Selective use of Peptide Receptor Radionuclide Therapy following comparative imaging of Ga-68 DOTATATE PET/CT against I-131 MIBG scintigraphy in a small Asian cohort of Adult Neuroblastoma.

Adult neuroblastoma (AN) is rare with an extremely poor prognosis. No standard therapy exists for this entity and treatment options are limited in recurrent or refractory disease. 131I-MIBG has been used in combination with myeloablative therapy before autologous bone marrow transplantation or in a salvage therapy setting. However, myelotoxicity is a dose-limiting factor in heavily pre-treated patients and response is not always sustained. Somatostatin receptor scintigraphy and theranostics with radiolabelled somatostatin receptor analogues are becoming more commonplace with the recognition of these receptors in over 90% of neuroblastoma cells. We describe three AN patients assessed for somatostatin receptor status and the novel use of 177Lu-based peptide recep-tor radionuclide therapy (PRRT) in two of them and a literature review.

Planning and coordination of the radiological response to the coronavirus disease 2019 (COVID-19) pandemic: the Singapore experience.

Coronavirus disease 2019 (COVID-19) has spread fast and extensively around the world, with significant mortality and morbidity. As this is a respiratory infection, chest radiography and computed tomography (CT) are important imaging techniques in the work-up of this disease. Given its highly infectious nature, cross-infection within the healthcare setting and radiology departments needs to be addressed actively and prevented. We describe the response of radiology departments in Singapore to this pandemic, in terms of diagnosis, re-configuration of the department, re-organisation and segregation of staff, infection control, managerial, and leadership issues.

Thermal and Fluid Dynamics Performance of MWCNT-Water Nanofluid Based on Thermophysical Properties: An Experimental and Theoretical Study.

There are many debates on the preparation methods and the role of ultrasonication on the stability, thermophysical properties, and heat transfer performance of nanofluids. The present study, which is the continuation of the authors previous study, the effects of ultrasonication on the thermal and fluid dynamic performance of MWCNT-water nanofluid, over a different range of temperatures and solid concentrations, based on the thermophysical properties of the nanofluid, has been investigated. The effects of ultrasonication time on the stability and thermophysical properties of the nanofluid were studied over 30 days of the samples preparation. The thermophysical properties of the nanofluid have been experimentally measured at the optimum ultrasonication time. Using the experimental data, and employing different figures-of-merit, the effects that the addition of MWCNTs had on the heat transfer effectiveness and pumping power have been studied. It was confirmed that the nanofluid is a good heat transfer fluid, with a negligible penalty in pumping power. The thermal and fluid dynamic performance of the nanofluid in a microchannel heat sink has also been studied, by comparing the enhancement ratio of the convective heat transfer coefficient and the increase in pumping power.

Visfatin and its genetic variants are associated with obesity-related morbidities and cardiometabolic risk in severely obese children.

BACKGROUND: Visfatin is an adipokine, associated with obesity and possibly glucose regulation. OBJECTIVE: The aim of this study was to examine the association of visfatin and its genetic variants with adiposity, cardiometabolic risk factors and obesity-related morbidities in obese children. METHODS: Anthropometric measurements, dual energy X-ray absorptiometry scan, fasting blood samples and oral glucose tolerance tests were performed for 243 obese children. We screened the visfatin gene of 24 obese subjects and then performed genotyping of identified genetic variants in other 219 obese children through direct DNA sequencing. RESULTS: Fasting serum visfatin correlated with measures of obesity and liver enzymes and was elevated in obese children with abnormal glucose tolerance and non-alcoholic fatty liver disease. The two upstream single nucleotide polymorphisms, -3187G>A (rs11977021) and -1537C>T (rs61330082), were at complete linkage disequilibrium. The AA genotype of -3187G>A was associated with higher serum visfatin (6.17 ± 0.76 ng mL(-1) vs. 3.92 ± 0.44 ng mL(-1)) and higher triglyceride (1.39 ± 0.08 mmol L(-1) vs. 1.19 ± 0.07 mmol L(-1)) as compared with the GG genotype. There was also a significant linear increase in serum visfatin across GG to GA to AA genotype of -3187G>A, indicating possible additive effect of A allele. The dominant GA + AA genotype model of +21426G>A (rs2302559) was associated with lower serum visfatin (3.83 ± 0.56 ng mL(-1) vs. 5.13 ± 0.34 ng mL(-1)) and lower plasma glucose (4.37 ± 0.08 mmol L(-1) vs. 4.77 ± 0.12 mmol L(-1)) as compared with the GG genotype. CONCLUSION: Visfatin and its genetic variants were associated with adiposity, obesity-related morbidities and adverse cardiometabolic parameters. This supported our hypothesis that visfatin plays a significant role in the development of obesity-related morbidities and cardiometabolic risk.

Prognostic value of adenosine stress myocardial perfusion by cardiac magnetic resonance imaging in patients with known or suspected coronary artery disease.

BACKGROUND: Cardiac magnetic resonance imaging (CMR) has been intensely researched in recent years, and its high diagnostic accuracy for myocardial ischemia has been demonstrated. However, its prognostic information is very limited. AIM: We sought to assess the value of adenosine stress myocardial perfusion by CMR in predicting cardiac events in patients with known or suspected coronary artery disease (CAD). DESIGN: Retrospective study. METHODS: From January 2003 to December 2008, we retrospectively reviewed consecutive patients with or without history of CAD referred for evaluation of suspected myocardial ischemia who had undergone adenosine stress CMR in our hospital. End points were cardiac death or non-fatal myocardial infarction (MI). RESULTS: After a mean follow-up of 3.2 ± 1.6 years in 203 patients, 15 (7.4%) cardiac events occurred. The 4-year event-free survival was 96.2% for patients with normal stress CMR perfusion and 71.5% for those with abnormal stress CMR perfusion. Univariate analysis showed that both adenosine-induced reversible perfusion defect and delayed gadolinium enhancement by CMR were significant predictors of cardiac events [Hazard ratio (HR) 9.31; 95% Confidence Interval (95% CI) 3.18-27.3; and HR 9.24; 95% CI 3.27-26.08; P < 0.001, respectively). By multivariate analysis, adenosine-induced reversible perfusion defect remained an independent predictor of cardiac events (HR 7.77; 95% CI 2.50-24.18; P < 0.001). In a stepwise multivariate model (Cox regression), an abnormal stress CMR perfusion result had significant incremental predictive value over clinical risk factors and resting regional wall motion abnormality (RWMA) (P < 0.001). CONCLUSION: In patients with known or suspected CAD, adenosine stress CMR could be used to identify patients at high risk for subsequent cardiac death or nonfatal MI. A normal CMR perfusion was associated with a very low long-term event rate and excellent long-term prognosis. In addition, stress CMR perfusion provided important incremental prognostic information over clinical risk factors and RWMA.

Gonadal mosaicism 45,X/46,X,psu dic(Y)(q11.2) resulting in a Turner phenotype with mixed gonadal dysgenesis.

A two-year-and-eight-month-old girl presented with clitoromegaly and short stature. Two cell lines, 45,X and 46,X,idic(Y)(q11.2), were observed. Cytogenetic and fluorescence in situ hybridisation investigations were carried out on her peripheral lymphocytes and gonadal cells, to determine the genotype-phenotype effect with respect to differential tissue distribution, effects of the sex determining region of the Y chromosome, and the break-points in the azoospermia factor region.

Role of Tc-99m DMSA (V) scanning and serum calcitonin monitoring in the management of medullary thyroid carcinoma.

INTRODUCTION: Medullary thyroid carcinoma (MTC) is a rare disease. Serum calcitonin levels and Tc-99m DMSA (V) scans are used in the follow-up of these patients after surgical resection. We present our experience in the follow-up of these patients at a tertiary institution. METHODS: A retrospective review of the medical records was performed. Patients with histologically-proven MTC, and who had serum calcitonin assays and DMSA (V) scans in their postoperative follow-up, were included. RESULTS: There were 17 patients with 56 DMSA (V) scans. Four out of seven patients with elevated preoperative calcitonin measurements had calcitonin normalisation within six months of surgery, and have remained disease-free. Two patients had persistently elevated calcitonin levels after six months, which predated positive DMSA (V) scans. Results of DMSA (V) scans and serum calcitonin levels were concordant in 38 of 48 instances (79.2 percent) and discordant in 10 of 48 instances (20.8 percent). Sensitivity of DMSA (V) scans for detecting recurrence was 71.4 percent. There were no false-positive scans. CONCLUSION: Serum calcitonin level is a sensitive and specific indicator of disease recurrence in postoperative follow-up of patients with MTC. Early (within six months) normalisation of calcitonin levels postsurgery may predict subsequent disease-free status. Discordant results between serum calcitonin levels and DMSA (V) scans may be due to undetectable lesions and follow-up scans or alternative radionuclide imaging may be required.

Isolated haploinsufficiency of exon 1 of the SHOX gene in a patient with idiopathic short stature.

This paper reports the case of a 16-year-old woman with idiopathic short stature (ISS) who was detected to be haploinsufficient in only exon 1 of the short stature homeobox-containing (SHOX) gene by RQ-PCR and had two copies of the other six exons intact. The translation of the SHOX protein and of the SHOX promoter may be potentially affected if the deletion of exon 1 is extended further upstream. Further studies may help in determining the significance of partial exonic deletions of the SHOX gene in relation to ISS.

Aortic aneurysmal disease and cutis laxa caused by defects in the elastin gene.

BACKGROUND: Cutis laxa is an acquired or inherited condition characterized by redundant, pendulous and inelastic skin. Autosomal dominant cutis laxa has been described as a benign disease with minor systemic involvement. OBJECTIVE: To report a family with autosomal dominant cutis laxa and a young girl with sporadic cutis laxa, both with variable expression of an aortic aneurysmal phenotype ranging from mild dilatation to severe aneurysm or aortic rupture. METHODS AND RESULTS: Histological evaluation of aortic aneurysmal specimens indicated classical hallmarks of medial degeneration, paucity of elastic fibres, and an absence of inflammatory or atherosclerotic lesions. Electron microscopy showed extracellular elastin deposits lacking microfibrillar elements. Direct sequencing of genomic amplimers detected defects in exon 30 of the elastin gene in affected individuals, but did not in 121 normal controls. The expression of mutant elastin mRNA forms was demonstrated by reverse transcriptase polymerase chain reaction analysis of cutis laxa fibroblasts. These mRNAs coded for multiple mutant tropoelastins, including C-terminally truncated and extended forms as well as for molecules lacking the constitutive exon 30. CONCLUSIONS: ELN mutations may cause severe aortic disease in patients with cutis laxa. Thus regular cardiac monitoring is necessary in this disease to avert fatal aortic rupture.

The perils of puberty.

Puberty and adolescence represent a transitional phase from childhood to adulthood, and are defined by the attainment of secondary sexual characteristics and reproductive capability, occurring concomitantly with psychological and social development. The perils of puberty lie in the difficult and complex inter-relationship of biological, psychological and social changes, as the adolescent strives to adjust to new social roles and identities, and new reproductive capacities. An appreciation of these changes in normal puberty is essential to all professionals caring for adolescents.

Tyrosine phosphatase-like protein (IA-2) and glutamic acid decarboxylase (GAD65) autoantibodies: a study of Chinese patients with diabetes mellitus.

Type 1 diabetes in most Asian populations may not have a salient autoimmune basis when assessed with single determinations of the major markers, islet cell antibodies (ICAs) and glutamic acid decarboxylase antibodies (GAD65ab). With the inclusion of antibodies to tyrosine phosphatase-like protein IA-2 (IA-2ab) as an additional major marker, we re-examined autoimmune diabetes in a group of Chinese patients. We studied 272 subjects at various stages of disease with blood samples procured for biochemical analysis. ICAs were measured by immunofluorescence, GAD65ab and IA-2ab by radioimmunoassay. Sixty-seven patients fulfilled clinical diagnosis of type 1 diabetes and the remaining 205 patients were type 2. Prevalence of single autoantibody type in recent-onset type 1 diabetes ( < 1 year duration; n = 47) showed 10.6% with ICAs, 44.7% GAD65ab and 36.2% IA-2ab. GAD65ab account for more than two-thirds of the markers found in type 1 diabetes. Combined analysis further showed that 51.1% had at least one antibody type, 31.9% with two or more antibodies and 8.5% with all three antibodies. Islet autoimmunity presence in childhood-onset type 1 diabetes improved with the addition of IA-2ab, though less impact was seen in the adult-onset. Similarly, combined analysis for type 2 patients with recent diabetes showed a modest increase to 13% with islet autoimmunity compared to 8% when assessed by GAD65ab alone. Combining IA-2ab and GAD65ab assays results detected slightly more immune-mediated diabetes, compared to using a single GAD65ab determination. Non-autoimmune causes need to be considered in the pathogenesis of type 1 diabetes in Chinese, particularly in adults.

Maternal thyrotoxicosis causing central hypothyroidism in infants.

We describe three infants born to mothers with poorly controlled Graves' disease, who developed transient central hypothyroidism in the immediate postnatal period. Suppression of the fetal pituitary-thyroid axis may be due to placental transfer of thyroxine from the hyperthyroid mother. This may persist for months postnatally, necessitating treatment to optimise neurodevelopmental outcome.

Epidemiology of 21-hydroxylase deficiency in Singapore.

We report the incidence and epidemiology of 21-hydroxylase deficiency in Singapore, based on a retrospective study of all known patients diagnosed with classical 21-hydroxylase deficiency in the past 21 years. The database was obtained from the case registry and questionnaire methodology, with 100% coverage of all practising pediatricians in Singapore. There were 42 patients affected with 21-hydroxylase deficiency in 964,558 live births over 21 years, comprising 64.3% salt wasters and 35.7% simple virilizers, of whom 50.0% were males and 50.0% females. The incidence of classical 21-hydroxylase deficiency is 4.5 per 100,000 live births, with a carrier frequency of 1:76, and a gene frequency of 0.0067. Although retrospective studies have inherent limitations, the gender and phenotype ratios suggest that the data provide a crude incidence level. This study underscores the necessity for prospective neonatal screening, so that the benefits of early diagnosis and treatment can be realized.

Molecular analysis of CYP-21 mutations for congenital adrenal hyperplasia in Singapore.

BACKGROUND: Congenital adrenal hyperplasia arising from 21-hydroxylase deficiency is associated with mutations in the CYP21 gene on chromosome 6p. This is the first report on the mutational spectrum of the CYP21 gene in Singapore. METHODS: To catalogue the mutations, ten exons of the CYP21 gene from 28 Singaporean patients were analyzed by PCR amplification and direct sequencing. RESULTS: Common mutations in descending order were the intron 2 splice site mutation (32.7% of the alleles), the I172N mutation (23.1% of the alleles), and the R356W mutation (19.2% of the alleles). Two potentially novel mutations were discovered: (1) duplication of 111 bp from codon 21 to codon 57 (exon 1) and (2) missense mutation (L261P, exon 7). There was generally a good genotype-phenotype correlation, allowing accurate prediction of the disease severity.

Mitochondrial tubulopathy: the many faces of mitochondrial disorders.

We report a rare presentation of mitochondrial disorder in a child with recurrent carpopedal spasms due to hypocalcemia and hypomagnesemia, secondary to renal proximal tubulopathy and possible hypoparathyroidism. At least two mutant mitochondrial DNA species were identified, and abnormal mitochondria were found in the muscle and renal biopsy specimens. The case illustrates the spectrum and diversity of mitochondrial presentations, arising because of heteroplasmy of mutations and the type of organs affected.

Prevalence of ICA and GAD antibodies at initial presentation of type 1 diabetes mellitus in Singapore children.

OBJECTIVE: To determine the prevalence of islet cell antibodies (ICA) and antibodies to glutamic acid decarboxylase (GAD) in Asian children with diabetes mellitus (DM) at the time of diagnosis. PATIENTS AND METHODS: 41 children were studied at their initial presentation from 1993 to 2000. RESULTS: Mean age of onset (+/- SD) of DM was 7.6 (+/- 4.2) years. One or both of the two autoantibodies, ICA and anti-GAD, were present in 17 of the 41 children (41.5%) at the time of diagnosis. Comparing the group of children with autoantibodies and the group without detectable autoantibodies, there were no significant differences in body mass index (15.4 vs. 16.3 kg/m2), age of onset (7.4 vs. 7.8 years), random C-peptide levels (203 vs. 311 pmol/l), HbA1c levels (13.2 vs. 12.7%), and frequency of diabetic ketoacidosis at presentation (53.3 vs. 55%). CONCLUSION: Prevalence of antibodies at presentation of DM in Singapore (41.5%) is lower than in Caucasian populations (60-90%). Other autoantibodies yet to be identified may be contributory. Alternatively, non-immune mediated mechanisms may be responsible for a significant proportion of type 1 DM in Singapore children.

Type II Gaucher disease: compound heterozygote with RecNciI and L444P mutations.

We report the phenotype and genotype of an Indonesian Chinese boy with type II Gaucher disease. He had a unique presentation of recurrent cyanosis from laryngospasm. He was compound heterozygous for L444P/L444P + A456P + V460V. There have been few reports of this heterozygosity and its phenoptype. This genotype-phenotype correlation will be important for physicians in genetic counselling. Type II Gaucher disease in Southeast Asia may not be as rare as was perceived, but may be a condition that is under-reported. The success of our technique together with the results have made it possible for us to perform prenatal diagnosis and carrier detection for the family.

Endothelial nitric oxide synthase plays an essential role in regulation of renal oxygen consumption by NO.

Nitric oxide (NO) regulates renal O2 consumption, but the source of NO mediating this effect is unclear. We explored the effects of renal NO production on O2 consumption using renal cortex from mice deficient (-/-) in endothelial (e) nitric oxide synthase (NOS). O2 consumption was determined polarographically in slices of cortex from control and eNOS-/- mice. NO production was stimulated by bradykinin (BK) or ramiprilat (Ram) in the presence or absence of an NOS inhibitor. Basal O2 consumption was higher in eNOS-/- mice than in heterozygous controls (919 +/- 46 vs. 1,211 +/- 133 nmol O(2). min(-1). g(-1); P < 0.05). BK and Ram decreased O2 consumption significantly less in eNOS-/- mice [eNOS-/-: BK -19.0 +/- 2.8%, Ram -20.5 +/- 3.3% at 10(-4) M; control: BK -29.5 +/- 2.5%, Ram -34 +/- 1.6% at 10(-4) M]. The NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME) attenuated this decrease in control but not eNOS-/- mice. An NO donor inhibited O2 consumption similarly in both groups independent of the presence of L-NAME. These results demonstrate that NO production by eNOS is responsible for regulation of renal O2 consumption in mouse kidney.