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T To

Publications and source records attributed to T To.

At least 19 recordsLinked to original sources
PubMed2001

Physician and population determinants of rates of middle-ear surgery in Ontario.

CONTEXT: Small-area variations in surgical rates raise concerns about access to care, treatment appropriateness, and the quality and cost of care. OBJECTIVE: To measure small-area variations in rates of myringotomy with insertion of tympanostomy tubes (TTs) and to identify determinants of rate variation. DESIGN AND SETTING: Retrospective analyses using hospital discharge data for patients who had undergone a myringotomy with insertion of TT by county in Ontario between April 1, 1996, and March 31, 1999. Information on possible determinants was taken from a survey of otolaryngologists and primary care physicians in 1996 and from the 1996 Canadian census and physician demographic databases for 1996-1999. PARTICIPANTS: A total of 75 358 hospitalizations for TT placement of children and adolescents (aged </=14 years). MAIN OUTCOME MEASURE: Small-area variation in rates of TT. RESULTS: An almost 10-fold difference between the areas with the highest and lowest rates was found (extremal quotient, 9.6; 95% confidence interval [CI], 8.2-11.1; P<.001). Higher rates occurred in counties with higher percentages of high school graduates (parameter estimate, 0.01; 95% CI, 0-0.02; P =.049); and where referring physicians were more likely to be male (parameter estimate, 0.01; 95% CI, 0-0.02; P =.01), North American-trained (parameter estimate, 0.01; 95% CI, 0.01-0.02; P<.001), and have higher propensities to refer for surgery (parameter estimate, 0.40; 95% CI, 0.09-0.72; P =.02). Otolaryngologist opinion was not a significant predictor. CONCLUSION: Substantial area variation in TT rates was observed. The opinion of primary care physicians was the dominant modifiable determinant, suggesting an area of research that may be important in reducing area variation in TT procedures.

Adolescent↗
PubMed2001

Breastfeeding and asthma in young children: findings from a population-based study.

OBJECTIVE: To evaluate the association between breastfeeding and asthma in young Canadian children. METHODS: Baseline data from the National Longitudinal Survey of Children and Youth (a population-based study of child health and well-being) were used. A weighted sample of 331 100 (unweighted n = 2184) children between the ages of 12 and 24 months, whose biological mother reported data on breastfeeding and asthma, were included. Outcomes included parental report of physician-diagnosed asthma and wheeze in the previous year. Breastfeeding was categorized by duration as follows: less than 2 months, 2 to 6 months, 7 to 9 months, and longer than 9 months. Logistic regression analyses were conducted with breastfeeding duration dichotomized at various cutoffs. Important potential confounders were considered in the adjusted analyses. Published statistical methods appropriate for the sampling strategy were used. RESULTS: The prevalence of asthma was 6.3%; and wheeze, 23.9%. Almost half of the children (44.0%) were breastfed for less than 2 months. After adjustment for smoking, low birth weight, low maternal education, and sex, a duration of breastfeeding for 9 months or less was found to be a risk factor for asthma (odds ratio, 2.39; 99% confidence interval, 0.95-6.03) and wheeze (odds ratio, 1.54; 99% confidence interval, 1.04-2.29). A dose-response effect was observed with breastfeeding duration. CONCLUSIONS: A longer duration of breastfeeding appears to be protective against the development of asthma and wheeze in young children. More public health efforts should be directed toward increasing the initiation and duration of breastfeeding.

Asthma↗
PubMed2001

Biological, social, and environmental correlates of preschool development.

Baseline data from the Canadian National Longitudinal Survey of Children and Youth (NLSCY, a population-based study of child health, development and well-being), were used to determine biological, social and environmental correlates of poor development among preschool children. A total weighted sample of 1233 500 (n = 6982 unweighted) children aged from birth to 3 years were studied. Developmental attainment was measured by the motor, social and development (MSD) scale. Children scoring amongst the lowest 15% for their age group were categorized as having poor developmental attainment (PDA). Correlates of PDA were determined using logistic regression. The MSD scale may not be discriminatory enough to identify PDA in children aged < 1 years. Among children aged between 1 and 3 years, biological factors remain important correlates of PDA, whereas the timing of social and environmental factors appears important to their effects on developmental attainment. The findings suggest a complex relationship between risk factors and developmental outcomes. Correlates of PDA vary according to the age of a child. Social and environmental factors appear to play a larger role among older children. Prospective studies are required to determine the effect of change in risk factor profiles on child development.

Birth Weight↗
PubMed2001

Timing of voiding cystourethrogram in the investigation of urinary tract infections in children.

OBJECTIVE: To determine whether the detection of vesicoureteral reflux (VUR) in children with a urinary tract infection (UTI) is more likely if the voiding cystourethrogram (VCUG) is performed early (within the first 7 days after diagnosis) or late (>7 days after diagnosis). STUDY DESIGN: We conducted a retrospective case review of children <5 years of age admitted with a first episode of UTI to a tertiary care pediatric hospital over a 2-year period. Timing of the VCUG was at the discretion of the attending pediatrician. Differences in age, sex, mean time to performing the VCUG, and incidence of VUR between the 2 groups (VCUG performed early vs late) were compared by using Student t test (for age) and chi(2) test (for sex and incidence of VUR). Potential confounders (age and sex) were included in a multiple logistic regression analysis. RESULTS: A total of 162 patients were eligible for inclusion. Mean age was 181 days, and 43.8% were female. The incidence of VUR was 21.6%. The early group consisted of 82 patients, and the late group consisted of 80. No significant difference was found for age or sex or for the incidence of reflux (17.1% vs 26.3%, P =.219), with a crude odds ratio of.59 (95% CI 0.3-1.2, P >.05). CONCLUSION: The rate of detection of VUR in children with a first episode of UTI does not increase when the VCUG is done early (within the first 7 days of diagnosis) rather than later.

Age Factors↗
PubMed2001

Cross-cultural comparisons of health status in Canada using the Health Utilities Index.

OBJECTIVE: The purpose of this study was to examine the differences in health status, as measured by the Health Utilities Index (HUI), among seven cultural groups in Canada defined by place of birth and language. DESIGN: The study analysed cross-sectional data from the National Population Health Survey conducted by Statistics Canada in 1994-95. RESULTS: Age-standardized prevalence of dysfunction, defined as HUI < 0.83, varied from 12.7% in English-speaking immigrants to 17.8% in French-speaking Canadians. Considerable differences between the groups were found in the reporting of pain, emotional function, and cognitive function. The variation in HUI scores across the cultural groups could not be explained by differences in socioeconomic status and self-reported chronic conditions. CONCLUSIONS: Although the healthy immigrant effect is probably responsible for some of the variation in health status among cultural groups in Canada, considerable differences exist within the immigrant and Canadian-born populations. Cultural factors may have a substantial effect on the reporting of pain and mental health problems. Further studies are needed to determine the cross-cultural validity of the HUI.

Canada↗
PubMed2000

The validity of a sore throat score in family practice.

BACKGROUND: Reducing the number of antibiotic prescriptions given for common respiratory infections has been recommended as a way to limit bacterial resistance. This study assessed the validity of a previously published clinical score for the management of infections of the upper respiratory tract accompanied by sore throat. The study also examined the potential impact of this clinical score on the prescribing of antibiotics in community-based family practice. METHODS: A total of 97 family physicians in 49 Ontario communities assessed 621 children and adults with a new infection of the upper respiratory tract accompanied by sore throat and recorded their prescribing decisions. A throat swab was obtained for culture. The sensitivity and specificity of the score approach in this population were compared with previously published results for patients seen at an academic family medicine centre. In addition, physicians' prescribing practices and their recommendations for obtaining throat swabs were compared with score-based recommendations. RESULTS: Of the 621 cases of new upper respiratory tract infection and sore throat, information about prescriptions given was available for only 619; physicians prescribed antibiotics in 173 (27.9%) of these cases. Of the 173 prescriptions, 109 (63.0%) were given to patients with culture-negative results for group A Streptococcus. Using the score to determine management would have reduced prescriptions to culture-negative patients by 63.7% and overall antibiotic prescriptions by 52.3% (both p < 0.01). Culturing of throat samples would have been reduced by 35.8% (p < 0.01). There was no statistically significant difference in the sensitivity or specificity of the score approach between this community-based population (sensitivity 85.0%, specificity 92.1%) and an academic family medicine centre (sensitivity 83.1%, specificity 94.3%). INTERPRETATION: An explicit clinical score approach to the management of patients presenting with an upper respiratory tract infection and sore throat is valid in community-based family practice and could substantially reduce the unnecessary prescribing of antibiotics for these conditions.

Adolescent↗
PubMed2000

Canadian National Breast Screening Study-2: 13-year results of a randomized trial in women aged 50-59 years.

BACKGROUND: Screening for breast cancer with mammography in women aged 50 years or more has been shown to reduce mortality from breast cancer. However, the extent to which mammography contributes to the reduction of mortality in women who also undergo physical examination of the breasts is not known. This study was designed to compare breast cancer mortality following annual screening consisting of two-view mammography and physical examination of the breasts with mortality following annual screening by physical examination only. Breast self-examination was taught to all participants. METHODS: This trial randomly and individually assigned 39 405 women aged 50-59 years, recruited from January 1980 through March 1985, to one of the study arms. The women were followed by record linkage with the Canadian National Cancer Registry and National Mortality Database to December 31, 1993, and by active follow-up of breast cancer patients to June 30, 1996. RESULTS: Randomization achieved virtually equal distribution of demographic and breast cancer risk variables. At the first annual screen, 21% of the cancers found by mammography alone (in the mammography plus physical examination group) were 20 mm or more in size compared with 46% of those found by physical examination in the mammography plus physical examination group and 56% in the physical examination-only group. The corresponding percentages for screens 2-5 were 10%, 42%, and 50%, respectively. Screening detected 267 invasive breast cancers in the mammography plus physical examination group compared with 148 in the physical examination-only group. By December 31, 1993, 622 invasive and 71 in situ breast carcinomas were ascertained in the mammography plus physical examination group, and 610 and 16 were ascertained in the physical examination-only group. At 13-year follow-up, with 107 and 105 deaths from breast cancer in the respective groups, the cumulative rate ratio was 1.02 (95% confidence interval = 0.78-1.33). CONCLUSION: In women aged 50-59 years, the addition of annual mammography screening to physical examination has no impact on breast cancer mortality.

Breast Neoplasms↗
PubMed2000

Disulfide connectivity in cerebroside sulfate activator is not necessary for biological activity or alpha-helical content but is necessary for trypsin resistance and strong ligand binding.

Cerebroside sulfate activator (CSAct) protein is exceptionally resistant to heat denaturation and proteolytic digestion. Although water soluble the protein binds membrane-associated lipids. Its biological role is thought to be to transfer certain lipids between membranes and to facilitate their catabolism in the lysosomes. An example of the latter is the removal of the sulfate group from cerebroside sulfate by arylsulfatase A. The mechanism of lipid sequestration from membranes and presentation of the lipid-protein complex to catabolic enzymes is a crucial aspect of the function of this protein. The widespread occurrence of the protein class of which CSAct is one of the best known members underscores the significance of this protein. The preparation, purification and chemical and biological properties of a stable disulfide blocked derivative of CSAct is described. The pyridoethylated protein was susceptible to tryptic attack and devoid of a significant population of solvent-protected exchange resistant protons. It apparantly formed a CS complex. However, unlike the complex with the native protein, this was not sufficiently stable to remain intact during size exclusion chromatography. The disulfide-blocked protein had a similar CD spectrum as native protein, indicating similar alpha-helical content. Unexpectedly, the activities of disulfide-blocked protein in the arylsulfatse A catalyzed sulfate hydrolysis from cerebroside sulfate were substantial. Hitherto, it had been assumed that the disulfide connectivities were essential for the protein to maintain a correctly folded configuration to bind lipid ligands and potentiate their hydrolysis. Some revision of our thoughts on the importance of the disulfide connectivities in the structure and function of the protein are necessary.

Amino Acid Sequence↗
PubMed2000

Hydrogen-deuterium exchange signature of porcine cerebroside sulfate activator protein.

Hydrogen-deuterium exchange can be a sensitive indicator of protein structural integrity. Comparisons were made between cerebroside sulfate activator protein (CSAct) in the native state and after treatment with guanidine hydrochloride plus dithiothreitol. Native protein has three internal disulfide bonds and treated protein has no internal disulfide bonds. The comparisons were made using hydrogen-deuterium exchange measured by electrospray ionization mass spectrometry, percentage alpha-helical content measured by circular dichroism and biological activity measured by the ability to support arylsulfatase A-catalyzed sulfate hydrolysis from cerebroside sulfate. In acidic solvent native protein has 59 exchange refractory protons and treated protein has 20 exchange refractory protons (44 and 14% of the exchangeable proton populations, respectively). In native protein the size of the exchange refractory proton population is sensitive to changes in pH, temperature and the presence of a ligand. It is uninfluenced by the presence or absence of glycosyl groups attached to Asn21. Helical content is virtually identical in native and treated protein. Biological activity is significantly reduced but not obliterated in treated protein. The hydrogen-deuterium exchange profile appears to be a sensitive signature of the correctly folded protein, and reflects a dimension of the protein structure that is not apparent in circular dichroic spectra or in the ability of the protein to support arylsulfatase A-catalyzed sulfate hydrolysis from sulfatide. The hydrogen-deuterium exchange profile will be a valuable criterion for characterizing mutant forms of CSAct produced by recombinant and synthetic paradigms and also the native and mutant forms of related proteins.

Animals↗
PubMed2000

Structure of the asparagine-linked sugar chains of porcine kidney and human urine cerebroside sulfate activator protein.

The specific sugar residues and their linkages in the oligosaccharides from pig kidney and human urine cerebroside sulfate activator proteins (saposin B), although previously hypothesized, have been unambiguously characterized. Exhaustive sequential exoglycosidase digestion of the trimethyl-p-aminophenyl derivatives, followed by either matrix-assisted laser desorption/ionization and/or mass spectrometry, was used to define the residues and their linkages. The oligosaccharides were enzymatically released from the proteins by treatment with peptidyl-N-glycosidase F and separated from the proteins by reversed-phase high-performance liquid chromatography (HPLC). Reducing termini were converted to the trimethyl-p-aminophenyl derivative and the samples were further purified by normal-phase HPLC. The derivatized carbohydrates were then treated sequentially with a series of exoglycosidases of defined specificity, and the products of each digestion were examined by mass spectrometry. The pentasaccharides from pig kidney and human urine protein were shown to be of the asparagine-linked complex type composed of mannose-alpha 1-6-mannose-beta 1-4-N-acetylglucosamine-N-acetylglucosamine(alpha 1-6-fucose). This highly degraded structure probably represents the final product of intra-lysosomal exoglycosidase digestion. Oligosaccharide sequencing by specific exoglycosidase degradation coupled with mass spectrometry is more rapid than conventional oligosaccharide sequencing. The procedures developed will be useful for sequencing other oligosaccharides including those from other members of the lipid-binding protein class to which cerebroside sulfate activator belongs. (c) 2000 John Wiley & Sons, Ltd.

Animals↗
PubMed2000

Methionine oxidation within the cerebroside-sulfate activator protein (CSAct or Saposin B).

The cerebroside-sulfate activator protein (CSAct or Saposin B) is a small water-soluble glycoprotein that plays an essential role in the metabolism of certain glycosphingolipids, especially sulfatide. Deficiency of CSAct in humans leads to sulfatide accumulation and neurodegenerative disease. CSAct activity can be measured in vitro by assay of its ability to activate sulfatide-sulfate hydrolysis by arylsulfatase A. CSAct has seven methionine residues and a mass of 8,845 Da when deglycosylated. Mildly oxidized, deglycosylated CSAct (+16 Da), separated from nonoxidized CSAct by reversed-phase high-performance liquid chromatography (RP-HPLC), showed significant modulation of the in vitro activity. Because oxidation partially protected against CNBr cleavage and could largely be reversed by treatment with dithiothreitol, it was concluded that the major modification was conversion of a single methionine to its sulfoxide. High-resolution RP-HPLC separated mildly oxidized CSAct into seven or more different components with shorter retention times than nonoxidized CSAct. Mass spectrometry showed these components to have identical mass (+16 Da). The shorter retention times are consistent with increased polarity accompanying oxidation of surface-exposed methionyl side chains, in general accordance with the existing molecular model. A mass-spectrometric CNBr mapping protocol allowed identification of five of the seven possible methionine-sulfoxide CSAct oxoforms. The most dramatic suppression of activity occurred upon oxidation of Met61 (26% of control) with other residues in the Q60MMMHMQ66 motif falling in the 30-50% activity range. Under conditions of oxidative stress, accumulation of minimally oxidized CSAct protein in vivo could perturb metabolism of sulfatide and other glycosphingolipids. This, in turn, could contribute to the onset and progression of neurodegenerative disease, especially in situations where the catabolism of these materials is marginal.

Amino Acid Sequence↗
PubMed1999

Relation between hospital surgical volume and outcome for pancreatic resection for neoplasm in a publicly funded health care system.

BACKGROUND: Recent studies from the United States have shown that institutions with higher numbers of pancreatic resection procedures for neoplasm have lower mortality rates associated with this procedure. However, minimal work has been done to assess whether the results of similar volume-outcome studies within a publicly financed health care system would differ from those obtained in a mixed public-private health care system. METHODS: A population-based retrospective analysis was used to examine pancreatic resection for neoplasm in Ontario for the period 1988/89 to 1994/95. Outcomes examined included in-hospital case fatality rate and mean length of stay in hospital. For each hospital, total procedure volume for the study period was defined as low (fewer than 22), medium (22-42) or high (more than 42). Regression models were used to measure volume-outcome relations. RESULTS: The likelihood of postoperative death was higher in low-volume and medium-volume centres than in high-volume centres (odds ratio 5.1 and 4.5 respectively; p < 0.01 for both). Mean length of stay was greater in low- and medium-volume centres than in high-volume centres (by 7.7 and 9.2 days respectively, p < 0.01 for both). INTERPRETATION: This study adds to growing evidence that, for pancreatic resection for neoplasm, patients may have better outcomes if they are treated in high-volume hospitals rather than low-volume hospitals.

Aged↗
PubMed1999

Natural history of dysplasia of the uterine cervix.

BACKGROUND: A historical cohort of Toronto (Ontario, Canada) women whose Pap smear histories were recorded at a major cytopathology laboratory provided the opportunity to study progression and regression of cervical dysplasia in an era (1962-1980) during which cervical squamous lesions were managed conservatively. METHODS: Actuarial and Cox's survival analyses were used to estimate the rates and relative risks of progression and regression of mild (cervical intraepithelial neoplasia 1 [CIN1]) and moderate (CIN2) dysplasias. In addition, more than 17,000 women with a history of Pap smears between 1970 and 1980 inclusive and who were diagnosed as having mild, moderate, or severe dysplasia were linked to the Ontario Cancer Registry for the outcome of any subsequent cervical cancers occurring through 1989. RESULTS: Both mild and moderate dysplasias were more likely to regress than to progress. The risk of progression from mild to severe dysplasia or worse was only 1% per year, but the risk of progression from moderate dysplasia was 16% within 2 years and 25% within 5 years. Most of the excess risk of cervical cancer for severe and moderate dysplasias occurred within 2 years of the initial dysplastic smear. After 2 years, in comparison with mild dysplasia, the relative risks for progression from severe or moderate dysplasia to cervical cancer in situ or worse was 4.2 (95% confidence interval [CI] = 3.0-5.7) and 2.5 (95% CI = 2.2-3.0), respectively. CONCLUSION: The risk of progression for moderate dysplasia was intermediate between the risks for mild and severe dysplasia; thus, the moderate category may represent a clinically useful distinction. The majority of untreated mild dysplasias were recorded as regressing to yield a normal smear within 2 years.

Chi-Square Distribution↗
PubMed1999

Cerebroside sulfate activator protein (Saposin B): chromatographic and electrospray mass spectrometric properties.

Cerebroside sulfate activator protein is a small, heat-stable protein that is exceptionally resistant to proteolytic attack. This protein is essential for the catabolism of cerebroside sulfate and several other glycosphingolipids. Protein purified from pig kidney and human urine was extensively characterized by reversed-phase liquid chromatography and electrospray mass spectrometry. These two sources revealed 20 and 18 different molecular isoforms of the protein, respectively. Plausible explanations of the structures of the majority of these isoforms can be made on the basis of accurate molecular mass assignments. The reversed-phase chromatographic and electrospray mass spectrometric properties of enzymatically deglycosylated and disulfide-reduced protein were also compared. In addition to a demonstration of the power of electrospray ionization mass spectrometry for revealing a wealth of information on protein microheterogeneity and structural detail, the results also demonstrate the utility of this technique for monitoring spontaneous chemical and enzymatically mediated changes that occur as a result of metabolic processing and protein purification.

Animals↗