Treatment efficiency and stability of skeletal Class III malocclusion with a surgery-first approach.

OBJECTIVES: To compare treatment duration in skeletal Class III malocclusion patients managed with a 2-step treatment (surgery-first approach, SFA) and conventional 3-step treatment, and to compare stability of surgical outcomes between segmentation and non-segmentation in the 2-step treatment group. SETTING AND SAMPLE POPULATION: The sample population consisted of 37 patients who completed orthognathic surgery (OGS) and orthodontic correction at the Charm Aesthetic Surgery Clinic (Taipei, Taiwan) between 2012 and 2015. Of these, 26 received 2-step treatment and 11 received 3-step treatment. MATERIALS AND METHODS: To compare treatment efficiency and stability, three time points were analysed: T0 , before treatment (before OGS in the 2-step group and before orthodontic treatment in the 3-step group); T1 , after OGS but before orthodontic correction (cone beam computed tomography (CBCT) was obtained within 2 weeks of OGS); and T2 , after orthodontic correction (CBCT was obtained on the day of bracket removal). The post-OGS (T1 ) CBCT items were individually superimposed on the pre-treatment (T0 ) CBCT items to determine the distance of B point migration. RESULTS: A significant difference was found in treatment times between 2-step treatment and conventional 3-step treatment. In addition, no significant difference was found when comparing B-X (mm) and B-Y (mm) at T2 -T1 for the segmentation and non-segmentation groups. CONCLUSIONS: Using SFA for skeletal Class III malocclusions saves approximately 6 months of treatment time over 3-step treatment; the stability of the segmentation group was comparable to that of the non-segmentation group, a result that is possibly associated with the fixation of 2 miniplates.

Upregulation of Haploinsufficient Gene Expression in the Brain by Targeting a Long Non-coding RNA Improves Seizure Phenotype in a Model of Dravet Syndrome.

Dravet syndrome is a devastating genetic brain disorder caused by heterozygous loss-of-function mutation in the voltage-gated sodium channel gene SCN1A. There are currently no treatments, but the upregulation of SCN1A healthy allele represents an appealing therapeutic strategy. In this study we identified a novel, evolutionary conserved mechanism controlling the expression of SCN1A that is mediated by an antisense non-coding RNA (SCN1ANAT). Using oligonucleotide-based compounds (AntagoNATs) targeting SCN1ANAT we were able to induce specific upregulation of SCN1A both in vitro and in vivo, in the brain of Dravet knock-in mouse model and a non-human primate. AntagoNAT-mediated upregulation of Scn1a in postnatal Dravet mice led to significant improvements in seizure phenotype and excitability of hippocampal interneurons. These results further elucidate the pathophysiology of Dravet syndrome and outline a possible new approach for the treatment of this and other genetic disorders with similar etiology.

Better adherence to antithyroid drug is associated with decreased risk of stroke in hyperthyroidism patients.

BACKGROUND: An increased risk for ischaemic stroke has been reported in young hyperthyroidism patients independent of atrial fibrillation (AF). However, whether the use of antithyroid drugs in hyperthyroidism patients can reduce the occurrence of ischaemic stroke remains unclear. METHODS: A total of 36,510 newly diagnosed hyperthyroidism patients during 2003-2006 were identified from the Taiwan National Health Insurance Research database. Each patient was individually tracked for 5 years from their index date (beginning the antithyroid drugs) to identify those who suffered from new episode of ischaemic stroke. Medication possession ratio (MPR) was used to represent the antithyroid drug compliance. The association between the MPR and the risk of stroke was examined. RESULTS: The stroke incidence rates for hyperthyroidism patients with age < 45 years and age ≥ 45 years were 0.42 and 3.76 per 1000 person-years, respectively. The patients aged < 45 years with MPR < 0.2 (adjusted hazard ratio, HR, 2.30; 95% CI, 1.13-4.70; p = 0.02) and 0.2 ≤ MPR < 0.4 (adjusted HR, 2.24; 95% CI, 1.06-4.72; p = 0.035) had a significantly increased risk of ischaemic stroke as compared to those with ≥ 0.6. In patients of the age ≥ 45 years, only the patients with MPR < 0.2 (adjusted HR, 1.44; 95% CI, 1.03-2.01; p = 0.036) had a significantly higher risk of ischaemic stroke as compared to those with MPR ≥ 0.6. In hyperthyroidism patients without AF, good antithyroid drugs compliance also reduced the incidence of stroke significantly (adjusted HR, range: 1.52-1.61; p = 0.02); but not in hyperthyroidism with AF. CONCLUSION: Hyperthyroidism patients with good antithyroid drug compliance had a lower risk of ischaemic stroke than patients with poor compliance.

Risks and predictors of osteoporosis in patients with inflammatory bowel diseases in an Asian population: a nationwide population-based cohort study.

BACKGROUND: We investigated the inflammatory bowel disease (IBD) specific predictors of osteoporosis and pathological fracture by analysing the Taiwan National Health Insurance Research Database. METHODS: Totally, we enrolled 3141 IBD patients and 12,564 age- and sex-matched controls. We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) of osteoporosis and pathological fracture in both cohorts. RESULTS: Inflammatory bowel disease patients had significantly higher comorbidity-adjusted rates of osteoporosis and pathological fracture compared with controls [adjusted hazard ratio (aHR), 1.31; 95% CI, 1.09-1.60, p = 0.004]. Further analysis indicated that women (aHR, 1.36; 95% CI, 1.09-1.70, p = 0.008), middle-aged patients (aHR, 1.74; 95% CI, 1.25-2.41, p = 0.001), patients with Crohn's disease (aHR, 1.33; 95% CI, 1.09-1.64, p = 0.006) and patients without comorbidities (aHR, 1.81; 95% CI, 1.23-2.67, p = 0.003) exhibited excessive risks of osteoporosis. Moreover, patients requiring hospitalisation for IBD exhibited the highest risk of developing osteoporosis (aHR, 4.46; 95% CI, 2.74-7.27, p < 0.001) and pathological fracture (aHR, 17.1; 95% CI, 5.78-50.9, p < 0.001). CONCLUSIONS: Patients with IBD, particularly women, middle-aged patients and patients without comorbidities, are associated with a long-term risk of osteoporosis. The risks of osteoporosis and pathological fracture were highest in patients requiring hospitalisation for IBD.

Multicentre surveillance of prevalence of the 23S rRNA A2058G and A2059G point mutations and molecular subtypes of Treponema pallidum in Taiwan, 2009-2013.

Resistance mutations A2058G and A2059G, within the 23S rRNA gene of Treponema pallidum, have been reported to cause treatment failures in patients receiving azithromycin for syphilis. Genotyping of T. pallidum strains sequentially isolated from patients with recurrent syphilis is rarely performed. From September 2009 to August 2013, we collected 658 clinical specimens from 375 patients who presented with syphilis for genotyping to examine the number of 60-bp repeats in the acidic repeat protein (arp) gene, T. pallidum repeat (tpr) polymorphism, and tp0548 gene, and to detect A2058G and A2059G point mutations by restriction fragment length polymorphism. Treponemal DNA was identified in 45.2% (n = 298) of the specimens that were collected from 216 (57.6%) patients; 268 (40.7%) specimens tested positive for the 23S rRNA gene, and were examined for macrolide resistance. Two isolates (0.7%) harboured the A2058G mutation, and no A2059G mutation was identified. A total of 14 strains of T. pallidum were identified, with 14f/f (57.5%) and 14b/c (10.0%) being the two predominant strains. Forty patients who presented with recurrent episodes of syphilis had T. pallidum DNA identified from the initial and subsequent episodes, with five cases showing strain discrepancies. One patient had two strains identified from different clinical specimens collected in the same episode. Our findings show that 14f/f is the most common T. pallidum strain in Taiwan, where the prevalence of T. pallidum strains that show A2058G or A2059G mutation remains low. Different genotypes of T. pallidum can be identified in patients with recurrent episodes of syphilis.

Spirochetemia due to Treponema pallidum using polymerase-chain-reaction assays in patients with early syphilis: prevalence, associated factors and treatment response.

Between 2009 and 2013, polymerase-chain-reaction assay was used to detect Treponema pallidum in the blood samples collected from 296 patients with early syphilis (241 being HIV infected) and 102 patients (34.5%) had spirochetemia. The presence of spirochetemia was associated with lower CD4 counts (per 10-cell/mm(3) decrease, adjusted odds ratio (AOR), 1.020; 95% CI, 1.006-1.036) and secondary syphilis (AOR, 4.967; 95% CI, 2.016-12.238). Patients with early latent syphilis were less likely to achieve serological response compared with those with primary or secondary syphilis (AOR, 0.317; 95% CI, 0.142-0.708). However, serological response was not affected by presence of spirochetemia or antibiotic regimens.

Upregulated ankyrin repeat-rich membrane spanning protein contributes to tumour progression in cutaneous melanoma.

BACKGROUND: We have previously demonstrated that overexpression of ankyrin repeat-rich membrane spanning (ARMS) protein facilitates melanoma formation via conferring apoptotic resistance. This study aims to investigate whether ARMS contributes to melanoma progression. METHOD: Using immunohistochemistry, we graded the expression level of ARMS in 54 cases of primary melanoma and 46 cases of metastatic melanoma. The immunointensity of ARMS was statistically correlated with individual clinicopathological characteristics. By RNA interference, stable melanoma cell clones with ARMS-knockdown were constructed, and were used for in vitro scratch wound, transwell invasion assays, and in vivo lung metastasis experiment. RESULTS: Stronger immunointensity of ARMS was observed mostly in melanomas with Breslow tumour thickness >1.0 mm (Fisher's exact test, P=0.002) or with nodal metastasis (Fisher's exact test, P=0.026), and was correlated with a worse overall survival in melanoma patients (log-rank test, P=0.04). Depletion of ARMS inhibited migration, invasion, and metastatic potential of melanoma cells in vitro and in vivo. Moreover, ARMS mediated melanoma cell migration and invasion through activation of the extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signalling pathway. CONCLUSION: Ankyrin repeat-rich membrane spanning expression, conjunctly with tumour thickness or ulceration, may serve as a prognostic factor in patients with cutaneous melanoma.

Autonomic neuropathy precedes cardiovascular dysfunction in rats with diabetes.

BACKGROUND: Our team previously demonstrated arterial stiffening and cardiac hypertrophy in type 2 diabetic rats at 8 but not 4 weeks after being administered streptozotocin (STZ) and nicotinamide (NA). The present study focused on investigating the effects of type 2 diabetes on cardiac autonomic nerve function in the STZ- and NA-treated animals, using modern spectral estimation technique. DESIGN: An autoregressive process was performed to each detrended signal of heart rate and systolic blood pressure measured in the 4- and 8-week STZ-NA rats with anaesthesia. The power of low-frequency and high-frequency oscillations was automatically quantified with each spectral peak by computing the residuals. The closed-loop baroreflex gain was estimated using the square root of the ratio between heart rate and systolic blood pressure powers in the low-frequency band. RESULTS: Compared with the age-matched controls, both the 4- and 8-week STZ-NA diabetic rats had significantly decreased low-frequency oscillations of heart rate but not systolic blood pressure variability, showing a decline in baroreflex gain (0.451 +/- 0.060 and 0.484 +/- 0.056 vs. 1.196 +/- 0.064 ms mmHg(-1), P < 0.05). On the other hand, the low frequency-high frequency power ratio of the heart period was also diminished in the two diabetic groups, indicating a shift in sympatho-vagal balance of the heart control (0.472 +/- 0.109 and 0.504 +/- 0.090 vs. 1.857 +/- 0.336, P < 0.05). CONCLUSIONS: The cardiac autonomic dysfunction in the absence of any significant changes in vascular dynamics, 4 but not 8 weeks after induction of type 2 diabetes, suggests that the diabetic autonomic neuropathy may precede arterial stiffening and cardiac hypertrophy in the STZ- and NA-treated rats.

Aminoguanidine prevents arterial stiffening in a new rat model of type 2 diabetes.

BACKGROUND: Formation of advanced glycation end-products (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study focused on investigating the role of aminoguanidine (AG), an inhibitor of AGE formation, in the prevention of noninsulin-dependent diabetes mellitus (NIDDM)-derived arterial stiffening and cardiac hypertrophy in rats. MATERIALS AND METHODS: The NIDDM was induced in male Wistar rats, which were administered intraperitoneally with 180 mg kg(-1) nicotinamide (NA) 30 min before an intravenous injection of 50 mg kg(-1) streptozotocin (STZ). After induction of diabetes mellitus type 2, animals receiving daily peritoneal injections with 50 mg kg(-1) AG for 8 weeks were compared with the age-matched, untreated, diabetic controls. RESULTS: After exposure to AG, the STZ-NA diabetic rats had improved aortic distensibility, as evidenced by 18.8% reduction of aortic characteristic impedance (P < 0.05). Treatment of the experimental syndrome with AG also resulted in a significant increase in wave transit time (+23.7%, P < 0.05) and a decrease in wave reflection factor (-26.6%, P < 0.05), suggesting that AG may prevent the NIDDM-induced augmentation in systolic load of the left ventricle. Also, the glycation-derived modification on aortic collagen was found to be retarded by AG. The diminished ratio of left ventricular weight to body weight suggested that prevention of the diabetes-related cardiac hypertrophy by AG may correspond to the drug-induced decline in aortic stiffening. CONCLUSIONS: Long-term administration of AG to the STZ-NA diabetic rats imparts significant protection against the NIDDM-derived impairment in vascular dynamics, at least partly through inhibition of the AGE accumulation on collagen in the arterial wall.

Diagnostic accuracy of tissue Doppler echocardiography for patients with acute heart failure.

BACKGROUND: Acute heart failure leads to high mortality and morbidity rates. The symptom of acute dyspnoea is non-specific and the diagnostic tools of acute heart failure are still not satisfactory. Tissue Doppler echocardiography is accurate in evaluating cardiac function; however, its efficacy in diagnosing patients with acute dyspnoea in emergency departments remains unclear. METHODS: Patients with acute dyspnoea were included prospectively while visiting the emergency department. Tissue Doppler echocardiography was carried out and the ratios of peak early diastolic transmitral blood flow velocity (E) to the peak early diastolic tissue velocity over mitral annulus (Ea) were recorded. The sensitivity, specificity and accuracy of tissue Doppler parameters and the receiver-operating characteristic curves for diagnosing acute heart failure were also evaluated. RESULTS: A total of 92 patients were enrolled. The ratio E:Ea was found to be a good diagnostic test to estimate the diagnostic performances of tissue Doppler echocardiography using receiver-operating characteristic curves in cases of acute heart failure in patients with preserved left ventricular systolic function (mean (SD) area under the curve = 0.875 (0.049); p<0.001; cut-off value = 11) and with left ventricular systolic dysfunction (mean (SD) area under the curve = 0.903 (0.061); p = 0.003; cut-off value = 16). E:Ea was an independent predictor of acute heart failure in multiple logistic regressions. For patients with a B-type natriuretic peptide level between 100 and 500 pg/ml, E:Ea provided an accuracy of 90.9% (p = 0.015) for diagnosing acute heart failure. CONCLUSIONS: Tissue Doppler echocardiography is accurate in diagnosing patients with acute heart failure in emergency departments. It can be a useful supplementary diagnostic tool for patients with inconclusive blood B-type natriuretic peptide level.

Interactions of the fucose-specific Pseudomonas aeruginosa lectin, PA-IIL, with mammalian glycoconjugates bearing polyvalent Lewis(a) and ABH blood group glycotopes.

Pseudomonas aeruginosa Fuc > Man specific lectin, PA-IIL, is an important microbial agglutinin that might be involved in P. aeruginosa infections in humans. In order to delineate the structures of these lectin receptors, its detailed carbohydrate recognition profile was studied both by microtiter plate biotin/avidin-mediated enzyme-lectin-glycan binding assay (ELLSA) and by inhibition of the lectin-glycan interaction. Among 40 glycans tested for binding, PA-IIL reacted well with all human blood group ABH and Le(a)/Le(b) active glycoproteins (gps), but weakly or not at all with their precursor gps and N-linked gps. Among the sugar ligands tested by the inhibition assay, the Le(a) pentasaccharide lacto-N-fucopentaose II (LNFP II, Galbeta1-3[Fucalpha1-4]GlcNAcbeta1-3Galbeta1-4Glc) was the most potent one, being 10 and 38 times more active than the Le(x) pentasaccharide (LNFP III, Galbeta1-4 [Fucalpha1-3]GlcNAcbeta1-3Galbeta1-4Glc) and sialyl Le(x) (Neu5Acalpha2-3Galbeta1-4[Fucalpha1-3] GlcNAc), respectively. It was 120 times more active than Man, while Gal and GalNAc were inactive. The decreasing order of PA-IIL affinity for the oligosaccharides tested was: Le(a) pentaose > or = sialyl Le(a) tetraose > methyl alphaFuc > Fuc and Fucalpha1-2Gal (H disaccharide)>2'-fucosyllactose (H trisaccharide), Le(x) pentaose, Le(b) hexaose (LNDFH I) and gluco-analogue of Le(y) tetraose (LDFT)>H type I determinant (LNFP I)>Le(x) trisaccharide (Galbeta1-4[Fucalpha1-3]GlcNAc) > sialyl Le(x) trisaccharide >> Man >>> Gal, GalNAc, and Glc (inactive). The results presented here, in accordance with the crystal 3D structural data, imply that the combining site of PA-IIL is a small cavity-type best fitting Fucalpha1- with a specific shallow groove subsite for the remainder part of the Le(a) saccharides, and that polyvalent glycotopes enhance the reactivity. The Fuc > Man Ralstonia solanacearum lectin RSL, which resembles PA-IIL in sugar specificity, differs from it in it's better fit to the B and A followed by H oligosaccharides vs. Fuc, whereas, the second R. solanacearum lectin RS-IIL (the structural homologue of PA-IIL) binds Man > Fuc. These results provide a valuable information on PA-IIL interactions with mammalian glycoforms and the possible spectrum of attachment sites for the homing of this aggressive bacterium onto the target molecules. Such information might be useful for the antiadhesive therapy of P. aeruginosa infections.

Expression of WW domain-containing oxidoreductase WOX1 in the developing murine nervous system.

WW domain-containing oxidoreductase WOX1, also known as WWOX or FOR, is a proapoptotic protein and a putative tumor suppressor. Hyaluronidases such as PH-20, Hyal-1 and Hyal-2 induce the expression of WOX1, and hyaluronidases and hyaluronan are involved in the embryonic development. In the present study, we document the expression of WOX1 in the developing murine nervous system. Immunohistochemical analysis revealed that WOX1 was differentially expressed in early dividing cells from all three germ layers from embryonic to perinatal stages. In murine fetuses, WOX1 was present prevalently in the brainstem, spinal cord and peripheral nerve bundles, but its expression decreased after birth. In parallel, the expression of WOX1, as determined by Western blotting, was significantly reduced in the brain stem and spinal cord of adult mice. Notably, high levels of WOX1 immunoreactivity was observed in the neural crest-derived structures such as cranial and spinal ganglia and cranial mesenchyme during the late fetal stage. In the adult brain, WOX1 is abundant in the epithelial cells of the choroids plexus and ependymal cells, while a low to moderate level of WOX1 is observed within white matter tracts, such as axonal profiles of the corpus callosum, striatum, optic tract, and cerebral peduncle. WOX1 is shown to mediate apoptosis synergistically with p53 in vitro. Nonetheless, the expression profiles of WOX1 were found to be similar in both p53 wild type and knockout mice, suggesting that WOX1 expression is not controlled by p53-mediated gene transcription. Taken together, in this study we have shown the expression and distribution of WOX1 in developing and adult murine nervous system. The potential role of WOX1 in the neuronal differentiation is discussed.

Pregnancy outcomes with increased nuchal translucency after routine Down syndrome screening.

OBJECTIVES: The purpose of this study was to evaluate the outcomes of pregnancies with nuchal translucency greater or equal to 3 mm for routine first trimester screening in unselected populations. METHODS: A total of 2980 pregnant women for first trimester ultrasonography were routinely offered crown-rump length (CRL) and nuchal translucency (NT) for screening for Down syndrome between 11 and 14 weeks' gestation. A complete follow-up was obtained in all cases by a review of medical records. RESULTS: Using a cut-off value of 3 mm, the prevalence of increased fetal NT was 0.7% (n=22). Among the 22 cases, there were five (22.7%) chromosomal abnormalities. Of the 17 chromosomally normal pregnancies, four resulted in fetal demise (spontaneous abortion, intrauterine death or termination of pregnancy due to fetal abnormalities). The remaining 13 pregnancies resulted in live births, including one gestational hypertension and one preterm delivery, respectively. The total incidence of an adverse outcome in the group of increased fetal NT was 45.5%. CONCLUSIONS: In a routine population with first-trimester ultrasonography, fetal NT measuring greater than or equal to 3 mm was associated with a poor pregnancy outcome with not only chromosomal abnormalities and congenital cardiac diseases, but also poor maternal and fetal health or adverse pregnancy outcomes. In addition, this study also demonstrated the necessity for fetal assessment and follow-up in cases where the fetal NT is increased in the first trimester.

Black cohosh, a menopausal remedy, does not have estrogenic activity and does not promote breast cancer cell growth.

Black cohosh is an increasingly popular alternative to estrogen replacement therapy for the relief of menopausal symptoms, primarily hot flushes. However, an important consideration for long-term therapy is potential toxicity and carcinogenicity. Therefore, we undertook a study to assess the estrogenic activity of black cohosh to examine its safety for those with, or at high risk of developing, breast cancer. Several assays were utilized as listed: RNAse protection assays, which ascertain the regulation of the expression of E2-responsive genes; estrogen-responsive-element (ERE)-luciferase, which determines modulation of the ER function by transactivation of the ERE; the Ishikawa cell system, which has an E2-regulated endogenous alkaline phosphatase; and colony formation of ER-expressing breast cancer cells, which indicates possible progression of early stage breast cancer into a more aggressive state. Black cohosh extracts did not demonstrate estrogenic activity in any of these assay systems. This is an encouraging step in the assessment of the safety of black cohosh for treatment of menopausal hot flushes.

Tuberculous wrist in the era of effective chemotherapy: an eleven-year experience.

BACKGROUND: The chronic course and non-specific clinical manifestations of tuberculous (TB) wrist often cause failure to make a timely diagnosis. OBJECTIVE: To better understand the rarely encountered TB wrist. PATIENTS AND METHODS: Retrospective review and analysis of cases of TB wrist between 1986 and 1997 in a medical centre in southern Taiwan. RESULTS: Thirty-seven cases (16 definitive, 13 probable and eight possible) of TB wrist (25 men, 12 women; mean age, 56.3 +/- 13.0 years) were found among a total of 4970 cases of tuberculosis. The most common presenting sign and symptom (mean duration 9.4 months) were local swelling and pain over the affected wrist. The mean white blood cell (WBC) count in peripheral blood was 7.04 x 10(9)/l, and the erythrocyte sediment rates (ESR) in seven of 31 patients who had ESR assayed were normal. Forty-six per cent of the patients had abnormal chest X-ray, and 35% had had previous manipulation of the affected wrist. CONCLUSION: Physicians should have a high index of suspicion for TB wrist among patients with chronic arthritis, even when their peripheral WBC count and ESR are normal. An abnormal chest X-ray and/or a history of previous manipulation of the affected wrist could be important clues for possible TB wrist.

Diagnosis of fetal acrania during the first trimester nuchal translucency screening for Down syndrome.

OBJECTIVES: Prenatal screening during the first-trimester using fetal nuchal translucency (NT) measurement and maternal serum levels of free beta-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein-A (PAPP-A) has become an established method for the detection of fetal Down syndrome. Increasing evidence has shown that some of the fetal structural abnormalities could be identified during NT scanning. Second trimester maternal serum alpha-fetoprotein (MSAFP) measurements and ultrasound scans have been widely used in clinical practice to identify fetal neural tube defects (NTDs). In this study, we evaluated the effectiveness of early diagnosis of fetal acrania during NT scanning. METHODS: We reviewed the medical records of 5890 pregnancies that were delivered in our hospital between January 1, 1999 and January 31, 2001. Among them, 3600 pregnant women received NT-based Down syndrome screening at 10-13 weeks' gestation. Pregnancies with fetal NTDs were evaluated and their maternal serum levels of free beta-hCG and PAPP-A were compared with those of the normal control pregnancies. RESULTS: Seven of the 3600 pregnancies were identified with fetal acrania and all of them were detected during first-trimester NT scanning. Among the seven cases, five had measurements of maternal serum concentration free beta-hCG and PAPP-A concentration, yet there were not significant difference between the pregnancies with fetal acrania and those of the control pregnancies (PAPP-A, 1.13 vs. 0.96; free beta-hCG, 1.10 vs. 1.06; P>0.05). Two of the seven affected patients did not have maternal serum biochemical measurements due to the immediate termination of pregnancies. CONCLUSIONS: We demonstrated that pregnancies with fetal acrania could be easily identified at the time of NT scanning. Careful ultrasound inspection of fetal structure during NT measurements at 10-13 weeks of gestation provides an encouraging advantage for early diagnosis of fetal acrania.

The chelating treatment is not useful in human's intoxication with acute herbicidal organic arsenic.

The clinical manifestations of acute organic arsenic intoxication in humans have seldom been described and the associated treatment has been thought to be the same as that of acute inorganic arsenic intoxication. We have studied a collection of patients from 1996 to 2001 who called the Poison Control Center of Kaohsiung Medical University Hospital asking for information regarding acute organic arsenic intoxication. The 17 patients ranged in age from 23 to 64 years old, with 5 females and 12 males. The cause of arsenic ingestion was attempted suicide. Abdominal pain and vomiting were the main symptoms. There were no differences in results between patients treated with and those treated without chelating agents. We therefore believe that the results of acute organic intoxication are not same as acute inorganic intoxication and it is unnecessary to use chelating agents in such conditions.

Hepatic Schistosomiasis japonica in a patient with gallstones and bile duct stones--a case report.

Schistosomiasis, a common parasitic disease in many countries, is found as imported cases in Taiwan. Responsible for human infections are five species, one of which, Schistosoma japonicum, is currently endemic in China and South-east Asia. Chronic infection with S. japonicum may lead to the development of liver fibrosis, calcification and portal hypertension. Under investigation by sonography and computed tomography (CT) scan, a peculiar "turtle-back" appearance of liver fibrosis and calcification may be found. Herein, we report a case referred to our department due to jaundice. The sonography of liver showed typical "turtle-back" appearance. Gallstones and bile duct stones were also found in this case. Surgical interventions with percutaneous transhepatic biliary drainage (PTBD), cholecystectomy and choledocholithotomy were performed to relieve the obstructive jaundice and remove the stones. There were no parasitic eggs in the extracted stones or in drained bile juice. However, deposits of calcified S. japonicum eggs in liver parenchyma and portal tracts were identified in liver biopsy. No special treatment was given for the schistosomiasis japonica because the calcified parasitic eggs were the sequelae of past infection.

Signaling molecules implicated in heregulin induction of growth arrest and apoptosis.

Heregulin (HRG) is one of the groups of polypeptide growth factors that activate the erbB-2 receptor via induction of heterodimerization with erbB-3 and erbB-4 receptors. The biological effects of HRG have been extensively studied. The vast majority of the reports indicate that HRG induces cell growth in breast cancer cells expressing normal levels of erbB-2 and growth inhibition and apoptosis in cells over-expressing erbB-2. However, the mechanism by which HRG promotes cell growth inhibition and apoptosis is still unknown. Previously we reported that constitutive expression of HRG in an erbB-2-overexpressing cell line (SKBr-3) induced growth arrest and apoptosis. We also demonstrated that constitutive expression of HRG promoted a marked morphological change, G2/M delay of the cell cycle, and DNA fragmentation. In this study, we demonstrate the mechanism by which HRG induces these cellular effects. The doubling time of the SK/HRG cells increased in relation to the level of HRG expression, and the level of HRG expression dictates the morphological change of the cells as well as their ability to grow or not grow in an anchorage-independent manner. We demonstrate that these effects are accompanied by downregulation of both erbB-2 and erbB-3 receptors at the transcriptional and translational levels and that down-regulation of the erbB-receptors results in reduced receptor tyrosine phosphorylation. The decrease in erbB-receptor phosphorylation in turn results in a marked reduction of ERK activity and a significant increase in JNK activity. Consequently, overexpression of HRG promoted the expression of PEA3, an Ets nuclear transcription factor. Taken together, our data demonstrate that the cellular effects induced by constitutive expression of HRG in SKBr-3 cells are correlated with the level of HRG expression. This is a first report demonstrating that HRG induction of apoptosis is directly correlated with decreased MAPK activity, increased JNK activity resulting in upregulation of PEA3 and down-regulation of the erbB-2 receptor. Overall, these data provide important clues regarding the mechanism and downstream molecules involved in HRG induction of apoptosis that can be used as targets for therapeutic prevention.