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1.  Polymorphism in the Angiotensin II Type 1 Receptor (AGTR1) is Associated with Age at Diagnosis in Pulmonary Arterial Hypertension 
Pulmonary arterial hypertension (PAH) is a rare, lethal disease associated with single gene disorders, connective tissue disease, exposures to anorexigens, and often idiopathic etiology. There is evidence that genes can modify the risk of PAH: 1) monogenic disorders associated with PAH are incompletely penetrant, and 2) not all patients with associated conditions at increased risk for PAH develop the disease. The renin angiotensin aldosterone system (RAAS) provides a set of candidate genes that could modulate pulmonary vascular disease similar to its effects on renal and peripheral vasculature.
We studied 247 subjects with PAH (177 subjects with idiopathic PAH (IPAH); 63 subjects with PAH/connective tissue disease (CTD); and 7 subjects with PAH associated with anorexigens). Subjects were genotyped for five common polymorphisms in angiotensinogen (AGT), angiotensin converting enzyme (ACE), cardiac chymase A (CMA1), angiotensin II type 1 receptor (AGTR1) and aldosterone synthase (CYP11B2). Genotypes were tested for associations with age at diagnosis, hemodynamic parameters at diagnosis, and/or response to acute pulmonary vasodilator testing at diagnosis.
Associations were demonstrated for AGTR1 and age at diagnosis in IPAH (p=0.005). Homozygotes for the C1166 allele (n=13) were associated with an age at diagnosis 26 years later than subjects with A/A (n=139) or A/C (n=90) genotypes. No associations were demonstrated for AGT, ACE, CMA1, or CYP11B2.
The 1166C polymorphism in AGTR1 appears to be associated with a later age at diagnosis in IPAH suggesting that this pathway could be involved in the biologic variability that is known to occur in PAH.
PMCID: PMC3712279  PMID: 19332265
genetic; pulmonary hypertension; renin; angiotensin; aldosterone
2.  FRAX or Fiction: Determining Optimal Screening Strategies for Treatment of Osteoporosis in Residents in Long Term Care Facilities 
Osteoporosis and fractures are common in long term care residents but little data are available on screening strategies for treatment of such patients.
Cross-sectional analysis to examine screening strategies for treatment.
Assisted living or skilled care facilities.
Two hundred and two frail elderly women age 65 and older, excluding those on bisphosphonates.
Treatment eligibility criteria included 1) clinical fractures of the hip or spine (Clin Fx), 2) clinical fractures or bone mineral density (BMD), 3) Clin Fx, BMD, or vertebral fractures (VF assessed by DXA based vertebral fracture assessments), 4) fracture risk algorithm using femoral neck BMD (FRAX-FN), 5) fracture risk algorithm using BMI (FRAX-BMI) or 6) Clin Fx or heel ultrasound (heel US).
Mean age was 85 years. Treatment eligibility ranged from 17% (Clin Fx) to 98% (FRAX-BMI). VFs were found in 47%, of whom 74% were silent. Criteria with Clin Fx, BMD or VF identified 73% of study participants for treatment. FRAX-FN suggested treatment in 81% but would have missed about 10% of patients with silent vertebral fractures. Clin Fx or heel ultrasound suggested 39% of participants treatment eligible.
In long term care residents, those eligible for osteoporosis treatment ranged from less than 20% to roughly all patients depending on screening criteria. Vertebral fractures are common and identify a subset of patients missed by conventional bone density or FRAX-FN. A reasonable clinical approach could consider treatment for those with clinical fractures of the hip or spine, radiologic evidence for a vertebral fracture or osteoporosis by bone density classification. Prospective studies are needed to determine optimal screening strategies for treatment in this cohort.
PMCID: PMC3477847  PMID: 22316237
osteoporosis; long term care; FRAX
3.  Reconstructing foveal pit morphology from optical coherence tomography imaging 
The British Journal of Ophthalmology  2009;93(9):1223-1227.
The aim of this study was to describe an automated method for extracting quantitative measures of foveal morphology from optical coherence tomography (OCT) images of the human retina.
We performed a methodological study and retrospective investigation of selected cases. Sixty-five human subjects were included: 61 healthy subjects and four female carriers of blue-cone monochromacy (BCM). Thickness data from B-scans traversing the foveal pit were fitted to a mathematical model designed to capture the contour of the foveal surface. From this model, various metrics of foveal morphology were extracted (pit depth, diameter and slope).
Mathematical descriptions of foveal morphology enabled quantitative and objective evaluation of foveal dimensions from archived OCT data sets. We found a large variation in all aspects of the foveal pit (depth, diameter and slope). In myopes and BCM carriers, foveal pits were slightly less deep and had a more shallow slope, although these differences were not significant.
Offline analysis of OCT data sets enables quantitative assessment of foveal morphology. The algorithm works on the Stratus™ and Cirrus™ macular thickness protocols, as well as the Spectralis® and Bioptigen© radial-line scan protocols, and can be objectively applied to existing data sets. These metrics will be useful in following changes associated with diseases such as retinopathy of prematurity and high myopia, as well as in studying normal postnatal development of the human fovea.
PMCID: PMC3327485  PMID: 19474001
4.  Effect of maternal restraint-stress during gestation on temporal lipopolysacharide-induced neuroendocrine and immune responses of progeny 
Domestic animal endocrinology  2010;40(1):40-50.
The impact of gestational dam restraint stress on progeny immune and neuroendocrine temporal hormone responses to lipopolysaccharide (LPS) challenge was assessed. Maternal stress (5-min snout snare restraint stress during d 84 to 112 of gestation) increased (P < 0.05) the magnitude of tumor necrosis factor (TNF)-α, interleukin (IL)-6, epinephrine (E), norepinephrine (NE) and serum amyloid A (SAA) production following LPS infusion in the offspring. Moreover, these effects appear to be dependent on gender for TNF-α, E, EPI and cortisol production. However, maternal stress did not affect (P > 0.05) the normalization of proinflammatory cytokines or neuroendocrine hormones produced following LPS. Collectively, these results indicate that maternal stress impacts aspects of the proinflammatory cytokine and stress hormone response in their progeny following LPS dosing of the offspring. This response is potentially responsible in part for the resultant changes to SAA production. As several of the changes observed here are dependent on pig gender, these results are also the first evidence that inherent epigenetic factors coupled with maternal stress impacts the cumulative response to stress and LPS in young pigs.
PMCID: PMC2996048  PMID: 20932703
cytokine; gender; lipopolysaccharide; maternal stress; pig
5.  Fluoresceinated Peanut Agglutinin (PNA) is a Marker for Live O2 Sensing Glomus Cells in Rat Carotid Body 
Experiments using live dissociated carotid body (CB) cells for patch clamping, [Ca++]i or other measurements require positive identification of the cell being recorded. At present, cell morphology is usually employed, but several cell types within the carotid body evidence similar morphologic characteristics. Therefore, we sought to develop a method utilizing a vital dye to identify glomus cells before and during experiments that require live cells, such as patch clamp studies. It was previously reported that the binding sites for peanut agglutinin (PNA) were highly expressed by all neuroendocrine-derivatives of the sympathoadrenal neural crest, including glomus cells, small, intensely fluorescent cells, PC-12 cells, and adrenal chromaffin cells in situ (Katz et al. 1995). By utilizing the binding characteristics of galactose-specific lectin peanut agglutinin (PNA) on the outer cell membrane, we tested the possibility that the fluoresceinated PNA may preferentially bind to CB glomus cells. The results to date show: (1) Rhodamine tagged PNA (Rhod-PNA) binds to the live dissociated glomus cells in less than one hour incubation and can be visualized in superfused cells; (2) Rhod-PNA labeled cells are perfectly matched with tyrosine hydroxylase (TH) positive glomus cells; (3) Rhod-PNA did not interfere with Fura-2 for Ca++ imaging; (4) Rhod-PNA bound to glomus cells in [Ca++]i studies does not affect O2 response of glomus cells. Thus fluoresceinated PNA may be a useful marker for live CB glomus studies, without adversely affecting their physiologic response.
PMCID: PMC2958663  PMID: 19536480
PNA; Peanut agglutinin; Lectin; CB; Glomus cells; Marker; O2 sensing; TH; Ca++ imaging; Double immunostaining
6.  Design of high reliability organizations in health care 
Quality & Safety in Health Care  2006;15(Suppl 1):i4-i9.
To improve safety performance, many healthcare organizations have sought to emulate high reliability organizations from industries such as nuclear power, chemical processing, and military operations. We outline high reliability design principles for healthcare organizations including both the formal structures and the informal practices that complement those structures. A stage model of organizational structures and practices, moving from local autonomy to formal controls to open inquiry to deep self‐understanding, is used to illustrate typical challenges and design possibilities at each stage. We suggest how organizations can use the concepts and examples presented to increase their capacity to self‐design for safety and reliability.
PMCID: PMC2464869  PMID: 17142607
high reliability organization; design; patient safety
7.  The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2 
Journal of Medical Genetics  2005;42(7):540-546.
Neurofibromatosis 2 (NF2) patients with constitutional splice site NF2 mutations have greater variability in disease severity than NF2 patients with other types of mutations; the cause of this variability is unknown. We evaluated genotype-phenotype correlations, with particular focus on the location of splice site mutations, using mutation and clinical information on 831 patients from 528 NF2 families with identified constitutional NF2 mutations. The clinical characteristics examined were age at onset of symptoms of NF2 and number of intracranial meningiomas, which are the primary indices of the severity of NF2. Two regression models were used to analyse genotype-phenotype correlations. People with splice site mutations in exons 1–5 had more severe disease than those with splice site mutations in exons 11–15. This result is compatible with studies showing that exons 2 and 3 are required for self-association of the amino terminal of the NF2 protein in vitro, and that deletions of exons 2 and 3 in transgenic and knockout mouse models of NF2 cause a high prevalence of Schwann cell derived tumours.
PMCID: PMC1736092  PMID: 15994874
8.  Redirecting traditional professional values to support safety: changing organisational culture in health care 
Quality & safety in health care  2004;13(Suppl 2):ii16-ii21.
Professionals in healthcare organisations who seek to enhance safety and quality in an increasingly demanding industry environment often identify culture as a barrier to change. The cultural focus on individual autonomy, for example, seems to conflict with desired norms of teamwork, problem reporting, and learning. We offer a definition and explication of why culture is important to change efforts. A cultural analysis of health care suggests professional values that can be redirected to support change. We offer examples of organisations that drew upon cultural strengths to create new ways of working and gradually shifted the culture.
PMCID: PMC1765803  PMID: 15576686
9.  Lessons learned from non-medical industries: root cause analysis as culture change at a chemical plant 
Quality & safety in health care  2002;11(3):266-269.

 Root cause analysis was introduced to a chemical plant as a way of enhancing performance and safety, exemplified by the investigation of an explosion. The cultural legacy of the root cause learning intervention was embodied in managers' increased openness to new ideas, individuals' questioning attitude and disciplined thinking, and a root cause analysis process that provided continual opportunities to learn and improve. Lessons for health care are discussed, taking account of differences between the chemical and healthcare industries.
PMCID: PMC1743627  PMID: 12486993
10.  Leading organisational learning in health care 
PMCID: PMC1743554  PMID: 12078370
11.  Resistance training enhances the stability of sensorimotor coordination. 
Strategies for the control of human movement are constrained by the neuroanatomical characteristics of the motor system. In particular, there is evidence that the capacity of muscles for producing force has a strong influence on the stability of coordination in certain movement tasks. In the present experiment, our aim was to determine whether physiological adaptations that cause relatively long-lasting changes in the ability of muscles to produce force can influence the stability of coordination in a systematic manner. We assessed the effects of resistance training on the performance of a difficult coordination task that required participants to synchronize or syncopate movements of their index finger with an auditory metronome. Our results revealed that training that increased isometric finger strength also enhanced the stability of movement coordination. These changes were accompanied by alterations in muscle recruitment patterns. In particular, the trained muscles were recruited in a more consistent fashion following the programme of resistance training. These results indicate that resistance training produces functional adaptations of the neuroanatomical constraints that underlie the control of voluntary movement.
PMCID: PMC1088595  PMID: 11217890
12.  Bacterial Reductive Dissolution of Crystalline Fe(III) Oxide in Continuous-Flow Column Reactors 
Bacterial reductive dissolution of synthetic crystalline Fe(III) oxide-coated sand was studied in continuous-flow column reactors in comparison with parallel batch cultures. The cumulative amount of aqueous Fe(II) exported from the columns over a 6-month incubation period corresponded to (95.0 ± 3.7)% (n = 3) of their original Fe(III) content. Wet-chemical analysis revealed that only (6.5 ± 3.2)% of the initial Fe(III) content remained in the columns at the end of the experiment. The near-quantitative removal of Fe was visibly evidenced by extensive bleaching of color from the sand in the columns. In contrast to the column reactors, Fe(II) production quickly reached an asymptote in batch cultures, and only (13.0 ± 2.2)% (n = 3) of the Fe(III) oxide content was reduced. Sustained bacterial-cell growth occurred in the column reactors, leading to the production and export of a quantity of cells 100-fold greater than that added during inoculation. Indirect estimates of cell growth, based on the quantity of Fe(III) reduced, suggest that only an approximate doubling of initial cell abundance was likely to have occurred in the batch cultures. Our results indicate that removal of biogenic Fe(II) via aqueous-phase transport in the column reactors decreased the passivating influence of surface-bound Fe(II) on oxide reduction activity, thereby allowing a dramatic increase in the extent of Fe(III) oxide reduction and associated bacterial growth. These findings have important implications for understanding the fate of organic and inorganic contaminants whose geochemical behavior is linked to Fe(III) oxide reduction.
PMCID: PMC91943  PMID: 10698772
13.  Women's experience of maternal serum screening. 
Canadian Family Physician  2000;46:614-620.
OBJECTIVE: To explore the ideas, opinions, feelings, and experiences of women regarding prenatal genetic screening, specifically maternal serum screening (MSS). DESIGN: Qualitative technique of focus groups. SETTING: Northern, rural, inner-city, urban, and suburban communities in Ontario. PARTICIPANTS: Women who had given birth to babies from January 1994 to May 1996, but who were not currently pregnant (n = 60). METHOD: Six focus groups composed of women living in various communities who had recently given birth to babies explored the experience of MSS. MAIN FINDINGS: Women want informed choice about prenatal genetic screening. Three factors influenced women's decisions to undergo or decline prenatal genetic screening: their personal values, including their philosophy of life, moral, and religious values, and attitudes regarding Down syndrome and disability; social support including their partners, families, and friends; and quality of information from health care providers. Women want their providers to give them information personally; they want to receive the information as early as possible in prenatal care to allow time for reflection; and they want unbiased, accurate information in order to make a decision that is in keeping with their personal values and beliefs. CONCLUSIONS: Knowledge of women's ideas, opinions, feelings, and experiences regarding MSS suggests specific ways health care providers can facilitate informed decision making in prenatal screening. Providing information about genetic testing needs to be individualized, with women actively participating in the decision-making process. Information needs described by these women could apply to other prenatal genetic tests that might be available in the future.
PMCID: PMC2144979  PMID: 10752000
14.  Family physicians in maternity care. Still in the game? Report from the CFPC's Janus Project. 
Canadian Family Physician  2000;46:601-611.
OBJECTIVE: To describe family doctors' contribution to maternity care in Canada and to observe the influence of age, sex, region of the country, and practice population on provision of maternity care. DESIGN: Survey: College of Family Physicians of Canada's Janus Project national family physician survey. SETTING: All 10 provinces and two territories. PARTICIPANTS: Random sample of family physicians and general practitioners, both members and non-members of the College. MAIN OUTCOME MEASURES: Proportion of family doctors participating in prenatal, intrapartum, postpartum, and newborn care, and proportion of doctors involved in intrapartum care by age, sex, location in Canada, and practice population. RESULTS: Overall response rate was 58%. Just over 50% of all family doctors in Canada are involved in some aspect of maternity care; 19% do intrapartum care; and 33% are involved in prenatal (shared) care. Similar proportions of men and women still do intrapartum care, but women care for more pregnancies than men. More family doctors serving rural areas are doing intrapartum care compared with doctors in urban areas, although those in urban areas tend to do more deliveries. The western provinces have the highest percentages of intrapartum caregivers. A gradual decline in percentage of intrapartum caregivers by age group increases among the 55- to 64-year-old cohort. Almost a quarter of women doctors younger than 35 years are doing intrapartum care. Most physicians doing prenatal (shared) care look after women until the third trimester. CONCLUSIONS: Family doctors are still providing a large proportion of maternity care in Canada. This contribution must be nurtured by the College through its Maternity and Newborn Care Committee and other contacts to encourage family doctors to continue offering this essential service to childbearing women in Canada.
PMCID: PMC2144974  PMID: 10751999
15.  Going the distance: the influence of practice location on the Ontario Maternal Serum Screening Program 
BACKGROUND: The Ontario Maternal Serum Screening (MSS) Program was introduced by the Ontario Ministry of Health as a province-wide pilot project in 1993. The objective of this study was to determine the influence of practice location on Ontario health care providers' use of and opinions regarding MSS, access to follow-up services and recommendations about the program. METHODS: A questionnaire was mailed to a random sample of 2000 family physicians, all 565 obstetricians and all 62 registered midwives in Ontario between November 1994 and March 1995. RESULTS: Among providers who were eligible (those providing antenatal care or attending births) the response rates were 91.4% (778/851), 76.0% (273/359) and 78.0% (46/59) respectively. Fewer respondents in the Northwest region (71.4%) and in rural areas (81.9%) stated that they routinely offer MSS to all pregnant women in their practices compared with respondents in other regions (84.4%-91.5%) and urban centres (90.1%). Fewer respondents in the northern regions (Northeast 49.2%, Northwest 25.0%) than in the Central East region (includes Toronto) (76.6%) felt that follow-up services were readily available. Respondents in the northern regions had less favourable opinions of MSS than those in the other regions in terms of its complexity, cost, the time involved in counselling and the high false-positive rate. More respondents in the Central East region (64.6%) and in urban centres (52.9%) recommended not changing the MSS program than did those in the Northwest (7.1%) and rural areas (39.8%). After provider characteristics were controlled for in a logistic regression analysis, practice location was not the most important factor. Instead, the model showed that respondents who cared for 50 or more pregnant women in the previous year were more likely to offer MSS routinely (OR 2.00, 95% CI 1.21-3.27) and that those who felt that patient characteristics affect the offering of MSS (OR 0.42, 95% CI 0.26-0.67) or that follow-up services were not readily available (OR 0.33, 95% CI 0.20-0.55) were less likely to offer it. INTERPRETATION: Health care providers in northern and rural Ontario were less likely to offer MSS routinely than those in other regions and were more likely to recommend changing or eliminating the program. Providers' concerns about the social and cultural sensitivity of MSS and the availability of follow-up services affected use.
PMCID: PMC1230538  PMID: 10478161
16.  Obstetrics anyone? How family medicine residents' interests changed. 
Canadian Family Physician  1999;45:638-647.
OBJECTIVE: To determine family medicine residents' attitudes and plans about practising obstetrics when they enter and when they graduate from their residency programs. DESIGN: Residents in each of 4 consecutive years, starting July 1991, were surveyed by questionnaire when they entered the program and again when they graduated (ending in June 1996). Only paired questionnaires were used for analysis. SETTING: Family medicine residency programs at the University of Toronto in Ontario. PARTICIPANTS: Of 358 family medicine residents who completed the University of Toronto program, 215 (60%) completed questionnaires at entry and exit. MAIN OUTCOME MEASURES: Changes in attitudes and plans during the residency program as ascertained from responses to entry and exit questionnaires. RESULTS: Analysis was based on 215 paired questionnaires. Women residents had more interest in obstetric practice at entry: 58% of women, but only 31% of men were interested. At graduation, fewer women (49%) and men (22%) were interested in practising obstetrics. The intent to undertake rural practice was strongly associated with the intent to practise obstetrics. By graduation, residents perceived lifestyle factors and compensation as very important negative factors in relation to obstetric practice. Initial interest and the eventual decision to practise obstetrics were strongly associated. CONCLUSIONS: Intent to practise obstetrics after graduation was most closely linked to being a woman, intending to practise in a rural area, and having an interest in obstetrics prior to residency. Building on the interest in obstetrics that residents already have could be a better strategy for producing more physicians willing to practise obstetrics than trying to change the minds of those uninterested in such practice.
PMCID: PMC2328441  PMID: 10099803
17.  Hereditary breast cancer. Psychosocial issues and family physicians' role. 
Canadian Family Physician  1999;45:126-132.
OBJECTIVES: To outline the psychosocial issues in hereditary breast cancer (HBC) assessment and discuss the role of family physicians. QUALITY OF EVIDENCE: A literature search using MEDLINE, CINAHL, CancerLit, and HealthStar databases was conducted from January 1990 to April 1998, using the key words breast cancer or neoplasm and familial or hereditary, genetic testing or screening, primary care or family physician or counseling, genetic counseling, psychosocial or psychological. We found only a few studies focusing on a small number of well-studied "research families." MAIN FINDINGS: Women with a family history of breast cancer were likely to be highly interested in genetic testing for cancer risk. The benefit of testing for those with negative results is reassurance. Those found to be carriers of genetic mutations might benefit from increased surveillance and prophylactic therapy. Risks of testing include anxiety, depression, guilt, altered self-image, and insurance and employment discrimination. A family physician's role is to assess risk, to provide information and support so women can make informed choices about referral to familial cancer clinics, to offer cancer surveillance, and to provide support once genetic test results are available. CONCLUSION: Genetic testing is rapidly moving from research to clinical applications. Family physicians play an integral role in educating and managing women at risk for HBC. Physicians must prepare themselves with knowledge and counseling skills to meet the challenges of this new technology.
PMCID: PMC2328025  PMID: 10889865
18.  Hereditary breast cancer. Identifying and managing BRCA1 and BRCA2 carriers. 
Canadian Family Physician  1999;45:114-124.
OBJECTIVES: To present a strategy for identifying candidates for consideration of BRCA1 and BRCA2 mutation testing. To discuss the implications of identifying patients as BRCA1 or BRCA2 mutation carriers, and to provide recommendations for managing them. QUALITY OF EVIDENCE: A MEDLINE search from January 1990 to May 1998 was performed using the terms genetic breast screening, BRCA1, and BRCA2. The bibliographies of articles found were searched for further relevant titles. There are no published, randomized controlled clinical trials of management strategies for known BRCA carriers. Many recommendations for management are based on expert opinion only. MAIN FINDINGS: About 5% of women with breast cancer are carriers of genetic mutations. An accurate and detailed family history is the most important tool for identifying potential BRCA1 and BRCA2 mutation carriers. Women identified as carriers have a substantially increased risk of breast and ovarian cancer. Male carriers have a moderately increased risk of prostate cancer. Management strategies for carriers are not well studied but include increased surveillance, preventive surgery, chemoprevention, and lifestyle modification. CONCLUSION: Family physicians must be able to identify people at risk, to discuss management strategies, and when appropriate, to offer referral for consideration of genetic testing. There is an urgent need for research to determine the effectiveness of surveillance strategies, preventive surgery, chemoprevention, and lifestyle modification for BRCA1 and BRCA2 mutation carriers.
PMCID: PMC2328074  PMID: 10889864
19.  Hereditary breast cancer. Risk assessment of patients with a family history of breast cancer. 
Canadian Family Physician  1999;45:104-112.
OBJECTIVES: To assist family physicians in stratifying women with a family history of breast cancer as being at low, moderate, or high risk of hereditary breast cancer (HBC). To present guidelines for managing each of these risk groups. QUALITY OF EVIDENCE: A MEDLINE search was conducted from January 1976 to December 1997 using key words related to breast cancer risk factors, risk assessment, prevention, and screening. Risk stratification criteria were derived empirically and assessed using retrospective chart review. MAIN FINDINGS: Although up to 20% of women in the general population have a family history of breast cancer, less than 5% are at high risk for HBC. Certain features in a family history suggest increased risk. Women with none of these features are at low risk for HBC and should have annual clinical breast examinations and mammography at least every 2 years starting at age 50. Women with one or more features of increased risk who do not meet criteria for referral to a familial cancer clinic are at moderate risk for HBC and should begin annual mammography and clinical breast examination at age 40. Women who meet referral criteria are at high risk for HBC and should be counseled regarding referral to a familial cancer clinic for more detailed risk assessment and consideration for genetic testing. All women should be taught proper breast self-examination technique and encouraged but not pressured to practise it monthly for life. CONCLUSION: A simple algorithm can assist physicians in stratifying women into low, moderate, and high HBC risk groups. Management strategies for each group are given in this article and the two following (Heisey et al page 114 and Carroll et al page 126).
PMCID: PMC2328077  PMID: 10889863
20.  Self-help groups. 
Canadian Family Physician  1998;44:2137-2142.
OBJECTIVE: To assess Ontario family physicians' attitudes toward, awareness of, and practices related to self-help groups in general and cancer self-help groups specifically. DESIGN: Mailed survey using a modified Dillman method. SETTING: Ontario family practices. PARTICIPANTS: A random sample of 1500 Ontario members of the College of Family Physicians of Canada, of whom 949 responded. A total of 911 completed questionnaires were received, for an eligible response rate of 64%. MAIN OUTCOME MEASURES: Physician demographics, practice characteristics; extent of awareness of self-help groups and their perceived value; attitudes toward self-help groups; practices related to interactions with patients about self-help groups. RESULTS: Only 40.2% of respondents were aware of six or more self-help groups in their region; 56.8% were aware of at least one cancer self-help group. Discussions with patients about groups were reported as occurring "frequently" by 12% of respondents, who indicated they made referrals to an array of groups. Ratings of group helpfulness were relatively high (83.8% scoring 3, 4, or 5 on a 5-point scale, where 5 is "very helpful"). There were low ratings of potential harm (1% scoring 4 or 5 on a 5-point scale, where 5 is "very harmful"). Confidence intervals for proportions reported on in this paper were all within 4%. CONCLUSIONS: Family physicians have predominantly positive attitudes about the potential benefits of self-help groups, and many are recommending groups to their patients.
PMCID: PMC2277928  PMID: 9805168
21.  Using the ALPHA form in practice to assess antenatal psychosocial health 
BACKGROUND: The assessment of the psychosocial health of pregnant women and their families, although recommended, is not carried out by most practitioners. One reason is the lack of a practical and evidence-based tool. In response, a multidisciplinary group created the Antenatal Psychosocial Health Assessment (ALPHA) form. This article describes the development of this tool and experience with it in an initial field trial. METHODS: A systematic literature review revealed 15 antenatal psychosocial risk factors associated with poor postpartum family outcomes of woman abuse, child abuse, postpartum depression, marital/couple dysfunction and increased physical illness. The ALPHA form, incorporating these risk factors, was developed and refined through several focus groups. It was then used by 5 obstetricians, 10 family physicians, 7 midwives and 4 antenatal clinic nurses in various urban, rural and culturally diverse locations across Ontario. After 3 months, these health care providers met in focus groups to discuss their experiences. A sample of pregnant women assessed using the ALPHA form were interviewed about their experience as well. Results were analysed according to qualitative methods. RESULTS: The final version of the ALPHA form grouped the 15 risk factors into 4 categories--family factors, maternal factors, substance abuse and family violence--with suggested questions for each area of enquiry. The health care providers uniformly reported that the form helped them to uncover new and often surprising information, even when the women were well known to them. Incorporating the form into practice was usually accomplished after a period of familiarization. Most of the providers said the form was useful and would continue to use it if it became part of standard care. The pregnant women in the sample said they valued the enquiry and felt comfortable with the process, unless there were large cultural barriers. INTERPRETATION: The ALPHA form appears to be an important tool in assessing psychosocial health in pregnancy and to be readily integrated into practice. More study is required to quantify the number of risks identified and resources used, to determine the form's reliability and validity and, ultimately, to assess the effect of its use on postpartum outcomes.
PMCID: PMC1229699  PMID: 9780969
22.  Repression of retrovirus-mediated transgene expression by interferons: implications for gene therapy. 
Journal of Virology  1997;71(12):9163-9169.
Retrovirus-mediated gene transfer is commonly used in gene therapy protocols and has the potential to provide long-term expression of the transgene. Although expression of a retrovirus-delivered transgene is satisfactory in cultured cells, it has been difficult to achieve consistent and high-level expression in vivo. In this investigation, we explored the possibility of modulating transgene expression by host-derived cytokines. Normal human keratinocytes and dermal fibroblasts were transduced with recombinant retroviruses expressing a reporter gene (lacZ). Treatment of transduced cells with a proinflammatory cytokine, gamma interferon (IFN-gamma), significantly reduced lacZ expression to less than 25% of that of nontreated cells. The inhibition was concentration dependent (peak at 5 ng/ml) and time dependent (maximal at 16 h for transcript and 24 h for protein); expression remained repressed in the continued presence of IFN-gamma but returned to normal levels 24 h after IFN-gamma withdrawal. The decrease in beta-galactosidase activity appeared to result from decrease in steady-state lacZ mRNA levels. Inhibitors of transcription and translation blocked IFN-gamma-induced repression, suggesting involvement of newly synthesized protein intermediates. Similar results were obtained by treatment of transduced cells with IFN-alpha but not with other proinflammatory cytokines, including tumor necrosis factor alpha, interleukin-2 (IL-1), IL-4, and granulocyte colony-stimulating factor. Although the level of lacZ mRNA was reduced by >70% following IFN treatment, the rate of lacZ transcription was not significantly different from that for nontreated cells. These results suggest that IFN-mediated regulation of transgene expression is at a posttranscriptional level. Interestingly, IFN-gamma also suppressed transgene expression driven by a cellular promoter (involucrin) inserted in an internal position in the retroviral vector. The presence of the overlapping 3' untranslated regions in transcripts initiated from the internal promoter and the long terminal repeat is suggestive of a posttranscriptional regulation, likely at the level of RNA stabilization. These results provide direct evidence for modulatory effects of IFNs on retrovirus-mediated transgene expression and suggest that gene therapy results may be altered by host inflammatory responses.
PMCID: PMC230218  PMID: 9371574
23.  Identification of a recombination event narrowing the Lafora disease gene region. 
Journal of Medical Genetics  1997;34(7):590-591.
Patients affected with progressive myoclonus epilepsy of the Lafora type present during late adolescence with a characteristic EEG pattern and Lafora bodies seen on skin biopsy. The critical region for the Lafora gene has been localised to chromosome 6q24 flanked by the dinucleotide repeat markers D6S292 and D6S420. This study for linkage of markers from the candidate gene region was performed in a previously unpublished family affected with Lafora disease. EEG and skin biopsy evaluation for Lafora bodies were performed on five of eight family members followed for seizure activity. Haplotype and linkage analysis of DNA from five family members were carried out using the nine dinucleotide repeat markers reported in the common region of homozygosity by Serratosa et al in 1995. The present study of an additional family affected by Lafora disease has narrowed the 17 cM critical region for the Lafora disease gene on chromosome 6q24 to a 4 cM region flanked by markers D6S308 and D6S311.
PMCID: PMC1051002  PMID: 9222970
24.  Maternity care and maternal serum screening. Do male and female family physicians care for women differently? 
Canadian Family Physician  1997;43:1078-1084.
OBJECTIVE: To examine whether male and female family physicians practise maternity care differently, particularly regarding the maternal serum screening (MSS) program. DESIGN: Mailed survey fielded between October 1994 and March 1995. SETTING: Ontario family practices. PARTICIPANTS: Random sample of 2000 members of the College of Family Physicians of Canada who care for pregnant women. More than 90% of eligible physicians responded. MAIN OUTCOME MEASURES: Attitudes toward, knowledge about, and behaviour toward MSS. RESULTS: Women physicians were more likely than men to practise part time, in groups, and in larger communities. Men physicians were more likely to perform deliveries; women were more likely to do shared care. Despite a shorter work week, on average, female physicians cared for more pregnant women than male physicians did. Among those providing intrapartum care, women performed more deliveries, on average, than men. Women physicians were more likely than men to offer MSS to all pregnant patients. Although average time spent discussing MSS before the test was similar, women physicians had better knowledge of when best to do the test and its true-positive rate. All differences reported were statistically significant (P < or = 0.001). CONCLUSIONS: Among family physicians caring for pregnant women, women physicians cared for more pregnant women than men did. Both spent similar time discussing MSS with their patients before offering screening, but more women physicians offered MSS to all their patients and were more knowledgeable about MSS than men physicians.
PMCID: PMC2255259  PMID: 9189296
25.  Ontario Maternal Serum Screening Program: practices, knowledge and opinions of health care providers 
OBJECTIVE: To determine the practices, knowledge and opinions of health care providers regarding a prenatal genetic screening program in Ontario. DESIGN: Cross-sectional self-reported survey. SETTING: Ontario. PARTICIPANTS: Random sample of 2000 family physicians, all 565 obstetricians and all 62 registered midwives in the province. Among subjects who were eligible (those providing antenatal care or attending births) the response rates were 91% (778/851), 76% (273/359) and 78% (46/59) respectively. MAIN OUTCOME MEASURES: Which patients were offered maternal serum screening (MSS), how results were being communicated, knowledge of the test's sensitivity, likes and dislikes about MSS and recommendations regarding the program. RESULTS: Most (97%) of respondents stated that they were offering MSS to the pregnant women in their practices; 88% were offering it routinely to all pregnant women (87% of the family physicians, 90% of the obstetricians and 100% of the midwives). Most (92%) of the respondents stated that they communicate positive results to their patients personally as soon as they are received; 23% did so for negative results. The respondents correctly identified the initial positive rate but underestimated the false-positive rate. About one-third did not respond to these knowledge questions. Of those who gave feedback on the screening program, 50% recommended that it not be changed, 29% suggested that it be changed, and 22% recommended that it be scrapped. CONCLUSIONS: Participation in the Ontario Maternal Serum Screening Program by health care providers has been good, although knowledge about MSS is far from ideal. Many providers have reservations about the program. In light of concerns raised about the high false-positive rate and the anxiety such results generate in pregnant women, there is a need for more education of providers and patients and a better understanding of women's experiences with genetic screening.
PMCID: PMC1227040  PMID: 9084382

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