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Biomedical subjects

J McNamee

Publications and source records attributed to J McNamee.

10 recordsLinked to original sources

DSM-IV internal construct validity: when a taxonomy meets data.

The use of DSM-IV based questionnaires in child psychopathology is on the increase. The internal construct validity of a DSM-IV based model of ADHD, CD, ODD, Generalised Anxiety, and Depression was investigated in 11 samples by confirmatory factor analysis. The factorial structure of these syndrome dimensions was supported by the data. However, the model did not meet absolute standards of good model fit. Two sources of error are discussed in detail: multidimensionality of syndrome scales, and the presence of many symptoms that are diagnostically ambiguous with regard to the targeted syndrome dimension. It is argued that measurement precision may be increased by more careful operationalisation of the symptoms in the questionnaire. Additional approaches towards improved conceptualisation of DSM-IV are briefly discussed. A sharper DSM-IV model may improve the accuracy of inferences based on scale scores and provide more precise research findings with regard to relations with variables external to the taxonomy.

Adolescent↗

Design of a chimeric 3-methyl-1,2,3-triazene with mixed receptor tyrosine kinase and DNA damaging properties: a novel tumor targeting strategy.

The mixed epidermal growth factor receptor (EGFR)-DNA targeting properties of SMA41, a 6-(3-methyl-1,2,3-triazen-1-yl)-4-anilinoquinazoline designed to release N(4)-m-tolyl-quinazoline-4,6-diamine henceforth referred to as SMA52 [an inhibitor of EGFR tyrosine kinase (TK)] and methyldiazonium (a DNA methylating species) were studied in the O(6)-methylguanine-DNA methyltransferase (MGMT)-proficient and high EGFR-expressing epidermoid carcinoma of the vulva cell line A431. The effects of SMA41 were compared with those of SMA52 alone, and temozolomide (TEM), a clinical prodrug of 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC) that is inactive in MGMT-proficient cells. The results showed that 1) the chimeric SMA41 could degrade in serum-containing medium (t(1/2) of approximately 30 min) to generate, as predicted, the free inhibitor SMA52 as the most abundant metabolite (approximately 81% yield); 2) in contrast to SMA52 alone, the chimeric SMA41 and TEM induced significant DNA damage in A431 cells after 30-min or 2-h drug exposures, as confirmed by alkaline single-cell gel microelectrophoresis (comet) assay; 3) SMA41 showed 5-fold greater affinity for the ATP binding site of EGFR than independently synthesized SMA52 in an enzyme assay and blocked EGF-induced tyrosine phosphorylation and EGFR autophosphorylation in A431 cells in a dose-dependent manner; 4) these mixed targeting properties of SMA41, combined with its ability to be converted to another potent EGFR TK inhibitor (e.g., SMA52) by hydrolytic cleavage, translated into over 8-fold greater antiproliferative activity than TEM, which showed no EGFR targeting properties (IC(50) competitive binding >100 microM); 5) under continuous drug exposure (3-6-day sulforhodamine and clonogenic assays), SMA41 was almost equipotent with SMA52; however, in a short 2-h drug exposure followed by incubation in drug-free media, SMA52 showed an almost complete loss of antiproliferative activity over the whole dose range. In contrast, SMA41 retained almost 100% of its activity, indicating a more sustained growth inhibitory activity. The results in toto suggest that the superior antiproliferative activity of SMA41 may be due to a combination of events associated with its binary EGFR TK and DNA targeting properties.

Antineoplastic Agents↗

Syphilis serology in blood donors: a possible surrogate marker for human immunodeficiency virus risk.

We report a preliminary study on whether syphilis serology might be reactive in some blood donors at risk for human immunodeficiency virus (HIV) infection. We retrospectively analyzed voluntary blood donations with reactive Treponema pallidum antibody (TPA) tests according to the type of donation, the presence of other safety markers, confidential unit exclusion, syphilis diagnosis, and HIV risk factors. Over 2 years (1987-1988), 1 in 8,900 regular homologous donations (n = 258,610) was TPA positive as compared with 1 in 2,200 directed donations (n = 6,685) and 1 in 300 autologous donations (n = 8,870; p less than 0.05 for both). The rate in directed donations was not significantly higher than in first-time regular donors (1 in 4,800; n = 57,000). TPA-positive donations had higher rates of antibody to hepatitis B core antigen and confidential unit exclusion than TPA-negative donations. Ten TPA-positive homologous or directed donors had latent or previously treated syphilis (1 in 26,500 such donations), and 2 of these had HIV risk factors. None of the autologous donors were determined to have active syphilis. Syphilis serology in blood donors bears further scrutiny as a possible surrogate marker for HIV risk.

Biomarkers↗

Predicting problems in school performance from preschool health, developmental and behavioural assessments.

To determine the accuracy of various predictors of school problems, we conducted a 3-year prospective study of 1999 children who began school in the Niagara region of Ontario in 1980. During the year before school entry the parents gave a health, developmental and behavioural history during an interview with a community health nurse, and the children underwent vision and hearing screening tests and the Denver Developmental Screening Test (DDST). At the end of the 1980-81 school year the kindergarten teachers rated the children's learning problems. At the end of the 1982-83 school year the presence of school problems was ascertained, and the predictive accuracy of items from the preschool history and examination and of the kindergarten teachers' ratings was calculated. The health, developmental and behavioural history with or without the DDST was found to predict later school problems with acceptable accuracy. The kindergarten teachers' ratings gave slightly more accurate predictions. We conclude that in communities where prompt diagnostic evaluation and effective therapeutic or preventive help can be provided to children identified as being at high risk, health professionals may play a useful role in screening for future school problems.

Age Factors↗

Evaluation of public health preschool child developmental screening: the process and outcomes of a community program.

We conducted a randomized controlled trial of a public health and education screening program aimed at all 4,797 four to five year old children registering for kindergarten in three school districts of southern Ontario, Canada. Children received either the Denver Developmental Screening Test (DDST) with a community health intervention program for positive screeness; the DDST with no intervention for positive screenees; or no screening test. The intervention program consisted of referral to the child's physician for assessment; a review conference between the child's teacher and the school health nurse; parent counseling; and monitoring of the child in school by the school health nurse. At the end of the third school year, no differences were found between positive screenees in the community health intervention group and the "no intervention" groups using individual academic achievement, cognitive, and developmental tests. Parents' reports revealed no differences between groups in children's mental, social, and behavioral well-being. However, parents of intervention program children had more worry about their child's school progress suggesting a potentially harmful labeling effect. In comparison to a random sample of children with normal DDST results, or a random sample of children who had randomly not been screened, the children with positive preschool DDSTs had substantially more school problems three years after screening.

Child Development↗

Value of the lateral radiologic view of the chest in children with acute pulmonary illness.

Although expert committees have questioned the usefulness of lateral radiologic views of the chest without specific indications, many physicians commonly order both posteroanterior and lateral views in assessing pediatric patients who have signs and symptoms of acute chest disease. To investigate the usefulness of lateral view in children, three experienced physicians independently reviewed and interpreted the posteroanterior view alone and the posteroanterior and lateral views for 179 children 1 to 10 years of age. The films were made between 1980 and 1982 at McMaster University Medical Centre, Hamilton, Ont. A high level of agreement was found between the interpretations based on the posteroanterior view alone and those based on both views. Addition of the lateral view did not improve agreement between the interpretations and the final hospital chart radiologic diagnosis in a clinically significant manner, nor did the lateral view improve the accuracy of localization of radiologic abnormalities. Obtaining a lateral view whenever radiologic examination of the chest is indicated but when specific indications are lacking is unlikely to prove useful to experienced physicians in diagnosing and managing acute pulmonary illness in children.

Acute Disease↗

Community professionals' compliance with consultants' recommendations for developmentally disabled children.

Much of the responsibility for managing children with developmental disabilities lies with professionals working in community services. In many instances advice and consultation for these frontline professionals is available from a regional consultation facility. The purpose of this study was to prospectively examine the relationship between community professional clients' perceptions of the quality of the consultations received and their subsequent compliance with the recommendations made to them for the management of children in their care. Two hundred and ninety-nine consultation recommendations were followed: 2 weeks after the advice had been provided, clients completed a general satisfaction questionnaire and a client perceptions questionnaire. Two months later, compliance with the recommendation was determined by a validated self-report questionnaire. Overall, compliance was good for 73% of the recommendations. Negative client perceptions regarding several aspects of the consultants' skills in conducting the consultation were strongly associated with subsequent noncompliance. The findings suggest that community professional compliance may be enhanced by attention to improving the process of consultation.

Child↗

An evaluation of suloctidil in the prevention of deep vein thrombosis in neurosurgical patients.

Suloctidil (200 mg t.i.d.) was compared with placebo in a randomized, double-blind trial to assess its value in preventing deep venous thrombosis (DVT) in high-risk neurosurgical patients, comprising 136 patients with brain or spinal tumour, head or spinal injury, or subarachnoid or intracranial hemorrhage. 125I fibrinogen leg scanning and impedance plethysmography were performed for up to 14 days to detect DVT. The two groups were also evenly balanced for DVT risk factors. Seventeen of 68 patients (25%) (95% confidence interval, 15-35%) treated with suloctidil and 12 of 68 patients (21%) (95% confidence interval, 11-32%) treated with placebo developed deep venous thrombosis. This observed difference in outcomes is not statistically significant (X2 = 1.096; p = 0.30). The estimated 95% confidence interval for the true difference in the incidence of DVT between suloctidil-treated and placebo-treated patients ranges from an 11% benefit in favour of suloctidil to an 18% benefit in favour of placebo. Major deep vein thrombosis occurred in two patients on suloctidil and three patients in the placebo group; there were no fatal pulmonary emboli during the 14-day study period, during which time four patients in each group died of non-thromboembolic complications. There was no observed difference in hemorrhagic complications. Long-term outcomes at three-months follow-up were similar between the two treatment groups. It is concluded that there is no real evidence that suloctidil (200 mg t.i.d.) is an effective regimen for the prevention of DVT in high-risk neurosurgical patients.

Brain Neoplasms↗

Newborn circumcision: an economic perspective.

The purpose of this study was to analyse the hypothesis that prophylactic circumcision of male newborns is economically beneficial to the health care system in Canada. The minimal dollar benefits that would justify this conclusion were determined. The cost of the procedure was calculated in three Hamilton, Ont. hospitals and found to average about $38. The health benefits of circumcision are uncertain, but a review of the literature suggested that penile carcinoma is the most serious (and costly) disease potentially prevented by circumcision. Published estimates of the incidence rates, age at onset and costs incurred as a result of this disease were used in calculations of the per-case cost of prevention: $13.6 million. The authors conclude that the monetary benefits of circumcising newborns will not exceed this cost. It is proposed that the procedure be regarded as cosmetic surgery and be paid for by parents who wish the procedure carried out rather than by taxpayer-funded health insurance plans.

Canada↗