The early external cephalic version 2 trial

Of almost 40,000 babies born in BC in 2002, nearly 2,000 (4.8 percent) were breech (their bottom and legs were born before their heads). Research shows that breech babies are most safely delivered by Caesarean section. However, Caesareans cause more complications than vaginal births, and the resulting scar on the uterus complicates subsequent pregnancies. When a baby is found to be in a breech position using ultrasound, care providers can try to turn a baby to a head down position by feeling the baby through the mother’s abdomen and moving the baby’s head downward and its bottom upward. This procedure is called external cephalic version (ECV), and studies have shown that the chance of both breech birth and Caesarean section is reduced if ECV is performed close to the end of pregnancy (after 37 weeks). Dr. Eileen Hutton and her team of researchers from across Canada are conducting The Early ECV 2 Trial, which is an international randomised controlled trial designed to investigate whether performing ECV earlier in pregnancy, at 34-35 weeks, further decreases the number of Caesarean sections without increasing the risk of preterm birth. Dr. Hutton, founder and editor of the Canadian Midwifery Journal of Research and Practice, is also involved in a large international trial investigating the best way for twins to be born (vaginally or by Caesarean section), and is doing work in BC investigating patient initiated Caesarean section.

Intestinal innate immunity: recognition and response to enteric bacterial pathogens

Bacterial infections of the gastrointestinal tract are very common, particularly among children. These infections cause diarrheal outbreaks and millions of deaths worldwide. Bacteria are also a major problem in Canada, with BC having one of the highest rates of intestinal bacterial infection in the country. Bacteria are believed to trigger a variety of gastrointestinal diseases, including inflammatory bowel disease, a debilitating and chronic condition that affects one in every 1,000 Canadians. Despite the prevalence of bacterial pathogens (disease-causing organisms), little is known about how the immune system recognizes and combats intestinal bacterial infections. This information is important because the immune response to these bacteria determines who is susceptible to infection, as well as the severity of the resulting disease. Dr. Bruce Vallance is researching how bacteria cause intestinal disease and how the immune system identifies and fights these infections. Dr. Vallance is investigating whether genetic differences in hosts influence susceptibility to food and water-borne bacteria. He aims to identify immune responses and genetic factors that either protects against intestinal bacteria or causes susceptibility to infection. This research could help explain how bacteria cause intestinal disease and ultimately lead to new treatments to prevent both bacterial infections and bacterial-induced gastrointestinal diseases.

Bioinformatics for the study of gene regulation

Genetic diseases can result from subtle variations in the DNA sequences of genes. Approximately three million differences exist between the DNA of any two individuals. While most of these differences have no functional impact, researchers have linked numerous variations to diseases. These linkages have provided insight into disease development, enabled the creation of diagnostic tests and accelerated the creation of therapeutics. Most of the known functional DNA variations result in decreased activity of proteins produced by a gene. But Dr. Wyeth Wasserman suspects many functional variations actually alter gene activity, rather than the sequence of proteins encoded by genes. This is because information flows from genes through an intermediate RNA molecule, and is translated to construct proteins. Variations that disrupt this flow could have dramatic consequences. Using bioinformatics (analysis of genetic data using advanced computing algorithms), Dr. Wasserman aims to identify regulatory variations that likely impact gene function and contribute to genetic diseases.

Role of Huntingtin phosphorylation by Akt in HD

Huntington’s disease (HD) is a fatal neurodegenerative disorder that usually begins in mid-life and causes progressive loss of motor control and mental capacity. One in 10,000 Canadians has this untreatable and devastating inherited disease. The HD gene produces the huntingtin protein, a protective molecule found in all regions of the human brain. However, when the HD gene mutates, it causes specific nerve cells to degenerate. Simon Warby aims to identify the factors that enable this location-specific and age-dependent degeneration in the brain. An important enzyme called Akt regulates the protective functions of huntingtin. Simon is investigating whether alterations in this enzyme and reduced levels of a molecule called BDNF (brain derived neurotrophic factor) turn off huntingtin’s protective functions. The research could contribute to therapies for reversing the degenerative process that characterize Huntington disease.

Regulation of energy balance in Stearoyl-CoA Desaturase-1 deficiency

Until recently, it was believed that the body burned fat only in response to hormones in the blood. However, new evidence shows that neurotransmitters in the brain play an active role in controlling energy use. Dr. William Gibson is studying how the brain uses the liver to control fat burning. He is investigating how the brain reduces activity of the SCD-1 enzyme (steroyl-CoA desaturase-1) to increase fat burning. Findings from this research may help to explain the molecular basis of human obesity, and lead to safe methods for reducing fat storage in people who are overweight and obese. Dr. Gibson also has a clinical interest in rare, monogenic obesity syndromes.

The nature and extent of genetic discrimination for presymptomatic individuals identified with an increased risk for Huntington's disease

A genetic test predicting onset of Huntington’s Disease (HD) has been available since 1986. Reports of discrimination resulting from genetic test results have been documented in the US and Great Britain and, while there are no published reports of such discrimination in Canada, research suggests that it occurs here as well. Yvonne Bombard is investigating discrimination faced by Canadians who test positive for genetic risk of HD, but have not yet developed outward symptoms. She is assessing the degree of discrimination they experience when trying to obtain extended health coverage, life and disability insurance, and employment, and comparing these findings to discrimination levels in the US and Australia. Results from the research could be used to inform social, legal and health policy related to predictive genetic testing.

FIND: Fundamental Innovation in Neurodegenerative Diseases

The goal of this research unit is to understand the molecular mechanisms leading to neuronal (brain cell) death in Huntington Disease, an incurable genetic disorder that usually strikes in mid-life, causing progressive, irreversible and ultimately fatal neurological damage. With a focus on the fundamental molecular structure and function of neurons, such research also has relevance in understanding the development and effects of other degenerative neurological disorders, such as Alzheimer’s and Parkinson’s Disease, and for understanding recovery from brain injury. As the study of disease reveals information about normal structure and function, this research will also contribute new knowledge about healthy brain development.

Continue reading “FIND: Fundamental Innovation in Neurodegenerative Diseases”

Focused attention, exploration and heart rate at 8-months in relation to prematurity and maternal interaction

Premature infants spend critical periods of early development in neonatal intensive care. The stress and pain experienced as part of early medical care can lead to the disorganization of infant behaviour or physiologic states, which may reflect risk for adverse neurodevelopment. Research links early stress to changes in brain stress circuits and heart rate regulation and follow-up studies show that high-risk premature infants have a high incidence of attention related deficits. Julianne Petrie-Thomas is examining the complex relationships between behavioural and physiological regulation of attention by studying focused attention and patterns of heart rate in premature infants at 8-months compared with term-born controls. As the infant’s interactions with its mother play an essential role in the regulation of behavioural as well as internal physiological systems, she is also studying the effects of maternal-infant interaction on infants’ behaviour and physiology. The findings could fill major gaps in understanding of how attention problems develop in premature infants and lead to interventions that significantly improve the developmental outcomes of these vulnerable babies.

CHIPS (control of hypertension in pregnancy study): a pilot trial

Almost 10 per cent of women who become pregnant develop hypertension (high blood pressure). Experts agree that pregnant women with severe hypertension should receive blood pressure medication to protect them from stroke. However, it is not clear if or how much the medication would benefit pregnant women with mild to moderate hypertension. A complicating factor is that the medication may also contribute to poorer growth and lower birth weight in babies, placing them at increased risk for health problems as newborns, children and adults. According to a national survey, Canadian obstetricians are unsure about prescribing blood pressure medication to women with mild to moderate hypertension. To help clarify the issue, Dr. Laura Magee and her research team have designed a Control of Hypertension in Pregnancy Study (CHIPS), aimed at determining if it is better for the baby (i.e. better growth before birth and better health thereafter) to allow a mother’s blood pressure to be higher than normal during pregnancy or to prescribe blood pressure medication to lower it. To begin, Dr. Magee is conducting a pilot trial to assess whether or not physicians would adhere to the treatment protocols in a full trial and to confirm if sufficient patients could be enrolled. If the pilot study indicates that CHIPS is feasible, the full trial will be conducted at major maternity centres across Canada.

Impact of delayed childbearing in BC, Canada

Women in developed societies around the world increasingly delay childbearing until the age of 35 or older. In BC, women who are 35 or older account for about 8,000 births a year. There has been little research into the effects of delayed childbearing, and studies that have been undertaken produced contrasting results. Some research suggested an increased risk of complications and other studies showed no greater risk. No research has compared differences in rural and urban settings. Sarka Lisonkova is investigating the impact of delayed childbearing on pregnancy outcomes and infants’ need for health care services in their first year. Using information on 200,000 births across the province from the BC Perinatal Database Registry, Sarka is comparing outcomes and health care utilization from births among 20 to 34-year-old mothers with those 35 and older. She is also reviewing the effect of risk factors for adverse pregnancy outcomes, such as smoking and fertility problems. The research could help improve prenatal counselling and risk assessment in prenatal care.