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D Dale

Publications and source records attributed to D Dale.

At least 19 recordsLinked to original sources

Measurement issues in the assessment of physical activity in children.

This paper reviewed the nature of children's physical activity patterns and how the unique nature of children can impact the assessment of physical activity. To accurately assess children's activity patterns, an instrument must be sensitive enough to detect, code, or record sporadic and intermittent activity. Care also must be used to select criterion measures that reflect appropriate physical activity guidelines for children. A number of different measurement approaches have been described for assessing children's activity, but no specific method can be identified as the best option for all studies. Selection of an appropriate instrument depends on the specific research question being addressed as well as the relative importance of accuracy and practicality (Baranowski & Simons-Morton, 1991). For example, accurate measures of energy expenditure using doubly-labeled water, indirect calorimetry, or heart rate calibration equations may be needed for certain clinical studies, but the cost and inconvenience would make them impractical for field-based assessments on larger samples. The "accuracy-practicality" trade-off presents a more challenging predicament with children than for adults. In adults, a number of self-report instruments have been found useful for large epidemiological studies or interventions where less precision is needed. Because of developmental differences, especially in ability to think abstractly and perform detailed recall (Going et al., 1999; Sallis, 1991), children are less likely to make accurate self-report assessment than adults. Though self-report methods are still likely to be a principal source of information for many studies, other approaches (or the use of combined measures) may be needed to better characterize children's activity levels. While objective instruments (e.g., direct observation or activity monitoring) require more time and resources than self-report, there are options available to simplify data collection. One approach may be to focus assessments on key times or places that allow children to be active. The time after school, for example, appears to be a critical period that defines their propensity for physical activity (Hager, 1999). Monitoring of entire groups for discrete periods of time (e.g., recess or physical education) may also be useful to understand variability in activity patterns since children would all be exposed to the same stimulus or opportunity to be active. Proxy measures may also be useful in studying activity in children. For example, several studies (Baranowski, Thompson, DuRant, Baranowski, & Puhl, 1993; Sallis et al., 1993) have demonstrated that time spent outside is strongly predictive of activity in children. Involvement in community sports programs may also be a useful proxy measure as sports programs have been found to account for approximately 55-65% of children's moderate to vigorous activity (Katzmarzyk & Malina, 1999). Another option for improving assessments in children is to employ multiple measures of physical activity. A number of studies (Coleman, Saelens, Wiedrich-Smith, Finn, & Epstein, 1997; McMurray et al., 1998; Sallis et al., 1998; Simons-Morton et al., 1994) have reported differences in levels of activity when activity monitors were compared with self-report data. The method of measurement has also been shown to influence the results of studies on the determinants of physical activity in children (Epstein, Paluch, Coleman, Vito, & Anderson, 1996). While we do not currently know which measure is most accurate, reporting the results with different instruments provides a more complete description of children's activity and permit a triangulation of outcomes. In summary, there remains no single way of obtaining a highly accurate account of physical activity or energy expenditure in children. The nature of children's movement patterns, the various types of activities engaged in, and the inherent limitations of each assessment tool limit the ultima

Child↗

Beta-catenin mutations are specific for colorectal carcinomas with microsatellite instability but occur in endometrial carcinomas irrespective of mutator pathway.

Some colorectal tumors with wild-type adenomatous polyposis coli gene have activating mutations in beta-catenin (encoded by CTNNB1) that result in decreased phosphorylation by GSK-3beta and increased signaling through the Tcf/Lef transcription factors. To investigate the relationship between CTNNB1 mutations and underlying pathways of genomic instability, we examined 80 colorectal cancers stratified by the presence or absence of microsatellite instability (MSI). CTNNB1 mutations were identified in 13 (25%) of 53 cancers with high frequency MSI (MSI-H), including 12 point mutations at exon 3 phosphorylation sites (codons 41 and 45) and one deletion of the entire exon 3 degradation box. No CTNNB1 mutations were identified in 27 microsatellite stable or low frequency MSI (MSI-L) colorectal cancers (P < 0.01). In contrast, CTNNB1 mutations were identified in 3 of 9 (33%) MSI-H and 10 of 20 (50%) MSS/MSI-L endometrial carcinomas, suggesting a more generalized involvement in these tumors. Only six (46%) of the endometrial carcinoma CTNNB1 mutations occurred at residues directly phosphorylated by GSK-3beta, and only one of these was at either codon 41 or 45. All point mutations in MSI-H cancers were transitions, whereas 64% of those in MSS/MSI-L cancers were transversions (P < 0.01). The differences in the mutation profiles suggest that there may be molecular fingerprints of CTNNB1 mutations, determined by biological factors related to both tumor type and underlying pathways of genomic instability.

Adenocarcinoma↗

Nicotinamide alters the calcium release pattern and the degradation of MPF activity after fertilisation in ascidian oocytes.

Fertilisation in ascidian oocytes triggers a plasma membrane current, the release of intracellular calcium and the degradation of Maturation Promoting Factor (MPF) activity leading to the completion of meiosis and the initiation of embryo development. We have previously shown that the fertilisation current in ascidians is produced through the metabolism of nicotinamide nucleotide (NN) metabolites to ADP ribose. In this study we have used nicotinamide to test whether NN metabolism plays additional roles in fertilisation in ascidians. Nicotinamide treatment blocked calcium-induced calcium release (CICR) and arrested the cell cycle prior to the completion of meiosis I. Nicotinamide further prevented the abolition of MPF activity after fertilisation. Interestingly, nicotinamide treatment caused ascidian oocytes to form interphase-like pronuclei after fertilisation, despite the high MPF activity. The data demonstrate that NN metabolism is involved in calcium signalling through CICR and further suggest that a NN metabolite acts as a messenger connecting MPF activity to the formation of the meiotic apparatus.

Animals↗

A randomized controlled trial of filgrastim as an adjunct to antibiotics for treatment of hospitalized patients with community-acquired pneumonia. CAP Study Group.

Because of the critical role of neutrophils in host defenses, it was hypothesized that stimulation of neutrophil production and function with Filgrastim would improve the outcome of hospitalized patients with community-acquired pneumonia. To test this hypothesis, a randomized, placebo-controlled, multicenter trial of Filgrastim (300 micrograms/day up to 10 days) as an adjunct to antibiotics was conducted for these patients. Outcome measures included time to resolution of morbidity (TRM, a composite measure of temperature, respiratory rate, blood oxygenation, and chest radiograph), 28-day mortality, length of stay, and adverse events. Filgrastim increased blood neutrophils 3-fold, but TRM, mortality, and length of hospitalization were not affected. Treatment, however, accelerated radiologic improvement and appeared to reduce serious complications (e.g., empyema, adult respiratory distress syndrome, and disseminated intravascular coagulation). Filgrastim administration was safe and well tolerated in these patients. Additional trials are needed to establish the value of this approach to treatment of infectious diseases.

APACHE↗

Allogeneic blood stem cell transplantation: considerations for donors.

Allogeneic transplantation of cytokine-mobilized peripheral blood stem cells (PBSCs) is now being increasingly performed, but safety considerations for hematologically normal PBSC donors have not been fully addressed. Progenitors are generally mobilized for collection from normal donors using recombinant human granulocyte colony-stimulating factor (rhG-CSF). Although the short-term safety profile of rhG-CSF seems acceptable, experience remains limited and its optimal dose and schedule have not been defined. Minimal data exist regarding long-term safety of rhG-CSF, primarily derived from experience in patients with chronic neutropenia or cancer. An "ad hoc" workshop was recently convened among a group of investigators actively involved in the field of allogeneic stem cell transplantation to discuss the safety issues pertaining to normal PBSC donors. There was agreement on the following points: (1) On the basis of available data, it appears that rhG-CSF treatment and PBSC collection have an acceptable short-term safety profile in normal donors. However, the need for continued safety monitoring was recognized. (2) rhG-CSF doses up to 10 microg/kg/d show a consistent dose-response relationship with the mobilization (and collection) of CD34+ progenitor cells, and this dose is acceptable for routine clinical use. Whether higher doses are superior (or cost effective) remains to be determined, and they may produce more severe side effects. The potential risks of marked leukocytosis (arbitrarily defined as a leukocyte count of more than 70 x 10(9)/L) have been a concern, and rhG-CSF dose reduction is performed by many centers to maintain leukocyte counts below this level. (3) Transient post donation cytopenias, involving granulocytes, lymphocytes, and platelets, may occur and are at least partly related to the leukapheresis procedure. These are generally asymptomatic and self-limited; follow-up blood counts are not necessarily required. Reinfusion of autologous platelet-rich plasma should be considered for donors with expected postdonation thrombocytopenia (platelet count < 80 to 100 x 10(9)/L). (4) Donors should meet the eligibility criteria which apply to donors of apheresis platelets, with the exception that pediatric donors may also be considered. Any deviation from these criteria should have supporting documentation. There is insufficient information at this time to clearly establish definite contraindications for PBSC collection in a hematologically normal donor. Potential contraindications include the presence of inflammatory, autoimmune, or rheumatologic disorders, as well as atherosclerotic or cerebrovascular disease. (5) The creation of an International PBSC Donor Registry is desirable to facilitate monitoring the long-term effects of the procedure. Individual institutions or donor centers are encouraged to establish their own PBSC donor follow-up system, preferably with a standardized approach to data collection.

Adult↗

Pathophysiology and treatment of severe chronic neutropenia.

Severe chronic neutropenia (SCN) include a heterogeneous group of diseases characterized by blood neutrophil counts chronically less than 0.5 x 10(9)/ L. In phase I-III studies in SCN patients, treatment with recombinant human granulocyte colony stimulating factor (r-metHuG-CSF; Filgrastim) resulted in a rise in the absolute neutrophil counts (ANC) to above 1.0 x 10(9)/L associated with a reduction in bacterial infections. Long-term treatment with filgrastim up to 8 years demonstrate a sustained ANC response, a significant reduction of the need for intravenous antibiotics and a dramatic improvement in the quality of life. In 1994 an international registry for severe chronic neutropenia (SCNIR) was established to improve care for chronic neutropenia and for further understanding the pathophysiology of this rare disease. Three-hundred and ten patients have been enrolled to this registry so far. Worldwide phase I-III studies with filgrastim and SCNIR provide information on 424 patients with severe chronic neutropenia. Adverse events include the development of acute myeloid leukemia in approximately 7% of the patients within the cohort of patients with congenital neutropenia (Kostmann's syndrome) suggesting that congenital neutropenia is a preleukemic syndrome. None of the patients with cyclic of idiopathic neutropenia developed leukemia suggesting that filgrastim is not involved in the development of leukemia.

Chronic Disease↗

Monosomy 7 and activating RAS mutations accompany malignant transformation in patients with congenital neutropenia.

Individuals with severe forms of congenital neutropenia suffer from recurrent infections. The therapeutic use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to increase the neutrophil count is associated with fewer infections and an improved quality of life. However, the long-term effects of this new therapy are largely unknown. In particular, it is unclear if myeloid leukemia, a known complication of some forms of congenital neutropenia, will occur with increased frequency among patients who receive long-term treatment with hematopoietic growth factors. We report 13 patients with congenital disorders of myelopoiesis who developed leukemic transformation with either myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) and 1 who acquired a clonal cytogenetic abnormality without evidence of MDS or AML while receiving rhG-CSF. The bone marrows of 10 patients showed monosomy 7 and 5 had activating RAS mutations. These abnormalities were not detected in pretreatment bone marrows and cessation of rhG-CSF was not associated with either clinical improvement or cytogenetic remission. We conclude that patients with severe forms of congenital neutropenia are at relatively high risk of developing MDS and AML. The occurrence of monosomy 7 and RAS mutations in these cases suggests that the myeloid progenitors of some patients are genetically predisposed to malignant transformation. The relationship between therapeutic rhG-CSF and leukemogenesis in patients with severe chronic neutropenia is unclear.

Adolescent↗

Pancreatic adenocarcinoma in two grey collie dogs with cyclic hematopoiesis.

A 3-year-old male grey collie and 4-year-old female grey collie were part of a cyclic hematopoiesis study. Both dogs had experienced numerous bacterial infections, and both dogs were receiving various treatment regimens, including lithium and hematopoietic growth factors, to control the cyclic hematopoiesis. The first dog was presented in acute collapse and had a rapid clinical course. The second dog was presented with pyrexia and subsequently developed anorexia, disorientation, tremors, mild diarrhea, and bruising at venipuncture sites. Postmortem examination revealed pancreatic adenocarcinoma with metastasis in both cases. Pancreatic adenocarcinoma is a rare neoplasm in dogs. The incidence of pancreatic adenocarcinoma noted in this report is more than 150 times that previously reported in dogs. The cause of the increased incidence of pancreatic malignancy in these grey collies is unknown; possible factors include chronic inflammation or infections, chronic drug therapy, or genetic predisposition. Development of an uncommon neoplasm in two young grey collies may offer an opportunity to study the mechanisms of carcinogenesis.

Adenoma↗

Long-term safety of treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) in patients with severe congenital neutropenias.

Congenital neutropenias include a heterogenous group of diseases characterized by a decrease in circulating neutrophils. In phase I/II/III studies in patients with severe congenital and cyclic neutropenia, treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) resulted in a rise in the absolute neutrophil counts (ANC) and a reduction in infections. We report the effects of long-term safety of subcutaneous r-metHuG-CSF administration in 54 patients (congenital n = 44. cyclic n = 10) treated for 4-6 years. A sustained ANC response was seen in 40/44 severe congenital neutropenia patients and 10/10 cyclic neutropenia patients. Two patients required an increase of > 25% in dose to maintain a clinical response; one patient became refractory to therapy. A significant decrease in the incidence of severe infections and the need for intravenous antibiotics was noted. Significant adverse events noted which may or may not be related to therapy included: osteopenia (n = 15), splenomegaly (n = 12), hypersplenism (n = 1), vasculitis (n = 2), glomerulonephritis (n = 1), BM fibrosis (n = 2), MDS/leukaemia (n = 3), and transient inverted chromosome 5q with excess blasts (n = 1). R-metHuG-CSF has been well tolerated in the majority of patients and resulted in a long-term improvement in their clinical status.

Adolescent↗

Parental opinions about attending parent support groups.

Parent support groups are often a routine part of the services provided to families who have children with special health care needs. Often times, however, the groups are poorly attended, despite expressions of interest from parents. A survey of 45 families was conducted to examine who participates, why, and what factors encourage attendance. This article describes the survey responses and offers suggestions regarding utilization of the results for those planning parent support groups.

Adult↗

Use of surnames to identify individuals of Chinese ancestry.

The objectives of this study were to develop and test surname lists for identifying Chinese ancestry. The Ontario all-cause mortality database for the period 1982-1989 was randomly split into source and test data sets. Frequencies by birthplace were compiled for each surname in the source data set, by sex, and the surnames were weighted based on their positive likelihood ratios. Lists of Chinese surnames were then assembled based on varying cutoff levels, and screening performance indicators for each list were calculated, including sensitivity, specificity, positive and negative predictive values, post-test odds, positive likelihood ratio, and yield. The internally generated lists were evaluated in the test data set. Results indicated that surnames have a good potential to identify individuals of Chinese origin. In the source data set, at a cutoff level of 100 for males (217 surnames) and females (210 surnames), both sensitivity and the positive predictive value of the surname lists for males and females were very high, above 80%, and the positive likelihood ratio was above 600. In the test data set and using the same surname lists, the sensitivity, positive predictive value, and positive likelihood ratio remained at a high level: 73%, 81%, and 603, respectively, for males; and 73%, 84%, and 772, respectively, for females. Various scenarios and their methodological implications are discussed.

China↗