberculosis among health care workers in Samara Oblast, Russia: analysis of notification data.

SETTING: Samara Oblast, Russia. OBJECTIVE: To compare the rates of tuberculosis (TB) in health care workers (HCWs) working in TB services, general health services (GHS) and the general population in a region of the Russian Federation. DESIGN: Analysis of notification rates of TB among HCWs, GHS workers and the general population during the 9-year period from 1994 to 2002. RESULTS: During 1994-2002, TB incidence among staff employed at the TB services in Samara Oblast was ten times higher than among the general population, reaching 741.6/100 000 person years at risk. Staff working at in-patient TB facilities were found to be at highest risk, with an incidence rate ratio of 17.7 (95% CI 11.6-27.0) compared to HCWs at the GHS. CONCLUSIONS: HCWs at TB services in the Russian Federation are at substantially increased risk for TB, suggesting significant risks from nosocomial transmission. Control of institutional spread of TB in the Russian Federation is an area that requires urgent attention, especially given the epidemic of human immunodeficiency virus that Russia is currently witnessing.

Adult↗
PubMed2004

Effects of Burch colposuspension on the relative positions of the bladder neck to the levator ani muscle: An observational study that used magnetic resonance imaging.

OBJECTIVE: The purpose of this study was to use magnetic resonance imaging to observe the changes of the position of the levator ani muscle relative to the bladder neck after Burch colposuspension. STUDY DESIGN: Women with urodynamic stress incontinence underwent Burch colposuspension. Magnetic resonance imaging was performed 1 week before surgery and 1 year after the operation. The levator ani muscle and the bladder neck were imaged in the parasagittal and sagittal planes, respectively; and their position was measured in relation to the pubococcygeal line. The reproducibility of these measures was investigated. Changes that occurred to levator ani muscle anatomy after the operation were correlated to surgical success. Surgical outcome was assessed objectively at 1 year with urodynamic testing. RESULTS: Of the 73 women who were studied, only 28 women were included in the study because the medial edge of the levator ani was visible clearly on a parasagittal magnetic resonance image. At the 1-year follow-up, the objective cure rate was 86%. Measures of bladder neck and levator ani position in relation to the pubococcygeal line were found to be reproducible. Burch colposuspension produces a significant elevation of the levator ani, with a reduced distance between the bladder neck and the levator ani muscle. Surgical success was associated significantly with a shorter distance between bladder neck and levator ani muscle. CONCLUSION: The anatomy of the levator ani muscle is changed by colposuspension. The apposition of the levator ani muscle to the bladder neck may play a role in the restoration of continence.

Anal Canal↗
PubMed2003

Evaluation of personal, environmental and biological exposure of paediatric anaesthetists to nitrous oxide and sevoflurane.

Paediatric anaesthetists are at higher risk of exposure to waste anaesthetic gases, which often exceed set safety limits. Recommended personal diffusive sampling techniques for monitoring exposure to waste anaesthetic gases may not give a true profile of exposure and hence biological sampling may also be necessary. We evaluated the exposure of paediatric anaesthetists to nitrous oxide and sevoflurane as assessed by personal environmental and biological samples. The influence of venue and technique, and the strength of the relationship among the various sampling techniques were analysed. The study found that exposure to nitrous oxide during paediatric anaesthetic inductions is still a major problem, although exposure to sevoflurane was usually within the accepted limits. The type of breathing system used and the presence of scavenging seem to influence this exposure, though surprisingly, the induction technique or the methods of airway control do not. No significant relationship was found between the various biological indicators measured.

Adolescent↗
PubMed2002

Association of cytokine single nucleotide polymorphisms with B7 costimulatory molecules in kidney allograft recipients.

African-American race is associated with an increased risk of allograft loss, suggesting that African-American patients may form an immunologically higher risk group. Previously, we demonstrated that immune cell costimulatory molecule expression is significantly higher in African-Americans than in Caucasians. Polymorphic variations in the genes for cytokines have been associated with a number of immunological conditions, and with transplant rejection. This study was performed to determine the distribution, in African-American and Caucasian renal transplant recipients, of single nucleotide polymorphisms (SNPs) in the following cytokine genes: tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-6, IL-10, and transforming growth factor-beta (TGF-beta). Cytokine production from blood cells was determined, and cell-surface B7 (CD80, CD86) expression was measured. There was a significant link between IL-10 genotype and acute rejection episodes, but only in African-American patients (p < 0.01). Also, African-American patients had a significantly higher probability of having the IL-6 G-allele (p < 0.0001), which is associated with a high production of IL-6 protein. Incubation of blood cells with IL-6 resulted in increased expression of surface CD80 and CD86, while IL-10 decreased CD80 expression. This study demonstrated a clear correlation of the IL-6 G-allele with increased cellular CD80 expression and the IL-10 G-allele with decreased CD80 expression. These data raise the possibility that specific genotypes are associated with local cytokine regulation of cell-surface costimulatory molecule expression. African-American patients may have a genetically determined, quantitatively different immune response than Caucasian patients, contributing to adverse transplant outcomes.

Adult↗
PubMed2002

Reduction in the use of surgery for glue ear: did national guidelines have an impact?

BACKGROUND: It is widely accepted that the passive dissemination of national clinical guidance has little or no impact on practice. OBJECTIVE: To assess the impact in England of an Effective Health Care bulletin on childhood surgery for glue ear issued in 1992 and to understand the reasons for any change (or lack of change) in practice that ensued. METHOD: Time series analysis of the rate of use of surgery by children under 10 years of age from 1975 to 1997/8 in 13 English health districts. RESULTS: Following a rise in the rate of surgery in public (National Health Service) hospitals from 1975 to 1985, the rate declined by 1.6% a year from 1986 to 1992/3. Following publication of the guidelines in November 1992, the rate of decline increased to 10.1% a year. Even after allowing for a slight increase in the use of independent (private) hospitals between 1992/3 and 1997/8, the overall rate of decline was at least 7.9%. It appears that the rate of referral of cases by primary care physicians (general practitioners) halved during this period. Several contextual factors are thought to have contributed to the effect of the guidelines, including pre-existing professional concern about the value of surgery, the introduction of an internal market into the NHS, and growing apprehension among parents fuelled by scepticism in the mass media. During this unprecedented period of rapid change in usage, staff delivering the service remained unaware of the alterations in their own practice. CONCLUSIONS: Passive dissemination of national guidelines can accelerate an existing trend in clinical practice if the context is hospitable. Policy makers should identify and target such situations.

Child↗
PubMed2001

Increased costimulatory responses in African-American kidney allograft recipients.

BACKGROUND: The issue of racial differences in immune responses has been seldom investigated, despite the increased incidence of transplant rejection and inferior allograft outcomes in African-Americans (AA). We previously reported significantly increased expression of costimulatory molecules on peripheral blood cells from healthy adult AA compared with Caucasian (CS) volunteers. This report extends the study to pediatric kidney allograft recipients. METHODS: Surface antigen expression by peripheral blood mononuclear cells (MNC) from AA and CS transplant patients was determined by flow cytometry, after staining with specific antibodies. In vitro proliferation, in a one-way mixed lymphocyte response (MLR), was measured after stimulation with allogeneic irradiated mononuclear cells. The concentration of cyclosporine (CsA) achieving 50% inhibition (IC50) of in vitro proliferative responses to PHA and OKT3 was calculated. RESULTS: MNC from AA patients were shown to have significantly higher expression of CD80 (CS 5.2% +/- 0.6, AA 9.6% +/- 1.2, P < 0.0001) than cells from CS patients. Additionally, the cells from AA transplant recipients proliferated significantly more in an MLR (stimulation index: CS 8 +/- S2, AA 25 +/- 8, P < 0.05), and the CsA IC50 values, during proliferation to PHA and OKT3, were significantly higher in AA compared to CS patients. CONCLUSIONS: Although socioeconomic factors and therapeutic compliance are undoubtedly important issues in long-term allograft survival, our data suggest that AA patients mount more vigorous immune responses to antigens. The increased requirement for immunosuppression may be linked to racial variations in costimulatory molecule expression on antigen-presenting cells.

Adolescent↗
PubMed2001

Random and systematic medication errors in routine clinical practice: a multicentre study of infusions, using acetylcysteine as an example.

AIMS: The nature and incidence of errors in prescribing and giving medicines have previously been estimated by trained observers, or by retrospective analysis of incidents in which patients have come to harm. We have examined prospectively in routine clinical practice the concentrations of intravenous infusions of a drug (acetylcysteine) which is given according to a complicated dosing schedule. METHODS: We prospectively collected samples before and, where possible, after the infusion of acetylcysteine in 66 anonymous patients requiring treatment for acetaminophen (paracetamol) overdose in four centres in the United Kingdom. We measured the concentration in each infusion bag, and deduced from the weight of the patient the percentage of the anticipated dose that had actually been given. RESULTS: The experimentally determined dose was within 10% of the anticipated dose in 68 of 184 individual bags (37%), and within 20% of the anticipated dose in 112 bags (61%). Doses in 17 bags were more than 50% from the anticipated doses. In three patients, values in all three bags appeared to be systematically wrong by 50% or more; in a further seven cases, individual bags differed by 50% or more from the anticipated value. The median difference between pre- and post-infusion samples was 0% [interquartile range -5.2% to +14.6%], but 9% showed a disparity of greater than +/- 50%. CONCLUSIONS: Our data suggest that there is large random variation in administered dosage of intravenous infusions. Systematic calculation errors occur in about 5% [95% confidence interval 2, 8%] of cases, and major errors in drawing up in a further 3% [1, 7%], with inadequate mixing in 9% [4, 14%]. While we have no evidence that patients were adversely affected, and while the regime of administration of the drug studied (acetylcysteine) is complicated, these data suggest that the delivered dose often deviates from the intended dose, and that methods of quality control are needed.

Acetaminophen↗
PubMed2001

Surgery for stress incontinence: a non-randomised trial of colposuspension, needle suspension and anterior colporrhaphy.

OBJECTIVE: To compare the outcome, 12 months after surgery, of three principal categories of procedure (colposuspension, needle suspension and anterior colporrhaphy) used for treating stress incontinence. METHODS: A non-randomised trial design comparing 221 colposuspensions, 54 needle suspensions and 130 anterior colporrhaphies performed by 49 surgeons in 18 hospitals in the North Thames health region in 1993-1994. Four outcomes were considered: complications, severity of stress incontinence, social impact of incontinence, and activities of daily living score. Results were adjusted, using logistic regression, for 13 case-mix variables. RESULTS: Significant differences existed between the three procedures in the characteristics of the patients. The cure rate varied by procedure (colposuspension 34% dry; needle suspensions 13%; anterior colporrhaphy 19%). Two thirds of women, however, reported an improvement (colposuspension 75%; needle suspension 68%; anterior colporrhaphy 55%). After adjusting for confounders, colposuspension was significantly more likely to result in an improvement than anterior colporrhaphy (odds ratio 2.2). While this was reflected in improvements in the social life of the women, the difference between procedures did not reach statistical significance (p = 0.05). CONCLUSION: These results suggest surgery for stress incontinence in typical settings is not as good as reported in textbooks. This is mostly because this study was based on women's own reports (and not surgeons' reports) and partly because of the unselected nature of the patients. The information on outcomes given to patients should be reviewed and a large, pragmatic randomised trial including patient-assessed outcomes is needed.

Female↗
PubMed2000

Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes.

We show here that Vav-2 is tyrosine phosphorylated following antigen receptor engagement in both B- and T-cells, but potentiates nuclear factor of activated T cells (NFAT)-dependent transcription only in B cells. Vav-2 function requires the N-terminus, as well as functional Dbl homology and SH2 domains. More over, the enhancement of NFAT-dependent transcription by Vav-2 can be inhibited by a number of dominant-negative GTPases. The ability of Vav-2 to potentiate NFAT-dependent transcription correlates with its ability to promote a sustained calcium flux. Thus, Vav-2 augments the calcium signal in B cells but not T cells, and a truncated form of Vav-2 can neither activate NFAT nor augment calcium signaling. The CD19 co-receptor physically interacts with Vav-2 and synergistically enhances Vav-2 phosphorylation induced by the B-cell receptor (BCR). In addition, we found that Vav-2 augments CD19-stimulated NFAT- dependent transcription, as well as transcription from the CD5 enhancer. These data suggest a role for Vav-2 in transducing BCR signals to the transcription factor NFAT and implicate Vav-2 in the integration of BCR and CD19 signaling.

Animals↗
PubMed2000

Preliminary screening of some traditional Zulu medicinal plants for antineoplastic activities versus the HepG2 cell line.

Aqueous and methanol extracts of nine traditional Zulu medicinal plants, Cissus quandrangularis L., Cyphostemma flaviflorum (Sprague) Descoings, Cyphostemma lanigerum (Harv.) Descoings ex Wild & Drum, Cyphostemma natalitium (Szyszyl.) J. v. d. Merwe, Cyphostemma sp., Rhoicissus digitata (L. F.) Gilg & Brandt, Rhoicissus rhomboidea (E. Mey. Ex harv.) Planch, Rhoicissus tomentosa (Lam.) Wild & Drum, R. tridentata (L. F.) Wild & Drum and Rhoicissus tridentata (L. F.) Wild & Drum subsp. cuneifolia (Eckl. & Zeyh.) N. R. Urton, all belonging to the Vitaceae family, were evaluated to determine their therapeutic potentials as antineoplastic agents. The antiproliferative activity in vitro against HepG2 cells was determined. Twenty-two of the twenty-seven crude plant extracts showed activities ranging from 25% to 97% inhibition of proliferation when compared with the control which showed no inhibitory activity. Higher degrees of growth inhibition were found in aqueous root extracts in comparison with the methanol extracts of the same plant parts. The results show potential antineoplastic activity, indicating some scientific validation for traditional usage.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Selective requirement for Cdc25C protein synthesis during meiotic progression in porcine oocytes.

Fundamental differences between meiosis and mitosis suggest that the shared central cell cycle machinery may be regulated differently during the two division cycles. This paper focuses on unique features of Cdc25C protein function during meiotic progression. We report on the existence of oocyte-specific CDC25C transcripts that differ from their somatic counterparts in the 3' untranslated region. While CDC25C mRNA levels remain constant in fully-grown oocytes, corresponding protein levels increase progressively during maturation to a maximum at metaphase II. Elevation of Cdc25C protein levels in G2-oocytes by mRNA injection failed to increase MPF-kinase levels or to induce premature entry into M-phase. Likewise, antisense-induced arrest of translation (translational arrest) had no effect on chromosome condensation, nucleolar disassembly, or nuclear membrane contraction. By contrast, translational arrest inhibited subsequent events including membrane disassembly and spindle formation. Neither up- nor down-regulation of Cdc25C synthesis after metaphase I plate formation influenced progression to metaphase II. However, translational arrest during metaphase resulted in incomplete chromosome decondensation and abnormal pronuclear membrane assembly after activation. We conclude that Cdc25 protein, translated from unique transcripts, is preferentially located in the oocyte nucleus and is essential for progress through late diakinesis. Subsequently, new synthesis of Cdc25C protein is required for the orderly transition from meiotic to mitotic cell division.

Animals↗
PubMed2000

A panel of monoclonal antibodies to ovine placental lactogen.

A panel of 11 rat monoclonal antibodies (mAbs) has been raised to ovine placental lactogen (PL). By competitive enzyme-linked immunoabsorbent assay (ELISA), confirmed by two-site ELISA, the antibodies were shown to recognize six antigenic determinants on the ovine PL molecule, two of which overlap. One antigenic determinant (designated 1) was shared by other members of the prolactin/growth hormone (GH)/PL family in ruminants, humans and rodents. The binding of (125)I-labelled ovine PL to crude receptor preparations from sheep liver (somatotrophic) or rabbit mammary gland (lactogenic) was inhibited by mAbs recognizing antigenic determinants 2-6. Both types of receptor preparation were affected similarly. In the local in vivo pigeon crop sac assay, mAbs directed against determinants 3 and 6 enhanced the biological activity of ovine PL.

Animals↗
PubMed2000

Patient determinants of mental health interventions in primary care.

BACKGROUND: A large proportion of a general practitioner's (GP's) caseload comprises patients with mental health problems. It is important to ensure that care is provided appropriately, on the basis of clinical need. It is therefore necessary to investigate the determinants of the use of mental health care in the primary care sector and, in particular, to identify any non-clinical characteristics of patients that affect the likelihood of their receiving appropriate care. AIM: To identify and compare the influence of non-clinical patient factors on GPs' acknowledgement of mental problems and on their provision of mental health care. METHOD: Cross sectional study of adults aged 16 to 65 years old (n = 802) attending one of eight practices (20 GPs in total) in inner west London. RESULTS: Multivariable analysis showed that the combination of factors that best predict GPs' acknowledgement of the presence of mental problems are general health questionnaire (GHQ) scores (odds ratio [OR] = 1.10 per unit increase in score, 95% confidence interval [CI] = 1.07 to 1.13), previous mental symptoms (OR = 7.5, 95% CI = 4.3 to 12.9), increasing age (OR = 1.03 per one-year increase, 95% CI = 1.01 to 1.04) and physical health status (OR = 0.98 per unit increase in short form-36 (SF-36) score, 95% CI = 0.96 to 1.00). Multivariable analysis showed that the combination of factors that best predict intervention (prescription for psychotropic medication; return visit to GP; referral to psychiatric inpatients/outpatients; referral to other [specified] health professionals, or social services) are previous symptoms (OR = 7.4, 95% CI = 3.8 to 14.4), white ethnic group (OR = 2.2, 95% CI 0.9 to 5.5); and not owning a property (OR = 2.1, 95% CI = 1.1 to 4.0). Life events influenced intervention only in the presence of low GHQ scores (OR = 8.1, 95% CI = 2.7 to 24.0). CONCLUSIONS: Mental problems are common in primary care and their acknowledgement is a necessary but not a sufficient condition for intervention. Our results show that GPs' decisions about mental health interventions can be influenced by non-clinical patient factors, regardless of patients' clinical needs. The results suggest that current practice may not always be equitable, and point to the need for better understanding of the basis of these potential inequalities and for focused training.

Adolescent↗
PubMed1999

Peripheral blood antigen-presenting cells from African-Americans exhibit increased CD80 and CD86 expression.

Despite the increased incidence and severity of many autoimmune diseases and transplant rejection in African-Americans (AA) compared with Caucasians (CS), very few studies have addressed issues of racial variation during antigen presentation. This investigation was performed as a preliminary exploration of differences in peripheral blood cell costimulatory functions between healthy AA (n = 20) and CS (n = 20) subjects. The expression of surface costimulatory molecules on peripheral blood cells, mononuclear cells enriched by Ficoll density centrifugation, and plastic adherent antigen-presenting cells (APC) was determined by flow cytometry using fluorescent-labelled MoAbs. The expression of both B7 costimulatory molecules was significantly higher on the cells from AA subjects compared with cells from CS subjects (CD80, P < 0.05; CD86, P < 0.05). Also, following 18 h of culture with rhIL-1beta, there was a significant increase in the percentage of APC from AA expressing high levels of the costimulatory molecule CD80 (P < 0.05). Costimulatory function during mitogen and antigen presentation was determined by 3H-thymidine incorporation during T cell proliferation. Purified T cells from AA subjects demonstrated significantly increased proliferation to phytohaemagglutinin (PHA). The differences reported here suggest that racial variations in peripheral blood APC characteristics may exist. Given the importance of costimulation in maintaining long-term immune responses, these data suggest a further direction for the investigation of racial disparity in autoimmune disease pathology and transplant rejection rates.

Adult↗