Search PubMed⌕ Search

Biomedical subjects

C Cameron

Publications and source records attributed to C Cameron.

At least 19 recordsLinked to original sources

Development of an integrated-care delivery model for post-fracture care in Ontario, Canada.

INTRODUCTION: The purpose of this study was to develop an integrated-care model for patients at highest risk for osteoporosis, those with a low-trauma fracture. Specific objectives were to describe the current processes and patterns of post-fracture care in hospitals in Ontario; to examine health-care professional and patient awareness of osteoporosis and the roles and responsibilities of various organizations and health care professionals; and to identify barriers and facilitators and obtain feedback on the model. METHODS: In 2002, questionnaires were completed for 178 eligible hospitals. RESULTS: Only 65% of hospitals inform primary-care physicians of a fracture for all patients and only 4% indicated that they provide information about osteoporosis. The main themes that emerged from the four patient focus groups (n=21) were lack of continuity of care, the absence of a link between the fracture and osteoporosis by both patients and health care providers, and need for information. Most participants agreed that something was needed to prompt their primary-care physician to investigate for osteoporosis. The four physician focus groups (n=26) identified a role for orthopaedic surgeons to flag cases. CONCLUSIONS: From 34 key informant interviews with community-based organizations, we found a lack of integration between health care professionals who provide fracture care and those who provide osteoporosis management and fall prevention. Based on these data, we developed an integrated local-resource-based post-fracture care model, which we obtained feedback on at a stakeholder consultation workshop. The model focuses on improving emergency department/fracture clinic communication, emphasizes the need for follow-up investigation by family physicians for osteoporosis, and incorporates other health care professionals and a telemedicine multidisciplinary osteoporosis clinic. We are currently evaluating whether this model leads to an increase in appropriate investigation of and treatment for osteoporosis in patients with low-trauma fractures.

Attitude of Health Personnel↗

Genetic linkage and association analysis in type 1 von Willebrand disease: results from the Canadian type 1 VWD study.

BACKGROUND: von Willebrand disease (VWD) is the most common bleeding disorder known in humans, with type 1 VWD representing the majority of cases. Unlike the other variant forms of VWD, type 1 disease represents a complex genetic trait, influenced by both genetic and environmental factors. AIM: To evaluate the contribution of the von Willebrand factor (VWF) and ABO blood group loci to the type 1 VWD phenotype, and to assess the potential for locus heterogeneity in this condition, we have performed genetic linkage and association studies on a large, unselected type 1 VWD population. METHOD: We initially collected samples from 194 Canadian type 1 VWD families for analysis. After the exclusion of families found to have either type 2 or type 3 VWD, and pedigrees with samples from single generations, linkage and association analysis was performed on 155 type 1 VWD families. RESULTS AND CONCLUSION: The linkage study has shown a low heterogeneity LOD score of 2.13 with the proportion of families linked to the VWF gene estimated to be 0.41. Linkage was not detected to the ABO locus in this type 1 VWD population. In the family-based association test, significant association was found between the type 1 VWD phenotype, the quantitative traits, VWF:Ag, VWF:RCo, and FVIII:C and the ABO 'O' and 'A' alleles and the VWF codon 1584 variant. There was also weak association with the -1185 promoter polymorphism and VWF:Ag, VWF:RCo, and FVIII:C plasma levels. These studies provide further evidence to support the role for genetic loci other than VWF and ABO in the pathogenesis of type 1 VWD.

ABO Blood-Group System↗

Sweeping-window arc therapy: an implementation of rotational IMRT with automatic beam-weight calculation.

Sweeping-window arc therapy (SWAT) is a variation of intensity-modulated radiation therapy (IMRT) with direct aperture optimization (DAO) that is initialized with a leaf sequence of sweeping windows that move back and forth periodically across the target as the gantry rotates. This initial sequence induces modulation in the dose and is assumed to be near enough to a minimum to allow successful optimization, done with simulated annealing, without requiring excessive leaf speeds. Optimal beam weights are calculated analytically, with easy extension to allow for variable beam weights. In this paper SWAT is tested on a phantom model and clinical prostate case. For the phantom, constant and variable beam weights are used. Although further work (in particular, improving the dose model) is required, the results show SWAT to be a feasible approach to generating deliverable dynamic arc treatments that are optimized.

Algorithms↗

Effect of fasting on thyroid hormone levels, and TR(alpha) and TR(beta) mRNA accumulation in late-stage embryo and juvenile rainbow trout, Oncorhynchus mykiss.

The accumulation of mRNA encoding for hepatic and intestinal T3-receptor (TR) and body and liver masses were measured in fed and 3-week fasted juvenile and swim up stage rainbow trout embryos. Plasma and total body thyroid hormone (TH) levels were measured for juvenile and swim up stages, respectively. Fasted juveniles exhibited a lower hepatosomatic index (HSI), liver mass and plasma T4 and T3 concentrations than fed animals, but there were no changes in body mass or the accumulation of mRNA encoding for either of the TR(alpha) or TR(beta) isoforms in liver or intestine. TR(beta) mRNA accumulation was greater than TR(alpha) mRNA accumulation in both tissues. Fasted embryos had lower whole body TH levels and body, liver and intestinal tract masses, in addition to a lower intestinosomatic index. However, there was no change in HSI. Fasting did not affect whole body or hepatic TR(alpha) and TR(beta) mRNA accumulation, although intestinal tract TR(alpha) and TR(beta) mRNA accumulation was lower in the fasted embryos. The HSI and body mass changes in fasted juvenile and embryo stages, respectively, indicated that both developmental stages were impacted by fasting. Both stages also showed evidence of decreased TH production. The lower TR gene expression in the intestinal tract of fasted embryos may suggest a role for THs in the transitional stage of intestinal development during this period of development.

Aging↗

Growth hormone secretion from the Arctic charr (Salvelinus alpinus) pituitary gland in vitro: effects of somatostatin-14, insulin-like growth factor-I, and nutritional status.

This study investigated the influence of nutritional status on the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis in Arctic charr (Salvelinus alpinus). The objectives were to study the regulation of GH secretion in vitro by somatostatin-14 (SRIF) and hIGF-I, and to determine whether pituitary sensitivity to these factors is dependent upon nutritional status. Arctic charr were fed at three different ration levels (0, 0.35, and 0.70% BWd(-1)), and pituitary glands were harvested at 1, 2, and 5 weeks for in vitro study. Both SRIF and hIGF-I inhibited GH secretion from Arctic charr pituitary tissue in long-term (18 h) static hemipituitary culture, as well as after acute exposure in a pituitary fragment perifusion system. This response appeared to be dose-dependent for SRIF in static culture over the range of 0.01-1 nM, but not for hIGF-I. The acute inhibitory action of hIGF-I on GH release in the perifusion system suggests an action that is initially independent of any effects on GH gene expression or protein synthesis. Nutritional status did not affect the sensitivity of Arctic charr pituitary tissue to either SRIF or hIGF-I in vitro, indicating that changes in abundance of pituitary SRIF or IGF-I receptors may not explain the alterations in plasma GH levels found during dietary restriction.

Animals↗

In the world of Dolly, when does a human embryo acquire respect?

For most of the 20th century, it was possible to regard fertilisation as the identifiable point when life begins, because this moment could be defined unequivocally and was thought to be the single most essential biological step in the establishment of a new human entity. Since the successful reproductive cloning of Dolly and other mammals, it is clear that any human cell has the potential to supply the full genome of an embryo, and hence a person, without going through fertilisation. At what point in time do such embryos acquire the respect accorded to human beings? The authors argue that the time of implantation is the most useful point at which the potential and the intention to create a new person are translated into reality, because from that point a new life develops. Implantation differentiates a somatic cell in culture (which is not due respect) from a human entity that has acquired its own identity and developmental potential. The authors examine the value of quickening or viability as alternative developmental stages in the process of acquiring respect for the Dolly embryo.

Animals↗

Should we recommend low-fat diets for obesity?

Dietary fat intake has been blamed for the increase in adiposity and has led to a worldwide effort to decrease the amount of fat in the diet. However, the comparative efficacy of this approach is debatable. Whilst short-term dietary intervention studies show that low-fat diets lead to weight loss in both healthy and overweight individuals, it is less clear if a reduction in fat intake is more efficacious than other dietary restrictions in the long term. The purpose of this systematic review was to determine the effectiveness of low-fat diets in achieving sustained weight loss when used for the express purpose of weight loss in obese or overweight people. A comprehensive search identified six studies that fulfilled our criteria for inclusion (randomized controlled trial, participants either overweight or obese, comparison of a low-fat diet with another type of weight-reducing diet, follow-up period that was at least 6 months in duration and inclusion of participants 18 years or older without serious disease). There were a total of 594 participants in the six trials. The duration of the intervention varied from 3 to 18 months with follow-up from 6 to 18 months. There were no significant differences between low-fat diets and other weight-reducing diets in terms of sustained weight loss. Furthermore, the overall weight loss at the 12-18-month follow-up in all studies was very small (2-4 kg). In overweight or obese individuals who are dieting for the purpose of weight reduction, low-fat diets are as efficacious as other weight-reducing diets for achieving sustained weight loss, but not more so.

Adolescent↗

Is there an ethical difference between preimplantation genetic diagnosis and abortion?

When a person at risk of having a child with a genetic illness or disease wishes to have an unaffected child, this can involve difficult choices. If the pregnancy is established by sexual intercourse, the fetus can be tested early in pregnancy, and if affected a decision can be made to abort in the hope that a future pregnancy with an unaffected fetus ensures. Alternatively, preimplantation genetic diagnosis (PGD) can be used after in vitro fertilisation (IVF) to select and implant an unaffected embryo that hopefully will proceed to term and produce a healthy baby. We are aware that many individuals at risk regard the latter as ethically more acceptable than the former, and examine whether there is an ethical difference between these options. We conclude that PGD and implantation of an unaffected embryo is a more acceptable choice ethically than prenatal diagnosis (PND) followed by abortion for the following reasons: Choice after PGD is seen as ethically neutral because a positive result ("a healthy pregnancy") balances a negative result ("the destruction of the affected embryo") simultaneously (assuming the pregnancy proceeds to full term and a healthy baby is born). While there is usually the intention to establish a healthy pregnancy after an abortion, this is not simultaneous; A woman sees abortion as a personal physical violation of her integrity, and as the pregnancy proceeds she increasingly identifies with and gives ethical status to the embryo/fetus as it develops in utero and not in the laboratory; Many people see aborting a fetus as "killing", whereas in the case of PGD the spare embryos are "allowed to die". We argue that this difference of opinion gives further weight to our conclusion, but note that this has been addressed and debated at length by others.

Abortion, Induced↗

Advice on low-fat diets for obesity.

BACKGROUND: Overweight and obesity are global health problems contributing to an ever increasing noncommunicable disease burden. Calorie restriction can achieve short-term weight loss but the weight loss has not been shown to be sustainable in the long-term. An alternative approach to calorie restriction is to lower the fat content of the diet. However, the long-term effects of fat-restricted diets on weight loss have not been established. OBJECTIVES: To assess the effects of advice on low-fat diets as a means of achieving sustained weight loss, using all available randomised clinical trials. This review focused primarily on participants who were overweight or clinically obese and were dieting for the purpose of weight reduction. Since we were particularly interested in the ability of participants to sustain weight loss over a longer period of time, we focused on studies of 'free living' men and women who were given dietary advice rather than provision of food or money to purchase food. SEARCH STRATEGY: We searched the Cochrane Library (issue 2, 2001), MEDLINE (up to February 20002), and EMBASE (up to February 20002). We also searched the Science Citation Index (up to January 2001) and bibliographies of studies identified. Date of latest search: February 2002. SELECTION CRITERIA: Trials were included if they fulfilled the following criteria: 1) they were randomised controlled clinical trials of low-fat diets versus other weight-reducing diets, 2) the primary purpose of the study was weight loss, 3) participants were followed for at least six months, 4) the study participants were adults (18 years or older) who were overweight or obese (BMI >25 kg/m2) at baseline. Studies including pregnant women or patients with serious medical conditions were excluded. Two people independently applied the inclusion criteria to the studies identified. Disagreement was resolved by discussion or by intervention of a third party. DATA COLLECTION AND ANALYSIS: Data were extracted by three independent reviewers and meta-analysis performed using a random effects model. Weighted mean differences of weight loss were calculated for treatment and control groups at 6, 12 and 18 months. MAIN RESULTS: Four studies were included at the six month follow-up, five studies at the 12 month follow-up and three studies at the 18 month follow-up. There was no significant difference in weight loss between the two groups at six months (WMD 1.7 kg, 95% CI -1.4 to 4.8 kg). The weighted sum of weight loss in the low fat group was -5.08 kg (95% CI -5.9 to -4.3 kg) and in the control group was -6.5 kg, (95% CI -7.3 to -5.7 kg). There was no significant difference in weight loss between the two groups at 12 months (WMD 1.1 kg, 95% CI -1.6 to 3.8 kg). The weighted sum of weight loss in the low fat group was -2.3 kg (95% CI -3.2 to -1.4 kg) and in the control group was -3.4 kg (95% CI -4.2 to -2.6 kg). There was no significant difference in weight loss between the two groups at 18 months (WMD 3.7 kg, 95% CI - 1.8 to 9.2). The weighted sum of weight loss in the control group was -2.3 kg (95% CI -3.5 to -1.2 kg) and in the low fat group there was a weight gain of 0.1 kg (95% CI -0.8 to 1 kg). There was significant heterogeneity in the results for weight loss at six months and 12 months. Apart from one study which showed a slight but statistically significant difference in total cholesterol in the low fat group at one year follow-up, there were no significant differences between the dietary groups for other outcome measures such as serum lipids, blood pressure and fasting plasma glucose. Studies measuring other factors such as perceived wellness and quality of life reported conflicting results. REVIEWER'S CONCLUSIONS: The review suggests that fat-restricted diets are no better than calorie restricted diets in achieving long term weight loss in overweight or obese people. Overall, participants lost slightly more weight on the control diets but this was not significantly different from the weight loss achieved through dietary fat restriction and was so small as to be clinically insignificant.

Diet, Fat-Restricted↗

Systemic delivery of an adenoviral vector encoding canine factor VIII results in short-term phenotypic correction, inhibitor development, and biphasic liver toxicity in hemophilia A dogs.

Canine hemophilia A closely mimics the human disease and has been used previously in the development of factor VIII (FVIII) protein replacement products. FVIII-deficient dogs were studied to evaluate an in vivo gene therapy approach using an E1/E2a/E3-deficient adenoviral vector encoding canine FVIII. Results demonstrated a high level of expression of the canine protein and complete phenotypic correction of the coagulation defect in all 4 treated animals. However, FVIII expression was short-term, lasting 5 to 10 days following vector infusion. All 4 dogs displayed a biphasic liver toxicity, a transient drop in platelets, and development of anticanine FVIII antibody. Canine FVIII inhibitor development was transient in 2 of the 4 treated animals. These data demonstrate that systemic delivery of attenuated adenoviral vectors resulted in liver toxicity and hematologic changes. Therefore, the development of further attenuated adenoviral vectors encoding canine FVIII will be required to improve vector safety and reduce the risk of immunologic sequelae, and may allow achievement of sustained phenotypic correction of canine hemophilia A.

Adenoviridae↗

Long-term care of people below age 65 with severe acquired brain injury: appropriateness of aged care facilities.

OBJECTIVE: To identify the number of people younger than 65 years with acquired brain injury (ABI) living in aged care facilities in Queensland, and to evaluate the appropriateness of this accommodation option. METHODS: A cross-sectional descriptive study of all 493 Commonwealth Department of Health and Aged Care registered aged care facilities in Queensland. Associations between a range of demographic factors, resources, care provision and client needs were examined, from the perspective of service providers. RESULTS: The response rate was 75%. Twenty-six per cent of facilities (n=97) were providing care for 209 people younger than 65 years with ABI. The social, cognitive and rehabilitation aspects of client care were found to be inadequate in facilities where staffing levels, training and funding resources were limited (p< 0.05). Smaller facilities (<60 beds) reported higher levels of family participation in specific aspects of client care (p<0.05). Almost 40% of the facilities indicated they did not adequately meet the specific and complex rehabilitation needs of these clients. Aged care facilities were the least favoured model of care for this client group (8%) compared with the most favoured model of small group homes (46%). CONCLUSIONS: The current use of aged care facilities for housing younger people with high-level care needs resulting from ABI is inappropriate and does not meet client needs.

Adult↗

A single nucleotide polymorphism at nucleotide -1793 in the von Willebrand factor (VWF) regulatory region is associated with plasma VWF:Ag levels.

von Willebrand Factor (VWF) is a large multimeric glycoprotein involved in the transport and protection of factor VIII and in mediating platelet-subendothelium and platelet-platelet interactions. We have documented the presence of a single nucleotide polymorphism (SNP) at nucleotide (nt) -1793 (G 0.36 or C 0.64) in the VWF 5'-flanking sequence. This polymorphism is in strong linkage disequilibrium with the previously reported SNPs at nts -1234, -1185 and -1051 and, like this other group of polymorphisms, shows a significant association with plasma VWF levels. This association is more marked in subjects who are more than 40 years of age. Further, circumstantial evidence to support a role for the -1793 sequence in regulating VWF expression comes from our demonstration of differential binding of endothelial cell nuclear proteins, including the transcription factor NFkappaB, by this sequence. In summary, the association of the -1793 SNP with plasma VWF levels provides additional evidence for the role of the VWF regulatory region between nts -1793 and -1051 in controlling VWF expression.

Adult↗

The complete DNA sequence of myxoma virus.

Myxomatosis in European rabbits is a severely debilitating disease characterized by profound systemic cellular immunosuppression and a high rate of mortality. The causative agent, myxoma virus, is a member of the poxvirus family and prototype of the Leporipoxvirus genus. As a major step toward defining the genetic strategies by which the virus circumvents host antiviral responses, the genomic DNA sequence of myxoma virus, strain Lausanne, was determined. A total of 171 open reading frames were assigned to cover the 161.8-kb genome, including two copies each of the 12 genes that map within the 11.5-kb terminal inverted repeats. Database searches revealed a central core of approximately 120 kb that encodes more than 100 genes that exhibit close relationships to the conserved genes of members of other poxvirus genera. Open reading frames with predicted signal sequences, localization motifs, or homology to known proteins with immunomodulatory or host-range functions were examined more extensively for predicted features such as hydrophobic regions, nucleic acid binding domains, ankyrin repeats, serpin signatures, lectin domains. and structural cysteine spacings. As a result, several novel, potentially immunomodulatory proteins have been identified, including a family with multiple ankyrin-repeat domains, an OX-2 like member of the neural cell adhesion molecule family, a third myxoma serpin, a putative chemokine receptor fragment, two natural killer receptor-like species, and a variety of species with domains closely related to diverse host immune regulatory proteins. Coupled with the genomic sequencing of the related leporipoxvirus Shope fibroma virus, this work affirms the existence of a conserved complement of poxvirus-specific core genes and expands the growing repertoire of virus genes that confer the unique capacity of each poxvirus family member to counter the immune responses of the infected host.

Amino Acid Sequence↗

In vivo evaluation of an adenoviral vector encoding canine factor VIII: high-level, sustained expression in hemophiliac mice.

Hemophilia A is the most common severe hereditary coagulation disorder and is caused by a deficiency in blood clotting factor VIII (FVIII). Canine hemophilia A represents an excellent large animal model that closely mimicks the human disease. In previous studies, treatment of hemophiliac dogs with an adenoviral vector encoding human FVIII resulted in complete correction of the coagulation defect and high-level FVIII expression [Connelly et al. (1996). Blood 88, 3846]. However, FVIII expression was short term, limited by a strong antibody response directed against the human protein. Human FVIII is highly immunogenic in dogs, whereas the canine protein is significantly less immunogenic. Therefore, sustained phenotypic correction of canine hemophilia A may require the expression of the canine protein. In this work, we have isolated the canine FVIII cDNA and generated an adenoviral vector encoding canine FVIII. We demonstrate expression of canine FVIII in hemophiliac mice at levels 10-fold higher than those of the human protein expressed from an analogous vector. Canine FVIII expression was sustained above human therapeutic levels (50 mU/ml) for at least 1 year in hemophiliac mice.

Adenoviridae↗

No impact from active dissemination of the Ottawa Ankle Rules: further evidence of the need for local implementation of practice guidelines.

BACKGROUND: Local implementation strategies are often required to promote consistent adherence to clinical guidelines, but they are time consuming and expensive. The authors tested an educational intervention designed to increase use of the Ottawa Ankle Rules, a widely publicized set of clinical guidelines previously shown to reduce the use of radiography for diagnosis of acute ankle injuries. METHODS: The study consisted of a quasi-experimental, before-and-after comparative analysis. Trained experts provided 1-hour educational sessions and supplied resource materials on the Ottawa Ankle Rules to health care professionals from 63 Ontario hospitals. Participants were asked to evaluate the intervention. The authors then compared, for periods before and after the educational sessions, the use of ankle radiography for adults with acute ankle injury in 10 hospitals that received the educational intervention and reported no (n = 5) or some (n = 5) prior use of the rules and in 5 control hospitals, which declined the educational intervention because they were already implementing the rules. RESULTS: Although participants gave highly positive appraisals of the Ottawa Ankle Rules and the educational sessions, there was no reduction in the use of ankle radiography for the 10 hospitals that received the educational sessions (73% before and 78% after the intervention, p = 0.11). In contrast, use of radiography decreased significantly, from 75% to 65%, in the 5 control hospitals (p = 0.022). INTERPRETATION: Even when a dissemination strategy is well received and involves a widely accepted clinical guideline, the impact on behaviour in clinical practice may be small. In addition to broad dissemination, an active local implementation strategy is necessary to encourage physicians to adopt clinical guidelines.

Acute Disease↗

Treponema pallidum major sheath protein homologue Tpr K is a target of opsonic antibody and the protective immune response.

We have identified a family of genes that code for targets for opsonic antibody and protective immunity in T. pallidum subspecies pallidum using two different approaches, subtraction hybridization and differential immunologic screening of a T. pallidum genomic library. Both approaches led to the identification of a polymorphic multicopy gene family with predicted amino acid homology to the major sheath protein of Treponema denticola. One of the members of this gene family, tpr K, codes for a protein that is predicted to have a cleavable signal peptide and be located in the outer membrane of the bacterium. Reverse transcription polymerase chain reaction analysis of T. pallidum reveals that Tpr K is preferentially transcribed in the Nichols strain of T. pallidum. Antibodies directed to purified recombinant variable domain of Tpr K can opsonize T. pallidum, Nichols strain, for phagocytosis, supporting the hypothesis that this portion of the protein is exposed at the surface of the treponeme. Immunization of rabbits with the purified recombinant variable domain of Tpr K provides significant protection against infection with the Nichols strain of T. pallidum. This gene family is hypothesized to be central to pathogenesis and immunity during syphilis infection.

Amino Acid Sequence↗