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Biomedical subjects

A Hutchings

Publications and source records attributed to A Hutchings.

At least 19 recordsLinked to original sources
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↗
PubMed1998

Surgery for stress incontinence: factors associated with a successful outcome.

OBJECTIVE: To investigate which patient and health-service factors are predictive of outcome after surgery for stress incontinence. PATIENTS AND METHODS: In all, 232 women were assessed before and 3, 6 and 12 months after surgery for stress incontinence. Twelve patient characteristics and seven health-service factors were considered. Successful outcome was assessed in four ways: avoidance of complications after discharge, reduction in symptom severity. reduction in the social impact of stress incontinence, and improvement in activities of daily living (ADL). Relationships between possible predictors and outcome were explored using logistic regression models. RESULTS: Complications were less likely (r2=0.11) in women over 50 years of age, with no comorbidity and no urgency/urge incontinence, operated on by a gynaecologist. Reduction in symptom severity was more likely (r2=0.21) in younger women (< or = 50 years) with little limitation in their ADL, who suffered from severe or very severe stress incontinence symptoms but no urgency or urge incontinence, and who underwent preoperative urodynamic tests. A reduction in symptom impact was more likely (r2 = 0.15) in women in whom symptoms were having a moderate or severe impact, who were not grossly overweight, and who underwent a colposuspension or needle suspension performed by a gynaecologist. The only factor associated with improvement in ADL was the preoperative ADL score, i.e. the more limited a woman, the greater the likelihood of improvement (r2=0.15). The study provided evidence to support several of the widely held views about surgical success. Good outcomes were more likely if there is no urge incontinence, there is no or only mild comorbidity, no or only slight obesity, urodynamic investigations are conducted, and the surgeon is a gynaecologist. In contrast, there was no evidence that outcomes are worse if patients have undergone previous surgery for incontinence. Outcomes were also not related to grade of surgeon, surgeon's workload, or teaching status of the hospital. CONCLUSION: The relative importance of different factors depends on the outcome of interest, i.e. impairment (complications), disability (symptom severity) or handicap (symptom impact and ADL). These findings might help to improve clinical practice by indicating those characteristics that are associated with a greater likelihood of a good outcome. The results could also aid evaluation and audit of surgery, having identified the main prognostic factors that need to be considered when comparing the outcome of different procedures, surgeons or hospitals. Before doing so, the predictive models described in this paper need to be tested using an independent dataset.

Activities of Daily Living↗
PubMed1997

A search for sex-specific antigens on bovine spermatozoa using immunological and biochemical techniques to compare the protein profiles of X and Y chromosome-bearing sperm populations separated by fluorescence-activated cell sorting.

Currently, the only successful method for separating X and Y chromosome-bearing spermatozoa is fluorescence-activated cell sorting. Although effective, this technique is of limited usefulness to the animal breeding industry as it cannot produce the large volumes of sexed spermatozoa needed for artificial insemination. An attractive alternative would be to identify an immunological marker confined to one sperm type and, therefore, significant scientific effort has been expended in examining antibodies that appear to recognize approximately 50% of spermatozoa in an ejaculate. However, no sex-specific antigens have yet been identified from spermatozoa. Using the opportunity afforded by the development of sperm separation by fluorescence-activated cell sorting, we have made a thorough search for differences between X and Y chromosome-bearing bull spermatozoa using both biochemical and immunological methods. Techniques for radiolabelling surface membrane proteins, in conjunction with SDS-PAGE, failed to show any differences between populations. Similarly, a wide range of monoclonal antibodies raised to ejaculated, cauda epididymidal and testicular spermatozoa failed to distinguish between the X and Y chromosome-bearing spermatozoa. Only after analysis by high resolution two-dimensional SDS-PAGE was an indication obtained that X-specific proteins occur. However, these proteins are not associated with the surface membrane and further work is necessary to confirm their association with the X chromosome and to characterize them more fully. Our inability to detect sex-specific differences in sperm surface antigenicity suggests that further work on this immunological approach to semen sexing is unlikely to be profitable.

Animals↗