Biomedical subjects

David Hill

Publications and source records attributed to David Hill.

At least 19 recordsLinked to original sources

PubMed2026

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 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 > =18 years, singleton pregnancy, < 20 weeks' gestation, BMI ≥ 29 kg/m2. Women with GDM < 20 weeks' gestation were excluded. In total, 962 pregnant women were divided into vitD deficient (< 30 nmol/L, n = 102), insufficient (30-50 nmol/L, n = 222) and sufficient (> 50 nmol/L, n = 638) groups. VitD levels and lipid concentrations were assessed at < 20, 24-28 and 35-37 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 ß-OH-butyrate at 24-28 weeks' gestation, in adjusted analysis. VitD in cord blood was highest in offspring of mothers with vitD sufficiency. In cord blood, significantly higher ß-OH-butyrate was observed with vitD deficiency; lipid concentrations were similar between groups. CONCLUSIONS: Early vitamin D deficiency before 20 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↗

PubMed2006

Pharmacological characterization of novel water-soluble cannabinoids.

Presently, there are numerous structural classes of cannabinoid receptor agonists, all of which require solubilization for experimental purposes. One strategy for solubilizing water-insoluble tetrahydrocannabinols is conversion of the phenolic hydroxyl to a morpholinobutyryloxy substituent. The hydrochloride salts of these analogs are water-soluble and active in vivo when administered in saline. The present investigation demonstrated that hydrochloride salts of numerous substituted butyryloxy esters are water-soluble and highly potent. The substitutions include piperidine, piperazine, and alkyl-substituted amino moieties. It was also discovered that incorporation of a nitrogenous moiety in the alkyl side chain increased the pharmacological potency of tetrahydrocannabinol. For example, an analog containing a pyrazole in the side chain (O-2545) was found to have high affinity and efficacy at cannabinoid 1 (CB(1)) and CB(2) receptors, and when dissolved in saline, it was highly efficacious when administered either intravenously or intracerebroventricularly to mice. A series of carboxamido and carboxylic acid amide analogs exhibited high pharmacological potency, but their hydrochloride salts were not water-soluble. On the other hand, incorporation of imidazoles into the terminus of the side chain led to water-soluble hydrochloride salts that were highly potent when administered in saline to laboratory animals. It is now possible to conduct cannabinoid research with agonists that are water-soluble and thus obviating the need of solubilizing agents.

Animals↗

PubMed2006

Australian public's views on privacy and health research.

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Attitude to Health↗

PubMed2006

Rescue intracytoplasmic sperm injection and preimplantation genetic diagnosis in combination can result in pregnancy.

OBJECTIVE: To report the birth of a baby from the transfer of one embryo after rescue intracytoplasmic sperm injection (ICSI) and preimplantation genetic diagnosis (PGD). DESIGN: Case report. SETTING: IVF center. PATIENT(S): A 42-year-old G2P0020 woman with unexplained infertility. INTERVENTION(S): Rescue ICSI followed by PGD. MAIN OUTCOME MEASURE(S): Pregnancy. RESULT(S): Rescue ICSI was performed on seven unfertilized oocytes, which resulted in three embryos. The PGD analysis revealed one normal embryo, which was transferred and resulted in pregnancy and delivery. CONCLUSION(S): Rescue ICSI in combination with PGD can result in a successful pregnancy.

Adult↗

PubMed2006

Stem cell research in a Catholic institution: yes or no?

Catholic teaching has no moral difficulties with research on stem cells derived from adult stem cells or fetal cord blood. The ethical problem comes with embryonic stem cells since their genesis involves the destruction of a human embryo. However, there seems to be significant promise of health benefits from such research. Although Catholic teaching does not permit any destruction of human embryos, the question remains whether researchers in a Catholic institution, or any researchers opposed to destruction of human embryos, could participate in research on cultured embryonic stem cells, or whether a Catholic institution could use any therapy that ultimately results from such research. This position paper examines how such research could be conducted legitimately in a Catholic institution by using an ethical analysis involving a narrative context, the nature of the moral act, and the principle of material cooperation, along with references to significant ethical assessments. It also offers tentative guidelines that could be used by a Catholic institution in implementing such research.

Aborted Fetus↗

PubMed2006

Transcript annotation in FANTOM3: mouse gene catalog based on physical cDNAs.

The international FANTOM consortium aims to produce a comprehensive picture of the mammalian transcriptome, based upon an extensive cDNA collection and functional annotation of full-length enriched cDNAs. The previous dataset, FANTOM2, comprised 60,770 full-length enriched cDNAs. Functional annotation revealed that this cDNA dataset contained only about half of the estimated number of mouse protein-coding genes, indicating that a number of cDNAs still remained to be collected and identified. To pursue the complete gene catalog that covers all predicted mouse genes, cloning and sequencing of full-length enriched cDNAs has been continued since FANTOM2. In FANTOM3, 42,031 newly isolated cDNAs were subjected to functional annotation, and the annotation of 4,347 FANTOM2 cDNAs was updated. To accomplish accurate functional annotation, we improved our automated annotation pipeline by introducing new coding sequence prediction programs and developed a Web-based annotation interface for simplifying the annotation procedures to reduce manual annotation errors. Automated coding sequence and function prediction was followed with manual curation and review by expert curators. A total of 102,801 full-length enriched mouse cDNAs were annotated. Out of 102,801 transcripts, 56,722 were functionally annotated as protein coding (including partial or truncated transcripts), providing to our knowledge the greatest current coverage of the mouse proteome by full-length cDNAs. The total number of distinct non-protein-coding transcripts increased to 34,030. The FANTOM3 annotation system, consisting of automated computational prediction, manual curation, and final expert curation, facilitated the comprehensive characterization of the mouse transcriptome, and could be applied to the transcriptomes of other species.

Animals↗

PubMed2006

GH in the dwarf dopaminergic D2 receptor knockout mouse: somatotrope population, GH release, and responsiveness to GH-releasing factors and somatostatin.

Recently, the importance of the dopaminergic D2 receptor (D2R) subtype in normal body growth and neonatal GH secretion has been highlighted. Disruption of D2R alters the GHRH-GH-IGF-I axis and impairs body growth in adult male mice. The D2R knockout (KO) dwarf mouse has not been well characterized; we therefore sought to determine somatotrope function in the adult pituitary. Using immunohistochemistry and confocal microscopy, we found a significant decrease in the somatotrope population in pituitaries from KO mice (P=0.043), which was paralleled by a decreased GH output from pituitary cells cultured in vitro. In cells from adult mice the response amplitude to GHRH differed between genotypes (lower in KO), but this difference was less dramatic after taking into account the lower basal release and hormone content in the KO cells. Furthermore, there were no significant differences in cAMP generation in response to GHRH between genotypes. By Western blot, GHRH-receptor in pituitary membranes from KO mice was reduced to 46% of the level found in wildtype (WT) mice (P=0.016). Somatostatin induced a concentration-dependent decrease in GH and prolactin (PRL) secretion in both genotypes, and 1x10(-7) M ghrelin released GH in cells from both genotypes (P=0.017) in a proportionate manner to basal levels. These results suggest that KO somatotropes maintain a regulated secretory function. Finally, we tested the direct effect of dopamine on GH and PRL secretion in cells from both genotypes at 20 days and 6 months of life. As expected, we found that dopamine could reduce PRL levels at both ages in WT mice but not in KO mice, but there was no consistent effect of the neurotransmitter on GH release in either genotype at the ages studied. The present study demonstrates that in the adult male D2R KO mouse, there is a reduction in pituitary GH content and secretory activity. Our results point to an involvement of D2R signaling at the hypothalamic level as dopamine did not release GH acting at the pituitary level either in 1-month-old or adult mice. The similarity of the pituitary defect in the D2R KO mouse to that of GHRH-deficient models suggests a probable mechanism. A loss of dopamine signaling via hypothalamic D2Rs at a critical age causes the reduced release of GHRH from hypophyseotropic neurons leading to inadequate clonal expansion of the somatotrope population. Our data also reveal that somatotrope cell number is much more sensitive to changes in neonatal GHRH input than their capacity to develop properly regulated GH-secretory function.

Animals↗

PubMed2006

Residential radon and lung cancer--detailed results of a collaborative analysis of individual data on 7148 persons with lung cancer and 14,208 persons without lung cancer from 13 epidemiologic studies in Europe.

OBJECTIVES: Studies seeking direct estimates of the lung cancer risk associated with residential radon exposure lasting several decades have been conducted in many European countries. Individually these studies have not been large enough to assess moderate risks reliably. Therefore data from all 13 European studies of residential radon and lung cancer satisfying certain prespecified criteria have been brought together and analyzed. METHODS: Data were available for 7148 persons with lung cancer and 14,208 controls, all with individual smoking histories and residential radon histories determined by long-term radon gas measurements. RESULTS: The excess relative risk of lung cancer per 100 Bq/m3 increase in the observed radon concentration was 0.08 [95% confidence interval (95% CI) 0.03-0.16; P=0.0007] after control for confounding. The dose-response relationship was linear with no evidence of a threshold, and it remained significant when only persons with observed radon concentrations of <200 Bq/m3 were included. There was no evidence that the excess relative risk varied with age, sex, or smoking history. Removing the bias induced by random uncertainties related to radon exposure assessment increased the excess relative risk of lung cancer to 0.16 (95% CI 0.05-0.31) per 100 Bq/m3. With this correction, estimated risks at 0, 100, and 400 Bq/m3, relative to lifelong nonsmokers with no radon exposure, were 1.0, 1.2, and 1.6 for lifelong nonsmokers and 25.8, 29.9, and 42.3 for continuing smokers of 15-24 cigarettes/day. CONCLUSIONS: These data provide firm evidence that residential radon acts as a cause of lung cancer in the general population. They provide a solid basis for the formulation of policies with which to manage risk from radon and reduce deaths from the most common fatal cancer in Europe.

Case-Control Studies↗

PubMed2005

Three dimensional/four dimensional ultrasound-guided embryo transfer using the maximal implantation potential point.

OBJECTIVE: To evaluate the use of maximal implantation potential (MIP) point in conjunction with a 3D/4D ultrasound in order to facilitate embryo transfers and potentially improve pregnancy rate. DESIGN: Retrospective, observational study. SETTING: IVF Center. PATIENT(S): Between October 1, 2002, and August 27, 2004, 1,222 patients who underwent 3D/4D-ultrasound guided embryo transfers. INTERVENTION(S): Ultrasound-guided embryo transfer using a 3D/4D ultrasound machine and the MIP point. MAIN OUTCOME MEASURE(S): Procedure feasibility with improved visibility. RESULT(S): Embryo transfers were performed at the MIP point and the pregnancy rate was 36.66% (average patient age, 37.6 years). Physicians reported improved visualization and a greater accuracy in the placement of embryos within the uterine cavity. CONCLUSION(S): The MIP point can be immediately identified and individualized for each patient. Embryo transfers at the MIP were associated with good implantation and pregnancy rates.

Embryo Implantation↗

PubMed2005

What features do patients notice that help to distinguish between benign pigmented lesions and melanomas?: the ABCD(E) rule versus the seven-point checklist.

The ABCD(E) rule and the seven-point checklist are diagnostic aids that have proven to be useful in the hands of physicians; however, little is known of their value to patients with respect to aiding self-detection. The objective of this study was to investigate features that patients notice when identifying melanomas and to explore how well these features correspond to the ABCD(E) rule and the seven-point checklist. A retrospective, modified, case-control study involving patient interviews was performed. All interviews were conducted through the private consulting rooms of a Melbourne dermatologist (JWK) and a Newcastle plastic surgeon (CH) prior to the result of pathology being known to the patients and the interviewers. Sixty-seven patients with benign pigmented skin lesions and 46 patients with melanomas were included. Using a logistic regression model, the change in size/new lesion and change in colour (major criteria, seven-point checklist) were most useful in differentiating between melanomas and benign pigmented lesions in the hands of patients [odds ratio (OR), 4.74; 95% confidence interval (CI), 1.85-12.19; P=0.001; OR, 4.27; 95% CI, 1.62-11.26; P=0.003, respectively). The ABCD(E) rule failed to discriminate between melanoma and other benign pigmented skin lesions. It can be concluded that, of the patients' observations, changes in size or colour were most important in distinguishing between benign pigmented lesions and melanomas. Such features therefore deserve emphasis in public education campaigns. Medical professionals should also remember to seek a history of change in assessing pigmented skin lesions.

Case-Control Studies↗

PubMed2005

A comparison of radial artery blood pressure determination between the Vasotrac device and invasive arterial blood pressure monitoring in adolescents undergoing scoliosis surgery.

UNLABELLED: The Vasotrac device (Medwave, Arden Hills, MN) allows noninvasive measurement of arterial blood pressure (BP) and arterial waveform. We have previously demonstrated agreement between the Vasotrac and continuous intraarterial BP monitoring in children with a stable circulation after cardiac surgery in the cardiac intensive care unit. To assess this monitor during different physiologic conditions, we studied the Vasotrac in anesthetized adolescent children undergoing scoliosis surgery in the prone position, with or without controlled hypotension. Eleven children undergoing surgery for idiopathic scoliosis were enrolled in this study. The anesthetic consisted of primarily a nitrous oxide and narcotic technique with controlled hypotension obtained using IV labetalol. Data were analyzed using correlations, mean error, and Bland-Altman plots. Noninvasive BP measured by the Vasotrac correlated closely with intraarterial BP. Waveforms displayed by the two systems were qualitatively similar. Correlation between the two methods for systolic, diastolic and mean BP was r = 0.82, r = 0.83, and r = 0.90, respectively. We conclude that noninvasive BP measurement using the Vasotrac monitor enables near-continuous and reliable monitoring of BP during anesthesia in the prone position and pharmacologic-induced hypotension. IMPLICATIONS: The Vasotrac, a noninvasive arterial blood pressure monitor, performs well in the prone position in adolescent patients undergoing scoliosis surgery using a technique of mild-to-moderate induced hypotension.

Adolescent↗

PubMed2005

The feasibility of voluntary counselling and HIV testing for pregnant women using community volunteers in Zimbabwe.

The purpose of this pilot project was to assess the feasibility and acceptability of voluntary counselling and HIV testing (VCT) by pregnant women using community volunteers in Zimbabwe to prevent mother to child transmission (MTCT) of HIV. From July 1999 to June 2001, a short-course zidovudine (ZDV)-based perinatal HIV prevention programme was initiated in two antenatal clinics. Community volunteers, recruited from local community organizations, underwent a two-week training course in VCT, which included HIV/AIDS facts, systematic counselling approach, and practical counselling techniques using scripts and role-play. Rapid HIV testing was performed after informed consent. Lay counsellors conducted individual pre- and post-test counselling for HIV. A total of 35 women community volunteers were trained in VCT; 34 graduated and committed to work four hours per week in the clinic. Of the 6051 pregnant women presenting for antenatal clinics (ANC), 1824 (30%) underwent pre-test counselling and 1547 (26%) were tested, and 429 (28%) were HIV infected. Overall, 1283 (83%) returned for their test results including 406 (95%) of HIV-infected women. Of the 406 HIV-infected women who collected their test results, only 203 (50%) opted for ZDV prophylaxis to prevent MTCT of HIV. Over the two-year study period, two counsellors died and three sought employment at other organizations. Adherence to duty roster was 97% and no breach of confidentiality was reported. Despite many challenges, VCT delivered by community volunteers is feasible and acceptable for pregnant women aiming to reduce their risk of transmitting HIV to their infants. This programme is being implemented at several urban and rural MTCT sites in Zimbabwe and can serve as a model for other resource-poor countries.

AIDS Serodiagnosis↗

PubMed2004

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↗

PubMed2004

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↗

PubMed2004

Skin cancer prevention: a commentary.

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Female↗

PubMed2004

Alternative for primary pericardial closure: sentry for re-entry.

BACKGROUND: Redo cardiac surgery is considered high-risk surgery as accidental injury to the aorta, the innominate vein, the ventricles and the atria is a possibility. Such accidental injury occurs when the cardiac chamber is adherent to the undersurface of the sternum. Closure of pericardium at the time of primary surgery can prevent adherence of cardiac chambers to the sternum, but may increase the risk of tamponade. This study aimed to show that covering heart with a pedicled pericardial fat pad not only serves the purpose of cover but also avoids the adverse haemodynamic effects of primary pericardial closure. METHODS: Forty patients undergoing elective cardiac surgery were randomised into two groups depending on the way pericardium was managed. Both techniques were already in routine use in our unit and in other units around the country. One method is to leave the pericardium widely open, the other is to loosely oppose the pericardial fat pad over the surface of the aorta and right ventricle. Twenty-three patients had a pedicled pericardial fat pad covering the heart: Closure Group. Seventeen patients had no pericardial fat pad cover over the heart: Open Group. A haemostasis clip was used as a radio-opaque marker over the epicardium in both groups. Post-operation heart rate, central venous pressure, pulmonary artery diastolic pressure, mean arterial pressure and cardiac index were measured and recorded 1, 3 and 8h after surgery. The distance between the haemoclip and the posterior table of the sternum was measured at 6 days and 6 months post-operation. Haemodynamic parameters and the retrosternal space depth were compared between the two groups. RESULTS: There were no important differences in haemodynamic parameters between the two groups. Post-operative lateral chest Roentgenograms showed that the distance between epicardial surface and the posterior table of sternum was larger in the Closure Group compared to Open Group on post-operative day 6, 17.5+/-1.0mm versus 13.4+/-1.3mm (P=0.0013) and 6 months later, 12.3+/-0.8mm versus 6.0+/-1.2mm (P<0.001). There was no mortality in either group. CONCLUSION: Pedicled pericardial fat pad cover is a good alternative to primary pericardial closure as there are no adverse haemodynamic effects in early post-operative period and the long-term benefit of protection of heart at the time of re-sternotomy can be expected.

Journal Article↗

PubMed2004

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↗

PubMed2004

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↗