Biomedical subjects

R Rajatanavin

Publications and source records attributed to R Rajatanavin.

At least 37 records · Page 2Linked to original sources

PubMed2000

Risk of calcium oxalate nephrolithiasis after calcium or combined calcium and calcitriol supplementation in postmenopausal women.

Although calcium supplementation can cause hypercalciuria, the risk of nephrolithiasis has been shown to decrease rather than increase among subjects who had a higher calcium intake. Hypercalciuria is also a well-established side effect of calcitriol administration. However, the risk of nephrolithiasis is not well defined. The present study was undertaken to prospectively determine the effect of calcium with or without calcitriol on physicochemical risk factors associated with calcium oxalate nephrolithiasis in Thai postmenopausal women with osteoporosis. Subjects consisted of 53 Thai women more than 10 years postmenopausal who were randomly allocated to receive 750 mg of calcium carbonate supplement alone (n = 28) or 750 mg of calcium carbonate plus 0.5 microg calcitriol (n = 25) daily. Mean +/- SEM for age was 65.3+/-1.1 years, body weight 53.5+/-1.3 kg. Urine samples for biochemical assays were collected at baseline and 3 months after treatment. Supersaturation for calcium oxalate stone formation was assessed from the 24 h urine constituents by the Tiselius's index, AP(CaOx). Three months of calcium supplement alone resulted in a modest, but not significant, increase in urinary calcium (baseline, 2.90+/-0.43 mmol/day; after treatment 3.58+/-0.54 mmol/day) with no change in urinary oxalate, citrate or magnesium. In contrast, calcium together with calcitriol caused a significant increase in urinary calcium (baseline, 2.87+/-0.41 mmol/day; after treatment, 4.08+/-0.57 mmol/day; p < 0.05). No significant change in other urine constituents after treatment with calcium and calcitriol was detected. Therefore, AP(CaOx) did not significantly increase either after calcium alone (baseline, 1.17+/-0.39; after treatment, 1.36+/-0.28) or after calcium plus calcitriol (baseline, 1.09+/-0.17; after treatment, 1.09+/-0.19). However, after treatments, 12 subjects (23%)--6 receiving calcium supplement alone and 6 receiving calcium plus calcitriol supplement--had high AP(CaOx) values (greater than the upper limit of 95% Cl for AP(CaOx) derived from non-stone-forming Thai women). The post-treatment/baseline ratio was 3.21+/-0.74 for urinary calcium, 1.01+/-0.19 for urinary oxalate, and 2.23+/-0.42 (median 1.15) for AP(CaOx). The post-treatment/baseline ratio of calcium, but not for urinary oxalate, had a significant correlation with the post-treatment/baseline ratio of AP(CaOx). Our findings suggest that the alteration in the risk of calcium oxalate nephrolithiasis based on urinary composition is related to the alteration in urinary calcium. The risk of calcium oxalate nephrolithiasis does not increase significantly after calcium or combined calcium and calcitriol supplement in the majority of postmenopausal women with osteoporosis.

Aged↗

PubMed2000

Oestrogen-receptor-alpha gene polymorphism affects response in bone mineral density to oestrogen in post-menopausal women.

OBJECTIVE: An oestrogen-receptor-alpha (ERalpha) gene polymorphism has been variably reported to be related to bone mass. To investigate whether this ERalpha gene polymorphism is associated with a functional difference, we assessed the response in bone mineral density (BMD) to oestrogen therapy in post-menopausal women in relation to ERalpha gene polymorphism. PATIENTS AND MEASUREMENTS: Subjects consisted of 124 Thai post-menopausal women. Sixty-three of the women were less than 6 years post-menopausal and 61 were more than 10 years post-menopausal with vertebral or femoral osteoporosis as defined by BMD T-score less than - 2.5. Subjects were randomly allocated to receive 0.3 mg (n = 67) or 0.625 mg (n = 57) of conjugated equine oestrogen (CEE). All subjects also took 5 mg medroxyprogesterone acetate. Vertebral and femoral neck BMD were measured at baseline and 1 year after treatment. Data were expressed as mean +/- SEM. Capital P represents the absence of the restriction site while lower-case p indicates the presence of the restriction site. RESULTS: For subjects on 0.625 mg CEE, BMD at L2-4 increased significantly after 1 year in those with pp (n = 20) Pp (n = 29) and PP genotypes (n = 8) (P < 0.001). However, in subjects on 0.3 mg CEE, BMD at L2-4 increased significantly after 1 year in subjects with Pp (n = 34, + 7.6 +/- 1.5%, P < 0.001) and PP genotypes (n = 13, + 6. 9 +/- 1.0%, P < 0.001), but not in those with pp genotype (n = 20, + 2.3 +/- 2.1%, P = NS). After adjusting for age and years since menopause, the change in vertebral BMD was still lower in those without the P allele compared to those with the P allele (P < 0.05). Femoral BMD did not significantly change regardless of dose of CEE and genotype. CONCLUSIONS: We conclude that ERalpha gene polymorphism affects skeletal response to oestrogen in post-menopausal women. The effect of ERalpha gene polymorphism appears to be site-specific and does not relate to biochemical markers of bone turnover. Determination of ERalpha genotype may help identify post-menopausal women who will have more skeletal benefit from oestrogen therapy.

Bone Density↗

PubMed2000

Bone mineral density in primary and secondary amenorrhea.

UNLABELLED: Amenorrhea in young women is one of the best clinical indicators for estrogen deficiency, except in the presence of gynecological structural pathology. This study aimed at investigating bone mineral density (BMD) in patients with primary and secondary amenorrhea. Thirty-six patients were enrolled in the study, seven with primary amenorrhea (mean age 24.3 +/- 4.5 yrs.) and twenty-nine with secondary amenorrhea (mean age 31.1 +/- 6.9 yrs.). Eighteen regularly menstruating women (mean age 31.8 +/- 3.7 yrs.) served as controls. BMD was measured at lumbar spine, femoral neck, Ward's triangle and trochanter. RESULTS: BMD was significantly decreased in both primary and secondary hypoestrogen amenorrheic patients. Primary amenorrheic patients were more severely affected with a BMD mean Z score below 80 per cent (osteopenia) at all sites measured. The age of primary amenorrheic women also strongly correlated with degree of demineralization. This should emphasize the importance of early diagnosis and treatment of young amenorrheic patients.

Absorptiometry, Photon↗

PubMed2000

Correlation between serum insulin and features of metabolic syndrome in Thais.

Several clinical and metabolic abnormalities, i.e. central obesity, hypertension, impaired glucose tolerance or diabetes and dyslipidemia often cluster together and are commonly found in patients with atherosclerotic cardiovascular disease. Hyperinsulinemia and insulin resistance are often evident in subjects with these metabolic abnormalities, so called insulin resistance or metabolic syndrome. In the present study, we looked into the correlations between serum insulin or index of insulin sensitivity and various clinical and metabolic abnormalities. Subjects consisted of 103 males and 118 females. Oral glucose tolerance test was performed on all subjects. Homeostasis model assessment of insulin sensitivity (HOMA-S) was used to determine insulin sensitivity. In males, HOMA-S was found to be significantly correlated with BMI, plasma glucose, insulin, triglycerides and waist circumference. Male subjects in the highest quartile of HOMA-S also had significantly higher systolic blood pressure compared to those in the lowest quartile. In females, HOMA-S was significantly correlated with BMI, blood pressure, plasma glucose, insulin, triglycerides, HDL-cholesterol, waist circumferences and waist-hip ratio. However, after adjustment for BMI, correlation between HOMA-S and blood pressure in women was no longer statistically significant. We, therefore, concluded that correlations between serum insulin or index of insulin sensitivity with certain metabolic abnormalities also existed in Thai subjects. Some of these correlations seem to be at least in part dependent on obesity.

Adult↗

PubMed2000

Correlation of apolipoprotein E gene polymorphism to serum lipid concentrations in healthy Thais.

This study determined the genotype distribution of apolipoprotein E (apo E) gene and its relation to serum lipids in 217 healthy Thais consisting of 79 males and 138 females. Serum total cholesterol (TC), HDL-cholesterol (HDL-C) and triglyceride (TG) concentrations were determined by enzymatic-colorimetric methods, while serum LDL-cholesterol (LDL-C) levels were calculated using Friedewald formula. Apo E genotypes were determined by PCR-RFLP. Out of 217 subjects, apo E genotype frequencies were 5.5 per cent for E2/E2, 12.4 per cent for E2/E3, 81.1 per cent for E3/E3 and 0.9 per cent for E4/E4. In men, advancing age was associated with increased serum TC (r = 0.28, P < 0.05) and LDL-C (r = 0.27, P < 0.01). Subjects having the E2 allele had lower TC (r = -0.27, P < 0.05) and LDL-C. (r = -0.25, P < 0.05). Age and apo E genotypes were not associated with HDL-C and TG in men. In women, increasing age was related to higher serum TC (r = 0.45, P < 0.001), LDL-C (r = 0.44, P < 0.001), TG (r = 0.40, P < 0.001) and lower HDL-C (r = -0.36, P < 0.001). The presence of E2 allele was related to lower TC (r = -0.24, P < 0.001), LDL-C (r = -0.26, P < 0.001), TG (r = -0.15, P < 0.05) and higher HDL-C (r = 0.20, P < 0.01) independent of age and menopausal status. We concluded that the epsilon 4 allele of apo E gene is rare in Thais. The presence of the epsilon 2 allele is associated with a more favorable lipid profile and there is a sexual dimorphism concerning the effect of apo E genotype on serum HDL-C and TG.

Adult↗

PubMed2000

Diabetes mellitus in young Thai adults.

The purposes of the present study were to 1) find the prevalence of various types of diabetes; 2) determine the prevalence of glutamate decarboxylase autoantibody (anti-GAD) and 3) identify clinical characteristics which may help in predicting insulin deficiency in young Thai adults with diabetes. Subjects consisted of 93 adults with diabetes mellitus aged 15-40 years. In each subject, basal and post glucagon C-peptide levels were determined by radioimmunoassay. Anti-GAD was measured by radioimmunoassay and mitochondrial 3243 tRNA(Leu(UUR)) gene mutation was detected by PCR-RFLP. Data were expressed as mean +/- SEM. The mean age of subjects was 31.0 +/- 0.7 years with age at diagnosis of 25.6 +/- 0.9 years. Thirty nine (41.9%) were males and 54 (58.1%) were females. Pancreatic calcification was found in 7 (7.5%) of the patients while 2 (2.2%) were identified as having Wolfram syndrome. Four (4.3%) had nonketotic diabetes with affected family members in multiple generations consistent with MODY. Mitochondrial 3234 tRNA(Leu(UUR)) gene mutation was detected in only one patient. After excluding 14 subjects with pancreatic calcification, Wolfram's syndrome, MODY or mitochondrial gene mutation, 45 (57.0%) were found to be insulin-deficient and 34 (43.0%) were insulin-sufficient based on post-glucagon C-peptide levels. Using stepwise logistic regression analysis, it was found that younger age at diagnosis (p<0.001), smaller waist circumference (p<0.01), previous history of DKA (p<0.01) was significantly associated with insulin deficiency. After excluding patients with DKA, younger age at diagnosis of diabetes (p<0.05) and lower BMI (p<0.01) were related to insulin deficiency. Concerning the role of autoimmunity, it was found that 13 (28.3%) of insulin-deficient subjects were positive for anti-GAD while 4 (11.8%) of those who were insulin-sufficient had positive results. Of the 54 patients currently on insulin, 42 (77.8%) are insulin deficient and 14 (25.9%) have positive anti-GAD. There were 10 (18.5%) who were both insulin sufficient and negative for anti-GAD suggesting that insulin therapy may not be required. We concluded that about half of young Thai adults with diabetes are not insulin-deficient and treatment with insulin may be unnecessary. The prevalence of glutamate decarboxylase antibody and mitochondrial 3234 tRNA(Leu(UUR)) gene mutation is low and as yet undefined factors are accountable for insulin deficiency in a significant number of patients.

Adolescent↗

PubMed1999

Relation of beta3-adrenergic receptor gene mutation to total body fat but not percent body fat and insulin levels in Thais.

A Trp64Arg mutation in the beta3-adrenergic receptor gene has been implicated in the pathophysiology of non-insulin-dependent diabetes mellitus and obesity. However, the findings have been controversial due to the use of different populations and different methods for the estimation of body fat. In the present study, the prevalence of Trp64Arg mutation of the beta3-adrenergic receptor gene was determined and its relation to body fat as assessed by dual-energy x-ray absorptiometry (DEXA) was evaluated in Thai men and women. The effect on insulin sensitivity as assessed by the serum insulin to glucose ratio was also examined. The subjects were 76 men and 135 women aged 20 to 80 years. Body fat and its regional distribution were assessed by DEXA. Mutation in the beta3-adrenergic receptor gene was determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Data are expressed as the mean +/- SEM. Fifty-nine subjects (28.0%) had the Trp64Arg mutation in the beta3-adrenergic receptor gene; 54 (25.6%) were heterozygotes and five (2.4%) were homozygotes. The gene frequency of Trp64Arg mutation was 15.2% in these subjects. In women, Trp64Arg mutation was not associated with the difference in total body fat (Trp/Arg or Arg/Arg, 19.4 +/- 1.0 kg; Trp/Trp, 19.2 +/- 0.6 kg) or percent body fat (Trp/Arg or Arg/Arg, 34.6% +/- 1.2%; Trp/Trp, 34.3% +/- 0.6%). In contrast to the findings in women, men with Trp64Arg mutation had lower total body fat after controlling for age (Trp/Arg or Arg/Arg, 13.2 +/- 1.1 kg; Trp/Trp, 15.8 +/- 0.7 kg; P < .05). However, no difference was found in percent body fat (Trp/Arg or Arg/Arg, 20.9% +/- 1.3%; Trp/Trp, 23.3% +/- 0.7%). No difference in the fasting insulin resistance index (FIRI) was found between subjects with and without Trp64Arg mutation. The data suggest that Trp64Arg mutation of the beta3-adrenergic receptor is common in Thais and appears to exert effects on total body fat but not percent body fat in men. Trp64Arg mutation is not associated with insulin resistance as assessed by the FIRI in Thais.

Adipose Tissue↗

PubMed1999

A T2S cross-reactive material (compound W) in hyperthyroid patients with trophoblastic disease.

In a previous study we observed increased serum levels of a 3,3'-diiodothyronine sulfate (T2S)-like material (compound W) in women who received human chorionic gonadotropin (hCG) treatment. In the present study we assessed serum compound W values in 113 women (total serum sample: 190) with trophoblastic disease, in 7 normal nonpregnant women during the menstrual cycle and 7 women given hCG treatment in the course of in vitro fertilization. Fifty-three women with trophoblastic disease had serum free thyroxine (FT4) concentrations greater than 3.0 ng/dL with suppressed serum thyrotropin (TSH) levels; 61 had FT4 values less than 3.0 ng/dL with a mean TSH of 0.83 mU/L. Mean (+/- SE) compound W concentrations in the high FT4 group were significantly higher than in the low FT4 group (76 +/- 8.1 vs. 21 +/- 1.7 ng T2S equivalent, p < 0.001) There were significant correlations between serum hCG and compound W concentrations (r = 0.472, p < 0.001), serum FT4 and hCG (r = 0.503, p < 0.0001) and serum FT4 and compound W (r = 0.585, p < 0.0001). In nonpregnant women serum compound W levels increased from 7.5 +/- 8 ng/dL at the end of the menstrual period to 15 +/- 1.7 ng/dL 21 days after the last menstrual period. Finally, a single dose of hCG (10,000 USP units, intramuscularly) increased mean (+/- SE) serum compound W levels from 12.8 +/- 2.3 to 64 +/- 9.7 ng/dL and 54 +/- 12 ng/dL at 9 and 16 days, respectively. These results indicate that hCG and perhaps luteinizing hormone (LH) increase serum compound W concentrations in women. The mechanism and significance presently are unclear.

Adolescent↗

PubMed1999

A de novo L330S point mutation in thyroid hormone receptor beta gene in a Thai female with resistance to thyroid hormone.

In the present study, we report a Thai female with a de novo mutation in thyroid hormone receptor-beta (TRbeta) gene causing resistance to thyroid hormone (RTH). The patient was a 19 year-old woman who presented with goiter for 1 year. Except for tachycardia she had no signs of thyrotoxicosis. Previously she was treated with propylthiouracil based on the diagnosis of thyrotoxicosis for 9 months and her goiter became more enlarged. The patient was the only child of the family. Her parents were alive and healthy, and did not have goiter or any other thyroid diseases. Physical examination revealed no sign of thyrotoxicosis. Her thyroid gland was diffusely enlarged with an estimated weight of 100 gm. Laboratory determinations revealed elevated free T4, T3 and nonsuppressed TSH levels. Exon 9 of the TRbeta gene was amplified by PCR and the DNA sequence was determined by dye terminator cycle sequencing. Heterozygous point mutation in which T was replaced by C was detected at position 1274 (TTG to TCG) corresponding to a leucine to serine substitution at codon 330. No mutation was found in the parents indicating that the mutation was de novo. The nucleotide change created a restriction site for Taq 1 restriction endonuclease and the mutation was confirmed by restriction fragments length polymorphism. The same nucleotide change has been reported in a family with RTH.

Adult↗

PubMed1999

Serum leptin concentrations in relation to body fat, gender, sex hormones and metabolic covariates in Thais.

In the present study, the relation of serum leptin to adiposity, gender and metabolic covariates in normal Thais was examined. Subjects consisted of 224 individuals aged between 20-79 years. Eighty two were men while 142 were women. Data were expressed as mean +/- SEM. Serum leptin was associated with total body fat assessed by dual-energy X-ray absorptiometry in both men (r = 0.80, P < 0.0001) and women (r = 0.73, P < 0.0001). Compared to women, serum leptin concentrations was lower in men (P < 0.0001). The difference still persisted after controlling the adiposity. Compared to premenopausal women, postmenopausal women had higher serum leptin independent of adiposity (P < 0.0001). In men, serum free testosterone was negatively associated with serum leptin (r = -0.36, P < 0.001) while there was no association between serum estradiol and leptin. The relation between serum FT and leptin in men no longer persisted after controlling for adiposity. Body fat was associated with fasting insulin levels in both men (r = 0.26, P < 0.05) and women (r = 0.18, P < 0.05). However, the association between fasting insulin levels and body fat in both men and women no longer existed after adjusting for leptin. We concluded that serum leptin concentrations are associated with total body adiposity and serum leptin may mediate the effect of body fat on insulin sensitivity. There appears to be a sexual dimorphism of serum leptin unrelated to sex hormone status and the amount of body fat.

Adipose Tissue↗

PubMed1999

Thyroid function in healthy Thai neonates.

OBJECTIVES: To construct a normative data for serum thyroxine (T4), free T4 (FT4), triiodothyronine (T3) and thyrotropin (TSH) in Thai neonates. STUDY DESIGN: A cross-sectional study of 275 healthy full-term neonates was conducted. Blood samples were obtained from umbilical cords of the neonates and from heel pads of infants aged 1-30 days. Hormone measurements included serum T4, FT4, T3 and TSH. RESULTS: Mean serum T4 and FT4 levels rapidly increased after delivery to the maximum level at 1-3 days of age. Thereafter, they declined to a steady state level within 2-4 weeks. Mean serum T3 level was very low at birth. The concentration increased 3-5 times and reached a steady state levels within 1 week. In contrast, mean serum TSH declined from birth and the level at 1-3 days of age was slightly less than that of the cord blood. It changed little after 3 days of age. Previous studies have shown a transient TSH surge in the first 24-48 hour of life. TSH surge was not apparent in our study because samples were not obtained from infants < 24 hours old. Therefore, if TSH is measured for screening of congenital hypothyroidism, samples should be obtained from umbilical cord or infants aged > 48 hours. CONCLUSIONS: This study provides the normative data for thyroid function tests in Thai full-term neonates. These data are useful for detection and verification of hypothyroidism in a screening program for congenital hypothyroidism.

Cross-Sectional Studies↗

PubMed1999

Five-year thyrotropin screening for congenital hypothyroidism in Ramathibodi Hospital.

OBJECTIVES: To detect newborns with congenital hypothyroidism (CH) and to treat the affected infants as early as possible. STUDY DESIGN: Cord blood thyrotropin (TSH) screening for CH in Ramathibodi Hospital began in 1993. From October 1993 to December 1998, 35,390 neonates were screened. The infants with elevated TSH level of greater than 30 mU/L were recalled for verification of CH. Confirmation tests included total thyroxine, free thyroxine and TSH level. Thyroid scan and uptake were performed in some affected infants. RESULTS: Twelve infants with CH were detected resulting in an incidence of one in 2,949 live-births. All affected infants were asymptomatic at birth. Of 12 infants with CH, one premature neonate had a delayed TSH elevation and was diagnosed as having primary hypothyroidism at 2 months of age. The recall rate for validation of CH based on a cut-off value at serum TSH level of greater than 30 mU/L is 1.1 per cent. If the cut-off value of serum TSH level was raised to greater than 40 mU/L, the recall rate would decrease to 0.43 per cent. None of the affected infants had cord blood TSH level of less than 50 mU/L except one premature patient. Therefore, beginning in January 1997, the cut-off value of TSH was raised to 40 mU/L or greater. Pitfalls in this program include incomplete blood-specimen collection and incomplete follow-up. To strengthen the program, improvements were made in the follow-up system from 1996 onward. Therefore, the coverage for blood-specimen collection progressively increased from 84 per cent in 1994 to 96 per cent in 1998. Simultaneously, the patients' return after recalls also increased from 38 per cent to 100 per cent. CONCLUSIONS: The incidence of CH in Ramathibodi Hospital is approximately 1:3,000 live-births. The optimal cord blood TSH level for recall is 40 mU/L or greater. The intensification of follow-up strategy resulted in better response to recall and earlier treatment in the affected infants.

Congenital Hypothyroidism↗

PubMed1998

Change in body weight after hormone replacement therapy in postmenopausal women is dependent on basal circulating leptin.

OBJECTIVE: To address the effect of leptin in the modulation of change in body weight after hormone replacement therapy (HRT), we prospectively examined the responses of body weight and serum leptin after estrogen-progestin replacement in postmenopausal women. PATIENTS: Subjects consisted of 63 postmenopausal women aged 54-82 years on HRT for osteoporosis. DESIGN: Thirty three of the subjects received 0.3 mg of conjugated equine estrogen (CEE) (group 1) while 30 were on 0.625 mg of CEE daily (group 2). All subjects also took 5 mg of medrogestone acetate and 750 mg elemental calcium supplement daily. MEASUREMENTS: Fasting serum leptin was measured by RIA at baseline, 1 and 3 months after treatment. Data were expressed as mean +/- S.E.M. RESULTS: Serum leptin was highly related to body weight both at baseline (r = 0.40, P < 0.001) and after 3 months of HRT (r = 0.42, P < 0.001). When divided the subjects into three equal groups according to baseline leptin levels, it was found that serum leptin significantly decreased in subjects with high baseline leptin at 3 months (-9.4 +/- 5.7%, P < 0.05) while it increased in subjects whose baseline leptin levels were in the lowest tertile at 1 month (33.2 +/- 8.3%, P < 0.001) and 3 month (27.8 +/- 8.3%, P < 0.01). In regards to body weight, those with leptin in the highest tertile demonstrated a reduction of body weight at 3 (-1.9 +/- 0.6%, P < 0.05) and 12 months (-3.2 +/- 0.5%, P < 0.05) after HRT while those whose serum leptin levels were in the lowest and middle tertiles did not demonstrate change in body weight. By repeated measured analysis of variance, it was found that the decrease in body weight in subjects with high serum leptin was independent of the doses of estrogen. CONCLUSION: Postmenopausal hormone replacement does not cause weight gain. However, it results in a small reduction in body weight particularly in subjects with higher basal leptin concentrations.

Aged↗

PubMed1998

Estrogen receptor gene polymorphism is associated with bone mineral density in premenopausal women but not in postmenopausal women.

In the present study, we examined the genotypes distribution of Pvu II estrogen receptor (ER) gene polymorphism and its association to bone mass in Thai females. Subjects consisted of 134 Thai females 54 of whom were premenopausal and 80 were postmenopausal. Pvu II ER gene polymorphism was determined by PCR-RFLP. Capital P represents the absence of the restriction site while small p indicates the presence of the restriction site. Forty nine (36.6%) of the subjects had pp genotype, while 59 (44.0%) had Pp genotype and 26 (19.4%) had PP genotype. There was no significant difference in age, body weight, height and calcium intake in premenopausal women with different genotypes. The results including years since menopause were similar in postmenopausal women. When including ER gene genotypes, age, body weight, height and dietary calcium intake in a stepwise multiple regression model, it was found that besides body weight ER gene polymorphism was associated with bone mineral density (BMD) at AP spine (p < 0.05), lateral spine (p < 0.05) femoral neck (p < 0.05) and femoral trochanter (p < 0.05) with the pp genotype having the least BMD. ER gene polymorphism was the only factor associated with BMD at Ward's triangle, (p < 0.05) while only body weight was associated with BMD at distal and mid radius. There was no difference in serum intact osteocalcin (OC) concentrations among subjects with different genotypes. ER gene polymorphism was not related to BMD in postmenopausal women at any skeletal site. Similarly, serum intact OC levels were not different among postmenopausal women with different genotypes. We concluded that Pvu II estrogen receptor gene polymorphism is associated with bone mineral density in premenopausal women but not in postmenopausal women. Estrogen receptor gene polymorphism may have a modulatory role in calcium and bone metabolism during adolescence and young adulthood.

Adult↗

PubMed1998

Suppression of bone resorption in early postmenopausal women by intranasal salmon calcitonin in relation to dosage and basal bone turnover.

In the present study, we assessed the ability of increasing doses of intranasal calcitonin to suppress urinary deoxypyridinoline cross-link (DPD), a specific biochemical marker of bone resorption, in early postmenopausal women. Subjects consisted of 30 healthy Thai women within 5 years of postmenopause, randomly assigned to 50, 100, or 200 IU of intranasal calcitonin 5 days/week for 3 months. Calcium supplementation by calcium carbonate capsules at 750 mg of elemental calcium per day was given to all subjects. Twenty four-hour urine for DPD and creatinine assays was collected at baseline, 1 month, and 3 months after treatment. All DPD values were corrected with urinary creatinine before analyses. Data were expressed as mean +/- SEM. DPD decreased significantly 1 month after intranasal calcitonin treatment (P < 0.01). However, at 3 months, DPD increased when compared with the values at 1 month (P < 0.01), suggesting that there may be a reduction in the suppression of bone resorption after prolonged calcitonin therapy. Using a stepwise multiple regression model to address whether dosage and DPD at baseline influence the response to intranasal calcitonin, it was found that DPD suppression after intranasal calcitonin was not related to dosage but was strongly associated with baseline DPD (P < 0.0001). Suppression of bone resorption in early postmenopausal women by intranasal calcitonin is determined more by the state of bone turnover at baseline than the dosage of calcitonin.

Administration, Intranasal↗

PubMed1998

The effects of oestrogen exposure on bone mass in male to female transsexuals.

OBJECTIVE: The importance of oestrogen on bone mineral density (BMD) in males was suggested by reports of patients with oestrogen resistance and aromatase deficiency who demonstrated osteoporosis and epiphyseal plate maturation defect despite high testosterone levels. In the present study, we examined the effects of oestrogen exposure on BMD in transsexual men. DESIGN: Cross-sectional study of BMD in male to female transsexuals. PATIENTS: Subjects consisted of two groups of transsexual male dancers aged 16-34 years who did not receive transsexual operations (n = 28). Group 1 (n = 11) and group 2 (n = 17) had used oestrogen for 2 years or less and more than 2 years, respectively. Twenty-four healthy adult males served as controls. RESULTS: Signs of feminization were presented in both group 1 and group 2, with Tanner's stage II-III breast development. BMD at various sites were correlated only to body weight and not to smoking or milk consumption. After controlling for body weight, it was found that group 2 had significantly higher BMD at L2-4 than controls (1.22 +/- 0.03 vs. 1.14 +/- 0.03 g/cm2, P < 0.05) and group 1 (1.22 +/- 0.03 vs. 1.08 +/- 0.04 g/cm2, P < 0.05). BMD at femoral neck was also higher in group 2 compared to controls (1.10 +/- 0.03 vs. 1.01 +/- 0.03 g/cm2, P < 0.05) and group 1 (1.10 +/- 0.03 vs. 0.95 +/- 0.04 g/cm2, P < 0.05). Group 1 subjects had lower BMD compared to controls at femoral trochanter (0.70 +/- 0.04 vs. 0.83 +/- 0.03 g/cm2, P < 0.05) and total femur (0.96 +/- 0.05 vs. 1.07 +/- 0.03 g/cm2, P < 0.05). CONCLUSIONS: Long-term oestrogen exposure transsexual men result in an increase in bone mineral density despite signs of feminization. This suggests that oestrogen has positive effects on bone density in males. The finding of the trend towards reduced bone density in group 1 remains unexplained.

Adolescent↗

PubMed1998

Serum oestradiol and oestrogen-receptor gene polymorphism are associated with bone mineral density independently of serum testosterone in normal males.

OBJECTIVES: The physiological effects of oestrogens on bone in men were largely unanticipated until recently, when oestrogen deficiency in males with aromatase deficiency and oestrogen resistance was found to cause osteoporosis and delayed fusion of epiphyses despite sufficient serum testosterone. This raises the possibility that in normal men oestrogens rather than androgens are of physiological importance in bone maturation. In the present study, we examined the association of serum oestradiol (E2) compared to that of free testosterone (FT) with bone mineral density (BMD) in normal men. The effect of oestrogen receptor (ER) gene polymorphism on BMD in men was also addressed. SUBJECTS: Eighty-one Thai men aged 20-79 years. All were healthy and did not take medication which may affect calcium and bone metabolism. BMD was assessed by DEXA. Dietary calcium was assessed by a 3-day dietary record. Serum E2 and FT concentrations were measured by radioimmunoassay. Polymorphism at intron 1 of the alpha isoform of ER gene was determined by PCR-RFLP. Small p represents the presence of the restriction site while capital P indicates the absence of the restriction site. RESULTS: Serum FT decreased with increasing age (r = -0.58, P < 0.0001) while E2 did not. However, there was a positive association between E2 and FT (r = 0.28, P < 0.05). Serum FT was related to BMD at femoral neck (r = 0.26, P < 0.05) and Ward's triangle (r = 0.30, P < 0.01) while E2 was related to BMD at anteroposterior (AP) lumbar spine (r = 0.29, P < 0.05), femoral neck (r = 0.23, P < 0.05) and femoral trochanter (r = 0.27, P < 0.05). Besides FT and E2, age, body weight, fat mass and fat-free mass were also correlated to BMD at various skeletal sites. Using stepwise multiple linear regression to control for the confounding effects among these factors, fat-free mass was found to be strongly associated with BMD at most skeletal sites. Serum E2 was related to BMD independently of other factors including FT at AP lumbar spine (r = 0.22, P < 0.05), femoral neck (r = 0.26, P < 0.01), femoral trochanter (r = 0.22, P < 0.05) and Ward's triangle (r = 0.26, P < 0.01) while serum FT was not associated with BMD at any site after controlling for E2 and other related factors. Concerning ER alpha gene polymorphism, 27 (33.3%) of the subjects had pp genotype, while 42 (51.9%) and 12 (14.8%) Pp and PP genotypes, respectively. After controlling for age, body weight, fat mass, fat-free mass, calcium intake, FT and E2, the presence of P allele was associated with higher BMD at AP L2-L4 (P < 0.05). CONCLUSIONS: Serum oestradiol is more related to bone mass than free testosterone in normal men. Oestrogen-receptor gene polymorphism is also associated with bone mass in men independently of oestradiol levels. Serum oestradiol together with oestrogen-receptor genotype may partly determine bone mass in males.

Adult↗

PubMed1998

Impediment of the progressions of microalbuminuria and hyperlipidemia in normotensive type 2 diabetes by low-dose ramipril.

In a randomized, double-blind, placebo-controlled study, we investigated in normotensive type 2 diabetics with microalbuminuria the effect of ramipril, an ACE inhibitor, on urine albumin excretion and serum lipids. A total of 1,882 patients were screened for urine microalbumin consecutively by dipstick test, Rapi Tex-Albumin test and RIA. The final 28 normotensive and microalbuminuric patients were assigned to receive either ramipril (1.25 mg/d, n = 16) or placebo (n = 12) for 12 weeks. Throughout the study, both groups had no changes in blood pressure, fasting plasma glucose, HbA1C, serum creatinine and electrolytes and no difference in creatinine clearance. At week 12 only the placebo group showed the significant increment of urine albumin excretion and triacylglycerol (30.6 +/- 38.3 to 39.0 +/- 19.7 and 167 +/- 64 to 208 +/- 77 mg/dl, respectively) but the decrement of HDL-cholesterol (46 +/- 16 to 35 +/- 6 mg/dl). During a 3 month period, increased urine albumin excretion was observed in normotensive type 2 diabetes with microalbuminuria who received only placebo. We conclude that ramipril may arrest the progression of albumin excretion and had favorable effects on serum lipids. Ramipril was safe and well-tolerated without untoward side effects during the study period.

Albuminuria↗