Hepatic Sarcoidosis: Diagnostic approach and management.

Sarcoidosis is a multi-systemic, non-caseating granulomatous disorder with an idiopathic aetiology. We report a 58-year-old Malay woman, with underlying type II diabetes mellitus, hypertension and history of stage II pulmonary sarcoidosis presenting with incidental finding of multiple hypodense liver lesions. Her recent contrasted enhanced computed tomography of the abdomen and pelvis demonstrated multiple intra-abdominal lymphadenopathies with evidence of liver and splenic infiltrations. Her ageappropriate malignancy screening was negative while liver biopsy showed non-caseating granulomatous hepatitis consistent with hepatic sarcoidosis. In view of her normal liver enzymes and normalised serum calcium levels, no immunosuppressive therapy was commenced. She remains asymptomatic and is currently under our close monitoring.

Evaluation of saliva and plasma cytokine biomarkers in patients with oral squamous cell carcinoma.

The aim of this study was to investigate potential biomarkers in human saliva and plasma to aid in the early diagnosis of oral squamous cell carcinoma (OSCC). Saliva and plasma samples obtained from OSCC patients (n=41) and non-oral cancer patients (n=24) were analyzed by Luminex Bead-based Multiplex Assay. Data were analyzed using the non-parametric Mann-Whitney U-test, Kruskal-Wallis test, and receiver operating characteristics curve (ROC) to evaluate the predictive power of 14 biomarkers individually for OSCC diagnosis. The plasma level of IP-10 in early OSCC differed significantly from that in controls. Among the salivary biomarkers, IL-1ß, IL-6, IL-8, MIP-1ß, eotaxin and IFN-γ and TNF-α showed significant differences between OSCC patients and controls. With respect to carcinogenesis, significant differences in plasma levels of eotaxin, G-CSF, and IL-6 were found between OSCC stages III/IV and OSCC stages I/II. The area under the curve (AUC) for OSCC vs. control was greater than 0.7 for plasma IP-10 and saliva IL-1ß, IL-6, IL-8, and TNF-α. The study findings indicate that salivary biomarkers may serve a useful role as a complementary adjunct for the early detection of oral OSCC. With regard to the evaluation of tumour progression, plasma eotaxin, G-CSF, and IL-6 may help in the detection of advanced OSCC. However, the correlation between saliva and plasma biomarkers in OSCC was weak.

Bronchiolitis obliterans organizing pneumonia following nitric acid fume exposure.

We describe a patient with clinical, radiological and pathological features of bronchiolitis obliterans organizing pneumonia. Investigation showed that this was likely to have been a delayed consequence of inhalation of nitric acid fumes (containing nitrogen dioxide) after a fire. This case shows that thorough investigation of the aetiology is important not only in clinical management but also in ensuring patients benefit from appropriate work injury compensation.

Prolonged time to pregnancy in residents exposed to ionising radiation in cobalt-60-contaminated buildings.

OBJECTIVES: Radiation-induced cytogenetic damage in somatic cells has raised concern that low-dose ionising radiation can also damage germ cells and influence gamete production and/or function, resulting in decreased fertility. Time to pregnancy (TTP) was used to investigate whether exposure to gamma-radiation affected fertility among the residents of cobalt-60-contaminated buildings in Taiwan. METHODS: This was a retrospective pregnancy-based study of 357 pregnancies born to 124 exposed couples. Both the cumulative dose and the dose rate for each pregnancy was estimated based on a physical dose reconstruction programme. The comparison population consisted of 612 pregnancies born to 225 couples randomly sampled from the Taiwan general population. Information on TTP was collected by personal interviews. Fecundability ratios (FRs) were calculated with a discrete proportional hazards model. RESULTS: For exposed mothers, fertility decreased significantly when unprotected intercourse began during the period of living in the radiation-contaminated buildings (FR 0.75, 95% CI 0.61 to 0.92). The effect was borderline significant for fathers (FR 0.83, 95% CI 0.68 to 1.02). There was evidence that prolonged TTP was associated with the rate of exposure for both mothers and fathers (tests for trend: female, p=0.0006; male, p=0.03), especially evident for dose rates > or =10 mSv/year (female, FR 0.60, 95% CI 0.43 to 0.84; male, FR 0.68, 95% CI 0.49 to 0.96). CONCLUSIONS: Our findings suggest that exposure to low-dose ionising radiation of cobalt-60-contaminated buildings may decrease fertility, especially in females. Fertility declined with increasing concurrent dose but not with cumulative dose.

Depression and diffuse physical symptoms in southern Chinese with temporomandibular disorders.

The study investigated the experience of depressive symptoms and the relationship with diffuse physical symptoms reporting in southern Chinese seeking professional care for temporomandibular disorders (TMD) in Hong Kong. Eighty-seven new patients [77 females/10 males; mean age 39.3 years (SD 12.7)] referred to the specialist TMD clinic at the Prince Philip Dental Hospital, Hong Kong participated in this study. The Research Diagnostic Criteria (RDC)/TMD history questionnaire was used to derive Axis II psychological data. Psychological status was assessed through depression and non-specific physical symptoms (NPS) scores (pain items included and excluded) measured with RDC/TMD Axis II instruments; 42.5% of patients experienced moderate/severe depression symptoms; 59.8% and 57.5% had moderate/severe NPS scores when pain items were included and excluded, respectively. Strong, positive and statistically significant correlations were noted between depression scores and the NPS scores that included pain items (r = 0.80) and those that did not (r = 0.80). The correlations remained consistent and were of similar magnitude when male patients were excluded from the computation and also when the possible effect of patient age was controlled. While taking into account the modest patient sample which was related to a low rate of treatment seeking, depressive symptoms were common and similar to other western and Chinese patient groups. NPS reports were higher than in Singapore Chinese patients. There appeared to be a clear association between depression and diffuse physical symptoms. The findings should be considered in the holistic care of Chinese people with TMD.

Molecular cloning and mRNA distribution of pituitary adenylate cyclase-activating polypeptide (PACAP)/PACAP-related peptide in the lungfish.

In this article, we report the isolation of a full-length cDNA clone encoding pituitary adenylate cyclase-activating polypeptide (PACAP)/PACAP-related peptide (PRP) from lungfish Protopterus dolloi. When comparing the deduced amino acid sequences, the lungfish PACAP was found to be highly conserved with other vertebrates; however, the PRP shares only lower levels of sequence identity with known PRP sequences. Consistently in phylogenetic analysis, the lungfish PRP, similar to sturgeon PRP, fails to cluster with other PRPs. In addition to the full-length clone, another cDNA encoding a short precursor that lacks the first 32 amino acids of the PRP was also isolated. Interestingly, similar isoforms were also identified in several nonmammalian vertebrates, and it was suggested that exon skipping of PRP/PACAP transcripts was a mechanism that regulated the expression ratio of PACAP to PRP in nonmammalian vertebrates. By real-time PCR, both long and short PRP/PACAP transcripts were found almost exclusively in the brain, and the short isoform is the more abundant transcript (3.7 times more), indicating that PACAP is the major product produced in lungfish brain. The expression patterns of lungfish and previously studied frog PRP/PACAP suggest that the PRP/PACAP gene in the tetrapod lineage may first express in the central nervous system; in the process of evolution, the functions of these peptides diversified and were later found in other tissues.

Neutron reflectivity study of the complexation of DNA with lipids and surfactants at the surface of water.

Complexation of lipids and surfactants with short DNA fragments at the air-water interface has been studied by neutron reflectivity. Complexation with zwitterionic lipids occurs in the presence of divalent cations, and ion specificity has been demonstrated (binding is less effective with Ba2+ than with Mg2+ or Ca2+). One and two DNA layers have been observed for dilute and more compact lipid monolayers, respectively. Two DNA layers have also been found with the soluble cationic surfactant dodecyltrimethylammonium bromide (DTAB), except close to the precipitation boundary. This result is opposite to that found in ellipsometry where very thick layers are found in this region. It is possible that the ellipsometry signal is due to highly hydrated bulk complexes adsorbing at the surface, not seen by neutrons because of unfavorable contrast conditions. Long DNA was found to be less keen to form surface complexes than short DNA fragments.

Diagnostic sub-types, psychological distress and psychosocial dysfunction in southern Chinese people with temporomandibular disorders.

The study aimed to assess the distribution of temporomandibular disorders (TMD) sub-types, psychological distress and psychosocial dysfunction in southern Chinese people seeking treatment for TMD using Research Diagnostic Criteria for TMD (RDC/TMD) and investigate potential cross-cultural differences in sub-type prevalence and psychosocial impact. Eighty-seven consecutive patients (77 females; 10 males) with a mean age of 39.3 years (s.d. 12.8) newly referred to the specialist TMD clinic at the Prince Philip Dental Hospital, Hong Kong over a 20-month period took part in the study. RDC/TMD history questionnaire and clinical assessment data were used to derive Axis I and II findings. Group I muscle disorders were the most common and found in 57.5% of patients. Group II (disc displacement) disorders were found in 42.5% and 47.1% of the right and left temporomandibular joints (TMJ) respectively. Group III disorders (arthralgia/arthrosis/arthritis) were revealed in 19.5% and 23.0% of right and left TMJ's respectively. In the Axis II assessment, 42.5% of patients had moderate/severe depression scores, 59.7% had moderate/severe somatization scores and based on graded chronic pain scores 15.0% had psychosocial dysfunction (grade III and IV). While acknowledging the small sample size, the distribution of RDC/TMD Axis I and II diagnoses was fairly similar in Chinese TMD patients compared with Western and other Asian patient groups. However, in Chinese patients, myofascial pain with limited jaw opening and TMJ disc displacement with reduction were more common and a significant number experienced psychological distress and psychosocial dysfunction. The findings have implications for the management of TMD in Chinese people.

Obesity and hepatitis B infection are associated with increased risk of metabolic syndrome in university freshmen.

OBJECTIVE: To investigate the prevalence of metabolic syndrome and its associated risk factors in a cohort of university freshmen. DESIGN: A cross-sectional study in a university health center in North Taiwan. SUBJECTS: A total of 8226 students (mean age: 19.2+/-2.3 years) receiving pre-entrance health examinations and lifestyle questionnaires during the 2005-2006 academic year were recruited. MEASUREMENTS: A fasting plasma glucose, lipids, uric acid and hepatitis B serology were measured for each subject. The prevalence of metabolic syndrome and its individual components were examined using the America Heart Association and National Heart Lung Blood Institute criteria. The risk factors for metabolic syndrome were identified using a multivariate logistic regression analysis. RESULTS: The prevalence of overweight, obesity and metabolic syndrome was 12.7% (17.0% in men and 7.6% in women), 13.0% (18.4% in men and 6.4% in women) and 4.6% (6.4% in men and 2.4% in women). The risk for metabolic syndrome increased with an increase of body mass index and plasma uric acid level, and decreased with the vigorous physical activity and current alcohol drinking. Furthermore, as compared to subjects with seroprotective titers from hepatitis B vaccination (anti-HBs(+) and anti-HBc(-)), those without protective titers of anti-HBs after vaccination or without hepatitis B infection (anti-HBs(-) and anti-HBc(-)) had 34% higher risk for metabolic syndrome, and those with natural infection of hepatitis B (anti-HBc(+)) had 58% higher risk for metabolic syndrome. CONCLUSIONS: Overweight, obesity and metabolic syndrome were more common among men than women in university freshmen. Hepatitis B vaccination with anti-HBs(+) was associated with a lower risk of metabolic syndrome as compared to anti-HBs(-). However, hepatitis B infection presented with anti-HBc(+) was associated with a higher risk of metabolic syndrome. The interplay between hepatitis B infection, hepatitis B vaccination and metabolic syndrome needs further investigation.

Emergency transcatheter embolization of ruptured hepatocellular carcinomas with tortuous conventional or aberrant hepatic vascular anatomy, or parasitic supply.

Emergency transcatheter embolization is a well-recognized measure to manage patients with life-threatening haemoperitoneum due to spontaneous ruptured hepatocellular carcinoma. Traditional embolization technique is to embolize the proper hepatic artery or the segmental hepatic artery by femoral approach using gelfoam pledgets. From 1997 to 2004, in 19 out of 96 embolizations, the embolization technique had to be modified because of tortuous conventional or aberrant hepatic vascular anatomy or parasitic supply to achieve successful embolization.

Latent membrane protein 1 suppresses RASSF1A expression, disrupts microtubule structures and induces chromosomal aberrations in human epithelial cells.

Epstein-Barr virus (EBV) infection is closely associated with nasopharyngeal carcinoma (NPC) and can be detected in early premalignant lesions of nasopharyngeal epithelium. The latent membrane protein 1 (LMP1) is an oncoprotein encoded by the EBV and is believed to play a role in transforming premalignant nasopharyngeal epithelial cells into cancer cells. RASSF1A is a tumor-suppressor gene commonly inactivated in many types of human cancer including NPC. In this study, we report a novel function of LMP1, in down-regulating RASSF1A expression in human epithelial cells. Downregulation of RASSF1A expression by LMP1 is dependent on the activation of intracellular signaling of NF-kappaB involving the C-terminal activating regions (CTARs) of LMP1. LMP1 expression also suppresses the transcriptional activity of the RASSF1A core promoter. RASSF1A stabilizes microtubules and regulates mitotic events. Aberrant mitotic spindles and chromosome aberrations are reported phenotypes in RASSF1A inactivated cells. In this study, we observed that LMP1 expression in human epithelial cells could induce aberrant mitotic spindles, disorganized interphase microtubules and aneuploidy. LMP1 expression could also suppress microtubule dynamics as exemplified by tracking movements of the growing tips of microtubules in live cells by transfecting EGFP-tagged EB1 into cells. The aberrant mitotic spindles and interphase microtubule organization induced by LMP1 could be rescued by transfecting RASSF1A expression plasmid into cells. Downregulation of RASSF1A expression by LMP1 may facilitate its role in transformation of premalignant nasopharyngeal epithelial cells into cancer cells.

Insulin resistance, obesity, and metabolic syndrome among non-diabetic pre- and post-menopausal women in North Taiwan.

OBJECTIVE: To investigate the relationship between the metabolic syndrome and its related factors among non-diabetic pre- and post-menopausal women in North Taiwan. DESIGN: A cross-sectional study in a medical center in North Taiwan. SUBJECTS: Five hundred and ninety-four, non-diabetic middle-aged women (age range=40-64 years, mean=48.9+/-5.4 years) were recruited. MEASUREMENTS: The fasting plasma glucose, insulin, lipids levels and anthropometric indices were measured. The homeostasis model assessment was applied to estimate the degree of insulin resistance (HOMA-IR). Metabolic syndrome was defined by using the National Cholesterol Education Panel (NCEP) criteria and modified NCEP criteria (waist circumference >80 cm). RESULTS: The prevalence of metabolic syndrome was 6.2% using NCEP criteria, and 8.9% using modified NCEP criteria. Post-menopausal women had a higher prevalence of metabolic syndrome and its individual components compared to pre-menopausal women except hyperglycemia and low HDL-C. In multiple logistic regression analysis with adjustment for age and menopausal status, both BMI and HOMA-IR were independently associated with the metabolic syndrome. CONCLUSION: The prevalence of metabolic syndrome was higher in post-menopausal than pre-menopausal women. Both obesity and insulin resistance may play an important role in the development of metabolic syndrome among the middle-aged women in North Taiwan.

Plasma leptin is associated with insulin resistance independent of age, body mass index, fat mass, lipids, and pubertal development in nondiabetic adolescents.

OBJECTIVE: The rising epidemic worldwide in overweight and obese children requires urgent attention. Leptin has been found to be associated with body weight control and possibly affects insulin sensitivity. Since insulin resistance is associated with obesity in adults and possibly in adolescents, we set out to investigate the association of plasma leptin level with various anthropometric indices, body fat mass (FM), lipids, and insulin resistance (IR) index in nondiabetic adolescents. DESIGN: A cross-sectional study from three high schools in Taipei City in Taiwan. SUBJECTS: A total of 402 nondiabetic subjects (162 boys and 240 girls; age range, 10-19 y; mean age, 15.8+/-1.9 y, and mean body mass index (BMI), 24.8+/-4.6 kg/m(2)) were recruited. MEASUREMENTS: The fasting plasma leptin, plasma glucose, insulin, lipids, and anthropometric indices including height, weight, waist (WC) and hip circumferences, and waist-to-hip ratio (WHR) were examined. Total body FM and percentage body fat (FM%) were obtained from dual-energy X-ray absorptiometry. The homeostasis model was applied to estimate the degree of IR. RESULTS: The plasma leptin levels were significantly higher in girls (17.45+/-10.13 ng/ml) than boys (8.81+/-6.71 ng/ml, P<0.001). The plasma leptin levels were positively correlated to BMI, WC, WHR, FM, FM%, and triglycerides (TG). The IR index was positively correlated to BMI, WC, WHR, FM, FM%, TG, and leptin. Using the multivariate linear regression models, we found that plasma leptin remains significantly associated with IR index even after adjusting for age, gender, BMI, FM, WC, Tanner stage, and TG. CONCLUSION: Plasma leptin was associated with IR index independent of age, gender, BMI, FM, WC, Tanner stage, and TG. Plasma leptin levels in adolescents could be a predictor for the development of the metabolic syndrome disorders and cardiovascular diseases.

Assessing progression and efficacy of treatment for diabetic retinopathy following the proliferative pathway to blindness: implication for diabetic retinopathy screening in Taiwan.

AIMS: The natural history and treatment efficacy of diabetic retinopathy (DR) play important roles in the evaluation of screening. Therefore, the natural history of DR and rates of transition after treatment (including metabolic control and laser photocoagulation) from no diabetic retinopathy (NDR) to blindness were quantified. METHODS: We studied a cohort of 795 patients with diabetes mellitus (DM) receiving fundus examination in the ophthalmology out-patient department of one medical centre between 1 January 1990 and 31 December 1992 in Taiwan. Follow-up data until 31 December 1998 were collected by chart review. Two multistate Markov models were proposed to assess the efficacy of the treatment regime in reducing progression to blindness. RESULTS: The average times spent in states (i) no diabetic retinopathy (NDR), (ii) background diabetic retinopathy (BDR), (iii) preproliferative diabetic retinopathy (PPDR), and (iv) proliferative retinopathy (PDR) were 10.86 years, 8.33 years, 1.67 years, and 2.17 years, respectively. Early detection of PPDR may lead to a 60% reduction in PDR and an 83% reduction in blindness. Simulated results based on these parameters show that an annual screening programme, a biennial screening regime and a 4-yearly screening regime can lead to 54% (95% confidence interval (CI): 44-62%), 51% (95% CI: 41-59%), and 46% (95% CI: 36-54%) reductions in blindness, respectively. CONCLUSIONS: Assessing the progression of DR following the proliferative pathway in this study suggests that screening for DR is worthwhile and that a 4-year interscreening interval for patients as yet without DR may be justified.

Optimal cut-off values for obesity: using simple anthropometric indices to predict cardiovascular risk factors in Taiwan.

BACKGROUND: The increased health risks associated with obesity have been found to occur in Asians at lower body mass indices (BMIs). To determine the optimal cut-off values for overweight or obesity in Taiwan, we examined the relationships between four anthropometric indices and cardiovascular risk factors. METHODS: The data were collected from four health-screening centers from 1998 to 2000 in Taiwan. Included were 55 563 subjects (26 359 men and 29 204 women, mean age=37.3+/-10.9 and 37.0+/-11.1 y, respectively). None had known major systemic diseases or were taking medication. Individual body weight, height, waist circumference (WC), and a series of tests related to cardiovascular risk (blood pressure, fasting plasma glucose, triglycerides, total cholesterol, low- and high-density lipoprotein cholesterol) were assessed and their relationships were examined. Receiver operating characteristic (ROC) analysis was used to find out the optimal cut-off values of various anthropometric indices to predict hypertension, diabetes mellitus and dyslipidemia. RESULTS: Of the four anthropometric indices we studied, waist-to-height ratio (WHtR) in women was found to have the largest areas under the ROC curve (women=0.755, 95% CI 0.748-0.763) relative to at least one risk factor (ie hypertension or diabetes or dyslipidemia). The optimal cut-off values for overweight or obesity from our study in men and women showed that BMIs of 23.6 and 22.1 kg/m(2), WCs of 80.5 and 71.5 cm, waist-to-hip ratios (WHpR) of 0.85 and 0.76, and WHtR of 0.48 and 0.45, respectively, may be more appropriate in Taiwan. CONCLUSIONS: WHtR may be a better indicator for screening overweight- or obesity-related CVD risk factors than the other three indexes (BMI, WC and WHpR) in Taiwan. Our study also supported the hypothesis that the cut-off values using BMI and WC to define obesity should be much lower in Taiwan than in Western countries.

Four anthropometric indices and cardiovascular risk factors in Taiwan.

OBJECTIVE: To examine the relationships between four anthropometric measurements and cardiovascular risk factors in Taiwan. DESIGN: The data was collected from four nationwide health screen centers in Taiwan from 1998 to 1999. SUBJECTS: A total of 38 556 subjects: 18 280 men and 20 276 women, mean age=37.0+/-11.1 y. None had any known major systemic diseases or were currently on medication. MEASUREMENTS: Individual body weight, height, waist circumference (WC), and cardiovascular risk factors (blood pressure, fasting plasma glucose, triglycerides, total cholesterol level, low-density and high-density-lipoprotein cholesterol level) were assessed and their relationships were examined. RESULTS: In both sexes, with increasing body mass index (BMI), WC, WHpR (waist-to-hip ratio) and WHtR (waist-to-height ratio), there were significantly higher risks of hypertension, impaired fasting glucose, diabetes and dyslipidemia (P<0.001) in almost all age groups. In the age groups older than 65, however, the relationships were statistically inconsistent. CONCLUSIONS: In Taiwan, the four anthropometric indexes (BMI, WC, WHpR, WHtR) are closely related to cardiovascular risk factors.

Molecular cloning of a teleost growth hormone receptor and its functional interaction with human growth hormone.

This paper reports the first full-length cDNA sequence of a growth hormone receptor (GHR) from a teleost fish and its functional expression in cultured eukaryotic cells. The cDNA sequence, from Carassius auratus (goldfish), encodes a protein of 602 amino acids (aa) akin in architecture to the GHRs of other species. Despite the presence of motifs characteristic of GHR, the overall homology between the goldfish GHR and other GHRs is very low ( approximately 40% aa identity). CHO cells transfected with this receptor cDNA can be stimulated to proliferate by human growth hormone (hGH). In addition, the transfected cells can transactivate a co-expressed mammalian serine protease inhibitor (Spi) 2.1 promoter upon stimulation by hGH, indicating the successful interaction of the fish receptor with the mammalian ligand to evoke the down-stream post-receptor events. Tissue distribution studies indicated that the receptor is mostly expressed in the liver and hypothalamus of goldfish. A single mRNA transcript of a size of about 4 kb was found in the goldfish liver.

Molecular cloning and expression studies of a prolactin receptor in goldfish (Carassius auratus).

A full-length cDNA clone, of a size of 4.6 kb, for the goldfish prolactin receptor has been isolated. This cDNA clone encodes a protein of 600 amino acids homologous to prolactin receptors of other species. A Kyte-Doolittle hydropathy analysis of the receptor indicates that the translated protein consists of a signal peptide of 22 amino acids, an extracellular domain of 228 amino acids, a single transmembrane domain of 24 amino acids, and an intracellular domain of 346 amino acids. Several characteristic landmarks of prolactin receptor could be identified in this clone. These include the four conserved cysteine residues and the WS motif within the extracellular domain, and the box 1 and box 2 regions of the intracellular domain. Among all the prolactin receptor sequences known to date, this clone bears the closest resemblance to the tilapia prolactin receptor, although homology between these two fish prolactin receptors is rather low. There are only 57.4% of nucleotide and 48.3% of amino acid sequence identities between these two fish receptors. This receptor cDNA was transfected into CHO-K1 cells for functional analysis. RT-PCR analysis with a pair of gene specific primers indicate that the receptor was transcribed in the transfected cells. Using a cell proliferation assay based on the reduction of the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, the receptor transfected CHO-K1 cells can be stimulated to proliferate upon the addition of ovine prolactin in the culture medium. The tissue distribution of the prolactin receptor in goldfish was studied by RT-PCR/Southern analysis and by Northern analysis. The results indicated that the receptor is expressed mostly in the kidney, the gill and the intestine of goldfish, corroborating with the osmoregulatory role of prolactin in fish. In addition, an appreciable level of the receptor is also found in the brain and gonads of goldfish. Northern analysis showed that there are two transcript sizes, a major 4.6 kb and a minor 3.5 kb mRNAs, in the kidney, gill and intestine.