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Biomedical subjects

J Grundy

Publications and source records attributed to J Grundy.

18 recordsLinked to original sources

Reliability and validity of a maternal food frequency questionnaire designed to estimate consumption of common food allergens.

BACKGROUND: Maternal food intake during pregnancy may influence the development of food hypersensitivity (FHS) in the child. A food frequency questionnaire estimating the frequency with which some of the mains food allergens are consumed was designed and validated. MATERIALS AND METHODS: Pregnant women were recruited at the ante-natal clinic of St. Mary's Hospital, Isle of Wight, UK. A food frequency questionnaire was developed and validated by comparing responses to information recorded in 7 days food diaries. The reliability of the food frequency questionnaire was evaluated by asking women to complete the questionnaire on two separate occasions at 30 and 36 weeks gestation. RESULTS: Fifty-seven women completed the validity study and 91 women completed the reliability study. For both validity and reliability, questions with dichotomous response categories showed the highest level of agreement. Frequency of intake of foods commonly "hidden" in foods produced the lowest validity and reliability scores. In the validity study responses to the food frequency questionnaire identically matched information recorded in the food diaries 80% of the time, on average. In the reliability study, responses were identical on both questionnaires 85% of the time on average. CONCLUSION: In this study a food frequency questionnaire estimating the frequency with which some of the main food allergens are consumed during pregnancy was designed and validated. This food frequency questionnaire could be used in future studies to assess the role of maternal food intake in the development of FHS in the infant.

Adolescent↗

Management systems response to improving immunization coverage in developing countries: a case study from Cambodia.

INTRODUCTION: In contrast to the initial success following the establishment of the National Immunization Program (NIP) in Cambodia in 1986, infant vaccination coverage rates against the six expanded program immunization diseases have not improved since 1995. In response, the NIP of the Ministry of Health has undertaken a series of institutional initiatives to address the problem of static or declining rates of coverage. The aim of this paper is to describe and assess management strategies undertaken by the NIP in Cambodia in support of improved immunization coverage. METHODS: Sources of information used in preparing this report include international literature, national coverage and surveillance data, government policy documentation, information generated by national strategic planning and health centre microplanning processes, a functional analysis of human resources, and data quality audits. RESULTS: The NIP has implemented planning, organizational development and human resource development responses to the problem of low coverage. These have included: integration of the nip strategic and operational plans into the health sector plan; strengthening of needs-based microplanning; establishment of a national monitoring and management support strategy; and the introduction of performance-based agreements between levels of government for improved immunization coverage. CONCLUSIONS: Our analysis of these findings, in particular of the international literature, suggests that NIP's responses have been appropriate, and that the development of NIP management systems and capacity will increase the likelihood for sustained immunization coverage gains within a reform environment of health system decentralization. In 2003, there are early signs that the reform processes undertaken by the NIP have resulted in improved immunization coverage in targeted areas, and this should place the national program in a stronger position to lift immunization coverage in 2004.

Journal Article↗

The effects of a double blind, placebo controlled, artificial food colourings and benzoate preservative challenge on hyperactivity in a general population sample of preschool children.

AIMS: To determine whether artificial food colourings and a preservative in the diet of 3 year old children in the general population influence hyperactive behaviour. METHODS: A sample of 1873 children were screened in their fourth year for the presence of hyperactivity at baseline (HA), of whom 1246 had skin prick tests to identify atopy (AT). Children were selected to form the following groups: HA/AT, not-HA/AT, HA/not-AT, and not-HA/not-AT (n = 277). After baseline assessment, children were subjected to a diet eliminating artificial colourings and benzoate preservatives for one week; in the subsequent three week within subject double blind crossover study they received, in random order, periods of dietary challenge with a drink containing artificial colourings (20 mg daily) and sodium benzoate (45 mg daily) (active period), or a placebo mixture, supplementary to their diet. Behaviour was assessed by a tester blind to dietary status and by parents' ratings. RESULTS: There were significant reductions in hyperactive behaviour during the withdrawal phase. Furthermore, there were significantly greater increases in hyperactive behaviour during the active than the placebo period based on parental reports. These effects were not influenced by the presence or absence of hyperactivity, nor by the presence or absence of atopy. There were no significant differences detected based on objective testing in the clinic. CONCLUSIONS: There is a general adverse effect of artificial food colouring and benzoate preservatives on the behaviour of 3 year old children which is detectable by parents but not by a simple clinic assessment. Subgroups are not made more vulnerable to this effect by their prior levels of hyperactivity or by atopy.

Analysis of Variance↗

Overview of devolution of health services in the Philippines.

INTRODUCTION: In 1991 the Philippines Government introduced a major devolution of national government services, which included the first wave of health sector reform, through the introduction of the Local Government Code of 1991. The Code devolved basic services for agriculture extension, forest management, health services, barangay (township) roads and social welfare to Local Government Units. In 1992, the Philippines Government devolved the management and delivery of health services from the National Department of Health to locally elected provincial, city and municipal governments. AIM: The aim of this review is to (i) Provide a background to the introduction of devolution to the health system in the Philippines and to (ii) describe the impact of devolution on the structure and functioning of the health system in defined locations. METHOD: International literature was reviewed on the subjects of decentralization. Rapid appraisals of health management systems were conducted in both provinces. Additional data were accessed from the rural health information system and previous consultant reports. RESULTS: Subsequent to the introduction of devolution, quality and coverage of health services declined in some locations, particularly in rural and remote areas. It was found that in 1992-1997, system effects included a breakdown in management systems between levels of government, declining utilization particularly in the hospital sector, poor staff morale, a decline in maintenance of infrastructure and under financing of operational costs of services. CONCLUSION: The aim of decentralization is to widen decision-making space of middle level managers, enhance resource allocations from central to peripheral areas and to improve the efficiency and effectiveness of health services management. The findings of the historical review of devolution in the Philippines reveals some consistencies with the international literature, which describe some negative effects of decentralization, and provide a rationale for the Philippines in undertaking a second wave of reform in order to 'make devolution work'.

Journal Article↗

Can parents accurately perceive hyperactivity in their child?

In all, 1872 children were recruited as part of a larger study concerning food additives and behaviours in preschool children. This figure represented 70% of the whole population of 3 1/4 -year-old children resident on the Isle of Wight, UK. Parents completed an assessment concerning their perceptions of their child's behaviour. The results of this assessment were compared with scores on two validated parental questionnaires, the Weiss Werry Peters (WWP) hyperactivity scale and the Emotionality, Activity and Sociability Temperament Questionnaire (EAS), which were used to assess hyperactivity. The accuracy of parents in perceiving hyperactivity in their children was found to be around 50% if the child was hyperactive, and 89% if the child was not hyperactive. The implications of these findings for services are discussed. Frequencies of potential risk groups for future Attention Deficit Hyperactivity Disorder (ADHD) and Conduct Disorder were also suggested.

Child Behavior↗

Diabetes screening. Does it make a difference in the Aboriginal and Torres Strait Islander population?

BACKGROUND: The prevalence of diabetes in the Aboriginal and Torres Strait Islander population is relatively high. A high proportion of cases are undiagnosed. Diabetes is one of a number of increasingly prevalent chronic diseases which have been described collectively as a noncommunicable disease epidemic. OBJECTIVE: To review the existing literature relating to the actual or potential benefit of screening for diabetes in the Aboriginal and Torres Strait Islander population. DISCUSSION: There is a strong case for screening for diabetes as part of an opportunistic or planned periodic health examination (PHE). As well as fasting venous plasma glucose, this integrated approach should include assessment of weight, blood pressure, presence of microalbuminuria and hyperlipidaemia. General practitioners need to be sensitive to cultural issues and power relationships, as well as considering 'structural' impediments to good health, such as affordability and availability of nutritious food, rather than focus solely on individual 'lifestyle' issues.

Australia↗

Crystallization and stabilization of MB-1, a de novo designed protein for optimized feeding technology.

Milk Bundle-1 is a de novo protein that was designed for application in agriculture. It has a high content of selected essential amino acids, and is intended to adopt an alpha-helical bundle fold. Crystallization experiments with MB-1 have been carried out on the ground and in reduced gravity on board Columbia orbiter during mission STS-80. Rather small crystals were obtained (< 0.05 mm) in both environments. Among other factors, the lack of stability of purified MB-1 has been detrimental to crystal growth. We report here on our progress with regard to optimizing crystal growth conditions, protein purification and protein stability. The first MB-1 mutant we present (MB-1-His) contains a poly-histidine tail, allowing the use of metal affinity chromatography for purification. MB-1-His has been found to keep its original mass for a month at room temperature, a spectacular improvement over MB-1. The other mutant (MB-1-Cys) was engineered to carry a cysteine residue on a solvent exposed face. The exposed cysteine binds readily to p-HMB, and allows for dimerization of MB-1-Cys. The dimer was found to be twice as stable as MB-1 during proteolytic degradation studies.

Amino Acid Sequence↗

Immunisations after bone marrow transplantation: results of a European survey and recommendations from the infectious diseases working party of the European Group for Blood and Marrow Transplantation.

Increased numbers of recipients of BMTs and autologous BMTs are becoming long-term survivors. Existing data support that loss of protective immunity to agents such as tetanus and poliovirus is common in patients who received BMTs and autologous BMTs. Thus, a reimmunisation programme is needed to ensure immunity. A questionnaire concerning immunisation practices was sent to EBMT member centres. The immunisation practices varied extensively in the 59 responding BMT and 48 responding autologous BMT centres. Sixty five per cent of responding centres routinely immunise patients who received allogeneic BMTs whereas 37% were routinely immunising recipients of autologous BMTs. Tetanus toxoid and inactivated poliovirus vaccine were the most frequently used vaccines in both BMT and autologous BMT centres. Immunisations of recipients of both BMTs and autologous BMTs with tetanus toxoid, diphtheria toxoid, inactivated poliovirus vaccine and influenza vaccine are recommended. Other vaccines, and in particular live attenuated vaccines, may be considered on an individual basis.

Bone Marrow Transplantation↗

The specific recognition by macrophages of CD8+,CD45RO+ T cells undergoing apoptosis: a mechanism for T cell clearance during resolution of viral infections.

During viral infections, CD8+,CD45RO+ T populations expand. These primed cells express abundant levels of cytoplasmic granules that contain perforin and TIA-1. Recent work has suggested that the majority of this CD8+ population downregulates Bcl-2 protein expression and is destined to undergo apoptosis. In this study we have investigated the elimination of these apoptotic CD8+ T cells by both human monocyte-derived and murine bone marrow macrophages. We have found that these phagocytes recognize and ingest both apoptotic CD8+ and CD4+ T cells using an alpha v beta 3 (vitronectin receptor)/CD36/thrombospondin recognition system, with the same receptors being used in the recognition of apoptotic neutrophils. These data provide new evidence for a mechanism that enables the clearance of greatly increased populations of CD8+ effector cells which are found during viral infections. This enables cellular homeostasis to occur in the host upon resolution of viral diseases in vivo.

Amino Acid Sequence↗

Ca(2+)-mobilising agonists potentiate forskolin- and VIP-stimulated cAMP production in human colonic cell line, HT29-cl.19A: role of [Ca2+]i and protein kinase C.

This study has examined the involvement of the Ca(2+)-signalling pathway in the regulation of agonist-stimulated cAMP responses in the human colonic adenocarcinoma cell line, HT29-cl.19A. The muscarinic agonist, carbachol (CCh) stimualted rapid increases in cellular IP3 and cytosolic Ca2+, [Ca2+]i in HT29-cl.19A cells. These were accompanied by a small but significant increase in basal cAMP levels and a marked (3-4-fold) potentiation of both forskolin- (FSK) and VIP-stimulated cAMP generation. Similar effects were observed with two other Ca(2+)-mobilising agonists, neurotensin and ATP. The failure of CCh to elicit potentiation of adenylate cyclase in broken cell preparations indicated an indirect action. Potentiation could be mimicked by the calcium ionophore, ionomycin, and thapsigargin and inhibited 70-90% by depleting intracellular Ca2+ stores suggesting that a rise in [Ca2+]i is the primary mediator of this response. In contrast, increasing [Ca2+]i levels to > 500 nM caused a significant inhibition of FSK-stimulated cAMP generation. The involvement of protein kinase C (PKC) was also assessed. PKC activators phorbol 12,13 dibutyrate (PDB) and 1-oleoyl-2-acetyl glycerol (OAG) potentiated FSK-stimulated cAMP production by 50-70% though PDB markedly inhibited the cAMP response to the receptor-mediated cAMP agonist, VIP. Neither effect could be elicited by the inactive phorbol ester, 4 alpha-phorbol, 12,13 didecanoate (PDD). PKC inhibitors staurosporine and H7 reduced by approximately 25% the CCh-induced potentiation of FSK-stimulated cAMP generation. In conclusion, these results suggest that stimulation of the phosphoinositidase C pathway in HT29-cl.19A colonocytes induces a 'sensitisation' of the adenylate cyclase system resulting in a dramatic amplification of agonist-stimulated cAMP generation. Increases in [Ca2+]i appear to be an important mediator of potentiation though activation of PKC may also play a significant role.

Adenocarcinoma↗

Impact of liver disease and hepatitis infections on allogeneic bone marrow transplantation in Europe: a survey from the European Bone Marrow Transplantation (EBMT) Group--Infectious Diseases Working Party.

This survey investigated allogeneic bone marrow transplantation (BMT) policy in European BMT units by questionnaire, in relation to pre-transplant liver disease. It also assessed diagnostic standards for viral hepatitis infections and their prevalence in BMT candidates. Sixty-three EBMT centers from 22 countries participated in the survey. Median pre-transplant prevalences of HBsAg and anti-HCV positivity were 3.5% (range 0-15%) and 5% (range 0-45%), respectively. Forty-six (73%) centers adopt the policy of cancelling or postponing BMT in patients with ALT abnormalities but in four of these centers, BMT is not delayed when progressive disease or acute leukemia is present. In 17 institutions (27%) BMT was reported to be carried out irrespective of transaminase values. Data on fatal post-BMT liver disease were provided by 45 centers. The overall mortality rate for liver failure was 4.5% (258 of 5788) with no differences between centers performing or not performing BMT in cases of ALT elevation. These results indicate that there is strong concern in most European BMT units about performing BMT in the presence of ALT elevation and prospective studies on its real impact on fatal post-BMT liver disease should be conducted.

Alanine Transaminase↗

Multiple G-protein-dependent pathways mediate the antisecretory effects of somatostatin and clonidine in the HT29-19A colonic cell line.

Using the functionally differentiated colonic cell line, HT29-19A, we have examined sites at which inhibitory G-proteins mediate the antisecretory actions of somatostatin (SST) and the alpha 2-adrenergic agonist, clonidine (CLON) at the epithelial level. Both agents caused a dose-dependent inhibition (EC50:SST 35 nM; CLON 225 nM) of Cl- secretion (assessed by changes in short circuit current) activated by cAMP-mediated agonists, PGE2 and cholera toxin. Inhibition was accompanied by a reduction in intracellular cAMP accumulation and could be blocked by pretreatment with pertussis toxin at a concentration (200 ng/ml) which activated ADP-ribosylation of a 41-kD inhibitory G protein in HT29-19A membranes. Secretion stimulated by the permeant cAMP analogue, dibutyryl cAMP, was also inhibited by SST and CLON (30-50%; P < 0.005), indicating additional inhibitory sites located distal to cAMP production. Both agents were effective inhibitors of secretion mediated through the Ca2+ signaling pathway. SST (1 microM) and CLON (10 microM) reduced the Isc response to the muscarinic agonist, carbachol, by 60-70%; inhibition was reversed in pertussis toxin-treated cells. These effects did not, however, involve inhibition of the carbachol-induced increase in cellular inositol 1,4,5-trisphosphate levels or the rise in cytosolic calcium, [Ca]i. Inhibition by SST of secretion induced by phorbol 12,13 dibutyrate but not by the calcium agonist, thapsigargin, suggests that SST may act at a distal inhibitory site in the Ca(2+)-dependent secretory process activated by protein kinase C. We conclude that SST and alpha 2-adrenergic agonists can act directly on intestinal epithelial cells to exert a comprehensive inhibition of Cl- secretion mediated through both cAMP and Ca2+/protein kinase C signaling pathways. Inhibition is mediated via pertussis toxin-sensitive G-proteins at sites located both proximal and distal to the production of second messengers.

Adenocarcinoma↗

Practices for cytomegalovirus diagnosis, prophylaxis and treatment in allogeneic bone marrow transplant recipients: a report from the Working Party for Infectious Diseases of the EBMT.

During the past few years major progress has been made in the diagnosis and therapy of CMV infection after allogeneic BMT. The aim of this survey was to investigate the use of diagnostic techniques, use of prophylaxis and the therapeutic strategies among members of the EBMT. Seventy centers from 20 countries responded to the survey. Sixty-seven centers (96%) routinely tried to diagnose CMV from the blood. Fifty-seven centers used standard or rapid isolation techniques. Thirty-seven centers used one of the newly developed techniques, antigenemia detection in leukocytes or PCR together with isolation, while 10 centers used one of these two techniques without standard isolation. Fifty-five centers regularly performed bronchoscopy and bronchoalveolar lavage on the suspicion of CMV pneumonia but only 12 centers required detection of CMV in specimens from the lavage or lungs as the indication to start therapy; 31 centers started therapy on symptoms of pneumonia combined with CMV detection from any site. Prophylaxis was used in 54 centers (84%). The most commonly used regimen was high-dose acyclovir which was used by 42 centers, while seven centers used ganciclovir. The strategy of early therapy was used by 53 centers (76%) and was most frequently based on detection of viremia or CMV antigen in the blood. CMV pneumonia was treated by a combination of ganciclovir and i.v. immunoglobulin by 64 centers, by foscarnet and immunoglobulin in 5 centers and by ganciclovir alone in 5 centers. CMV gastrointestinal disease was treated by antiviral therapy alone in 18 centers and by a combination of antiviral therapy and iv immunoglobulin in 46 centers.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗

Production of anti-cytomegalovirus antibody following T-cell depleted bone marrow transplant.

The serological status to cytomegalovirus (CMV) was examined in 24 patients with no detectable CMV excretion, following T-lymphocyte depleted bone marrow transplantation. The results show that seropositive recipients continue to produce CMV antibody regardless of the serological status of the donor but that seronegative recipients fail to produce CMV antibody even when the donor is seropositive. These findings suggest that when an effective CMV vaccine becomes available vaccination of the donor would be unlikely to confer protection on the recipient but that vaccination of the recipient may achieve this.

Antibodies, Viral↗

T lymphocyte regeneration after transplantation of T cell depleted allogeneic bone marrow.

The regeneration of T cell subsets was studied with double immunofluorescence marker methods in 37 patients who received HLA matched T lymphocyte depleted bone marrow transplants (BMT) as part of the treatment for their haematological disease. A cocktail of anti-pan-T (CD6: MBG6) and anti-suppressor/cytotoxic-T cell (CD8: RFT8) monoclonal antibodies was used with rabbit serum as a source of cytolytic complement to achieve selective T cell lysis. The T8+ cells reached low normal values around 60 days post-transplant and remained within the normal range throughout the study (greater than 150 days). This observation is in contrast to our previously published results in patients who, after receiving BMT without efficient T cell depletion, had increased numbers of circulation T8+ cells from 60 days post-transplant. In the present study Leu-7+, RFT8- cells reached normal values rapidly but the reconstitution of T4+ lymphocytes was slow: low normal levels were reached only around day 150 following BMT. The degree of graft-versus-host disease (GVHD) seemed to be related to the number of residual T cells infused: two of the three patients who received the highest numbers of T cells developed Grade II III; otherwise GVHD was minimal. Among the clinical parameters studied cytomegalovirus (CMV) immune status moderately influenced reconstitution: at 55-90 days post-transplant T8+ cells were present at the upper normal levels in seven out of 15 patients receiving BMT from CMV seronegative donors, but in none of the 16 individuals receiving BMT from seropositive donors. CMV related complications were relatively uncommon. Thus the most significant factor in preventing 'T8+ cell overshoot' and T cell imbalance during regeneration appears to be the depletion of T (including T8+) lymphocytes from marrow. The differences of T8+ cell reconstitution in this and previous studies may reflect a different regeneration pattern from T cell precursors as opposed to inoculated mature T cells.

Adolescent↗

Dual-purpose midwifery.

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Community Health Nursing↗