Subclinical thyroid dysfunction, bone mineral density, and osteoporosis in a middle-aged Korean population.

Thyroid dysfunction is associated with the loss of bone density (osteoporosis). However, the connection between subclinical thyroid dysfunction and osteoporosis remains controversial. This study found no apparent association between subclinical hypothyroidism or subclinical hyperthyroidism and bone mineral density (BMD) in the lumbar spine and femur. INTRODUCTION: The present study examined the relationship between subclinical thyroid dysfunction and BMD in healthy middle-aged adults. METHODS: A total of 25,510 healthy Koreans with normal free thyroxine levels were enrolled from January 2011 to December 2016, and 91% of subjects visited only once. The average age of the 15,761 women was 45, and the average age of the 9749 men was 48. Levels of thyroid-stimulating hormone (TSH) and BMD were recorded in all subjects. BMD was measured using dual-energy X-ray absorptiometry. RESULTS: No apparent association was found between subclinical thyroid dysfunction and BMD in the lumbar spine, femur-neck, and proximal femur sites compared with a euthyroid group. Age, body mass index (BMI), and postmenopausal status affected BMD in women, and only BMI affected BMD in men. Subclinical hypothyroidism was independently associated with a lower risk of osteoporosis (odds ratio 0.657, 95% confidence interval 0.464-0.930) in 4710 postmenopausal women. CONCLUSIONS: No apparent association was found between subclinical hypothyroidism or subclinical hyperthyroidism defined on single TSH measurement and BMD at the lumbar spine and femur in a large cohort of middle-aged men and women. Subclinical hypothyroidism was independently associated with a lower risk of osteoporosis in postmenopausal women.

Weight gain within the normal weight range predicts ultrasonographically detected fatty liver in healthy Korean men.

OBJECTIVES: We performed a prospective study to determine whether weight gain predicts future ultrasonographically detected fatty liver (USFL) in a lean adult population. METHODS: Among 15,347 Korean male workers, aged 30-59 years, who participated in a health check-up programme in 2002, a USFL-free cohort of 4246 non-diabetic men was followed until September 2007. Alcohol consumption was assessed by a questionnaire. Weight change for each subject was calculated as the difference between baseline and subsequent measurements. Biochemical tests for liver and metabolic function were done. The primary outcome was ultrasound-diagnosed fatty liver. A standard Cox proportional hazards model and time-dependent Cox model were performed. RESULTS: During 16,829.7 person-years of follow-up, 622 participants developed USFL. After adjusting for age, the period from visit 1 to visit 2, BMI, HDL-C, triglyceride, uric acid, alanine aminotransferase, and HOMA-IR, the risk for USFL increased with increasing quartiles of weight change (p for trend <0.001). This association remained significant when weight change and covariates, except age and the period from visit 1 to visit 2, were modelled as time-dependent variables. Subjects in the fourth quartile (weight gain > or =2.3 kg) were at significantly elevated risk for USFL (adjusted hazard ratio (aHR), 1.26; 95% CI, 1.01 to 1.58). These associations did not change, even in normal weight men with a baseline BMI between 18.5 and 22.9 kg/m(2) (n = 2186). CONCLUSION: Weight gain per se appears to increase the risk for developing USFL. Thus, avoiding weight gain, even among lean adult individuals, can be helpful in preventing this disease.

Evaluation of dual priming oligonucleotide-based multiplex PCR for detection of HBV YMDD mutants.

We evaluated the usefulness of dual priming oligonucleotide (DPO)-based multiplex PCR, Seeplex HBV Lami-DR assay (Seegene Institute of Life Sciences, Seoul, Korea), to detect lamivudine-resistant HBV mutants in a comparison with the use of TRUGENE HBV genotyping and restriction fragment mass polymorphism (RFMP). Sera from 44 chronic hepatitis B patients were analyzed for the presence of mutations at codons 180 and 204 by performing DPO-based multiplex PCR, RFMP, and TRUGENE. The overall concordance rate among the three assays was 40.9% (18/44). Concordance rates between multiplex PCR and RFMP or multiplex PCR and TRUGENE were 61.4% (27/44) and 50.0% (22/44), respectively. In ten patients, multiplex PCR identified additional mutants not found using the other two methods. DPO-based multiplex PCR is a highly sensitive method to identify minor mutant populations and could be a practical tool in the monitoring of lamivudine resistance.

Microbial contamination of multiply used preservative-free artificial tears packed in reclosable containers.

BACKGROUND/AIMS: To evaluate microbial contamination of multiply used preservative-free artificial tears packed in reclosable containers after daily use. METHODS: Subjects were provided with preservative-free artificial tears (Groups 1 and 2) and artificial tears containing a preservative (Group 3). After administration three times or more per 10 h, bottles were collected, and any remaining fluid in the bottles was cultured. A risk factor analysis for microbial contamination was performed by the use of univariate and multivariate analysis. RESULTS: A total of 242 eye-drop bottles were evaluated. Five (2.0%) of the 242 bottles had bacterial contamination. In group 1, four (3.9%) of 102 bottles were contaminated, and identified bacteria were all coagulase-negative Staphylococcus. In group 2, one (1.0%) of 105 bottles was contaminated, and it was a Gram-negative Acinetobacter species. No bottles from group 3 showed any contamination. Based on multivariate analysis, advanced age and fingertip touch were statistically significant risk factors for microbial contamination (p<0.05). CONCLUSION: Preservative-free artificial tears in reclosable containers are at risk of contamination in a daily and multiple use setting, especially in patients with a poor administering technique, which is associated with fingertip touch and advanced age.

Mechanism for acute oral desensitization to antibiotics.

BACKGROUND: Despite the widespread use of an acute oral desensitization procedure in patients with allergic reactions to a variety of antibiotics, the precise mechanism of this procedure is poorly understood. OBJECTIVE: To investigate the mechanisms underlying acute oral desensitization to antibiotics. METHODS: Using a murine model of active systemic anaphylaxis to penicillin V (Pen V), mice previously sensitized to Pen V were desensitized by oral feeding of Pen V. The dose was doubled every 15 min and five feedings were given. The achievement of acute oral desensitization was evaluated by induction of active systemic and active cutaneous anaphylaxis, and by measuring the plasma levels of platelet-activating factor and histamine. Antigen-specific serum IgE antibody (Ab) levels were determined by passive cutaneous anaphylaxis. RESULTS: Mice fed more than 3 mg of cumulative dose of Pen V were completely protected from fatal systemic anaphylactic reaction and the desensitized state lasted approximately 1 h. Antigen-specific mast cell desensitization, but not hapten inhibition, consumption of IgE Abs, or depletion of mast cell mediators, occurred during acute oral desensitization. CONCLUSIONS: Acute oral desensitization to Pen V occurred in the mice, and antigen-specific mast cell desensitization was associated with the underlying mechanism for oral desensitization.

Increased frequencies of glutathione S-transferase (GSTM1 and GSTT1) gene deletions in Korean patients with acquired aplastic anemia.

Patients with reduced ability to metabolize environmental carcinogens or toxins may be at risk of developing aplastic anemia. Glutathione S-transferase (GST) has been implicated in detoxifying mutagenic electrophilic compounds. This study asked whether the homozygous gene deletions of GSTM1 and GSTT1 affect the likelihood of developing aplastic anemia. The incidence of GSTM1 and GSTT1 gene deletions was significantly higher for aplastic anemia patients (odds ratio [OR]: 3.1, P =.01 and OR: 3.1, P =.004, respectively) than for healthy controls. Among the aplastic anemia patients, 17.5% (10:57) had chromosomal abnormalities at the time of diagnosis, and all aplastic anemia patients with chromosomal abnormalities showed GSTT1 gene deletions (P =.048). Individuals with GSTM1 and GSTT1 gene deletions may have greater susceptibility to aplastic anemia. It is possible that genetic instability or chromosomal damage due to abnormal detoxification of environmental toxins might have worked as an important pathophysiologic mechanism of aplastic anemia for patients with GSTT1 gene deletions.

Effect of exogenous arachidonic acid metabolites applied on round window membrane on hearing and their levels in the perilymph.

Our previous studies revealed that treatment with sodium salicylate or indomethacin caused hearing loss, a decrease in prostaglandin (PG) levels, and an increase in leukotriene (LT) levels of the arachidonic acid (AA) cascade in the perilymph. We suspected that decreased PG-levels and/or elevated LT-levels in the inner ear may be responsible for the salicylate ototoxicity. In order to test this hypothesis, effects of exogenous treatments with PGs, PG-analog, LTs, and other lipoxygenase products on hearing and levels of AA metabolites in the perilymph were studied in chinchillas. Cyclooxygenase products, PGI2, 6-keto-PGF1 alpha, Iloprost (PGI2 analog), PGE2, and LTB4, LTC4, and 15-hydroxyeicosatetraenoic acid (15-HETE) in the lipoxygenase products in the dose of 150 ng were applied on the round window membrane (RWM); cochlear function tested by auditory brainstem response (ABR) and samples of perilymph were collected at 0.5, 1, 2, and 4 hours after the application. Samples of perilymph were assayed for all spectra of AA metabolites by high performance liquid chromatography (HPLC) and radioimmunoassay (RIA). PG-treated animals developed minimal or no hearing loss. LT-treated animals exhibited hearing loss of 20 to 40 dB, peaking at one hour after the treatment. Elevated levels of arachidonic acid metabolites were measured in the perilymph of the ears treated with respective AA metabolites, with peak levels at one hour from the application. The findings of this study indicate that hearing loss can be induced by altered levels of PGs or LTs in the perilymph. This is another strong evidence that salicylate induced ototoxicity can be mediated by abnormal arachidonic acid metabolism in the inner ear.

Effect of round window membrane application of salicylate and indomethacin on hearing and levels of arachidonic acid metabolites in perilymph.

Our previous studies revealed that systemic salicylate-induced ototoxicity is associated with altered levels of arachidonic acid metabolites (AAMs) in the perilymph. In order to eliminate the possibility of systemic toxic effects of salicylate when it is given parenterally, an animal model of salicylate-induced ototoxicity was developed by applying it on the round window membrane (RWM). Using chinchillas as experimental animals, sodium salicylate (150 micrograms) or another nonsteroidal anti-inflammatory drug (NSAID), indomethacin (20 micrograms) was applied on the RWM, cochlear function was determined by auditory brainstem response (ABR) and perilymph assayed for AAMs both prostaglandins (PGs) and leukotrienes (LTs) by high performance liquid chromatography (HPLC) and radioimmunoassay (RIA) at different time intervals. When salicylate or indomethacin was applied on the RWM, dose-dependent ABR threshold losses of 20 to 50 dB was observed in 1 to 2 hours associated with decreased concentrations of 6-keto-PGF1 alpha and elevated levels of LTs. The hearing loss recovered to normal threshold over a period of 8 hours. The control group showed no hearing loss or any change in PG or LT-levels in the prilymph. The results of this study suggest that the method of inducing ototoxicity by applying salicylate or indomethacin on the RWM seems to be a reliable method for avoiding systemic toxicity of the parenteral treatment method and that ototoxicity induced by salicylate or indomethacin may be mediated by decreased PGs and elevated LTs.