Lipid treatment assessment project II in Thailand (LTAP-II Thailand).

OBJECTIVE: Evaluate treatment practices and their outcomes in Thai patients with hyperlipidemia. The factors contributing to success of treatment were also determined. MATERIAL AND METHOD: A multi-center cross-sectional survey with the support of 98 physicians from 48 hospitals was done. Each physician enrolled up to 20 dyslipidemic patients by simple randomization. RESULTS: One thousand nine hundred twenty one cases, 45.1% males with a mean age of 58.6 years (SD = 9.6) were recruited. The patients were divided into three groups: 1,178 patients with coronary heart disease (CHD) and CHD equivalents, 424 patients with high risk, and 319 patients with low risk. The main targets for treatment were LDL-C levels of< 100, < 130 and < 160 mg/dL for each respective group. As a whole, the risk factors listed in order of frequency were age at risk (78%), hypertension (69. 8%), diabetes mellitus (43.6%), smoking (24.6%), and family history of CHD (6.9%). Obesity (body mass index > or = 25 kg/m2) was found in 53.8% of the patients. Twenty eight percent of the patients experienced CHD or other atherosclerotic diseases. Statin was the commonest prescribed drug (64%) followed by fibrate (25%). The overall success rate was 46.5%. Percentage of cases achieving LDL-C targets in the CHD and CHD equivalents, high and low risk group was 34.6%, 56.4%, and 76.8%, respectively. The patients in the low risk group, being under specialist care and receiving statin therapy reached target of treatment at a significantly higher rate. CONCLUSION: The present study showed that statin was the most common drug used in the management of hyperlipidemia. Patients with CHD and CHD equivalents were the group with least achievement of LDL-C target. The factors contributing to achievement of LDL-C target were lower risk patient, specialist care, and statin therapy.

Glycemic and lipid responses to glucomannan in Thais with type 2 diabetes mellitus.

OBJECTIVE: To evaluate the benefits of glucomannan supplement on glycemic and lipid controls in type 2 diabetic patients. MATERIAL AND METHOD: A single-blind, placebo-controlled, crossover trial with two treatments separated by a 2-week washout period was performed in 10 men and 10 women with type 2 diabetes mellitus. Two separated protocols of experiments were sequentially followed. Initially, purified glucomannan (1 g) or placebo was ingested 30 min before 75-g glucose load to evaluate their effects on glucose absorption and insulin secretion in oral glucose tolerance test (OGTT). Later, the glycemic and lipid changes after 4-week intervention with 3 g/day glucomannan comparing to the placebo were determined. The standard OGTT was performed before and after ending of each intervention. RESULTS: Glucomannan taken before performing the OGTT can lower the rise of blood glucose and insulin from 1 to 2 hour in comparison with the placebo, though a statistically significance of insulin was not achieved. Long-term glucomannan supplement significantly reduced the 120-min glucose area under the curve of OGTT. Glucomannan also decreased the rise of low-density lipoprotein cholesterol (LDL-C). Reductions of HOMA-insulin resistance index and body mass index were detected in glucomannan-treated group though the former was shown only in females. No within- and between-group differences of insulin, fructosamine, and other lipids were observed in glucomannan- nor placebo- treated groups. CONCLUSION: In type 2 diabetes, pre-prandial glucomannan ingestion attenuated a rise of blood glucose without significantly affecting insulin levels. Long-term supplement of glucomannan to the regular diabetic regimen lessened post challenge glucose AUC and impeded the rise of LDL-C. Supplement of glucomannan may be beneficial to the glycemic and lipid controls in type 2 diabetes mellitus.

Hypercalcemia of malignancy: a study of clinical features and relationships among circulating levels of calcium, parathyroid hormone and parathyroid hormone-related peptide.

OBJECTIVE: Examine the clinical and biochemical features including serum intact PTH (iPTH) and plasma PTH-related peptide (PTHrP) levels in patients with malignancy-associated hypercalcemia (MAHC). MATERIAL AND METHOD: Forty-eight patients with histopathological or cytological proven malignancies and MAHC who were admitted to Siriraj Hospital were studied. RESULTS: The malignancies that caused MAHC were squamous cell carcinoma (45.8%), non-squamous cell solid tumors (31.3 %), and hematological malignancies (22.9%). Most patients (93.8%) had advanced stage malignancies. Corrected serum total calcium (cTCa) levels were 10.8-19.1 mg/dL (13.6 +/- 2.4) and severe hypercalcemia was observed in 17 cases (40.5%). Serum iPTH levels were 0.95-17.1 pg/mL (3.9 +/- 3.6). Most patients had suppressed serum iPTH levels of < 10 pg/mL. Plasma PTHrP levels were 0.2-44.0 pmol/L (3.8 +/- 6.8). There were 27 cases (56.3%) that had humoral hypercalcemia of malignancy (HHM) with plasma PTHrP levels of > 1.5 pmol/L, and 22 cases had squamous cell carcinoma. There was no difference in serum cTCa, phosphorus, alkaline phosphatase, and iPTH levels between patients with HHM and non-HHM. In 48 MAHC patients, serum cTCa correlated to plasma PTHrP (r = 0.35, p = 0.029) and to serum iPTH (r = 0.49, p = 0.003). In 25 patients with HHM, a stronger correlation between serum cTCa and serum iPTH (r = 0.55, p = 0.005) but not between serum cTCa and plasma PTHrP levels (r = 0.41, p = 0.05) was observed. Stepwise multiple regression analyses showed that serum iPTH but not plasma PTHrP levels independently correlated to serum cTCa levels (r = 0.39, p = 0.04). CONCLUSION: The clinical manifestations of MAHC observed in the present study were similar to those previously reported. Serum calcium correlated to serum iPTH more strongly than to plasma PTHrP levels. The low but detectable serum iPTH level might play a role in the development of severe MAHC particularly in HHM.

The Atorvastatin Goal Achievement Across Risk Levels: (ATGOAL) study in Thailand.

OBJECTIVE: To evaluate the efficacy and safety of atorvastatin at the starting doses of 10, 20, 40 mg and evaluate the effectiveness of 1 step titrate up regimen. MATERIAL AND METHOD: Two hundred and forty two subjects with dyslipidemia were enrolled and assigned the appropriate dose in relation to their individual cardiovascular risk status and baseline LDL-C levels. If the NCEP targets were not achieved, the doses were titrated up at week 4 and the primary efficacy was evaluated at week 8. RESULTS: A majority of subjects (88.8%) achieved their LDL-C goals at week 8. Almost all of the subject's LDL-C levels reached their goals by week 2 and 4 (81.6% and 87.1%, respectively). Only 10.7% (n = 25) required the sole titration. Each dose provided significant decreases in LDL-C (average -46.4%). Only 36 subjects experienced treatment related adverse events, the majority of these were in the high-risk group (n = 22) with only one subject registering a serious adverse event. CONCLUSION: Atorvastatin is effective and safe for Thai patients with dyslipidemia. The appropriate starting dose has contributed in the achievement of cholesterol reduction.

A survey study on diabetes management and complication status in primary care setting in Thailand.

OBJECTIVE: Healthcare service in Thailand is stratified into three levels with different facilities of care. This cross-sectional survey study described diabetes management, diabetes control, and late complication status among patients managed in urban primary health care clinics. MATERIAL AND METHOD: Thirty-seven primary health care units were randomly selected. Each unit enrolled up to 30 patients having been managed in the unit for at least one year. The patients were interviewed, and the medical records such as demographic data, management practice, glycemic control, and complications were retrospectively reviewed for a period of one year. All data were entered in the case record forms, transferred into a database by electronic scanning, and analyzed by SAS version 6.12. One thousand and seventy-eight patients, including 300 males and 778 females, were recruited in the present study. RESULT: Their mean +/- SD of age, onset age, and diabetes duration were 58.2 +/- 11.3, 52.2 +/- 11.4 and 6.2 +/- 4.0 years, respectively. Six percent of the patients were type 1, and 94% were type 2 diabetes. Two-thirds of the patients engaged in diabetes education > or = 5 days during the previous year. Monitoring of glycemic control was largely by measurement of fasting plasma glucose (FPG) in the unit. Determination of hemoglobin A1c (HbA1c), total cholesterol, triglyceride, HDL-cholesterol, serum creatinine, urinary protein, and microalbuminuria were observed in 0.7, 17.4, 11.7, 6.9, 38.2, 33.0, and 0.9% of the patients, respectively. Mean +/- SD of FPG was 8.3 +/- 2.7 mmol/l, and HbA1c was 8.6 +/- 1.9%. The percentage of patients with FPG < 6.7 mmol/l and HbA1c < 7% were 28.7 and 19.6%, respectively. An annual eye and foot examination was performed in 21.5% and 45% of the patients, respectively. The prevalence of late complications included retinopathy (13.6%), proteinuria (17.0%), end stage renal failure (0.1%), peripheral neuropathy (34%), acute foot ulcer/gangrene (1.2%), healed foot ulcer (6.9%), stroke (1.9%), and myocardial infarction (0.7%). CONCLUSION: The present study results demonstrated that necessary, routine assessments were not regularly practiced by caregivers in primary care units. In addition, peripheral neuropathy was the most common observed complication and this might explain the high rate of foot ulcers in this cohort.

Craniopharyngioma : A review of 14 cases at Siriraj Hospital.

Objective: 1) To characterize clinical presentations of craniophryngioma in the hypothalamic- pituitary region. 2) To examine both pre-treatment and post-treatment endocrine dysfunction of patients with craniopharyngioma. Methods: Medical records of patients with craniopharyngiomas from the Endocrine Division, Department of Medicine from 1997 to 2005 (9 years) were retrospectively reviewed. Data were expressed as mean+ SD (range) or percent as appropriate. Results: There were 14 cases (7 males and 7 females) with histological-proven diagnosis of craniopharyngioma. Their mean age was 32.3 + 13.0 years (15-56). The major distinguishing feature leading to diagnosis was visual field defects (85.7%), and a quarter of them were blind. Other distinguishing symptoms were headaches (78.6%), and menstrual disorders (28.6%). Pre-operative evaluations of their pituitary function revealed hypogonadotropic hypogonadism (55.6%), diabetes insipidus (DI) (42.9%), secondary adrenal insufficiency (18%) and elevated prolactin levels (36.4%) with a mean level of 36.1+39.2 ng/ml (12-138). All tumors were confirmed by pituitary CT or MRI. Mean tumor size was 3.83+1.3 cm. (2-6), and hydrocephalus was found in 54.5% of all patients. Craniotomy was performed in 13 cases with one transphenoidal surgery. Post-operative endocrine evaluations revealed more frequent hypogonadotropic hypogonadism (90%), both secondary adrenal insufficiency and diabetes insipidus (85.7%). 50% of DI cases were permanent DI. Secondary hypothyroidism was found post-operatively (78%). All cases of elevated serum prolactin levels became normal post-operatively and 44% of all patients had visual field improvement within a follow up period of 2.1+2.3 years (0-7). Conclusion: Craniopharyngioma is associated with high morbidity pre and post-operation. Visual field tests should be carefully evaluated in all patients with headaches to make early diagnosis in order to improve the treatment outcome.

Abnormal kinetics of erythrocyte sodium lithium countertransport in patients with diabetic nephropathy in Thailand.

BACKGROUND: In essential hypertension and diabetic nephropathy, sodium-lithium counter transport (Na/Li CT) is an inherited marker for metabolic influences of cardiovascular risk. The kinetics of Na/Li CT are modified by two types of thiol group in the membrane. In choline medium, the type 1 thiol reacts with N-ethtyl maleimide (NEM) to cause a decrease in Km and increase Vmax/Km ratio. However in the presence of external Na or Li both the type 1 or type 2 thiols react so that both Km and Vmax are reduced. Low Km of Na/Li CT has been previously reported to be a major abnormality in diabetic nephropathy (DN) and can be used to identify diabetic patients who are at high risk for DN. A recent study showed that the type 1 thiol protein controlling the Km of Na/Li CT was a 33-kD protein and the gene for this protein is going to be cloned. OBJECTIVE: The authors sought to identify Na/Li CT kinetic abnormalities in Type 2 diabetes in Thai patients. MATERIAL AND METHOD: Erythrocyte Na/Li CT kinetics and their modulation by thiol proteins were measured in erythrocytes from 22 patients with Type 2 diabetes and 42 normal control subjects. RESULTS: The kinetics of Na/Li CT in untreated erythrocytes were similar Thiol protein alkylation with NEM generally caused both Vmax and Km to fall, but caused Km to rise in erythrocytes of diabetic patients, whose native Km was low. Thus, abnormalities in the regulation of Na/Li CT by key thiol proteins were found in about one-third of subjects with Type 2 diabetes in Thailand. CONCLUSION: Membrane abnormalities may indicate a common pathway of pathological mechanism found in essential hypertension and diabetic nephropathy and may be used as a phenotype for further genetic studies of this transporter.

Improved glycemic control among Thai children and young adults with type 1 diabetes participating in the diabetes camp.

Diabetes Education Program, Faculty of Medicine Siriraj Hospital has provided summer camps for Thai children with type 1 diabetes since 1990. The objective of this study was to evaluate the effectiveness of the diabetes camp in glycemic control. Twenty male and forty-two female patients participated in the 5-day diabetes camp held in Karnchanaburi, Thailand in 2003. The mean age was 14.1 +/- 4.3 years and the mean duration of disease was 4.5 +/- 3.5 years. Fifty out of sixty-two patients returned for a 3-month-postcamp visit. The glycemic control improved significantly. The mean precamp and postcamp HbA1c levels were 10.0 +/- 3.1% and 9.0 +/- 2.6% (p = 0.008) respectively. The diabetes camp is a valuable program for patients to learn diabetes-self management skills, especially in countries where the diabetes education programs are not always available.

Association between estrogen receptor concentration in breast cancer tissue and bone mineral density.

Both bone and the breast are major target tissues of estrogen actions. The biological actions of estrogen depend on the interaction between estrogen and estrogen receptors (ER) in the target tissues. Therefore, ER concentration in tissues such as breast cancer might be associated with the amount of bone mass. The present study was aimed to examine whether there is a relationship between ER concentration in breast cancer tissue (ER-BCA) and bone mineral density (BMD). Forty-seven pre-menopausal and 34 post-menopausal women with newly diagnosed breast cancer were studied. The ER-BCA ranged from 0 to 339 fmol/mg cytosol protein (mean +/- SD = 68.6 +/- 97.0). Pearson's correlation analyses showed that ER-BCA negatively correlated to BMD of the spine (r = -0.251, p = 0.024), forearm (r = -0.341, p = 0.002), hip (r = -0.373, p = 0.001) and total body (r = -0.317, p = 0.004) in all 81 women. In 47 pre-menopausal women, the ER-BCA negatively correlated to the hip (r = -0.455, p = 0.001) and total body (r = -0.395, p = 0.006) but not to the spine and forearm BMD. Whereas, in 34 post-menopausal women, the ER-BCA negatively correlated to forearm BMD (r = -0.399, p = 0.019). Stepwise multiple regression analyses showed that the ER-BCA independently correlated to hip BMD in all 81 women (r = -0.373, p < 0.01) and in pre-menopausal women (r = -0.486, p < 0.001) and independently correlated to forearm BMD in post-menopausal women (r = -0.399, p < 0.05). The results of this study suggest that the presence of high estrogen receptor concentration in breast cancer tissue might induce a deleterious effect on bone mass particularly in pre-menopausal women.

Primary hyperparathyroidism due to parathyriod carcinoma: Report of a case and review of literature.

A 21-year-old male with a history of bone pain for four months is described. He lost 2 cm of his height and also had polyuria and weight loss. Physical examination revealed a cachectic and mildly pale man with a firm mass of 0.8 cm in diameter on the fight side of his neck, generalized muscle wasting and proximal muscle weakness. kyphoscliosis and deformed thoracic cage. Skeletal X-ray showed finding compatible with the changes found in primary hyperparathyroidism. Biochemical parameters revealed a serum corrected total calcium of 15 mg/dl (8.5-10.5 mg/dl), inorganic phosphate of 3.7 mg/dl (305-5.0 mg/dl) and alkaline phosphatase of 1,008 U/l (39-117 U/l). Primary hyperparathyroidism was confirmed by a serum parathyroid hormone level of 1,733 pmol/l (0.100 pmol/l), Ultrasonography and computerized tomography of the neck showed a right neck mass with a diameter of 2 x 2.2 x 3 cm cm which was visualized by 99mTc-sestamibi scan. The patient underwent an uneventful surgical exploration of the neck. Histopathological study of the excised neck mass showed findings consistent with parathyroid carcinoma.

The use of low calorie diet supplement in weight reduction: A preliminry report.

Low calorie diet (LCD) supplement has gained popularity in weight control programs. The efficacy, acceptance and adverse effects of LCD (Modellim 40R, Medicfast) were evaluated during a 12 week weight reduction program in 11 obese volunteers. They were 2 males and 9 females, age 37.4 + 9.4 year old (mean + SD) whose body mass indices (BMI) ranged from 28.8 – 40.7 kg/m2 (mean + SD = 31.44 + 4.84). During the weight reduction period, a diet containing 800 kcal/day was prescribed in every case with a supplement of 1 packet of LCD (40 kcal) before lunch and dinner, and whenever they felt hungry. Regular exercise were also encouraged. At the beginning and at the end of the program, blood specimens were analysed for liver, kidney and thyroid function, electrolytes and other macro minerals. Lipid profiles and complete blood count were also done. All volunteers were interviewed and examined initially and every 2 weeks thereafter by one of the investigators. One female volunteer was withdrawn from the study after the first week because of aversion to LCD. The others tolerated the LCD well. They were consumed 1-3 packets daily (mean + SD 1.44 + 0.7). At the end of twelfth week, the weight loss was 3.1 + 2.9 kg (range -1.4 – 8.1 kg). There was no well-accepted in most of the cases and can be used as a supplement during weight reduction without any serious side effects.