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Biomedical subjects

David Hill

Publications and source records attributed to David Hill.

At least 19 recordsLinked to original sources

Vitamin D Deficiency During Pregnancy Is Associated With Greater LDL-C Increase, Elevated β-Hydroxybutyrate and Altered Neonatal Metabolic Markers-A Secondary, Pooled Analysis of the Randomized, Controlled Vitamin D and Lifestyle for Gestational Diabetes Prevention Trial (DALI).

INTRODUCTION: Vitamin D (vitD) plays a role in metabolic regulation, including lipid metabolism and insulin sensitivity. During pregnancy, profound physiological changes in lipid handling and ketogenesis occur to support fetal development. However, the extent to which maternal vitamin D status influences these metabolic adaptations and fetal metabolic markers remains unclear. METHODS: In this secondary analysis, we examined lipid distribution throughout pregnancy-from before 20&#x2009;weeks' gestation to delivery-in women with overweight or obesity, stratified by vitamin D status (deficiency, insufficiency, or sufficiency), assessing both maternal and cord blood. Main inclusion criteria were: age&#x2009;>&#x2009;=18&#x2009;years, singleton pregnancy, <&#x2009;20&#x2009;weeks' gestation, BMI &#x2265;&#x2009;29&#x2009;kg/m2. Women with GDM <&#x2009;20&#x2009;weeks' gestation were excluded. In total, 962 pregnant women were divided into vitD deficient (<&#x2009;30&#x2009;nmol/L, n&#x2009;=&#x2009;102), insufficient (30-50&#x2009;nmol/L, n&#x2009;=&#x2009;222) and sufficient (>&#x2009;50&#x2009;nmol/L, n&#x2009;=&#x2009;638) groups. VitD levels and lipid concentrations were assessed at <&#x2009;20, 24-28 and 35-37&#x2009;weeks' gestation and in cord blood. RESULTS: Compared with vitD sufficient women, women with vitD deficiency had significantly larger increases in LDL-C throughout pregnancy and &#xdf;-OH-butyrate at 24-28&#x2009;weeks' gestation, in adjusted analysis. VitD in cord blood was highest in offspring of mothers with vitD sufficiency. In cord blood, significantly higher &#xdf;-OH-butyrate was observed with vitD deficiency; lipid concentrations were similar between groups. CONCLUSIONS: Early vitamin D deficiency before 20&#x2009;weeks of gestation was associated with altered metabolic trajectories during pregnancy, including greater increases in LDL cholesterol and ketone body concentrations in women with overweight or obesity, as well as higher cord blood ketone levels in their offspring. These findings suggest that early maternal vitamin D status may influence maternal and fetal metabolic adaptations, although causal relationships and clinical implications require further investigation. TRIAL REGISTRATION: Trial registered at ISRCTN registry (https://doi.org/10.1186/ISRCTN70595832) trial number ISRCTN70595832. Registration date 02/12/2011.

Humans↗

GoArrays: highly dynamic and efficient microarray probe design.

MOTIVATION: The use of oligonucleotide microarray technology requires a very detailed attention to the design of specific probes spotted on the solid phase. These problems are far from being commonplace since they refer to complex physicochemical constraints. Whereas there are more and more publicly available programs for microarray oligonucleotide design, most of them use the same algorithm or criteria to design oligos, with only little variation. RESULTS: We show that classical approaches used in oligo design software may be inefficient under certain experimental conditions, especially when dealing with complex target mixtures. Indeed, our biological model is a human obligate parasite, the microsporidia Encephalitozoon cuniculi. Targets that are extracted from biological samples are composed of a mixture of pathogen transcripts and host cell transcripts. We propose a new approach to design oligonucleotides which combines good specificity with a potentially high sensitivity. This approach is original in the biological point of view as well as in the algorithmic point of view. We also present an experimental validation of this new strategy by comparing results obtained with standard oligos and with our composite oligos. A specific E.cuniculi microarray will overcome the difficulty to discriminate the parasite mRNAs from the host cell mRNAs demonstrating the power of the microarray approach to elucidate the lifestyle of an intracellular pathogen using mix mRNAs.

Algorithms↗

The management of early breast carcinoma before and after the introduction of clinical practice guidelines.

BACKGROUND: Clinical practice guidelines for the management of breast carcinoma were introduced in Australia in October, 1995. This article describes the management of early-stage breast carcinoma both before and after the introduction of these guidelines. METHODS: All cases of early breast carcinoma that were diagnosed over the same 6-month period in 1995 and 1999 and registered with a state-based cancer registry were identified. Treating surgeons completed a survey assessing tumor characteristics and primary treatment. In 1995, 95% of 188 surgeons who were approached participated and 96% of the surveys were returned. In 1999, 92% of 159 surgeons who were approached participated and 91% of the surveys were returned. Analyses are based on 1066 cases from 1995 and 1001 cases from 1999. RESULTS: The pathologic disease stage of the patients was similar in both study years. The proportion of patients who underwent breast-conserving therapy (BCT) increased from 54% in 1995 to 69% in 1999. This increase was noted across most levels of disease characteristics but was not evident among those patients treated by the least active surgeons. The proportion of patients treated with BCT who received radiotherapy increased from 59% in 1995 to 80% in 1999. This trend was observed across most levels of tumor characteristics and surgeon caseload. The proportion of women with receptor-positive tumors who were treated with endocrine therapy increased, whereas the proportion of patients with receptor-negative tumors who received this therapy decreased from 39% in 1995 to 17% in 1999. CONCLUSIONS: The management of early breast carcinoma in the state of Victoria appeared to change between 1995 and 1999 in the direction expected if the national guidelines had been incorporated into the practice patterns of surgeons treating breast carcinoma patients.

Adult↗

The potential role of ultrasound in differentiating solid and cystic swellings of the true vocal fold.

UNLABELLED: This study was designed to investigate the potential role of ultrasound in the diagnosis of cysts of the true vocal fold. MATERIALS AND METHODS: Grayscale ultrasound of the larynx was carried out in 29 patients with a swelling of the true vocal fold and dysphonia. The findings were then compared with those at subsequent microlaryngoscopy, in the majority of cases. RESULTS AND CONCLUSIONS: Whereas preoperative laryngeal ultrasound correctly predicted the surgical findings of a cystic lesion in only 5 of 11 cases, it correctly identified that no cyst was present in 15 of 16 instances when this had been queried. This study suggests that ultrasound may have some role in investigation of unilateral vocal fold pathology, but that further fine-tuning of the technique may be necessary.

Adolescent↗

Dietary prevention of allergic diseases in infants and small children. Part I: immunologic background and criteria for hypoallergenicity.

The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light into this issue, a group of experts of the Section of Pediatrics EAACI critically reviewed the existing literature on the subject. In this paper, the immunology of the fetus and newborn is reviewed as well as the post-natal development of the immune system. The influence of post-natal environment and breastfeeding on tolerance induction and sensitization are examined. Allergic diseases result from a strong relationship between genetic and environmental factors. Sensitization to food allergens occurs in the first year of life and cow's milk allergy is the first food allergy to appear in the susceptible infants. Hypoallergenicity of food formulas to be used is a critical issue both for treatment of cow's milk-allergic children and for prevention. Methods to document hypoallergenicity are discussed and evaluated in the preclinical and clinical steps.

Breast Feeding↗

Dietary prevention of allergic diseases in infants and small children. Part III: Critical review of published peer-reviewed observational and interventional studies and final recommendations.

The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light on this issue, a group of experts of the Section of Pediatrics EAACI reviewed critically the existing literature on the subject. An analysis of published peer-reviewed observational and interventional studies was performed following the statements of evidence as defined by WHO. The results of the analysis indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is unequivocally effective in the prevention of allergic diseases in high-risk children. In these patients breastfeeding combined with avoidance of solid food and cow's milk for at least 4-6 months is the most effective preventive regimen. In the absence of breast milk, formulas with documented reduced allergenicity for at least 4-6 months should be used.

Breast Feeding↗

Dietary prevention of allergic diseases in infants and small children. Part II. Evaluation of methods in allergy prevention studies and sensitization markers. Definitions and diagnostic criteria of allergic diseases.

The role of primary prevention of allergic disease has been a matter of debate for the last 40 years. In order to shed some light into this issue a group of experts of the Section of Pediatrics EAACI critically reviewed the existing literature on the subject. The design of observational and interventional studies was evaluated with relevance to the important factors influencing outcome of studies on allergy development/prevention. in this analysis the statements of evidence as defined by WHO were applied. Best evidence of recommendations are those fulfilling the criteria for statements category 1 and 2 and grade of recommendations A and B as proposed by WHO. This survey include target group for dietary prevention and methods and diagnostic criteria of atopic dermatitis, asthma and food allergy for prevention studies.

Asthma↗

Bone marrow-derived stem cells initiate pancreatic regeneration.

We show that transplantation of adult bone marrow-derived cells expressing c-kit reduces hyperglycemia in mice with streptozotocin-induced pancreatic damage. Although quantitative analysis of the pancreas revealed a low frequency of donor insulin-positive cells, these cells were not present at the onset of blood glucose reduction. Instead, the majority of transplanted cells were localized to ductal and islet structures, and their presence was accompanied by a proliferation of recipient pancreatic cells that resulted in insulin production. The capacity of transplanted bone marrow-derived stem cells to initiate endogenous pancreatic tissue regeneration represents a previously unrecognized means by which these cells can contribute to the restoration of organ function.

Animals↗

WorfDB: the Caenorhabditis elegans ORFeome Database.

WorfDB (Worm ORFeome DataBase; http://worfdb.dfci.harvard.edu) was created to integrate and disseminate the data from the cloning of complete set of approximately 19 000 predicted protein-encoding Open Reading Frames (ORFs) of Caenorhabditis elegans (also referred to as the 'worm ORFeome'). WorfDB serves as a central data repository enabling the scientific community to search for availability and quality of cloned ORFs. So far, ORF sequence tags (OSTs) obtained for all individual clones have allowed exon structure corrections for approximately 3400 ORFs originally predicted by the C. elegans sequencing consortium. In addition, we now have OSTs for approximately 4300 predicted genes for which no ESTs were available. The database contains this OST information along with data pertinent to the cloning process. WorfDB could serve as a model database for other metazoan ORFeome cloning projects.

Animals↗

Rectal surgery for endometriosis--should we be aggressive?

STUDY OBJECTIVE: To assess the outcome of aggressive but conservative laparoscopic surgery in the treatment of severe endometriosis involving the rectum. DESIGN: Retrospective study (Canadian Task Force classification III). SETTING: Endosurgery unit of a tertiary referral center. PATIENTS: One hundred sixty-nine women. INTERVENTION: Laparoscopy or laparotomy. MEASUREMENTS AND MAIN RESULTS: The procedure was completed successfully laparoscopically in 145 (86%) and by laparotomy in 24 women (14%). The rate of preoperative symptoms was higher in 25 women who underwent bowel resection compared with those who had other bowel surgery. In addition to bowel surgery, excision of uterosacral ligaments, adhesiolysis, excision of endometrioma, and oophorectomy were the four most commonly performed procedures. At 35-month follow-up 61 patients (36%) required further surgery for pain. The average time between primary and repeat surgery was 16 months. This second operation was performed by laparoscopy in over three-fourths of the women. Overall recurrent endometriosis was found in 26 patients (15%). Overall morbidity associated with all surgery was 12.4%. CONCLUSION: Surgery for endometriosis of the cul-de-sac and bowel involves some of the most difficult dissections encountered, but it can be accomplished successfully with the low postoperative morbidity typical of laparoscopy.

Adult↗

Taurine supplementation of a low protein diet fed to rat dams normalizes the vascularization of the fetal endocrine pancreas.

In rats, an isoenergetic low protein diet (LP) given throughout gestation perturbs the development of the endocrine pancreas by reducing beta-cell mass and islet vascularization at birth. Taurine, an important amino acid during development, has been found to be low in fetal and maternal plasma. When added to a LP diet, taurine normalizes beta-cell mass. Therefore, we investigated the ability of taurine to correct altered islet vascularization. Rats were given 20% [control (C)] or 8% (LP) protein in the diet with or without supplementation with 25 g/L taurine (T) in drinking water (C+T and LP+T) during gestation and lactation. Immunostaining for vascular endothelial growth factor (VEGF) and fetal liver kinase-1 (Flk-1), a VEGF receptor, was performed on fetal and neonatal pancreatic sections. Blood vessel density and blood vessel number were analyzed morphometrically on semi-thin sections. Taurine supplementation restored a normal volume and numerical density of vessels in fetal islets. The number of cells showing immunoreactivity for VEGF and Flk-1 was reduced by 33 and 45%, respectively, in islet cells from LP fetuses. In 1-mo-old pups, VEGF-positive cells remained decreased by nearly 22%. Both VEGF and Flk-1 were restored in pancreatic endocrine cells of fetuses and pups given taurine. The LP diet induced a threefold overexpression of Flk-1 in ductal cells, which contain precursors of beta cells. However, taurine supplementation was without effect. In conclusion, underexpression of VEGF and Flk-1 is associated with the lower fetal islet vascularization induced by the maternal malnutrition. The addition of taurine to the maternal diet prevents such damage and has a potential role in islet vasculogenesis.

Animals↗

Association between exposure to workplace secondhand smoke and reported respiratory and sensory symptoms: cross-sectional study.

The purpose of this work was to assess the relation between exposure to secondhand smoke (SHS) at work and reported respiratory and sensory symptoms. A cross-sectional telephone survey of 382 nonsmoking indoor workers in Victoria, Australia was used. After controlling for potential confounders, exposure to SHS at work for part of the day was significantly associated with an increased risk of wheeze (OR = 4.26), frequent cough (OR = 2.26), sore eyes (OR = 3.77), and sore throat (OR = 2.70). Among workers who had not experienced a cold in the past 4 weeks, we found strong dose-response relationships between increasing levels of exposure to SHS at work and morning cough, frequent cough, sore eyes and sore throat, and a positive relationship for wheeze. These findings provide compelling evidence that nonsmoking indoor workers are adversely affected by exposure to SHS at work and underline the importance of workplace smoke-free policies in protecting the health of workers.

Adult↗

Management of mental illness by the British Army.

BACKGROUND: The Ministry of Defence has its own hospital for soldiers requiring admission for mental health problems. AIMS: To assess the efficiency of the army psychiatric hospital at restoring patients to full active duty. To assess whether a new military training and rehabilitation unit (MTRU) that emphasises military-skills training, improves outcome. METHOD: A 2-year, inception-cohort outcome study of hospital in-patients. A 12-month, case-matched, 'before and after' outcome study compared MTRU patients with hospital in-patients. RESULTS: I (hospital in-patients, n=309): at 2-year follow-up 67 (22%) were fully fit for active duty. Military psychiatrists' success rate at predicting recovery to active duty was 27%. 2: the odds of a soldier in the MTRU cohort (n=35) returning to active duty were 14 times greater than for the hospital cohort (n=35). The odds of remaining in the army while unfit for active duty were 20 times less for the MTRU than for the hospital cohort. CONCLUSIONS: The army hospital is inefficient at rehabilitation to active duty. The MTRU significantly increased the odds of returning to active duty and reduced the odds of remaining in the army while still unfit. These findings may be applicable to the emergency services.

Adolescent↗

Bridging the information and support gap: evaluation of a hospital-based cancer support nurse service.

Health professionals play an important role in meeting the information and support needs of individuals following a diagnosis of cancer. The aim of this study was to evaluate the acceptability and impact of a hospital-based cancer support nurse (CSN) service. A total of 98 patients completed a structured telephone interview after discharge concerning their use, perceptions and satisfaction with the service. The majority of patients perceived service delivery to be appropriate and reported that they had gained both information and support. The service also had a positive impact on behavioural, cognitive and affective outcomes. Overall satisfaction with the service was very high. Results indicate that a hospital-based cancer support nurse service provides a promising model for meeting the early information and support needs of patients, thereby promoting continuity of care.

Adaptation, Psychological↗

A prospective randomised double-blind placebo controlled trial to assess whether gas drains reduce shoulder pain following gynaecological laparoscopy.

OBJECTIVE: To assess the effects on patient discomfort of an intraabdominal passive gas drain left for four hours postoperatively following gynaecologic laparoscopic surgery. DESIGN: A prospective randomised double-blinded placebo controlled trial. SETTING: University tertiary hospital and private hospital. POPULATION OR SAMPLE: Eighty women having a laparoscopic gynaecological procedure for benign disease. METHODS: A drain was placed via the umbilical port at the conclusion of the surgical procedure and was removed four hours postoperatively. The researcher, assessor and patient were all blinded as to the patency or occlusion of the drain. Patients were asked to complete questionnaires at regular intervals up to five days postoperatively. MAIN OUTCOME MEASURES: Visual analogue scale (VAS) to assess overall pain, shoulder and chest pain, abdominal pain, bloating and energy prior to surgery and at intervals up to five days postoperatively. RESULTS AND CONCLUSIONS: No complications were attributed to the presence and withdrawal of the drain tube. Shoulder pain following operative or diagnostic laparoscopy was significantly reduced for 12, 24, 48 and 72 hours by the presence of a patent passive gas drain for the first four hours postoperatively. The drains were easy to use and had no associated morbidity We recommend that in the absence of the need for an active drain, all patients undergoing laparoscopy should have a gas drain inserted for a period of four hours after the completion of the procedure.

Adult↗

Changes in the use of tobacco among Australian secondary students: results of the 1999 prevalence study and comparisons with earlier years.

OBJECTIVE: To estimate smoking prevalence among Australian secondary students in 1999 and to examine trends in smoking-related behaviours since 1984. METHOD: A randomly selected representative sample of 399 secondary schools from across Australia participated in the study. At each school, up to 80 randomly selected students completed a pencil-and-paper questionnaire anonymously. Data from 25,486 students aged between 12 and 17 years are reported. RESULTS: Current smoking (smoking in the week before the survey) was 6% in boys and girls aged 12, and rose to a peak prevalence among 17-year-olds of 33% for boys and 30% for girls. Comparisons across survey years showed that while fewer 12-to-15-year-olds were current smokers in 1999 than in 1996, among 16- and 17-year-olds, the proportion of current smokers in 1999 and 1996 was similar. Students who smoked were less likely to buy their cigarettes in 1999 than in previous surveys. Both older and younger secondary students were more likely to have received lessons about tobacco in the school year prior to the 1999 survey than were students in the 1996 survey. CONCLUSION: The rise in the prevalence of smoking among younger secondary students seen in the 1990s seems to have stopped and smoking prevalence has declined. IMPLICATIONS: Extrapolating from this survey, we estimate that nearly 269,000 12-to-17-year-old students were current smokers in 1999. If they all continue to smoke, 134,000 would die prematurely.

Adolescent↗