Biomedical subjects
C Cameron
Publications and source records attributed to C Cameron.
Stay in the humble: a double footling breech birth.
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Immunological effects of interleukin 12 administered by bolus intravenous injection to patients with cancer.
The immunological effects of recombinant human interleukin 12 (rhIL-12) administration were examined during the conduct of a Phase I clinical trial. Forty patients with advanced cancer received bolus i.v. injections of rhIL-12 in doses ranging between 3 and 1000 ng/kg. Dose-dependent increases in serum IFN-gamma levels were seen during rhIL-12 therapy. Significant lymphopenia was observed 24 h after single i.v. injections of rhIL-12 at each dose level. The degree of lymphopenia was dose dependent, and a plateau effect was seen with rhIL-12 doses of 100 ng/kg and higher. Lymphocyte counts reached nadir levels at approximately 10 h after rhIL-12 injection and returned to baseline within 14 days postinjection. Rebound lymphocytosis, as seen after interleukin 2 therapy, was not observed after recovery from rhIL-12-induced lymphopenia. rhIL-12-induced lymphopenia involved all major lymphocyte subsets, although natural killer (NK) cell numbers were the most profoundly affected, and CD4 T-cell numbers were the least affected. CD2, LFA-1, and CD56 were transiently up-regulated on the surface of NK cells exposed to rhIL-12 in vivo. Peripheral blood mononuclear cells obtained from cancer patients before rhIL-12 therapy exhibited defective NK cell cytotoxicity and T-cell-proliferative responses. Peripheral blood mononuclear cells obtained after lymphocyte recovery following the administration of a single 500 ng/kg dose of rhIL-12 displayed augmented NK cell cytolytic activity in four of four patients tested and enhanced T-cell proliferation in three of four patients tested. These studies confirm that doses of rhIL-12 resulting in significant immunological activity can be administered with acceptable toxicity to cancer patients. Furthermore, rhIL-12 therapy can reverse defects in NK cell and T-cell function that are associated with advanced cancer in humans.
One-on-one peer support and quality of life for breast cancer patients.
The Canadian Cancer Society's Reach to Recovery program provides one-on-one support for breast cancer patients that is delivered by breast cancer survivors. Professionally-led social support programs have generally been found to influence positively the quality of life of cancer patients. However, there is a lack of evidence on the benefits of one-on-one peer support programs. An evaluation of the Reach to Recovery program was completed in 1995 to determine if cancer patients who received the program were satisfied with the program and to determine if participation in Reach to Recovery affected the quality of life of program participants compared to patients who did not receive the program. We found that Reach to Recovery program participants were generally satisfied with the program they received and that the program has incremental benefits to the quality of life of patients with breast cancer. Peer-led, volunteer breast cancer support programs can be effective in enhancing the quality of life of breast cancer patients.
Androgen effects on factor IX expression: in-vitro and in-vivo studies in mice.
A role for steroid hormones has been proposed for the post-pubertal factor IX increment of approximately 25% seen in both normal males and females, as well as in the post-pubertal phenotypic recovery seen in haemophilia B Leyden. We have evaluated androgen receptor binding to the factor IX promoter and have assessed transcriptional activation of the factor IX gene in hepatocytes through transient transfection studies and through expression of factor IX in a murine model of androgen insensitivity. Whereas transfection of the androgen receptor alone did not activate expression from the factor IX promoter, co-transfection with the CCAAT enhancer binding protein resulted in a synergistic 17-fold enhancement of transcriptional activity. Using liver nuclear extracts and recombinant androgen receptor protein we have confirmed binding of this protein to the factor IX proximal promoter and disruption of binding with a mutation at nucleotide -26. Finally, studies in normal and testicular feminized male mice showed different developmental patterns of factor IX expression. In normal mice, expression recapitulates that seen in humans, with early post-natal levels being approximately 50% of the adult values and with a post-pubertal increment of approximately 25%. In contrast, testicular feminized animals did not show a significant post-pubertal increment of factor IX. These studies provide further support for the role of androgen receptor binding to the factor IX promoter in regulating the developmental expression of factor IX.
The welfare of the child. An emerging issue in the regulation of assisted conception.
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The canine factor VIII cDNA and 5' flanking sequence.
Factor VIII is a trace plasma glycoprotein involved as a cofactor in the activation of factor X by factor IXa. Inherited deficiency of factor VIII results in the X-linked bleeding disorder hemophilia A which has been documented in humans, horses, sheep and dogs. In this report, the putative proximal promoter, 5' untranslated region, complete coding sequence and 3' untranslated region of the canine factor VIII gene have been characterized. When compared to the human gene, the 5' flanking region shows conservation of transcription factor binding sites in the 5' untranslated region. Alignment of the amino acid sequence with that of the previously reported human, mouse and pig proteins demonstrates sequence identity of between 77 and 92% for the A1, A2, A3, C1 and C2 domains but an identity of only between 44 and 62% for the central B domain. The three thrombin cleavage sites are conserved in the canine sequence as are the protein C cleavage sites and the von Willebrand factor binding region. In addition, all six tyrosine residues that are known to undergo sulfation in the human protein are conserved in the dog. The 3' untranslated region of the canine gene extends 1.5 kilobases. The initial 700 basepairs of this sequence are highly GC rich and the sequence terminates with 2 alternative potential polyadenylation sites. The knowledge of this sequence, in combination with a well described canine model of hemophilia A, provides the necessary starting point for studies addressing the long-term evaluation of factor VIII gene therapy using a homologous transgene.
Promotion of regeneration and axon growth following injury in an invertebrate nervous system by the use of three-dimensional collagen gels.
We describe the application of three-dimensional collagen matrices to the study of nerve cord repair in the leech. Our experiments show that ganglia and connectives of the leech ventral nerve cord can be maintained for up to four weeks embedded in 3D gels constructed from mammalian type I collagen. Severed nerve cords embedded in the collagen gel reliably repaired within a few days of culture. The gel was penetrable by cells emigrating from the cut ends of nerves and connectives, and we consistently saw regenerative outgrowth of severed peripheral and central axons into the gel matrix. Thus, 3D gels provide an in vitro system in which we can reliably obtain repair of severed nerve cords in the dish, and visualize cell behaviour underlying regenerative growth at the damage site: and which offers the possibility of manipulating the regenerating cells and their extracellular environment in various ways at stages during repair. Using this system it should be possible to test the effect on the repair process of altering expression of selected genes in identified nerve cells.
Community commitment in action: a look at a parish nursing pilot project.
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Perspectives on Reach to Recovery and CanSurmount: informing the evaluation model.
The Canadian Cancer Society requested that the Centre for Behavioural Research and Program Evaluation of the National Cancer Institute of Canada evaluate Reach to Recovery and CanSurmount, 1-on-1 peer-support programs that provide information and support to individuals with cancer and their families. Key informant interviews (with program participants and volunteer visitors) were conducted to gather qualitative data and to help us develop a framework and tools to evaluate these programs. We found that 1) there are program objectives from the perspective of volunteers and participants in addition to those outlined in the program materials; 2) there are variations in how the programs are delivered and how patients or family members are recruited into the program; and 3) there is evidence that Reach to Recovery and CanSurmount volunteers are in a unique position to deliver the programs, either because they have personally experienced cancer or have family members who have had cancer. We describe the key informant exercise developed for this evaluation project and present the results of preliminary data-gathering activities.
Relationships among sleep dimensions and factors that impair sleep after cardiac surgery.
Factors associated with the attempted length, disturbance, effectiveness, and nap supplementation of sleep were analyzed in 97 patients recovering from cardiac surgery a few days before hospital discharge. Patients rated sleep for the prior night and factors that impaired their sleep after transfer from the critical care unit. The group averaged little sleep, with moderate disturbance and effectiveness and low nap supplementation. The disturbance, effectiveness, and attempted length of sleep were associated with an inability to perform their usual routine before sleep, inability to get comfortable, pain, noises, procedural care, and an unfamiliar bed. Patients encounter difficulties with sleep, even near discharge from the hospital. Interventions should be tested to mitigate specific factors that affect selected dimensions of sleep.
Patient compliance: recognition of factors involved and suggestions for promoting compliance with therapeutic regimens.
Patient compliance is paramount in the effectiveness of therapeutic regimens. Without compliance therapeutic goals cannot be achieved, resulting in poorer patient outcomes. The social and psychological factors thought to influence compliance are identified as (a) knowledge and understanding including communication, (b) quality of the interaction including the patient-provider relationship and patient satisfaction, (c) social isolation and social support including the effect of the family, (d) health beliefs and attitudes-health belief model variables, and (e) factors associated with the illness and the treatment including the duration and the complexity of the regimen. Noncompliance is a significant problem and a major challenge for the health care team. Practical advice is offered for nurses and other health care professionals to increase patient compliance with therapeutic regimens. These include factors involved in the patient-provider relationship, communication skills and information-giving, and the mobilization of existing social support networks. Further research is needed to provide more conclusive results into the factors involved in patient compliance and to test the effectiveness of compliance-enhancing strategies.
Patient advocacy: a role for nurses?
There is much controversy surrounding the issue of nurses in the role of patient advocate. Cancer patients are vulnerable due to their diagnoses, the anxiety that it generates, the nature of the disease and subsequent treatment and may diminished autonomy as a result. It is questionable whether the nurse is able to promote the best interest of the patient in this situation. Models of advocacy and the nurse-patient relationship are discussed. The main arguments for taking on the role of patient advocate include: reference to long periods of time spent with patient and the chance to build a relationship; on duty to care and the duty to do no harm. Criticisms of the appropriateness of advocacy role for nurses include: inability for the patient to choose his or her nurse; promotion of self interests; charges of paternalism; challenges from other health care professionals and multiple and/or conflicting obligations. It is concluded that perhaps the most ethical way of caring is by empowering patients and promoting self-advocacy. This concept needs to be further explored.
Haemolytic-uraemic syndrome in Western Australia, 1980 to 1994.
A retrospective, population-based study of patients hospitalised with the haemolytic-uraemic syndrome in Western Australia from 1980 to 1994 was undertaken to describe the epidemiology of the disease in this state. We identified 41 patients. Episodes were commonest in children under five years of age (63.4 per cent) and were more frequent in females (58.5 per cent) than in males; only one Aboriginal patient was detected. More than 90 per cent of episodes had a gastrointestinal prodrome lasting from one to 22 days; in 47.6 per cent of these episodes patients had bloody diarrhoea. The average hospital stay was 26 days, and 63.4 per cent of patients required dialysis (mean 10 days). More than 20 per cent of patients developed chronic renal failure, 9.7 per cent died, two patients developed hypertension and one child became epileptic; three of the 10 patients over 16 years of age (30 per cent) died. The haemolytic-uraemic syndrome is potentially fatal, affects mostly young children, and is usually preceded by a gastrointestinal illness. Episodes can occur in common-source outbreaks but, with the exceptions of related cases in families, that appears not to have been so in Western Australia since 1980. There is a need for increased awareness of the haemolytic-uraemic syndrome to enhance prospects for earlier detection and better clinical outcomes. Improved public health surveillance is also needed to reduce the risks of the syndrome in the community.
Characterization of a cell line, NKL, derived from an aggressive human natural killer cell leukemia.
Cell line NKL was established from the the peripheral blood of a patient with CD3-CD16+CD56+ large granular lymphocyte (LGL) leukemia. The neoplastic LGL of this patient mediated natural killing and antibody-dependent cellular cytotoxicity (ADCC) and exhibited proliferative responses similar to normal CD16+CD56dim natural killer (NK) cells. The Morphology of NKL cells resembles that of normal activated NK cells. The karyotype of NKL is 47, XY, add (1) (q42), +6 del (6) (q15 q23), del (17) (p11). NKL cells express CD2, CD6, CD11a, CD26, CD27, CD29, CD38, CD43, CD58, CD81, CD94, CD95, class II MHC, and the C1.7.1 antigen, but do not express detectable levels of CD3, CD4, CD5, CD8, CD14, CD19, CD20, CD28, alpha/beta or gamma/delta T cell receptors on the cell surface. The density of the CD16, CD56, and CD57 antigens declined markedly on NKL cells during prolonged im vitro culture. Nevertheless, NKL cells can mediate ADCC as well as natural killing. NKL cells are strictly dependent on interleukin-2 (IL-2) for sustained growth and die if deprived of IL-2 for more than 7 days. NKL cells proliferate in response to concentrations of IL-2 as low as 1 pM, but an optimal proliferative response requires approximately 100 pM IL-2. NKL cells growing in the presence of IL-2 express abundant IL-2R alpha with little or no detectable IL-2 beta or gamma chain on the cell surface; NKL cells deprived of IL-2 express high levels of both IL-2R alpha and beta. IL-4, IL-7, and IL-12, unlike IL-2, do not maintain the viability of NKL cells. Furthermore, IL-1, IL-4, IL-6, IL-7, IL-12, tumor necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha) and IFN-gamma do not support the growth of NKL cells. The NKL cell line may prove useful for studies of human NK cell biology.
Patients' perceptions of environmental factors that disturb sleep after cardiac surgery.
BACKGROUND: Effective management of sleep disturbances after cardiac surgery requires insight into patients perceptions of which factors disturb sleep in the intensive care unit and after transfer from the intensive care unit. OBJECTIVE: To describe patients perceptions of environmental factors that disturbed sleep after cardiac surgery. SAMPLE: A convenience sample of 102 patients was surveyed in a 300-bed, acute-care teaching hospital. METHOD: Patients were interviewed several days before discharge from the hospital and rated the extent to which specific factors disturbed their sleep while in the intensive care unit and after transfer. RESULTS: The group mean for the extent of disturbance scores, averaged across all 35 environmental factors studied, was low during and after stay in the intensive care unit. However, selected items such as pain, and inability to get comfortable and perform a familiar nighttime routine, were moderately disturbing to many patients across phases of recovery. Patients varied widely in the number of factors, ranging from 0 to 33 factors, that disturbed sleep at least to some extent. Patients added factors that were not included in the original monitoring instrument. CONCLUSIONS: Patients attribute disturbed sleep to specific factors after cardiac surgery. The number of factors that disturb sleep varies among patients. Nurses can modify many of the factors that disturb sleep to promote an environment that will facilitate improved sleep, thereby enhancing the acute phase of recovery from cardiac surgery.
School-age children's perceptions of mental illness.
The purpose of this study was to describe how school-age children perceive mental illness. The specific aims of this study were to describe the impact of age and sex on children's ability to identify and classify deviant behavior, and to identify how school-age children perceive mental illness by looking at how they define the concept, characterize the mentally ill, and understand causality and treatment. The random sample consisted of 90 school-age children. Thirty children were in grade 1, 30 in grade 4, and 30 in grade 7. A multimethods approach combining qualitative and quantitative techniques was used to analyze data. Major study findings indicated that age was not a significant factor in children's ability to classify deviant behavior; however, there was a sex main effect: Boys were able to better identify deviant behaviors than girls. A developmental trend was noted in children's ability to be aware of what mental illness is, to acknowledge characteristics of people who are mentally ill, to differentiate between mental illness and mental retardation, to identify various etiologies of mental illness, and to choose appropriate treatment modalities.