ORIGINAL ARTICLE: Associations of the growth hormone receptor (GHR) gene polymorphisms with adiposity and IGF‐I activity in adolescents

Objective: To explore the genetic effect of the GH receptor (GHR) on obesity and related metabolic parameters in Hong Kong Chinese adolescents. Context: Obesity is a growing global epidemic. Increasing evidence suggests that the GH‐IGF‐I axis plays an important role in regulating adiposity and insulin sensitivity. Design: We examined the associations of genetic variants of GHR with serum IGF‐I and IGFBP‐3 levels as well as obesity‐related metabolic traits in Hong Kong Chinese adolescents. Patients: Nine hundred and eighty‐one randomly selected Hong Kong Chinese adolescents from 14 schools. Measurements: We genotyped 17 single nucleotide polymorphisms (SNP) at GHR and measured serum IGF‐I and IGFBP‐3 levels as well as obesity‐related metabolic traits including fasting plasma glucose, insulin and lipid levels. Results: There were significant associations between rs4410646 and the body composition (P = 0·0044) and blood pressure factor scores (P = 0·00017). Carriers of the CC genotype had lower body mass index, percentage body fat, waist and hip circumferences than AC and AA genotype carriers (P = 0·00030–0·0094). There was also association between rs7703713 and the IGF‐I activity factor score (P = 0·0033). The GA and AA carriers of rs7703713 had higher serum IGF‐I, higher serum IGFBP‐3 and higher IGF‐I/IGFBP‐3 molar ratio (P = 0·00069–0·025). Haplotype analysis did not increase the significance of associations. Conclusion: Our results support the role of GHR gene polymorphisms in modulating adiposity and IGF‐I activity in adolescents. Examination of interactions of these SNPs with lifestyle, environmental and perinatal factors may provide further insights into their long‐term effects on obesity and metabolic risks.     

A nested case-control study on treatment-related risk factors for early relapse of tuberculosis

This nested case-control study aimed at evaluating treatment-related risk factors of relapse of tuberculosis under a service program of directly observed treatment. Out of 12,183 patients with pulmonary tuberculosis who completed treatment within 1 year, 113 relapsed within 30 months after commencement of therapy. The overall 30-month relapse rate was 0.9% (95% confidence interval [CI] 0.8-1.1%). On matching 113 cases with 226 control subjects in a conditional logistic model, thrice-weekly treatment increased the risk of relapse in comparison with daily treatment (odds ratio 3.92, 95% CI 1.78-8.63), whereas prolonging both intensive phase and overall treatment by 50% or more protected against relapse (odds ratio 0.24, 95% CI 0.08-0.70). When pretreatment culture was positive and cavitation was absent, the 30-month relapse rate for standard thrice-weekly regimen was 1.1% (95% CI 0.6-2.0%). The corresponding rates in the presence of cavitation were 7.8% (95% CI 4.0-14.6%) for standard thrice-weekly regimen; 3.3% (95% CI 1.9-5.5%) for standard daily regimen; 0.5% (95% CI 0.1-2.6%) for extended thrice-weekly regimen; and 0.4% (95% CI 0.1-0.9%) for extended daily regimen. Further studies are required to reduce the risk of relapse under program settings.     

Comparison of 4 functional indexes in psoriatic arthritis with axial or peripheral disease subgroups using Rasch analyses

OBJECTIVE: Rasch item response theory analysis is essential in evaluating measurement tools in specific disease cohorts. We compared the performance of 4 functional indexes in patients with psoriatic arthritis (PsA) in axial or peripheral disease subgroups. METHODS: A cross-sectional study was performed in a single center. Functional outcomes assessed by the Health Assessment Questionnaire (HAQ), Bath Ankylosing Spondylitis Functional Index (BASFI), Dougados Functional Index (FI), and the physical functioning scale of the Medical Outcome Study Short-form 36 (SF-36-PF) were analyzed by the Rasch model for item fit, item separation, measurement span, and distribution properties. Patient subgroups with axial or peripheral disease were analyzed for differential item functioning (DIF). RESULTS: One hundred eight patients with PsA were assessed. The 4 functional indexes were highly correlated with each other and moderately correlated with patients' perception of health and pain scores. Floor effects were less marked in SF-36-PF. The 4 indexes satisfied the unidimensionality assumption of the Rasch model. HAQ and SF-36-PF had better information-weighted fit statistics (INFIT) and outlier-sensitive (OUTFIT) statistics. HAQ had the poorest item separation. SF-36-PF had the highest item separation (6.99), reliability (0.85), and the longest span of item threshold (9.03 logits). Only 1 and 2 items in BASFI and Dougados-FI had DIF in patients with sacroiliitis. CONCLUSION: HAQ, BASFI, Dougados-FI, and SF-36-PF provide unidimensional measures of functional disability in PsA. SF-36-PF was the best in terms of less floor effect, highest item separation, longest span of item threshold, and better distributional properties. BASFI and Dougados-FI behaved similarly in patients with and without sacroiliitis and conferred no superiority in patients with axial disease.     

Diagnosis and catheter treatment of innominate artery stenosis following stage I Norwood procedure.

Four infants aged 20-115 days (mean, 57.8 days) who had undergone stage I Norwood procedure for hypoplastic left heart syndrome came to early cardiac catheterization (6-112; mean, 47.3 days) following surgery because of significant arterial desaturation (pulse oximetry indicating oxygen saturations consistently in the 40%-70% range). Cardiac catheterization demonstrated a significant systolic pressure gradient between the ascending aorta and innominate artery (30-65; mean, 51 mm Hg) as the likely cause of diminished pulmonary blood flow in these patients. Routine angiography by itself was not conclusive in identifying a discrete area of obstruction, but selective angiography coupled with a knowledge of the obstruction did reveal the stenosis. All patients were successfully treated with balloon dilatation of the stenotic area, with the pressure gradient being reduced to 7-25 (mean, 17 mm Hg) immediately following dilatation. On follow-up catheterization in three patients, the systolic gradients were 3, 6, and 9 mm Hg. Arterial oxygen saturations rose from 63.5% predilatation to 77.3% immediately postdilatation and 81% on follow-up evaluation. In conclusion, innominate artery stenosis is an important cause of diminished blood flow through a modified right Blalock-Taussig shunt. Routine angiography will often miss the diagnosis. Pressure gradients and selective angiograms are necessary in order to make the diagnosis, although careful noninvasive assessment should also be diagnostic of this problem. Catheter dilatation is therapeutic in this situation and can be performed early after surgery in the absence of a fresh suture line.