Correlation of 25-Hydroxyvitamin D Levels in Serum vs. Breastmilk in Vitamin D-Supplementation Breastfeeding Women during Lactation: Randomized Double Blinded Control Trial.

Background: Vitamin D deficiency in pregnancy and lactation increases the risk of adverse perinatal outcomes; however, although Vitamin D supplementation during pregnancy and lactation is recommended, suggested dose ranges vary. Objective: To determine whether vitamin D31,800 IU/d supplementation in lactating mothers improves their vitamin D status and breast-feeding milk. Material and Method: This was a randomized, placebo­controlled study of Thai pregnant women in their third trimester. A total of 76 Thai lactating mothers and their breast-fed infants were studied with maternal 25 Hydroxyvitamin D 25 (OH) D levels of 10-30 ng/ml determined using Liquid Chromatography Mass Spectrometry Tandem (LC-MS/MS). One group received vitamin D3 1,800 IU/d supplementation for 6 weeks, and members of the other group were given a placebo. 25 (OH) D level of colostum and 6-week serum from breast-fed milk were measured by High Performance Liquid Chromatography (HPLC). The data from the two groups were analyzed and compared. Results: The mean (±SD) maternal age was 27.16±5.13 years, and mean body mass index (BMI) was 22.29±5.08 kg/m(2). At 6 weeks, maternal 25 (OH) D levels had increased significantly in the vitamin D group (VD) 68.30±15.40 nmol/L compared to 55.15±13.57 nmol/L in the placebo group (p<0.001) measured using the Liquid Chromatography-Mass Spectrometry Tandem (LC-MS/MS) method. Breast-fed milk did not show any significant incremental change in 25 (OH) D levels measured by High Performance Liquid Chromatography (HPLC); however, the change in 25 (OH) D levels in breast milk in the VD group was significantly different from that of the placebo group (p = 0.005).` Conclusion: Vitamin D3 supplementation during lactation can increase 25 (OH) D levels in Thai breast-fed mothers. Further work is needed to determine the duration of vitamin D supplementation to normalize breast milk and breast-fed infants' 25 (OH) D level at over 75 nmol/L.

Prevalence of Diabetic Foot Ulcers and Risk Classifications in Type 2 Diabetes Mellitus Patients at Rajavithi Hospital.

BACKGROUND: Diabetic foot ulcers are a major cause of non-traumatic lower limb amputation in patients with type 2 diabetes. In 2014, the Diabetes Association of Thailand issued new guidelines for classifying type 2 diabetes patients' levels of risk of developing foot ulcers, but no research on the prevalence of type 2 diabetes using these new classification criteria had been performed prior to the current study. OBJECTIVE: To study the prevalence of diabetic foot ulcers overall and in different risk groups in type 2 diabetes mellitus patients in Rajavithi Hospital, and to evaluate risk factors of these groups and correlations with ankle brachial index (ABI) and cardio-ankle vascular index (CAVI). MATERIAL AND METHOD: 593 type 2 diabetes patients at Rajavithi Hospital were studied and classified into risk groups based on the classification criteria issued by the Thailand Diabetes Association in 2014. ABI measurements were taken from 132 patients, and measurements of CAVI were taken from 101 patients. RESULTS: The prevalence of foot ulcers was 3.4% and 2.2% of patients had a history of amputation. The percentages of patients at low, intermediate and high risk of developing foot ulcers were 55.8%, 33.6% and 10.6%, respectively. Age, duration of diabetes, estimated glomerular filtration rate (eGFR), history of hypertension, dyslipidemia, nephropathy, cardiovascular disease (CVA), deformity of foot, numbness, abnormal protective sensation, pulse deficit, ulcer, and amputation were factors significantly associated with a high risk of foot ulcers (p < 0.05), but fasting plasma glucose (FPG) and HbA1c were not significant factors. There was an association between cerebrovascular accident and abnormal ABI. CONCLUSION: Nearly half of these type 2 diabetes patients were in the groups with an intermediate or high risk of developing foot ulcers. Screening of patients at risk of foot ulceration is necessary in order to classify patients into risk groups and provide appropriate education, as well as proper monitoring and management.

Somatic HRPT2 Mutation (Arg234X) of Parathyroid Carcinoma Associated with Slipped Capital Femoral Epiphysis: A First Case Report.

A 14-year-old boy was admitted to the orthopedic clinic of Rajavithi Hospital complaining of pain in the left hip. A year earlier, pain had developed in his left joint and had gradually increased in intensity in both hips. A month before he was referred, radiographs obtained at another hospital showed bilateral slipped capital femoral epiphysis (SCFE). The patient's biochemical laboratory data showed hypercalcemia, hypophosphatemia, and a high level of intact parathyroid hormone (iPTH) compatible with primary hyperparathyroidism. HRPT2 gene analysis found heterozygosity for c. 700 C > T mutation (Arg234X) of HRPT2 gene at exon 7. This is the first report in the literature about somatic mutation of the HRPT2 gene of parathyroid carcinoma associated with slipped capital femoral epiphysis.

Comparison effect of loading calcitriol and titrating calcitriol treatment to control hypocalcemia after parathyroidectomy in chronic kidney disease: randomized control trial, open labeled.

BACKGROUND: Postoperative parathyroidectomy hypocalcemia probably results from acute reversal of the parathyroid hormone induced contribution of bone to maintain serum calcium concentration. OBJECTIVE: Compare the effective treatment of calcitriol regimens (loaded and titrated) in control hypocalcemic hyperparathyroid (HPT) patients who were referred for parathyroidectomy. MATERIAL AND METHOD: A randomized control, open labeled study of 25 patients who underwent parathyroidectomy in Rajavithi Hospital from August 2009 to September 2010 was conducted. The authors randomized 25 patients with chronic kidney disease in two treatment arms of calcitriol (A: Titrated dose regimen, B: Loaded dose regimen), that met criteria. Biochemical factors available within 2 weeks before and after surgery were recorded and analyzed. RESULT: No significant difference was observed in amount of calcium gluconate intravenous use, hypocalcemia and hospital admission durations between titrated and loaded regimen groups, i.e., p = 0.160, 0.645 and 0.460, respectively. Loaded regimen ameliorated the mean reduction of day 7 postoperative mean change of serum calcium level by 0.33±0.99 mg/dl and median change by 2.88 mg/dl (min, max = -0.80, 5.64) compared with titrate regimen mean change ofserum calcium level by 2.68±2.16 mg/dl; median change 0.28 mg/dl (min, max = -0.84, 1.80) with significance, p = 0.036. CONCLUSION: Loaded calcitriol regimen was superior to titrated calcitriol regimen compared with the control group the first 7 days postparathyroidectomy. Amount of calcium gluconate intravenous used, hypocalcemia and duration of hospital stay did not show any significance.

Multimerization of glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) and familial chylomicronemia from a serine-to-cysteine substitution in GPIHBP1 Ly6 domain.

GPIHBP1, a glycosylphosphatidylinositol-anchored glycoprotein of microvascular endothelial cells, binds lipoprotein lipase (LPL) within the interstitial spaces and transports it across endothelial cells to the capillary lumen. The ability of GPIHBP1 to bind LPL depends on the Ly6 domain, a three-fingered structure containing 10 cysteines and a conserved pattern of disulfide bond formation. Here, we report a patient with severe hypertriglyceridemia who was homozygous for a GPIHBP1 point mutation that converted a serine in the GPIHBP1 Ly6 domain (Ser-107) to a cysteine. Two hypertriglyceridemic siblings were homozygous for the same mutation. All three homozygotes had very low levels of LPL in the preheparin plasma. We suspected that the extra cysteine in GPIHBP1-S107C might prevent the trafficking of the protein to the cell surface, but this was not the case. However, nearly all of the GPIHBP1-S107C on the cell surface was in the form of disulfide-linked dimers and multimers, whereas wild-type GPIHBP1 was predominantly monomeric. An insect cell GPIHBP1 expression system confirmed the propensity of GPIHBP1-S107C to form disulfide-linked dimers and to form multimers. Functional studies showed that only GPIHBP1 monomers bind LPL. In keeping with that finding, there was no binding of LPL to GPIHBP1-S107C in either cell-based or cell-free binding assays. We conclude that an extra cysteine in the GPIHBP1 Ly6 motif results in multimerization of GPIHBP1, defective LPL binding, and severe hypertriglyceridemia.

A randomized study on the effect of vitamin D3 supplementation on skeletal muscle morphology and vitamin D receptor concentration in older women.

CONTEXT: Studies examining whether vitamin D supplementation increases muscle mass or muscle-specific vitamin D receptor (VDR) concentration are lacking. OBJECTIVE: Our objective was to determine whether vitamin D3 4000 IU/d alters muscle fiber cross-sectional area (FCSA) and intramyonuclear VDR concentration over 4 months. DESIGN AND SETTING: This was a randomized, double-blind, placebo-controlled study in a single center. PARTICIPANTS: Participants were 21 mobility-limited women (aged ≥ 65 years) with serum 25-hydroxyvitamin D (25OHD) levels of 22.5 to 60 nmol/L. MAIN OUTCOME MEASURES: Baseline and 4-month FCSA and intramyonuclear VDR were measured from vastus lateralis muscle cross-sections probed for muscle fiber type (I/IIa/IIx) and VDR using immunofluorescence. RESULTS: At baseline, mean (±SD) age was 78 ± 5 years; body mass index was 27 ± 5 kg/m², 25OHD was 46.3 ± 9.5 nmol/L, and a short physical performance battery score was 7.95 ± 1.57 out of 12. At 4 months, 25OHD level was 52.5 ± 17.1 (placebo) vs 80.0 ± 11.5 nmol/L (vitamin D [VD]; P < .01), and change in 25OHD level was strongly associated with percent change in intramyonuclear VDR concentration-independent of group (r = 0.87, P < .001). By treatment group, percent change in intramyonuclear VDR concentration was 7.8% ± 18.2% (placebo) vs 29.7% ± 11.7% (VD; P = .03) with a more pronounced group difference in type II vs I fibers. Percent change in total (type I/II) FCSA was -7.4% ± 18.9% (placebo) vs 10.6% ± 20.0% (VD; P = .048). CONCLUSION: Vitamin D3 supplementation increased intramyonuclear VDR concentration by 30% and increased muscle fiber size by 10% in older, mobility-limited, vitamin D-insufficient women. Further work is needed to determine whether the observed effect of vitamin D on fiber size is mediated by the VDR and to identify which signaling pathways are involved.

Maternal 25 hydroxyvitamin D level and its correlation in Thai gestational diabetes patients.

OBJECTIVE: To identify 25 hydroxyvitamin D (250HD) levels in Thai pregnant women with gestational diabetes and nongestational diabetes. MATERIAL AND METHOD: This prospective study was conducted on 197 pregnant women at Rajavithi Hospital, a tertiary care medical center in Bangkok from October 2010 to July 2011. Plasma 25 hydroxyvitamin D concentration and HbA1c level during the 75 g OGTT in gestational diabetes mellitus (GDM) and non-GDM were evaluated. The recommendations of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) were used for diagnosis of GDM in the present study. RESULTS: In the selected 197 Thai pregnant women aged from 18 to 49 years, the mean age was 32.1 years, and the mean plasma 250OHD level was 34.3 ng/dl. The percentages of patients classified as having 25OHD deficiency (< 20 ng/dl), 25OHD insufficiency and normal 25OHD were 3.1%, 22.3% and 74.6%, respectively. Among the 197 women, 70 patients (34.8%) had GDM. In the GDM group, 29 patients (41.4%) had abnormal 25OHD level of which 5.7% had 25OHD deficiency and 35.7% had 25OHD insufficiency. Among those with GDM, plasma 25OHD concentration was significantly lower than in the non-GDM subjects (32.3 +/- 10.3 vs. 35.5 +/- 6.7 ng/dl, p = 0.001). Fasting blood glucose and HbA1C independently predicted low 25OHD levels in Thai GDM subjects after applying regression model and adjusting for age, BMI, trimester and family history of DM (p = 0.031, p = 0.014 respectively). Higher pre-pregnancy BMI was associated with GDM and lower 25OHD level. CONCLUSION: Thai pregnant women with GDM had lower levels of 25OHD compared to those without GDM. Only fasting plasma glucose independently predicted low 25OHD levels in GDM subjects.

Novel COL1A1 gene mutation (R1026X) of type I osteogenesis imperfecta: A first case report.

A 22-year-old Thai man with blue sclera, normal height and absence of deformity sustained an open fracture at the right talus and talo-navicular dislocation while playing in a volleyball match. The patient had a history of several fractures of his elbows, wrists and ankles from minor impacts. Novel COL1A1 nonsense mutation (c. 3202 C-->T), a C to T transition at position 3,203, resulting in arginine to stop codon at codon 1026 (R102 6X) mutation in exon 42 was found, and this is the first case reported in the literature.

Fulminant type I diabetes: the first case report in Thailand.

Type 1 diabetes is classified as either autoimmune (type IA) or idiopathic (type IB) diabetes. Fulminant type 1 diabetes is a recently-discovered subtype of idiopathic type 1 diabetes. It is defined as diabetes with complete abrupt onset of beta cell destruction and progression to hyperglycemia and ketoacidosis within a short period of time, but with a near-normal HbA1c level. The patients often have flu-like or abdominal symptoms at onset and elevated levels of pancreatic exocrine enzymes. Their diabetes-related autoantibodies are usually negative. In the present report, the authors present a case of fulminant type 1 diabetes in a 43-year-old Thai woman who presented with sudden onset of flu-like symptoms and abdominal pain. Findings on admission included a high blood glucose level and ketoacidosis, but a prediabetes range ofHbA1c level. Autoantibodies to glutamic acid decarboxylase (GAD) were negative. This subtype of type 1 diabetes was first identified in 2000 and there have been case reports from Japan, Korea, the Philippines and the Netherlands. Nonetheless, no case had been reported in Thailand until the present study. Here the authors report the first case of fulminant type 1 diabetes in Bangkok, Thailand.

An evaluation of the reliability of muscle fiber cross-sectional area and fiber number measurements in rat skeletal muscle.

BACKGROUND: The reliability of estimating muscle fiber cross-sectional area (measure of muscle fiber size) and fiber number from only a subset of fibers in rat hindlimb muscle cross-sections has not been systematically evaluated. This study examined the variability in mean estimates of fiber cross-sectional area as a function of the number of fibers measured, and tested whether counting a subset of fibers in a cross-section could predict total fiber number in middle-aged rats. RESULTS: Soleus and extensor digitorum longus (EDL) muscle cross-sections from 23-month-old, male Fisher 344 x Brown Norway rats were stained for myofibrillar ATPase activity to identify muscle fiber type (either type I [slow-twitch] or II [fast-twitch]) and laminin to facilitate fiber cross-sectional measurements. We outlined the circumference of 1000 to 1600 single muscle fibers for measurement of fiber cross-sectional area within muscle sections. Mean type I fiber cross-sectional area was based on soleus muscle sections which were predominantly composed of type I muscle fibers. Mean type II fiber cross-sectional area was based on EDL muscle sections which were predominantly composed of type II muscle fibers. A bootstrapping resampling technique demonstrated that variability in sampling distribution of mean type I and II fiber cross-sectional areas decreased and gradually stabilized as the number of fibers measured increased with large declines in variability occurring at numbers below 150 fibers. Coefficients of variation for bootstrapped mean type I fiber cross-sectional areas were lower than for type II. In the same muscle sections, total fiber number was compared to fiber numbers within 1, 2, 3, and 4 fixed field areas (10x magnification; 1000 x 1500 pixels in size/field) on the cross-section. Fiber numbers from 3 to 4 fields (approximating 15 to 20% of the cross-section) provided a reasonably predictive value of total fiber number (r=0.57-0.59, P=0.003). CONCLUSIONS: These data describe a pattern of improved precision in estimating mean fiber cross-sectional area as sample size of fibers measured increases to at least 150 in this rat model. Counting 15-20% of the fibers in cross-sections provides a reasonably reliable estimate of the total fiber number.

Type of dietary fat is associated with the 25-hydroxyvitamin D3 increment in response to vitamin D supplementation.

CONTEXT: Mono- and polyunsaturated fats may have opposing effects on vitamin D absorption. OBJECTIVE: The purpose of this study was to determine whether intakes of different dietary fats are associated with the increase in serum 25-hydroxyvitamin D (25OHD) after supplementation with vitamin D(3). DESIGN, SETTING, AND PARTICIPANTS: This analysis was conducted in the active treatment arm of a randomized, double-blind, placebo-controlled trial of vitamin D and calcium supplementation to prevent bone loss and fracture. Subjects included 152 healthy men and women age 65 and older who were assigned to 700 IU/d vitamin D(3) and 500 mg/d calcium. Intakes of monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), and saturated fatty acids (SFA) were estimated by food frequency questionnaire. MAIN OUTCOME MEASURE: The change in plasma 25OHD during 2 yr vitamin D and calcium supplementation was assessed. RESULTS: The change in plasma 25OHD (nanograms per milliliter) during vitamin D supplementation was positively associated with MUFA, (ß = 0.94; P = 0.016), negatively associated with PUFA, (ß = -0.93; P = 0.038), and positively associated with the MUFA/PUFA ratio (ß = 6.46; P = 0.014). CONCLUSION: The fat composition of the diet may influence the 25OHD response to supplemental vitamin D(3). Diets rich in MUFA may improve and those rich in PUFA may reduce the effectiveness of vitamin D(3) supplements in healthy older adults. More studies are needed to confirm these findings.

Sensitivity of HRPT2 mutation screening to detect parathyroid carcinoma and atypical parathyroid adenoma of Thai patients.

OBJECTIVE: Detected HRPT2 mutation in parathyroid carcinoma or atypical parathyroid adenoma in sporadic hyperparathyroidism in Thai patients. MATERIAL AND METHOD: Samples of parathyroid carcinoma, typical (atypical) adenoma or hyperplasia were obtained for HRPT2 gene (17 exons) study since September 2001 to August 2010 both somatic and germline by SyBr Green PCR method. RESULTS: Parathyroid carcinomas and atypical parathyroid adenoma from 5 of 26 patients (10 of 32 samples) were tested for HRPT2 mutations. Only somatic HRPT2 mutations were found in tumor from 2 patients but three patients found both somatic and germline HRPT2 mutations. Exon 15 of HRPT2 gene was the best sensitivity (sensitivity 80.0%; p < 0.001, 95% CI 0.75-1.05) followed by exon 2 and exon 11 (sensitivity 60.0%; p = 0.007, 95% CI 0.60-0.99) to detected parathyroid carcinoma or atypical parathyroid adenoma. CONCLUSION: HRPT2 mutations by SyBr Green PCR sensitive method to detected parathyroid carcinoma or atypical adenoma from benign parathyroid tissues. Exon 15 was the best sensitive to detected parathyroid carcinoma or atypical adenoma. Genotyping of such family members for germline mutation would focus implementation of clinical and biochemical monitoring of carriers of these mutations.

Langerhans' cell histiocytosis (LCH) in adolescence presented with central diabetes insipidus: a case report.

A 19-year-old Thai man presented with symptoms of central diabetes insipidus, exopthalmos and multiple ostolytic lesions of the cranial vault. Skin biopsy showed strongly positive CD 1a and S100. Electron microscopy showed rod shape and pentalaminar granules called "Birbeck" granules, a diagnosis compatible with Langerhans' cell histiocytosis (LCHs) or histiocytosis X. He was successfully treated with systemic chemotherapy.

Role of loading calcitriol to control hypocalcemia after parathyroidectomy in chronic kidney disease.

OBJECTIVE: To compare the effective calcitriol regimens in hypocalcimic hyperparathyroidism (HPT) patients who were referred to parathyroidectomy. MATERIAL AND METHOD: Retrospective study of fifty patients who underwent parathyroidectomy in Rajavithi Hospital between September 2001 and August 2009 was performed. The authors defined three regimens of calcitriol (A; fixed dose regimen, B; titrated dose regimen and C; loading dose regimen) by reviewing 41 charts of patients with chronic kidney disease. Biochemical factors available within two weeks before and after surgery were recorded and analyzed. RESULTS: Postoperative hypocalcemia was a common complication found in 82.93% (n = 34/41) of patients with chronic kidney disease, 80.61% (n = 25/31) and 90% (n = 9/10) of secondary HPT and tertiary HPT, respectively. In multiple logistic regression analysis; calcium-phosphorus product was the independent predictor of postoperative hypocalcemia requiring intravenous calcium gluconate with statistical significance atp = 0.008, ROC analysis showed calcium phosphorus products more than 53 mg2/dl2 represented the best compromise between sensitivity (0.71) and specificity (0.67) by area under the curve = 0.755). The amount of intravenous calcium gluconate after parathyroidectomy in the loading calcitriol regimen (initial dose 2.25-4 mcg/day) was significantly lower than that in the titrated calcitriol regimen (0.75-1.5 mcg/day) (p = 0.001). CONCLUSION: Loading calcitriol regimen reduced hypocalcemic morbidity in postoperative parathyroidectomy in patients with chronic kidney disease.