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Biomedical subjects

M L Lawson

Publications and source records attributed to M L Lawson.

At least 19 recordsLinked to original sources
PubMed2006

Glucose tolerance of offspring of mother with gestational diabetes mellitus in a low-risk population.

AIMS: To describe the prevalence of impaired glucose tolerance and obesity in offspring of mothers whose pregnancies were complicated by gestational diabetes mellitus (GDM) in a low-risk population and to investigate the effect on these outcomes of minimal intervention compared with tight control for management of GDM. METHODS: Eighty-nine children (mean age 9.1 years, 93% Caucasian) were recruited through a follow-up study of women previously involved in a randomized controlled trial of minimal intervention (control group) vs. tight glycaemic control (treatment group) for GDM. Fasting blood glucose (FBG) and 2-h glucose tolerance tests (2hGTT) were performed on offspring and body mass index (BMI) calculated. Glucose tolerance and BMI of treatment groups were compared using non-inferiority tests (non-inferiority margin -15%). RESULTS: Of those offspring, 6.9% (5/72) had abnormal glucose metabolism [four children had impaired glucose tolerance (IGT) and one had Type 2 diabetes mellitus (DM) (all Caucasian)]. Of the four children with IGT, three were male, three had normal BMI, and three had a family history of Type 2 diabetes. Of the 71 offspring who underwent 2hGTT, 25/25 (100%) of the control offspring and 46/46 (100%) of the treatment offspring had normal FBG (FBG < 5.7 mmol/l). Twenty-five of 25 (100%) of control and 42/46 (91.3%) of the treatment offspring had normal glucose tolerance (2hGTT < 7.8 mmol/l) (% difference 8.7, 95% CI -5.6, 20.3). BMI < 85th percentile was found in 25/33 (75.8%) of the treatment group and 44/52 (84.6%) of the control group (difference in percentage -8.9, 95% CI -27.2, 7.8). CONCLUSIONS: School-age children of mothers with GDM are at risk of IGT and overweight, even if from a low-risk ethnic population. FBG was not adequate for screening this population. Minimal intervention for glycaemic control in GDM pregnancies appears to be as effective as tight control for preventing IGT in childhood but not for preventing obesity.

Adult↗
PubMed2005

Type 1 diabetes and the OAS gene cluster: association with splicing polymorphism or haplotype?

BACKGROUND: The 2',5'-oligoadenylate synthetase genes (OAS1, OAS2, and OAS3) map to human chromosome 12q24 and encode a family of enzymes pivotal to innate antiviral defence. Recently, the minor allele of an OAS1 single nucleotide polymorphism (SNP) that alters splicing (rs10774671) was found to be associated with increased enzymatic activity and, in a case-sibling control study, with type 1 diabetes (T1D). METHODS: We have confirmed this T1D association in 784 nuclear families (two parents and at least one affected offspring) by the transmission disequilibrium test (TDT; G:A = 386:329, p = 0.033). However, because of linkage disequilibrium within OAS1 and with the other two OAS genes, functional attribution of the association to this SNP cannot be assumed. To help answer this question, we also genotyped two non-synonymous SNPs in OAS1 exons 3 and 7. RESULTS: All three SNPs showed significant transmission distortion. Three of the eight possible haplotypes accounted for 98.4% of parental chromosomes and two of them carried the non-predisposing A allele at rs10774671. Parents heterozygous for these two haplotypes showed significant transmission distortion (p = 0.009) despite being homozygous at rs10774671. CONCLUSIONS: We confirm the T1D association with rs10774671, but we conclude that it cannot be attributed (solely) to the splicing variant rs10774671. A serine/glycine substitution in OAS1 exon 3 is more likely a functional variant.

2',5'-Oligoadenylate Synthetase↗
PubMed2003

The inclusion of reports of randomised trials published in languages other than English in systematic reviews.

OBJECTIVE: To assemble a large dataset of language restricted and language inclusive systematic reviews, including both conventional medicinal (CM) and complementary and alternative medicine (CAM) interventions. To then assess the quality of these reports by considering and comparing different types of systematic reviews and their associated RCTs; CM and CAM interventions; the effect of language restrictions compared with language inclusions, and whether these results are influenced by other issues, including statistical heterogeneity and publication bias, in the systematic review process. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Centralised Information Service for Complementary Medicine. REVIEW METHODS: Three types of systematic reviews were included: language restricted; language inclusive/English language (EL) reviews that searched RCTs in languages other than English (LOE) but did not find any and, hence, could not include any, in the quantitative data synthesis; and systematic reviews that searched for RCTs in LOE and included them in the quantitative data synthesis. Fisher's exact test was applied to compare the three different types of systematic reviews with respect to their reporting characteristics and the systematic review quality assessment tool. The odds ratio of LOE trials versus EL trials was computed for each review and this information was pooled across the reviews to examine the influence that language of publication and type of intervention (CM, CAM) have on the estimates of intervention effect. Several sensitivity analyses were performed. RESULTS: The LOE RCTs were predominantly in French and German. Language inclusive/LOE systematic reviews were of the highest quality compared with the other types of reviews. The CAM reviews were of higher quality compared with the CM reviews. There were only minor differences in the quality of reports of EL RCTs compared with the eight other languages considered. However, there are inconsistent differences in the quality of LOE reports depending on the intervention type. The results, and those reported previously, suggest that excluding reports of RCTs in LOE from the analytical part of a systematic review is reasonable. Because the present research and previous efforts have not included every type of CM RCT and the resulting possibility of the uncertainty as to when bias will be present by excluding LOE, it is always prudent to perform a comprehensive search for all evidence. This result only applies to reviews investigating the benefits of CM interventions. This does not imply that systematic reviewers should neglect reports in LOE. We recommend that systematic reviewers search for reports regardless of the language. There may be merit in including them in some aspects of the review process although this decision is likely to depend on several factors, including fiscal and other resources being available. Language restrictions significantly shift the estimates of an intervention's effectiveness when the intervention is CAM. Here, excluding trials reported in LOE, compared with their inclusion, resulted in a reduced intervention effect. The present results do not appear to be influenced by statistical heterogeneity and publication bias. CONCLUSIONS: With the exception of CAM systematic reviews, the quality of recently published systematic reviews is less than optimal. Language inclusive/LOE systematic reviews appear to be a marker for a better quality systematic review. Language restrictions do not appear to bias the estimates of a conventional intervention's effectiveness. However, there is substantial bias in the results of a CAM systematic review if LOE reports are excluded from it.

Complementary Therapies↗
PubMed2003

Technology failure analysis: understanding why a diabetes management tool developed for a Personal Digital Assistant (PDA) didn't work in a randomized controlled trial.

Managing Type 1 Diabetes Mellitus is a challenging feat especially for young patients. It is a tedious and demanding disease which requires painful self-monitoring and injections multiple times per day. Many patients are unable to achieve good blood sugar control, in spite of strong evidence that good control leads to better outcomes. Many caregivers believe that more communication between caregivers and patients could lead to better control. This paper describes a tool that was developed to improve communication between caregivers and patients, its testing, how it failed to achieve its outcomes and recommendations for improvement.

Blood Glucose Self-Monitoring↗
PubMed2001

Disordered eating attitudes and behaviours in teenaged girls: a school-based study.

BACKGROUND: Disordered eating attitudes and behaviours are common in older teens and young women in Western countries. Recent evidence suggests that the prevalence of these disorders is rising and that the age of onset has fallen. In the present study, disturbed eating attitudes and behaviours were evaluated in a large school-based population in Ontario in order to determine their prevalence and demographic distribution. METHODS: Females, aged 12-18 years, from schools in Toronto, Hamilton and Ottawa were invited to complete questionnaires, including 3 subscales of the Eating Disorder Inventory (Drive for Thinness, Body Dissatisfaction, Bulimia), the Eating Attitudes Test-26 (EAT-26) and the Diagnostic Survey for Eating Disorders (DSED). RESULTS: Questionnaires were completed by 1739 (70%) of the 2483 adolescent females who were approached. The mean age of subjects in the sample was 14.6 (standard deviation 1.9) years. Thirteen percent of those aged 12-14 years and 16% of those aged 15-18 years had scores above the recommended cut-off (> or = 20) for disordered eating on the EAT-26. Current dieting to lose weight was reported by 23% of participants. Binge eating with associated loss of control was reported by 15% of participants, self-induced vomiting by 8.2% and the use of diet pills by 2.4%. Laxative and diuretic misuse were uncommon. Dieting was associated with an increased risk of binge-eating and purging behaviours. Older age and body mass index in the highest quartile were independently related to symptoms of eating disorders. INTERPRETATION: Disordered eating attitudes and behaviours were present in over 27% of girls aged 12-18 years and were seen to increase gradually throughout adolescence. Prevention programs to diminish the progression and impact of these disorders should be implemented and assessed.

Adolescent↗
PubMed2000

Eating disorders in adolescent females with and without type 1 diabetes: cross sectional study.

OBJECTIVE: To determine the prevalence of eating disorders in adolescent females with type 1 diabetes mellitus compared with that in their non-diabetic peers. DESIGN: Cross sectional case-control led study. SETTING: Diabetes clinics and schools in three Canadian cities. SUBJECTS: 356 females aged 12-19 with type 1 diabetes and 1098 age matched non-diabetic controls. MAIN OUTCOME MEASURE: Eating disorders meeting Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. RESULTS: Eating disorders that met DSM-IV criteria were more prevalent in diabetic subjects (36, 10%) than in non-diabetic controls (49, 4%) (odds ratio 2.4, 95% confidence interval 1.5 to 3.7; P<0.001). Subthreshold eating disorders were also more common in those with diabetes (49, 14%) than in controls (84, 8%) (odds ratio 1.9, 95% confidence interval 1.3 to 2.8; P<0.001). Mean haemoglobin A(1c) concentration was higher in diabetic subjects with an eating disorder (9.4% (1.8)) than in those without (8.6% (1.6)), P=0.04). CONCLUSIONS: DSM-IV and subthreshold eating disorders are almost twice as common in adolescent females with type 1 diabetes as in their non-diabetic peers. In diabetic subjects, eating disorders are associated with insulin omission for weight loss and impaired metabolic control.

Adolescent↗
PubMed2000

Does dietary protein intake correlate with markers suggestive of early diabetic nephropathy in children and adolescents with Type 1 diabetes mellitus?

AIMS: To examine the relationship between dietary protein intake and possible early markers of diabetic nephropathy (creatinine clearance (CrCI), kidney volume and albumin excretion rate (AER)). METHODS: One hundred and forty-five subjects with diabetes for 5-10 years, divided into three pubertal groups, participated. Kidney volume was measured by ultrasound, and serum creatinine and HbA1c were assayed. Two or three 24-h urine collections were obtained for albumin, creatinine and urea excretion rates. Dietary protein intake was estimated from urinary urea nitrogen excretion rate. Glomerular filtration rate was estimated by creatinine clearance. RESULTS: Mean protein intake was 1.22 +/- 0.48 g x kg(-1) x day(-1) Protein intake was significantly higher in males than females (P < 0.0001) and highest in prepubertal compared to mid-pubertal and post-pubertal subjects (P < 0.001). In multiple regression analysis, protein intake was positively associated with CrCl (P < 0.0001), and male sex (P < 0.0001) and negatively associated with body surface area (P = 0.0013) and age (P = 0.01). Kidney volume and AER were not related to dietary protein intake. CONCLUSIONS: This cross-sectional study failed to show a significant relationship between dietary protein intake and markers of early nephropathy, other than CrCl. However, a longitudinal, prospective study is required to definitively assess the role of protein intake in the evolution of diabetic nephropathy.

Adolescent↗
PubMed2000

Intensive diabetes management in adolescents with type 1 diabetes: the importance of intensive follow-up.

Minimal information exists on the education and follow-up required to successfully initiate intensive diabetes management (IDM) in adolescents with type 1 diabetes. We performed a retrospective analysis of HbA1c 3 and 15 months after initiation of IDM in two cohorts: (1) 17 patients who received individualised education in IDM and intensive early follow-up, and (2) 11 patients who participated in group education for initiation of IDM with standard follow-up. Entry HbA1c was higher in the individualised education patients (9.5 +/- 0.3% [mean +/- SE] versus 8.2 +/- 0.4%, p = 0.02). After 3 months of IDM, HbA1c improved in both cohorts reaching similar levels (individualised: 7.0 +/- 0.1%, p < 0.0001 vs entry; group: 7.3 +/- 0.2%, p = 0.05). During the following year, with routine follow-up for both cohorts, HbA1c levels rose approximately 1% as patients reverted to a multiple daily injection regimen. Irrespective of the educational approach, we believe maintenance of IDM and optimal HbA1c requires long-term intensive follow-up.

Adolescent↗
PubMed1999

A single sample subcutaneous luteinizing hormone (LH)-releasing hormone (LHRH) stimulation test for monitoring LH suppression in children with central precocious puberty receiving LHRH agonists.

The effectiveness of LHRH agonist therapy in central precocious puberty depends upon suppression of LH secretion. The iv LHRH stimulation test is the gold standard for evaluating LH suppression, but is difficult to administer because it requires an iv line and multiple blood samples. We hypothesized that a sc LHRH test followed by a single LH measurement 40 min later would be as accurate in the assessment of LH suppression in children receiving LHRH analogs. Eleven children received the sc test 1 month before or after their regularly scheduled iv LHRH treatment. Each child was receiving Lupron to suppress central puberty. Twenty-five comparisons of the iv and sc LHRH tests were completed over 14 months. We developed a clinical score for pubertal suppression using Tanner staging, skeletal maturation, and growth velocity. The best correlation between this clinical score and the iv LHRH test was achieved when biochemical suppression was defined as peak LH less than 2 IU/L (100% sensitivity, 95% specificity). Using this definition, the sc LHRH test was 96% accurate (in 24 of 25 subjects), with a sensitivity of 75% and a specificity of 100% compared to the iv LHRH test. We conclude that the single sample sc LHRH test can accurately determine LH suppression and adequacy of LHRH agonist therapy in central precocious puberty.

Adolescent↗
PubMed1999

Effect of intensive therapy on early macrovascular disease in young individuals with type 1 diabetes. A systematic review and meta-analysis.

OBJECTIVE: We conducted a systematic review of randomized controlled trials (RCTs) of intensive insulin therapy (IIT) in type 1 diabetes to determine the effect on macrovascular complications. RESEARCH DESIGN AND METHODS: MEDLINE (1966-1996), Citation Index, reference lists, and personal files were used to identify RCTs of > 2 years' duration comparing IIT to conventional therapy (CT) in type 1 diabetes. Two independent reviewers applied selection criteria and identified 11 studies; 5 were subsequently excluded because no data were available for macrovascular complications. Data were extracted on macrovascular disease and cardiovascular risk factors. Macrovascular disease was defined as angina, myocardial infarction, angioplasty, coronary artery bypass graft, stroke, claudication, or peripheral bypass. The first event of each type was counted. RESULTS: IIT decreased the number of macrovascular events (odds ratio [OR] 0.55, [95% CI 0.35-0.88], P = 0.015) but had no significant effect on the number of patients developing macrovascular disease (OR 0.72, [95% CI 0.44-1.17], P = 0.22) or on macrovascular mortality (OR 0.91, [95% CI 0.31-2.65], P = 0.93). CONCLUSIONS: IIT decreases the extent of early macrovascular disease in young individuals with type 1 diabetes but has no effect on the number of patients affected or on macrovascular mortality. These data suggest that IIT may stabilize macrovascular disease or prevent progression in those at risk.

Adolescent↗
PubMed1998

The gene responsible for pseudohypoparathyroidism type Ib is paternally imprinted and maps in four unrelated kindreds to chromosome 20q13.3.

Hypocalcemia and hyperphosphatemia caused by parathyroid hormone (PTH)-resistance are the only discernible abnormalities in pseudohypoparathyroidism type Ib (PHP-Ib). Because mutations in the PTH/PTH-related peptide receptor, a plausible candidate gene, had been excluded previously, we conducted a genome-wide search with four PHP-Ib kindreds and established linkage to a small telomeric region on chromosome 20q, which contains the stimulatory G protein gene. We, furthermore, showed that the genetic defect is imprinted paternally and thus is inherited in the same mode as the PTH-resistant hypocalcemia in kindreds with PHP-Ia and/or pseudo-pseudohypoparathyroidism, two related disorders caused by different stimulatory G protein mutations.

Chromosome Mapping↗
PubMed1998

Objective markers of condom failure.

BACKGROUND: Studies of condom efficacy rely on self-reported behavior. Objective markers of exposure to semen may provide a more valid assessment of condom failure and failure to use condoms. GOALS OF THIS STUDY: To compare three semen biomarkers: acid phosphatase (AP) activity, prostate specific antigen (PSA), and the human seminal plasma antigen (MHS-5). STUDY DESIGN: Twenty women were intravaginally inoculated with six measured, increasingly larger amounts of their partners' semen. Vaginal fluid was collected by the participant using swabs and tested. RESULTS: Background levels of PSA were low (0.00-1.25 ng/ml), background levels of AP were variable (0-350 U/l), and all preinoculation samples were negative for MHS-5. All postinoculation samples were positive for PSA, 64 of 117 (55%) for AP, and 14 of 120 (12%) for MHS-5. CONCLUSION: The PSA immunoassay was the best semen biomarker under these sampling and testing conditions.

Acid Phosphatase↗
PubMed1998

Motion perception in global versus local attentional modes.

PURPOSE: Global and local attention are two forms of selective visual attention which activate different areas of the cortex. The purpose of this experiment was to test subjects' motion coherence thresholds under conditions of global or local attention. It was hypothesized that thresholds in global attention would be lower than in local attention. METHODS: Eleven adult subjects participated in this study. Subjects were required to identify direction of motion at variable coherence levels, while simultaneously identifying either the global or local letter. Three velocities were used for coherent motion (3, 6 and 18 degrees/s). RESULTS: The results showed that letter identification (global or local) did not significantly affect motion coherence thresholds; however, thresholds were significantly higher at 18 degrees/s than in the lower velocities. CONCLUSIONS: These results highlight the attentional limitations of visual information shown by increased motion coherence thresholds when two objects must be identified simultaneously in a brief display.

Adolescent↗
PubMed1998

Attentional blink in global versus local attentional modes.

PURPOSE: Brain imaging studies have shown that global and local attention activate different areas of the brain, with implication for dependence of perception on attentional state. The aim of the present experiment was to investigate the duration of the attentional blink in global versus local attention. METHODS: Rapid Serial Visual Presentation (RSVP) sequences of global/local stimuli were presented to 34 adult subjects who had to identify a target red figure followed by a determination of whether a certain probe letter, 'X' (specified to be either the global or local form), was present in the subsequent string of letters. RESULTS: Attentional blinks were longer than any previously reported (1.67 s global; 2.97 s local) and were significantly different.Thus, the length of the attentional blink is dependent on the attentional state of the subject. CONCLUSION: This pattern of results is consistent with the hypothesis that global attention mechanisms receive predominantly M-pathway input.

Adolescent↗
PubMed1998

Contribution of growth hormone and IGF-I to early diabetic nephropathy in type 1 diabetes.

In children and adolescents with type 1 diabetes, we have reported an association between duration of puberty and the prevalence of nephromegaly and microalbuminuria (MA), which are early markers of diabetic nephropathy. Growth hormone (GH), IGF-I, testosterone, and prorenin are potential mediators of this effect. This study examined the relationship of these hormonal factors to kidney volume (KV) and MA in 155 subjects (78 males, age 13.2 +/- 3.5 years [mean +/- SD]) with similar diabetes duration (6.83 +/- 1.6 years) but varying pubertal experience (0-10 years). KV (by ultrasound), plasma IGF-I, testosterone, prorenin, and NaLi countertransport, and urinary albumin, urinary GH, and urinary IGF-I from three 24-h collections were measured. Multiple regression analysis showed that BSA (P < 0.0001) and urinary IGF-I (P = 0.001) were significantly associated with KV. MA subjects (albumin excretion rate 15-200 microg/min) had higher urinary IGF-I (P = 0.005) and urinary GH (P = 0.05) compared with normoalbuminuric subjects. Only 9% of the variance in urinary IGF-I could be attributed to plasma IGF-I (r = 0.30, P < 0.0001). Testosterone and prorenin were not associated with MA, but they were associated with KV in univariate analyses. The strong association of urinary IGF-I with KV, a marker for glomerular hypertrophy, and of both urinary IGF-I and urinary GH with MA suggests a role for these growth factors in the development of human diabetic nephropathy. Together, these data support animal studies that have shown that renal GH and IGF-I may contribute significantly to the pathogenesis of early diabetic nephropathy.

Adolescent↗
PubMed1996

Primary hyperparathyroidism in a paediatric hospital.

We retrospectively reviewed the presentation and management of children with primary hyperparathyroidism (PHPT) from 1973 to 1995 at a paediatric tertiary-care centre. There were 11 patients (6 females), aged 12.3-17.7 years at presentation, with sporadic PHPT confirmed by histopathology (single adenoma). Presentation consisted of renal colic, or non-specific gastrointestinal, musculoskeletal or neurological symptoms. Misdiagnosis was common until hypercalcaemia was identified, 0.5-24 months after onset of symptoms (mean 7.7 months). All patients had hypercalcaemia and low-normal serum phosphate. The parathyroid hormone (PTH) radioimmunoassay used before 1986 was elevated in 1/4 patients; the intact PTH assay used after 1986 was elevated in 7/7 patients. At presentation, six had end-organ damage: band keratopathy, renal lesions, and/or bone disease. Preoperative localization was accurate in 0/4 patients diagnosed before 1986, but 5/7 patients diagnosed after 1986: three by ultrasound or sestamibi scan alone, and two by ultrasound and technetium scan. Surgical outcome was not dependent upon the accuracy of pre-operative localization. PHPT is rare in children but usually associated with end-organ damage, presumably due to delayed diagnosis. It should be considered in the differential diagnosis of unexplained non-specific complaints. The intact PTH assay greatly assists pre-operative diagnosis. The usefulness of pre-operative localization requires further research.

Adolescent↗