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ABSTRACT: The mutations of bone morphogenetic protein receptor type 2 (BMPR2) in patients with idiopathic pulmonary hypertension has been well defined. We investigated the occurrence of BMPR2 mutation and genetic polymorphisms in children with pulmonary hypertension associated with congenital heart disease (aPH/CHD) and correlated with the pulmonary haemodynamic and vasoreactivity. METHODS: BMPR2 mutation/polymorphisms were determined in 30 aPH/CHD children. All children underwent cardiac catheterization to obtain baseline haemodynamic data. The 5'UTR containing promoter region and all the exons [1-13] of BMPR2 gene were genotyped for possible genetic variants that may be related to the aPH/CHD. RESULTS: None of our 30 patients (median-age 90 months) with aPH/CHD (mean PAP 48±17mmHg, PVR 6.7±4.2WUm(2)) has had any BMPR2 mutation. Fifteen of them had single nucleotide polymorphism, rs1061157 and/or 5'UTR-polymorphism, specifically GGC repeat variant in seven patients; AGC repeat variant in one patient; and nine base pairs duplication (CTTCTTCGG) in one patient. The GGC repeat ≥13 was found in 3 out of 6 of children with aPH/CHD with normal PVR vs. 2 out of 24 children with aPH/CHD with high PVR. The odd ratio between these two subgroups of aPH/CHD is 0.09 (95% CI 0.02-0.34). CONCLUSIONS: In our cohort, there was no BMPR2 mutation in children with aPH/CHD while 9 out of 30 of them have 5'UTR repeat polymorphisms. Our data suggests the occurrence of GGC repeat ≥13 at the 5'UTR region may have some protective effect towards pulmonary vasculopathy in children who have been exposed to high pulmonary blood flow due to CHD.
Heart Lung & Circulation 10/2012; · 1.20 Impact Factor
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ABSTRACT: Cyproheptadine, an appetite stimulant, has been used in poor-appetite underweight children. Its beneficial effects on enhancing growth rate have been demonstrated. In contrast, an adverse effect on blunting growth hormone (GH) secretion has also been reported. To date, however, its effect on insulinlike growth factor-I (IGF-I), a GH-mediated growth factor, has not been documented.
To examine the effect of cyproheptadine therapy on growth and serum IGF-I in underweight children.
Twenty-one underweight, otherwise healthy children were recruited. They were randomly assigned into cyproheptadine administration (n = 10) and placebo (n = 11) groups. The former received cyproheptadine for 4 months. Serum IGF-I levels were measured in both groups.
Weight and height velocities and IGF-I z-scores during cyproheptadine therapy were significantly greater in the intervention group than those of the placebo group.
Cyproheptadine therapy in underweight children increased caloric intake and serum IGF-I concentration and consequently enhanced growth velocity.
Journal of pediatric endocrinology & metabolism: JPEM 06/2009; 22(5):425-32. · 0.88 Impact Factor
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Journal of pediatric gastroenterology and nutrition 04/2009; 48(3):370-3. · 2.18 Impact Factor
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ABSTRACT: To describe a simple technique of cultivating human corneal epithelial stem cells using an Epilife culture medium under serum- and feeder-free conditions.
Cadaveric donor limbal corneal epithelial cells were cultured on denuded amniotic membranes using an explant technique that was free of serum and feeder cells in the Epilife medium containing a growth supplement of defined composition. These cells were assessed by phase contrast microscope. The expressions of the proposed corneal epithelial stem cell markers (p63, ATP-binding cassette member 2 (ABCG2), and cytokeratin 15 and 19) and differentiation markers (cytokeratin 3, 12, connexin 43, and p75) were analyzed using reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemical staining.
Successful cultures were obtained, resulting in a monolayer to double layer cell sheets with a cobblestone-like morphology. RT-PCR and immunocytochemistry disclosed an expression of both putative limbal stem cell (LSC) markers and differentiation-associated markers in the cultured cells. Most of the cultured corneal epithelial cells that were immunopositive for putative LSC markers were smaller, more uniform, and closer to the limbal explant than cells positively stained with differentiation-associated markers.
A serum- and feeder-free culture system using Epilife medium may grow human corneal epithelial equivalents, minimizing the risk of contamination during culture. The technique may also be useful for the clinical application of limbal stem cell culture.
Molecular vision 02/2009; 15:1294-302. · 2.20 Impact Factor
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ABSTRACT: Increased marrow erythropoiesis in patients with thalassemia syndromes results in the expansion of bone marrow cavities and consequently decreases bone tissues, leading to osteoporosis. Whether the soluble transferrin receptor (sTfR), a marker of erythropoietic activity, correlates with the bone mineral density (BMD) in thalassemic patients has not previously been addressed. Forty-six children and adolescents with thalassemia syndromes, who were either not transfused or suboptimally transfused, were studied. BMD was determined by dual-energy X-ray absorptiometry. Blood samples were obtained in order to determine sTfR and hemoglobin. The patients were categorized into four groups: 1, beta-thalassemia/hemoglobin E (beta-thal/E) with transfusion-dependency (TD) (n = 18); 2, beta-thal/E with transfusion-independency (TI) (n = 15); 3, beta-thalassemia major (beta-major) (n = 6); 4, hemoglobin H (HbH) (n = 7). All patients had normal serum free thyroxine (FT4) and thyroid-stimulating hormone (TSH), and intact parathyroid hormone (PTH), serum calcium (Ca), phosphate (P), and 25-OH-vitamin D levels. The BMD of patients in the beta-major and beta-thal/E with TD groups were not significantly different. In comparison with the beta-major and beta-thal/E with TD groups, the beta-thal/E with TI and HbH groups had significantly higher BMD of the total body (TB), femoral neck (FN), and lumbar spine (LS), as well as higher levels of hemoglobin. In contrast, the sTfR levels of the beta-major, beta-thal/E with TI, and HbH groups were significantly lower than those of the beta-thal/E with TD group. The BMD of TB, FN, and LS was negatively correlated with the sTfR level, but positively correlated with the hemoglobin level. In conclusion, increased marrow erythropoiesis is one of the major determinants of reduced bone mass in thalassemic patients with either no transfusion or suboptimal transfusion.
Journal of Bone and Mineral Metabolism 02/2006; 24(2):146-52. · 2.27 Impact Factor
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ABSTRACT: X-linked agammaglobulinemia is caused by mutations in the human BTK gene, leading to recurrent pyogenic infections. We describe four novel and three known BTK-mutations in seven patients from seven (six Thai and one Burmese) families. All but one were sporadic cases. Patients 1 and 2 had recurrent mutations in exon 10 (R288W) and exon 17 (R562W), respectively. Patient 3, a previously healthy individual who presented with pseudomonas sepsis with ecthyma gangrenosum had a known mutation in exon 17 (1749delT), leading to frameshift effect (F583fsX586). Patient 4 manifested with sepsis and concurrent acute appendicitis and pneumonia. He had a mutation, IVS8 + 1G > A, which led to an insertion of intron 8 into the transcripts. In Patient 5, a novel change in exon 7, c.588G > C, initially presumed Q196H, was found to cause a leaky splicing mutation, resulting in three distinct transcripts containing 17, 108, and 190 bp of the 5'-terminal of intron 7, which led to truncated peptides consisting of 203 and 211 amino acid residues (or Q196fsX204 and Q196fsX212, respectively). Patient 6 had a mutation in exon 14 (W421X), while patient 7 had a newly defined large deletion of exons 6-9. All of the mothers tested were mutation carriers. Transcript analysis in three mothers who were heterozygous for frameshift mutations revealed a minimal amount of aberrant transcripts, while their affected children had full expression of the mutant alleles, suggesting rapid degradation due to nonsense-mediated mRNA decay in the mothers. This is the first report of mutations of BTK from Thailand.
Journal of Human Genetics 01/2006; 51(11):1006-14. · 2.57 Impact Factor
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ABSTRACT: Thalassemia/hemoglobinopathy is a hereditary disease that causes chronic anemia and increased erythropoiesis. Consequently, an expansion of bone marrow spaces may contribute to osteopenia/osteoporosis. However, the pathogenesis of bone changes is not yet known. We, therefore, carried out the study on bone histomorphometry and biochemical and hormonal profiles in children and adolescents with suboptimally treated beta-thalassemia disease with the hope of gaining some new insight into the cellular and structural alterations of thalassemic bone. Seventeen patients underwent iliac crest bone biopsy for histomorphometric analyses. Bone mineral density (BMD) measurements were performed by dual energy x-ray absorptiometry. Most patients had growth retardation and delayed bone age. BMD was low especially at the lumbar spine. Serum IGF-I levels were almost always low. Bone histomorphometry revealed increased osteoid thickness, osteoid maturation time, and mineralization lag time, which indicate impaired bone matrix maturation and defective mineralization. In addition, iron deposits appeared along mineralization fronts and osteoid surfaces. Moreover, focal thickened osteoid seams were found together with focal iron deposits. Dynamic bone formation study revealed reduced bone formation rate. These findings indicate that delayed bone maturation and focal osteomalacia are the pathogenesis of bone disease in suboptimally blood-transfused thalassemics with iron overload. Iron deposits in bone and low circulating IGF-I levels may partly contribute to the above findings.
Journal of Clinical Endocrinology & Metabolism 09/2003; 88(8):3966-72. · 6.50 Impact Factor
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ABSTRACT: Thalassaemia/haemoglobinopathy is a hereditary disease causing increased erythropoiesis and expansion of the bone marrow cavity. As a consequence, there is a reduction in trabecular bone tissue resulting in osteopenia/osteoporosis. The present study was performed to assess bone mineral density (BMD) in children and adolescents with beta-thalassaemia disease and to determine biochemical and hormonal changes that may affect BMD.
Forty-eight children and adolescents with beta-thalassaemia were divided into two groups, transfusion-dependent (TD) (n = 16) and transfusion-independent (TI) (n = 32). All patients were treated suboptimally. BMD was determined by dual-energy X-ray absorptiometry. Bone maturation was assessed by radiographic bone age (BA). Blood and urine samples were obtained for the determination of biochemical and hormonal profiles, which included PTH, 25-hydroxyvitamin D (25-OHD), osteocalcin, bone-specific alkaline phosphatase, IGF-1, fT4, TSH and urine deoxypyridinoline.
Most of the patients were short and underweight, and they had delayed BA with mean Z-scores of -2.77 in the TD and -2.04 in TI groups. The mean Z-scores of BMD in the TD vs. TI groups of total body, radius, femoral neck and lumbar spine were -2.09 vs.-1.49, -0.73 vs. -0.54, -1.93 vs.-1.17 and -3.45 vs.-2.43, respectively. Although the means BMD values in the TD group were lower than those in the TI group, they were not significantly different. Mean serum IGF-1 levels were lower in the TD than the TI groups, 11.6 and 24.9 nmol/l, respectively (P < 0.05). Other biochemical and hormonal profiles did not differ between these two groups.
Patients with undertransfused severe beta-thalassaemia had more bone marrow expansion, lower serum IGF-1 levels and more delayed bone age than did patients with untransfused moderately severe beta-thalassaemia. Therefore, the severity of the disease appeared to be a primary factor for low bone mineral density in undertransfused patients in association with bone age delay and low serum IGF-1.
Clinical Endocrinology 03/2003; 58(3):273-9. · 3.17 Impact Factor
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ABSTRACT: Hypoglycemia is an emergency condition requiring treatment as soon as possible. Therefore, rapid and reliable blood glucose measurements are necessary. There are 2 systems of glucose meters (GMs), the reflectance photometer system (RPS) and the electrochemical biosensor system (BSS). GMs are widely used in monitoring blood glucose (BG) in patients with diabetes. BG values measured by GMs have been confirmed to be accurate especially in measuring normal and high BG levels. However, the data on the accuracy of GMs in measuring low BG levels are limited.
To compare accuracy and reliability of different systems of GMs in the measurement of low BG values.
Venous and capillary whole blood specimens were collected from patients who were investigated for pituitary dysfunction. The patients underwent an insulin-induced hypoglycemia test by intravenously administering human regular insulin. The low BG level was defined as having venous plasma glucose (PG) of less than 60 mg/dl (mean +/- SD = 36.59 +/- 9.19, n = 54). Capillary blood samples were obtained from fingertips. Venous BG (vBG) and capillary BG (cBG) were measured by GMs. Venous PG which considered a reference value was measured by the glucose dehydrogenase method.
The correlation coefficient (r) between vBG measured by GMs-RPS and PG was 0.86 (p < 0.001), whereas, that between vBG by GMs-BSS and PG was 0.75 (p < 0.001). Similarly, the r between cBG by GMs-RPS and PG was 0.73 (p < 0.001), whereas, that between cBG by GMs-BSS and PG was 0.69 (p < 0.001). The mean difference between vBG by GMs-RPS and PG values was 0.01 +/- 4.90 mg/dl, whereas, that between vBG by GMs-BSS and PG values was 10.50 +/- 7.07 mg/dl which was significantly greater than the former (p<0.001). Moreover, the mean difference between cBG by GMs-RPS and PG values was 14.45 +/- 8.76 mg/dl, whereas, that between cBG by GMs-BSS and PG values was 23.87 +/- 9.48 mg/dl which was also significantly greater than the former (p < 0.001). These results demonstrated that vBG measured by GMs-RPS was comparable to PG values. In addition, cBG values by GMs-RPS and GMs-BSS were approximately 14 mg/dl or 38 per cent and 24 mg/dl or 65 per cent greater than PG values, respectively.
In measuring low blood glucose levels, glucose meters using the reflectance photometer system are more accurate than those using the electrochemical biosensor system.
Journal of the Medical Association of Thailand = Chotmaihet thangphaet 11/2002; 85 Suppl 4:S1104-10.
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ABSTRACT: Homozygous beta-thalassemia is a hereditary hematological disease due to defective beta-globin synthesis. Consequently, there is ineffective erythropoiesis and increased peripheral hemolysis. Increased erythropoiesis in bone marrow results in expansion of marrow cavity and reduced bone mass. Patients with heterozygous beta-thalassemia or beta-thalassemia trait may have mild anemia, and consequently mildly increased erythropoiesis. Whether modestly increased erythropoiesis might decrease bone mass is not well established.
To evaluate bone mineral density (BMD) in children and young adults with beta-thalassemia trait.
Thirty-one healthy young adults aged 20-45 yr and 26 healthy children aged 8-15 yr with beta-thalassemia trait were enrolled in the study. BMD was determined by dual X-ray absorptiometry (DEXA). Determinations of intact parathormone (PTH), 25-hydroxyvitamin D (25-OHD), and bone markers were performed.
In adults, all had z-scores of BMD more than -2 above the mean. The mean z-scores of BMD of lumbar spine, radius and femoral neck were 0.11, -0.10 and 0.41, respectively. In children, only two of 26 had z-scores of lumbar spine BMD more than -2 below the mean. The mean z-scores of BMD of total body, lumbar spine, radius and femoral neck were 0.12, -0.28, 0.30 and -0.14, respectively. All subjects had normal PTH, 25-OHD and bone markers levels.
beta-Thalassemia trait is not a contributing factor for osteopenia/osteoporosis in children and young adults.
Journal of pediatric endocrinology & metabolism: JPEM 15(9):1531-5. · 0.88 Impact Factor
