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Biomedical subjects

A Hayward

Publications and source records attributed to A Hayward.

At least 19 recordsLinked to original sources
PubMed2006

Tuberculosis screening in migrants in selected European countries shows wide disparities.

Well-established tuberculosis screening units in Western Europe were selectively sampled. Three screening units in Norway, two in the UK, one in the Netherlands and one in Switzerland were evaluated. The aim of this study was to describe a range of service models used at a number of individual tuberculosis units for the screening of new entrants into Europe. Semi-structured interviews were conducted with clinicians, nurses and administrators from a selected sample of European tuberculosis screening units. An outline of key themes to be addressed was forwarded to units ahead of scheduled interviews. Themes included the history of the unit, structure, processes and outputs involved in screening new entrants for tuberculosis. Considerable variation in screening services exists in the approaches studied. Units are sited in transit camps or as units within hospital facilities. Staff capacity and administration varies from one clinic per week with few dedicated staff to fully dedicated units. Only one site recorded symptoms; tuberculin testing was universal in children, but varied in adults; chest radiograph screening was universal except at one site where a positive tuberculin skin test or symptoms were required in those <35 yrs of age before ordering a radiograph. Few output data are routinely and systematically collected, which hinders comparison and determination of effectiveness and efficiency. Service models for screening new immigrants for tuberculosis appear to vary in Western Europe. The systematic collection of data would make international comparisons between units easier and help draw conclusions that might usefully inform service development.

Adult↗
PubMed2004

Patient and health service delays in initiating treatment for patients with pulmonary tuberculosis: retrospective cohort study.

SETTING: Catchment population of the North Middlesex University Hospital (NMUH), London, UK. OBJECTIVE: To measure patient and health care delays in treatment of pulmonary tuberculosis. DESIGN: Retrospective cohort study of patients notified with pulmonary tuberculosis between 1 April 2001 and 1 March 2002. RESULTS: The median case finding delays were between 78 and 99 days. Median patient-related delay was between 34.5 and 54 days. Median health care-related delay was 29.5 days. Shorter case finding delays were found in patients born in a high prevalence country, patients presenting first to Accident and Emergency department (A&E), younger patients, and those with sputum smear-positive disease. In those presenting first to A&E, those born in a high prevalence country, and those with sputum-positive disease, this effect was predominantly due to shorter health care delays. Limitations of TB service capacity and organisational factors appeared responsible for up to half of the difference in delay between those presenting to A&E or general practitioners (GPs). CONCLUSION: Patient and health service delays contribute substantially to delays in patients accessing treatment. Considerable reduction in case finding delays may be achieved through changes in the capacity of tuberculosis services, and coordination of associated health services.

Adult↗
PubMed2004

Screening programmes for tuberculosis in new entrants across Europe.

Screening foreign-born groups with high rates of tuberculosis may help to ensure that they can benefit from early treatment and minimise onward transmission. In January 2003, we surveyed new entrant screening programmes in Europe. Of the 26 countries from whom a response was received, 13 (50%) conducted no specific tuberculosis screening. Of 13 countries with programmes, none conducted pre-entry screening, three conducted screening at ports of entry, and nine screened in other centres. All 13 principally screened refugees. All programmes used chest X-rays as a screening tool, but no two countries took the same specific clinical approach.

Europe↗
PubMed2003

Factors influencing hepatitis B vaccine uptake in injecting drug users.

BACKGROUND: Hepatitis B infection in injecting drug users is an important public health problem. Active immunization against hepatitis B is immunogenic and safe, but uptake rates in targeted vaccination programmes are low. This study was undertaken to identify factors associated with the uptake of hepatitis B vaccination in injecting drug users attending a needle exchange service. METHODS: A retrospective cross-sectional survey of case-note data of injecting drug users who had no markers of hepatitis B infection or immunity was undertaken within a drop-in needle exchange service for injecting drug users in a large urban area in England. A qualitative study using semi-structured interviews with needle exchange staff was also conducted. RESULTS: Of 207 injecting drug users, 180 (87 per cent) had been offered vaccine, 123 (59 per cent) accepted at least one dose and 55 (27 per cent) received three or more doses. Vaccine was less likely to be offered to those sharing injecting equipment or known to have hepatitis C. Needle sharing was also associated with failure to accept vaccine, as was increasing age and the length of contact with the service. CONCLUSIONS: Those who are most at risk are least likely to be offered vaccine and accept it. This calls into doubt the effectiveness of hepatitis B vaccination strategies targeted at high-risk groups and adds weight to arguments for universal vaccination.

Adolescent↗
PubMed2003

Who is being tested for genital chlamydia in primary care?

OBJECTIVES: To explore current patterns of testing for genital chlamydial infection in primary care, and to identify practice characteristics influencing testing rates. METHOD: Aggregate numbers of chlamydia tests and results for each practice in Nottingham Health District were matched to practice characteristics. Age specific testing rates and diagnosed prevalence were calculated, and characteristics of the practice tested for association with chlamydia testing rates. RESULTS: Most tests (63.1%) were performed on women over the age of 25, but the proportion of positive tests was highest in 15-19 year olds (13.3%) followed by 20-24 year olds (8.2%). A higher ratio of GP principals to female practice population was associated with higher testing rates and more chlamydia isolations, but the ratio of female GP principals to patients was associated with higher testing rates only in 20-24 year olds. Diagnosed incidence was greatest in more socioeconomically deprived practice populations, and this was not explained by higher testing rates. Men were rarely tested. CONCLUSION: Current testing practice in primary care does not reflect the known epidemiology of genital chlamydia infection. Practices with lower doctor-patient ratios do less testing, and measures to enable their active participation in the envisaged screening programme will be important in reaching all at-risk groups.

Adolescent↗
PubMed2001

The effectiveness of interventions aimed at increasing handwashing in healthcare workers - a systematic review.

Handwashing is widely accepted as being key to the prevention of hospital-acquired infection but the frequency of handwashing by healthcare workers has been found to be low. A systematic critical literature review was conducted to establish the effectiveness of interventions aimed at increasing compliance with handwashing in healthcare workers. The results showed that one-off educational interventions have a very short-term influence on handwashing behaviour. Use of strategically placed reminders, or asking patients to remind staff of the need to conduct handwashing can have a modest but more sustained effect. Feedback of performance can increase levels of handwashing but if feedback is not repeated regularly, then this effect is not maintained over long periods. Automated sinks increase the quality of handwashing but healthcare workers can be discouraged from using these because of the additional time involved. Provision of moisturized soaps appears to make little difference to handwashing behaviour but providing 'dry' hand rubs near patient beds may lead to a minimal increase in the frequency with which staff decontaminate their hands. Multifaceted approaches which combine education with written material, reminders and continued feedback of performance can have an important effect on handwashing compliance and rates of hospital-acquired infection.

Cross Infection↗
PubMed2000

Eradication of Cryptosporidium parvum infection by mice with ovalbumin-specific T cells.

CD154 is necessary for mice to clear a Cryptosporidium parvum infection, but whether this ligand has to be expressed on T cells with specificity for C. parvum has not been determined. We infected DO11.10 (ovalbumin specific) T-cell receptor transgenic mice that had been bred to a RAG(-/-) background with C. parvum and found that the infection was cleared within 6 weeks, while RAG(-/-) controls were unable to clear C. parvum infection. Recovery was accompanied by an increase in the number of splenic T cells with the CD44(high) phenotype that characterizes memory cells. To determine whether a C. parvum-infected environment sufficed to activate transgenic T cells, we reconstituted C. parvum-infected BALB/c SCID mice with DO11.10 RAG(-/-) splenocytes. Fecal excretion of C. parvum antigen ceased in the 12 weeks following the adoptive transfer, unless the mice were also injected with tolerizing doses of ovalbumin. DO11.10 T cells were found in the submucosa of C. parvum-infected, but not uninfected, BALB/c SCID hosts within 48 h of injection. The transferred DO11.10 T cells divided and acquired a CD44(high) memory phenotype in C. parvum-infected, but not uninfected, recipients. DO11.10 splenocytes from CD154 knockout donors failed to clear a C. parvum infection, confirming a requirement for CD154 in recovery. In vitro, the DO11.10 cells did not proliferate in response to C. parvum antigen, and a tBlast GenBank search revealed no matches between the ovalbumin peptide and C. parvum DNA sequences. C. parvum-infected SCID mice given RAG(-/-) CD8(+) T cells with a Listeria-specific transgene did not recover from C. parvum infection. Our data suggest that antigen-nonspecific CD4(+) T-cell effector mechanisms in combination with the innate arm of the immune system are sufficient for the eradication of C. parvum infection.

Animals↗
PubMed2000

Stimulation of the gonadotropic axis by the neuropeptide Y receptor Y1 antagonist/Y4 agonist 1229U91 in the male rat.

Neuropeptide Y (NPY) is a highly potent orexigenic substance that is also known to modulate gonadotropin secretion. Five receptor subtypes for NPY have been identified, and a potent antagonist for the receptor subtype 1 (Y1), 1229U91, also known as GW1229 or GR231118, has been described. Subsequently, 1229U91 was also shown to represent a highly potent agonist for the Y4 receptor subtype. Very unexpectedly, intracerebroventricular administration of 1229U91 elicited an intense, dose-dependent surge of both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in intact male rats that lasted for 6 h. Such stimulation was absent when a potent gonadotropin-releasing hormone antagonist was administered systemically, suggesting that 1229U91 acts centrally to stimulate gonadotropin-releasing hormone release. 1229U91 administration had no effect on growth hormone, thyroid-stimulating hormone, and corticosterone secretions. In addition to 1229U91, four other parent dimer molecules described earlier produced a marked and sustained stimulation of LH when injected intracerebroventricularly that was proportional to their binding affinity for the Y4 receptor. Central administration of the specific Y1 antagonist BIBO3304 (20 microgram) had no effect on LH secretion, making it unlikely for 1229U91 to stimulate LH secretion by an antagonistic action on the Y1 receptor subtype, thus suggesting a Y4 receptor mediation. In conclusion, the 1229U91 molecule displays an interesting conformational epitope that is able to generate large LH surges, possibly by activating Y4 or Y4-like receptor subtypes or by acting on a NPY receptor unrelated target.

Animals↗
PubMed2000

Mechanical stretch-induced fibronectin and transforming growth factor-beta1 production in human mesangial cells is p38 mitogen-activated protein kinase-dependent.

Hemodynamic abnormalities are important in the pathogenesis of the excess mesangial matrix deposition of diabetic and other glomerulopathies. p38-Mitogen-activated protein (MAP) kinase, an important intracellular signaling molecule, is activated in the glomeruli of diabetic rats. We studied, in human mesangial cells, the effect of stretch on p38 MAP kinase activation and the role of p38 MAP kinase in stretch-induced fibronectin and transforming growth factor-beta1 (TGF-beta1) accumulation. p38 MAP kinase was activated by stretch in a rapid (11-fold increase at 30 min, P < 0.001) and sustained manner (3-fold increase at 33 h, P < 0.001); this activation was mediated by protein kinase C (PKC). Stretch-induced fibronectin and TGF-beta1 protein levels were completely abolished (100% inhibition, P < 0.001; and 92% inhibition, P < 0.01, respectively) by SB203580, a specific p38 MAP kinase inhibitor. At 33 h, TGF-beta1 blockade did not affect stretch-induced fibronectin production, but partially prevented stretch-induced p38 MAP kinase activation (59% inhibition, P < 0.05). TGF-beta1 induced fibronectin accumulation after 72 h of exposure via a p38 MAP kinase-dependent mechanism (30% increase over control, P < 0.01). In human mesangial cells, stretch activates, via a PKC-dependent mechanism, p38 MAP kinase, which independently induces TGF-beta1 and fibronectin. In turn, TGF-beta1 contributes to maintaining late p38 MAP kinase activation, which perpetuates fibronectin accumulation.

Biomechanical Phenomena↗
PubMed1999

Liver and bile duct pathology following Cryptosporidium parvum infection of immunodeficient mice.

Patients with acquired immune deficiency syndrome (AIDS) and boys with mutations of the CD154 gene (causing congenital X-linked immunodeficiency with hyper-IgM [XHIM]) are susceptible to chronic infections of the biliary tract with Cryptosporidium parvum (CP) that may lead to biliary sclerosis and ultimately to cholangiocarcinoma. To determine whether the CP infection and the consequent immune response contribute independently to this morbidity, we infected mice with severe combined immunodeficiency (SCID) or with disrupted genes for CD154, CD40, or interferon gamma (IFN-gamma) with CP. Even when CP infection persisted for 16 weeks, the SCID mice developed only mild triaditis, without apoptosis of biliary epithelial cells (BEC). Fifty percent of the CD154 knockout mice developed lobular hepatitis with acute and chronic triaditis. The CD40 knockout mice developed marked triaditis, and the IFN-gamma knockouts either succumbed to enteritis or survived to develop marked triaditis, portal fibrosis, biliary sclerosis, necrosis with dilation of duct-like structures within the porta hepatis, and dysplastic changes. CP-infected SCID mice reconstituted with T cells from IFN-gamma knockout donors either developed severe enteritis or survived to develop triaditis, cholangitis, lobular hepatitis with periductular sclerosis, and scarring. Mice with disruptions of both the CD40 and IFN-gamma genes remained infected by CP and developed bile duct and liver disease, but not enteritis. Our results suggest that T-cell cytokines are required for the inflammatory and sclerosing responses to CP infection in immunodeficient animals. The response of immunodeficient mice to CP infection may model at least the initial steps toward the development of sclerosing cholangitis or bile duct cancers in XHIM patients.

Animals↗
PubMed1999

Crisis telephone consultation for deliberate self-harm patients: effects on repetition.

BACKGROUND: No interventions have been shown to be effective in reducing deliberate self-harm (DSH) repetition in this group of patients as a whole. AIMS: To investigate the effect on repetition of offering emergency telephone support in a group of hospital-admitted DSH patients. METHOD: A total of 827 DSH patients admitted to medical wards were randomly allocated to either control or intervention (green card) groups. In addition to treatment as usual, the intervention group was offered telephone support should any further crises occur. The main outcome measure was DSH repetition within six months of the index event. RESULTS: The intervention had no significant effect on the overall DSH repetition rate (odds ratio 1.20, 95% CI 0.82-1.75). Sub-group analysis suggested that response to the intervention differed according to the past history of DSH--subjects with a previous history repeating more often and first-timers appearing to benefit. CONCLUSIONS: No overall effect of the intervention was shown. Conclusions concerning sub-groups must be regarded as speculative, but they suggest that further assessment of the value of telephone support in first-timer DSH patients is indicated.

Adult↗
PubMed1999

Evidence that the inhibition of luteinizing hormone secretion exerted by central administration of neuropeptide Y (NPY) in the rat is predominantly mediated by the NPY-Y5 receptor subtype.

A number of studies have indicated that neuropeptide Y (NPY) is a central regulator of the gonadotropic axis, and the Y1 receptor was initially suggested to be implicated. As at least five different NPY receptor subtypes have now been characterized, the aim of the present study was to reinvestigate the pharmacological profile of the receptor(s) mediating the inhibitory action of NPY on LH secretion by using a panel of NPY analogs with different selectivity toward the five NPY receptor subtypes. When given intracerebroventricularly (icv) to castrated rats, a bolus injection of native NPY (0.7-2.3 nmol) dose-dependently decreased plasma LH. Peptide YY (PYY; 2.3 nmol) was as potent as NPY, suggesting that the Y3 receptor is not implicated. Confirming previous data, the mixed Y1, Y4, and Y5 agonist [Leu31,Pro34]NPY (0.7-2.3 nmol) inhibited LH release with potency and efficacy equal to those of NPY. Neither the selective Y2 agonist C2-NPY (2.3 nmol) nor the selective Y4 agonist rat pancreatic polypeptide affected plasma LH, excluding Y2 and Y4 subtypes for the action of NPY on LH secretion. The mixed Y4-Y5 agonist human pancreatic polypeptide (0.7-7 nmol) as well as the mixed Y2-Y5 agonist PYY3-36 (0.7-7 nmol) that displayed very low affinity for the Y1 receptor, thus practically representing selective Y5 agonists in this system, decreased plasma LH with potency and efficacy similar to those of NPY, indicating that the Y5 receptor is mainly involved in this inhibitory action of NPY on LH secretion. [D-Trp32]NPY, a selective, but weak, Y5 agonist, also inhibited plasma LH at a dose of 7 nmol. Furthermore, the inhibitory action of NPY (0.7 nmol) on LH secretion could be fully prevented, in a dose-dependent manner (6-100 microg, icv), by a nonpeptidic Y5 receptor antagonist. This antagonist (60 microg, icv) also inhibited the stimulatory action of NPY (0.7 nmol) on food intake. The selectivity of PYY3-36, human PP, [D-Trp32]NPY, and the Y5 antagonist for the Y5 receptor subtype was further confirmed by their ability to inhibit the specific [125I][Leu31,Pro34]PYY binding to rat brain membrane homogenates in the presence of the Y1 receptor antagonist BIBP3226, a binding assay system that was described as being highly specific for Y5-like receptors. With the exception of [D-Trp32]NPY, all analogs able to inhibit LH secretion were also able to stimulate food intake. Taken together, these results indicate that the Y5 receptor is involved in the negative control by NPY of the gonadotropic axis.

Animals↗
PubMed1999

Effect of Bacillus Calmette-Guerin vaccination on new-onset type 1 diabetes. A randomized clinical study.

OBJECTIVE: We undertook this study to test whether Bacillus Calmette-Guerin (BCG) vaccine preserves beta-cell function and increases the remission rate in children with new-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: This was a randomized double-blind placebo-controlled trial offered to children referred to the Barbara Davis Center for Childhood Diabetes or the Baystate Medical Center with a diagnosis of new-onset type 1 diabetes. There were 94 children aged 5-18 years who received either BCG or saline intradermally within 4 months of onset of symptoms and who were then evaluated at 3-month intervals for 2 years. The primary end point was remission, defined as insulin independence for 4 weeks. Secondary end points were C-peptide levels (fasting and in response to a mixed meal challenge), insulin dose, and HbA1c. RESULTS: Of the patients, 47 were randomized to each arm; 7 in the placebo group and 9 in the BCG group did not complete 1 year of the study and are not included in the analysis. One patient from each group achieved remission. Fasting and stimulated C-peptide levels did not differ by treatment arm but declined in both groups and were lower initially and during the entire 2-year period in younger children. Insulin requirements and HbA1c levels did not differ in the two groups. CONCLUSIONS: Vaccination with BCG at the time of onset of type 1 diabetes does not increase the remission rate or preserve beta-cell function.

Adolescent↗
PubMed1998

The carboxyl-terminal domain of insulin-like growth factor-I receptor interacts with the insulin receptor and activates its protein tyrosine kinase.

Receptors for insulin and insulin-like growth factor-I (IR and IGFIR) consisting of the alpha2beta2 structure are protein tyrosine kinases (PTKs). Carboxyl-terminal (CT) domains of their beta subunits are structurally diverse while the PTK domains share the highest homology. Interactions between CT and PTK domains of IR and IGFIR were studied by means of PTK activity, fluorescence energy transfer or surface plasmon resonance using BIAcore. We present evidence that IGFIR CT directly interacts with both IGFIR and IR. Although binding to both receptors, stimulation of PTK activity only occurs with IR but not IGFIR.

Animals↗
PubMed1998

The gene for severe combined immunodeficiency disease in Athabascan-speaking Native Americans is located on chromosome 10p.

Severe combined immunodeficiency disease (SCID) consists of a group of heterogeneous genetic disorders. The most severe phenotype, T-B- SCID, is inherited as an autosomal recessive trait and is characterized by a profound deficiency of both T cell and B cell immunity. There is a uniquely high frequency of T-B- SCID among Athabascan-speaking Native Americans (A-SCID). To localize the A-SCID gene, we conducted a genomewide search, using linkage analysis of approximately 300 microsatellite markers in 14 affected Athabascan-speaking Native American families. We obtained conclusive evidence for linkage of the A-SCID locus to markers on chromosome 10p. The maximum pairwise LOD scores 4.53 and 4.60 were obtained from two adjacent markers, D10S191 and D10S1653, respectively, at a recombination fraction of straight theta=.00. Recombination events placed the gene in an interval of approximately 6.5 cM flanked by D10S1664 and D10S674. Multipoint analysis positioned the gene for the A-SCID phenotype between D10S191 and D10S1653, with a peak LOD score of 5.10 at D10S191. Strong linkage disequilibrium was found in five linked markers spanning approximately 6.5 cM in the candidate region, suggesting a founder effect with an ancestral mutation that occurred sometime before 1300 A.D.

Alleles↗