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Biomedical subjects

L Stewart

Publications and source records attributed to L Stewart.

At least 37 records · Page 2Linked to original sources

High prevalence of celiac disease in patients with type 1 diabetes detected by antibodies to endomysium and tissue transglutaminase.

OBJECTIVE: To establish the prevalence of celiac disease (CD) in children with type 1 diabetes in British Columbia. PATIENTS AND METHODS: Two hundred thirty-three children with type 1 diabetes were prospectively screened for CD using blind testing with the current 'gold standard', immunoglobulin A endomysium antibody (EmA), and the novel immunoglobulin A tissue transglutaminase (tTG) antibody. Those children with positive results were offered small bowel biopsy; a gluten-free diet was recommended if CD was confirmed. RESULTS: Nineteen children were positive for EmA and had an elevated tTG level. One patient from this group was already known to have CD, and the other 18 patients consented to biopsy. One biopsy was normal, three biopsies demonstrated elevated intraepithelial lymphocyte counts with normal morphology and 14 biopsies had morphological changes consistent with CD. Growth parameters were normal in all patients, and nine of 19 children who were positive for EmA were asymptomatic. Seven patients had mild elevation of tTG levels alone. Two children from this latter group had normal biopsies, and five declined biopsy. CONCLUSIONS: At least 14 new cases of CD were detected in addition to four known cases, yielding an overall biopsy-confirmed prevalence of CD of 7.7% (18 of 233). The present study confirms that CD is as prevalent in the pediatric type 1 diabetic population in British Columbia as it is in Europe. Serological screening of these children is important because many children have no symptoms or signs suggestive of CD. This study suggests that tTG serology may also be useful in monitoring response and compliance with a gluten-free diet.

Adolescent↗

Does the family APGAR effectively measure family functioning?

BACKGROUND: The Family APGAR has been widely used to study the relationship of family function and health problems in family practice offices. METHODS: Data were collected from 401 pediatricians and family physicians from the Pediatric Research in Office Settings network and the Ambulatory Sentinel Practice Network. The physicians enrolled 22,059 consecutive office visits by children aged 4 to 15 years. Parents completed a survey that included the Family APGAR and the Pediatric Symptom Checklist. Clinicians completed a survey that described child psychosocial problems, treatments initiated or continued, and specialty care referrals. RESULTS: Family dysfunction on the index visit often differed from dysfunction at follow-up (kappa=0.24). Only 31% of the families with positive Family APGAR scores at baseline were positive at follow-up, and only 43% of those with positive scores at follow-up had a positive score at the initial visit. There were many disagreements between the Family APGAR and the clinician. The Family APGAR was negative for 73% of clinician-identified dysfunctional families, and clinicians did not identify dysfunction for 83% of Family APGAR-identified dysfunctions (kappa=0.06). CONCLUSIONS: Our data do not support the use of the Family APGAR as a measure of family dysfunction in the primary care setting. Future research should clarify what it does measure.

Adolescent↗

Melanoma differentiation associated gene-7 (mda-7): a novel anti-tumor gene for cancer gene therapy.

BACKGROUND: The mda-7 gene (melanoma differentiation associated gene-7) is a novel tumor suppressor gene. The anti-proliferative activity of MDA-7 has been previously reported. In this report, we analyze the anti-tumor efficacy of Ad-mda7 in a broad spectrum of cancer lines. MATERIALS AND METHODS: Ad-mda7-transduced cancer or normal cell lines were assayed for cell proliferation (tritiated thymidine incorporation assay, Alamar blue assay, and trypan-blue exclusion assay), apoptosis (TUNEL, and Annexin V staining visualized by fluorescent microscopy or FACs analysis), and cell cycle regulation (Propidium Iodide staining and FACs analysis). RESULTS: Ad-mda7 treatment of tumor cells resulted in growth inhibition and apoptosis in a temporal and dose-dependent manner. The anti-tumor effects were independent of the genomic status of p53, RB, p16, ras, bax, and caspase 3 in these cells. In addition, normal cell lines did not show inhibition of proliferation or apoptotic response to Ad-mda7. Moreover, Ad-mda7-transduced cancer cells secreted a soluble form of MDA-7 protein. Thus, Ad-mda7 may represent a novel gene-therapeutic agent for the treatment of a variety of cancers. CONCLUSIONS: The potent and selective killing activity of Ad-mda7 in cancer cells but not in normal cells makes this vector a potential candidate for cancer gene therapy.

Adenoviridae↗

Expression of human topoisomerase I with a partial deletion of the linker region yields monomeric and dimeric enzymes that respond differently to camptothecin.

Human topoisomerase I is a 765-residue protein composed of four major domains as follows: the unconserved and highly charged NH(2)-terminal domain, a conserved core domain, the positively charged linker region, and the highly conserved COOH-terminal domain containing the active site tyrosine. Previous studies of the domain structure revealed that near full topoisomerase I activity can be reconstituted in vitro by fragment complementation between recombinant polypeptides approximating the core and COOH-terminal domains. Here we demonstrate that deletion of linker residues Asp(660) to Lys(688) yields an active enzyme (topo70DeltaL) that purifies as both a monomer and a dimer. The dimer is shown to result from domain swapping involving the COOH-terminal and core domains of the two subunits. The monomeric form is insensitive to the anti-tumor agent camptothecin and distributive during in vitro plasmid relaxation assays, whereas the dimeric form is camptothecin-sensitive and processive. However, the addition of camptothecin to enzyme/DNA mixtures causes enhancement of SDS-induced breakage by both monomeric and dimeric forms of the mutant enzyme. The similarity of the dimeric form to the wild type enzyme suggests that some structural feature of the dimer is providing a surrogate linker. Yeast cells expressing topo70DeltaL were found to be insensitive to camptothecin.

Baculoviridae↗

Fat absorption in cystic fibrosis after correction of hypokalaemia.

Extracellular potassium up-regulates exocrine pancreatic function in tissue preparations of mammalian pancreatic lobules. We report on a child with cystic fibrosis in whom clinical evidence suggested that this laboratory observation may be of relevance to clinical practice.

Administration, Oral↗

Postcholecystectomy abdominal bile collections.

HYPOTHESIS: The clinical syndromes caused by bile collections in the abdomen span a wide spectrum and their natural history and risks are not fully appreciated. DESIGN: Analysis of 179 patients with bile fistulas after cholecystectomy, of which 154 patients had undrained bile collections. OBJECTIVE: To characterize the manifestations and natural history of abdominal bile collections. SETTING: A tertiary care teaching hospital. PATIENTS AND METHODS: The clinical findings in 179 patients with bile fistulas resulting from iatrogenic laparoscopic bile duct injuries and other miscellaneous operations between 1990 and 1999 were analyzed. The group of main interest consisted of 154 patients with undrained bile collections. Of these 154 patients, 21% had serious complications, including sepsis and multiorgan failure. The data were analyzed to identify the variables associated with this undesirable outcome. MAIN OUTCOME MEASURES: Symptoms, physical findings, course of illness, and laboratory and imaging findings. RESULTS: The clinical manifestations of intra-abdominal bile collections were initially discounted in 77% of patients, so the problem went unsuspected for a variable and often lengthy period. Abdominal pain and tenderness (bile peritonitis) gradually developed in 18% of patients with bile ascites. There were no differences in the initial clinical findings in this group compared with those who did not develop peritonitis. Nineteen percent of patients with undrained bile collections experienced serious morbidity. The initial clinical findings did not differ in these patients compared with those with a less complicated illness. Serious illness, however, was associated with the following: (1) a longer period of undrained bile (15.4 vs 9.2 days, P=.04) and (2) a higher incidence of infected bile (45% vs 7%, P=.001). CONCLUSIONS: (1) Prominent abdominal pain and tenderness developed in only 21% of patients with abdominal bile collections; (2) the symptoms caused by bile collections were often subtle and their significance was overlooked, which resulted in a delay in diagnosis; (3) the early clinical findings could not distinguish patients who did become critically ill from those who did not; and (4) seriously ill patients more often had delayed drainage and infected bile. Still, failure to drain a bile collection within just 5 days resulted in serious illness in a few patients. Surgeons must watch for the clinical manifestations of bile ascites after laparoscopic cholecystectomy. This diagnosis should be suspected whenever persistent bloating and anorexia last for more than a few days; failure to recover as smoothly as expected is the most common early symptom of bile ascites. If bile collections were promptly diagnosed and drained, the rate of serious illness resulting from this complication would decline.

Adolescent↗

Chemotherapy for advanced ovarian cancer. Advanced Ovarian Cancer Trialists Group.

BACKGROUND: Ovarian carcinoma is the seventh most common cancer of women in the world and is responsible for the greatest number of deaths from gynaecological malignancy in Europe and North America. Although many studies have explored the use of chemotherapy in this disease, most individual trials have been too small to show clear benefit of one type of chemotherapy over another. OBJECTIVES: The type and intensity of chemotherapy used routinely for women with advanced ovarian cancer has varied because of uncertainty about the effectiveness of the different regimens. The objective of this review was to compare single drugs versus combinations of drugs, platinum versus non-platinum, and carboplatin versus cisplatin-based chemotherapy in women with advanced ovarian cancer. SEARCH STRATEGY: Search strategy: We searched MEDLINE, and CancerLit bibliographic databases and the National Cancer Institute and the UK Co-ordinating Committee on Cancer Research registers of trials. We also handsearched the proceedings of meetings and contacted experts in the field and drug companies. SELECTION CRITERIA: Randomised trials of: (1) single non-platinum versus non-platinum combination chemotherapy (2) single non-platinum versus platinum combination chemotherapy (3) non-platinum regimen versus the same regimen plus cisplatin (4) single platinum versus platinum combination chemotherapy (5) cisplatin versus carboplatin-based chemotherapy in women with advanced ovarian cancer. DATA COLLECTION AND ANALYSIS: Individual patient data were obtained from the trial investigators, checked by the reviewers and finally verified by the trial investigator. MAIN RESULTS: Main results: 49 trials involving 8763 women were included. The data were combined to calculate hazard ratios (HR) for survival on an intention-to-treat basis. For single non-platinum versus platinum combination chemotherapy the overall HR for survival was 0.93, 95% confidence interval (CI) 0.83-1.05 in favour of platinum-based combination chemotherapy. For non-platinum regimens compared with the same regimen plus cisplatin the survival HR was 0.88, 95% CI 0.79- 0.98 in favour of the addition of platinum to drug regimens. Single platinum compared with platinum combination therapy gave a HR of 0.91, 95% CI 0.79-1.05 in favour of combination chemotherapy. Cisplatin versus carboplatin gave a HR of 1.02, 95% CI 0.93-1.12. Sub-group analyses for age, stage, grade, histology, resection, bulk of residual tumour and performance status were undertaken for cisplatin versus carboplatin only. No difference in effect was found. REVIEWER'S CONCLUSIONS: The available evidence, although not conclusive, suggests that platinum-based chemotherapy is better than non-platinum therapy. There is some evidence that combination therapy improves survival compared with platinum alone. No difference in effect has been shown between cisplatin and carboplatin.

Antineoplastic Agents↗

Developing a model of collaborative research: the complexities and challenges of implementation.

While the benefits of collaborative research have been well documented, fewer publications exist regarding the complex, problematic issues involved in these undertakings. This paper offers an integrated collaborative research model to depict the complexities and challenges of initiation and implementation of a 2 1/2 year joint research project between a community hospital and a university school of nursing in Southern Ontario, Canada. A sampling of the experiences of the researchers are analyzed to clarify the dynamic and often competing issues and interactions involved in encouraging hospital-wide research involvement during periods of organizational growth and change. The model reflects the simultaneous interaction of organizational, change and collaborative processes while maintaining the rigor of the research (RCT), and ensuring minimal disruption to the service agency. Quantitative outcomes of this collaboration are presented through an analysis of participant involvement on multiple organizational levels. Recommendations for future collaborative research, including design and methodological issues and collaborative and change strategies are offered. The complexity of balancing the necessary trade-offs required of successful collaborative research are highlighted and will be useful to those considering and planning future collaborations.

Clinical Nursing Research↗

Treatment outcome among child psychiatric outpatients in a community mental health center.

The study evaluated the effectiveness of mental health center treatments for children aged 5-12 years. The Child Behavior Checklist (CBCL) was administered before and after treatment to the parents of the treatment group (N = 71). The results were analyzed and compared to the results of the pretest and posttest CBCL administered to the parents of a matched group of comparison subjects (N = 33). The results showed that the treatment subjects significantly improved on both the externalizing and internalizing scales of the CBCL. The controls showed no significant change between pretest and posttest scores. As a result, it appears that clinic treatments can help clients with measurable problems decrease problematic behaviors. More data is needed to determine whether clinic treatments such as the ones described in this study can substantially help the most seriously disturbed school-age children.

Ambulatory Care↗

Amelioration of established collagen induced arthritis by systemic IL-10 gene delivery.

A novel formulation of cationic liposomes containing the novel cytofectin ACHx was used for delivery of an anti-inflammatory cytokine gene, IL-10, to mice with established collagen induced arthritis. A single intraperitoneal injection of human IL-10 expression plasmid complexed with liposomes 2 to 4 days after the onset of arthritis was sufficient to give significant and prolonged amelioration of arthritis for 30 days. Preliminary experiments suggested that the therapeutic effect was IL-10 dose-dependent. The distribution of the human IL-10 DNA after injection was widespread, including the inflamed paws. Human IL-10 mRNA was also detected in the paws 24 h after injection. IL-10 protein was below the level of detection in paws and serum but was detected in some tissues up to 10 days after injection. The target cell of transfection was demonstrated to be the macrophage. These results suggest that systemic therapy with plasmid DNA complexed with cationic liposomes merits further development as an alternative method for anti-inflammatory treatment of arthritis.

Animals↗

The manifestation and nursing management of agitation in institutionalised residents with dementia.

This participatory action research study is the first formal research study undertaken by nurses in a nursing development unit. The study emerged as the result of nurses brainstorming issues that they perceived to be problematic in their nursing practice and their unit environment. The nurses of the psycho-geriatric nursing development unit, Wallsend Aged Care Facility, New South Wales, Australia identified that the management of agitated behaviour manifested by their severely demented clients was a major challenge in their practice. As a result, a pilot participatory action research study was designed to measure how agitation manifested, to measure the severity of agitation and to identify current nursing practices used to manage it and their outcome. Results of the study demonstrated that nurse actions triggered the majority of most highly rated episodes of agitated behaviour in this group of elderly residents, and that the majority of these nurse actions related to those involved in carrying out activities of daily living for the residents.

Aged↗

Air flight disaster, posttraumatic stress, and postventive rescue and response: the aftermath of the San Diego PSA 182 plane crash recovery operation, 20 years on.

San Diego in 1978 was the scene of one of the USA's most tragic and traumatic air flight disasters, when an inbound Boeing 727 collided with a small private Cessna 172. The collision occurred in the vicinity of North Park, a suburb of San Diego. All aircraft occupants were killed or injured and many residents were injured. The wreckage was mainly concentrated in an area about the size of a city block, in a temperature of 100 degrees F or more. The whole experience was unlike anything any of the professionals involved had been prepared for, and beyond anything the civilians involved could have imagined. Many sought out intervention and help and counselling, and this paper examines the implications of the event 20 years on.

Accidents, Aviation↗

Increased prevalence of celiac disease in girls with Turner syndrome detected using antibodies to endomysium and tissue transglutaminase.

OBJECTIVE: To establish the prevalence of celiac disease (CD) in girls with Turner syndrome (TS) in British Columbia. METHODS: Forty-five girls with TS were prospectively screened for CD using blinded testing with the current 'gold standard' - immunoglobulin A (IgA) endomysium antibody (EmA) and the novel IgA tissue transglutaminase antibody (tTG). Those with positive results were offered small bowel biopsies, and a gluten-free diet was recommended if CD was confirmed. RESULTS: One asymptomatic prepubertal East Indian girl was positive for EmA, had an elevated tTG concentration of 560 U/mL and histological evidence of CD. Seven girls were negative for EmA but had elevated tTG concentrations (175 to 250 U/mL); five were white, one was Asian and one was East Indian. Small bowel biopsies were performed on three girls, and the histologies were normal. The remaining four patients declined biopsy. CONCLUSIONS: One girl with TS was identified with CD from 45 screened, giving an overall biopsy-confirmed prevalence of 2.2%. This study confirms previous observations placing girls with TS at higher risk for CD and suggests a similar high prevalence in British Columbia.

Adolescent↗

Emergency department staff responses to a protocol of care for abused women.

While there is increasing recognition by health care providers of the need to identify and intervene in cases of partner abuse, there has been little evaluation of the interventions that have been implemented. This article documents emergency department staff responses to a five-step protocol of care on partner abuse implemented in a public hospital. It draws on in-depth interviews with a range of emergency department staff members, undertaken as part of the project's process evaluation. Findings suggest protocol training provided staff members with an opportunity to gain a greater awareness and understanding of partner abuse. Protocol use improved and consolidated existing practices; however, staff members were concerned about screening all women for abuse and highlighted areas in which further support and resources are required. Taking these factors into account may assist the appropriate and effective introduction of such protocols in other health care settings.

Attitude of Health Personnel↗