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Summary Background Increased blood pressure is the biggest contributor to the global burden of disease and mortality. Data suggest that less than half of the population with hypertension is aware of it. May Measurement Month was initiated to raise awareness of the importance of blood pressure and as a pragmatic interim solution to the shortfall in screening programmes. Methods This cross-sectional survey included volunteer adults (≥18 years) who ideally had not had their blood pressures measured in the past year. Each participant had their blood pressure measured three times and received a a questionnaire about demographic, lifestyle, and environmental factors. The primary objective was to raise awareness of blood pressure, measured by number of countries involved, number of people screened, and number of people who have untreated or inadequately treated hypertension (defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or both, or on the basis of receiving antihypertensive medication). Multiple imputation was used to estimate the mean of the second and third blood pressure readings if these were not recorded. Measures of association were analysed using linear mixed models. Findings Data were collected from 1 201 570 individuals in 80 countries. After imputation, of the 1 128 635 individuals for whom a mean of the second and third readings was available, 393 924 (34·9%) individuals had hypertension. 153 905 (17·3%) of 888 616 individuals who were not receiving antihypertensive treatment were hypertensive, and 105 456 (46·3%) of the 227 721 individuals receiving treatment did not have controlled blood pressure. Significant differences in adjusted blood pressures and hypertension prevalence were apparent between regions. Adjusted blood pressure was higher in association with antihypertensive medication, diabetes, cerebrovascular disease, smoking, and alcohol consumption. Blood pressure was higher when measured on the right arm than on the left arm, and blood pressure was highest on Saturdays. Interpretation Inexpensive global screening of blood pressure is achievable using volunteers and convenience sampling. Pending the set-up of systematic surveillance systems worldwide, MMM will be repeated annually to raise awareness of blood pressure. Funding International Society of Hypertension, Centers for Disease Control and Prevention, Servier Pharmaceutical Co.

PurposeTo investigate the impact of socioeconomic status (SES) on vision-related quality of life (VRQOL) in patients with primary open-angle glaucoma (POAG).Patients and methodsThis prospective cross-sectional study included consecutive patients with POAG at a tertiary hospital between March 2012 and January 2013. All patients had visual acuity no worse than 20/60 in the better eye and reliable visual field tests. VRQOL was assessed by the validated Taiwan version 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25). Sociodemographic characteristics, medical history, and ocular parameters were recorded. SES was evaluated based on educational attainment and monthly income, both stratified into three levels. Analysis of variance and linear regression analysis were used to evaluate the relationship between SES, VRQOL, and clinical parameters.ResultsAmong the 186 patients recruited, intergroup differences were not observed among educational or monthly income levels for binocular vision or integrated visual field defects. Patients of lower educational and monthly income levels had lower self-reported general health ratings. After adjustment for visual function, treatment complexity, and general health in the multiple linear regression model, patients with a college degree or higher reported better NEI VFQ-25 scores for the composite score (P=0.041), mental health (P=0.035), and peripheral vision (P=0.05) than did those with education below junior high school. Monthly income levels did not affect the NEI VFQ-25 scores.ConclusionEducational attainment significantly affects VRQOL in patients with POAG. Additional counseling may be provided to patients with lower educational background to help them cope with the disease.

BackgroundIn China, ethnic minorities often live in frontier areas and have a relatively small population size, and tremendous social transitions have enlarged the gap between eastern and western China, with western China being home to 44 ethnic minority groups. These three disadvantages have health impacts. Examining ethnicity and health inequality in the context of western China is therefore essential.MethodsThis paper is based on data from the 2010 China Survey of Social Change (CSSC2010), which was conducted in 12 provinces, autonomous regions and province-level municipalities in western China and had a sample size of 10,819. We examined self-rated health and disparities in self-rated health between ethnic minorities and Han Chinese in the context of western China. Self-rated health was coded as poor or good, and ethnicity was coded as ethnic minority or Han Chinese. Ethnic differences in self-rated health was examined by using binary logistic regression. Associations among sociodemographic variables, SES variable, health behaviour variable, health problem variables and self-rated health were also explored.ResultsFourteen percent of respondents reported their health to be poor. A total of 15.75% of ethnic minorities and 13.43% of Han Chinese respondents reported their health to be poor, indicating a difference in self-rated health between ethnic minorities and Han Chinese. Age, gender, marital status, education, alcohol, and health problems were the main factors that affected differences in self-rated health.ConclusionIn western China, there were obvious ethnic disparities in self-rated health. Elderly ethnic minorities, non-partnered ethnic minorities, ethnic minorities with an educational level lower than middle school, and ethnic minorities with chronic disease had higher odds of poor self-rated health.

Increasing evidence has revealed that microRNAs (miRNAs) act as key players in the regulation of tumor growth and metastasis in epithelial ovarian cancer (EOC). However, the clinical role and functional effects of miR-1294 in EOC remain unknown.We examined the expression of miR-1294 in 69 cases of EOC tissues and cell lines by quantitative Real-time polymerase chain reaction (qRT-PCR). The associations of miR-1294 expression with clinicopathologic features and overall survival of EOC patients were analyzed. Biological functional effects of miR-1294 expression on cell growth were analyzed using Cell Counting Kit-8 (CCK8) assays and flow cytometry assays in vitro.In the present study, we identified that miR-1294 expression was lower in 76 specimens of EOC compared to adjacent normal tissues. Lower miR-1294 expression was related to FIGO stage, lymph node metastasis and shorter overall survival rate in EOC patients. Multivariate Cox analysis demonstrated that miR-1294 expression was an independent prognostic indicator of EOC patients. Gain function assays showed that miR-1294 overexpression inhibited cell proliferation and cell cycle progression in EOC.Our results indicated that miR-1294 acted as a prognostic biomarker and potential target of EOC treatment.

SummaryBackground The KIT gene plays an important role in the pathogenesis of malignant melanoma (MM). In recent years, activating mutations in KIT have been recognized as oncogenic. A number of therapies have been established, which provide significant clinical benefits for patients with MM with KIT mutations. Thus, detection of KIT mutations can have profound therapeutic implications. Aim To investigate KIT gene expression in MMs in Chinese Uyghur and Han patients with mutations in KIT, and to identify the clinical features associated with KIT mutations and c-KIT expression. Methods In total, 105 MMs (56 from Uyghur and 49 from Han patients) were selected from patients in the Uyghur Autonomous region. Formalin-fixed, paraffin wax-embedded tumour sections were analysed for c-KIT expression using immunohistochemistry. Exons 11 and 13 of KIT were analysed for the presence of mutations using PCR amplification and DNA sequencing. Results Of the 105 MMs, 13 (10 Han and 3 Uyghur) were found to have mutations in KIT. Thus, the frequency of KIT mutations in Han patients was significantly higher than that in Uyghur patients (P = 0.02). We detected c-KIT expression in 71.4% and 42.9% of the tumour tissue samples collected from the Uyghur and Han patients, respectively. Conclusion In the Xinjiang Uyghur Autonomous Region in China, chronic sun-induced damage MM is the most prevalent MM among Chinese Uyghur patients, whereas acral and mucosal MMs are the most prevalent in Uyghur patients. Mutations in the KIT gene do not correlate with c-KIT expression.

Both neurocognitive deficits and schizophrenia are highly heritable. Genetic overlap between neurocognitive deficits and schizophrenia has been observed in both the general population and in the clinical samples. This study aimed to examine if the polygenic architecture of susceptibility to schizophrenia modified neurocognitive performance in schizophrenia patients. Schizophrenia polygenic risk scores (PRSs) were first derived from the Psychiatric Genomics Consortium (PGC) on schizophrenia, and then the scores were calculated in our independent sample of 1130 schizophrenia trios, who had PsychChip data and were part of the Schizophrenia Families from Taiwan project. Pseudocontrols generated from the nontransmitted parental alleles of the parents in these trios were compared with alleles in schizophrenia patients in assessing the replicability of PGC-derived susceptibility variants. Schizophrenia PRS at the P-value threshold (PT) of 0.1 explained 0.2% in the variance of disease status in this Han-Taiwanese samples, and the score itself had a P-value 0.05 for the association test with the disorder. Each patient underwent neurocognitive evaluation on sustained attention using the continuous performance test and executive function using the Wisconsin Card Sorting Test. We applied a structural equation model to construct the neurocognitive latent variable estimated from multiple measured indices in these 2 tests, and then tested the association between the PRS and the neurocognitive latent variable. Higher schizophrenia PRS generated at the PT of 0.1 was significantly associated with poorer neurocognitive performance with explained variance 0.5%. Our findings indicated that schizophrenia susceptibility variants modify the neurocognitive performance in schizophrenia patients.

The purpose of this study was to examine whether the prevalence of Parkinson's disease (PD) continues to rise after 80 years of age.This is a two-stage, multi-center, cross-sectional study using a stratified cluster sampling approach was employed. Subjects included veterans at ≥ 60 years of age living in veterans' communities for at least one month in 18 major cities across China. In the first step, possible PD was screened using a PD screening scale. Demographic and relevant information were collected. In the second step, PD diagnosis was established using the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) diagnostic criteria.The study was conducted during the period from December 2009 to December 2012. The study included 277 veterans' communities. Among the approached 11,593 subjects, 9676 subjects, (9096 men, 580 women) responded. The response rate was 83.46%.The age was ≥ 80 years in 6722 (69.47%) subjects. A diagnosis of PD was established in 228 subjects (2.36%) in the entire sample. The rate of PD was 2.65% in those with an age of ≥ 80 years. The rate of PD increased with increasing age (0%, 1.84%, 2.60% and 3.68% in the subjects at70, 70-79, 80-89 and ≥ 90 years of age, respectively; χ2 = 10.891, p = 0.001 in chi-square test). The rate of PD was higher in men (2.44%) than in women (1.46%) on the surface. However, no significant difference was detected (p = 0.241).The prevalence of PD continues to increase beyond the age of 80 years. The prevalence of PD in Chinese veterans is not lower than that in other countries and regions.

Summary. We assessed the efficacy of interferon (IFN) alpha-2b plus ribavirin therapy in patients with hepatitis C virus (HCV)-related cirrhosis, and elucidated the risk factors for the development of hepatocellular carcinoma (HCC) to determine whether these therapies might reduce the incidence of HCC. One hundred and thirty-two HCV-cirrhotic patients receiving IFN alpha-2b (3 or 5 MU thrice weekly) and oral ribavirin (1000–1200 mg/day) for 24 or 48 weeks were analysed. Cumulative incidence of HCC was estimated by the Kaplan–Meier method. The prognostic relevance of clinical variables and HCC occurrence was evaluated by univariate analysis with the log-rank test and by multivariate Cox's regression analysis. A total of 116 patients completed the treatment and 73 (55%) achieved a sustained virological response (SVR). Stepwise logistic regression analysis showed that nongenotype 1b (P

Background Calreticulin (CRT), an endoplasmic reticulum protein, has been reported to be essential for the differentiation of neuroblastoma (NB) cells, suggesting that CRT may affect the tumor behavior of neuroblastoma. The aim of this study was to evaluate the association of clinicopathologic factors and patient survival with the expression of CRT in patients with NB. Patients and methods Sixty-eight NBs were investigated by immunohistochemical staining against CRT, and were divided into positive and negative immunostaining groups. Correlations between calreticulin expression, various clinicopathologic and biologic factors, and patient survival were studied. In seven tumor samples, CRT mRNAs and proteins were evaluated with real-time PCR and western blot, respectively, and correlated with immunohistochemical findings. Results Among 68 NBs, 32 (47.1%) showed positive CRT expression. Positive CRT immunostaining strongly correlated with differentiated histologies, as well as known favorable prognostic factors such as detected from mass screening, younger age (≤1 year) at diagnosis and early clinical stages, but inversely correlated with MYCN amplification. Kaplan–Meier analysis revealed that NB patients with CRT expression did have better survival. Multivariate analysis demonstrated CRT expression to be an independent prognostic factor. Moreover, CRT expression also predicted better survival in patients with advanced-stage NBs, and its absence predicted poorer survival in patients whose tumor had no MYCN amplification. The amount of CRT mRNAs and proteins in NB tumor samples tested correlated well with the immunohistochemical expressions. Conclusions CRT expression correlates with the differentiation of NB and predicts favorable survival, thereby suggesting CRT to be a useful indicator for planning treatment of NB.

Overexpression of extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN CD147) has been implicated in the growth and survival of malignant cells. However, its presence and role in cervical cancer cells has not been well-studied. In the present study, small interfering RNA (siRNA) was designed and synthesized to breakdown the expression of CD147. The present data demonstrated that 24 and 48 hours after transfecting CD147 siRNA, both the CD147 mRNA and protein expression were significantly inhibited as determined by quantitative real-time polymerase chain reaction (RT-PCR) and immunocytochemistry. Meanwhile, simultaneous silencing of CD147 resulted in distinctly increasing MMP-9, VEGF, and MDR-1. Further studies demonstrated decreased CD147 expression, resulted in G1/S phase transition with flow cytometry analysis, as well as the resistance of the cells to 5-FU. These findings provide further evidence that CD147 may become a promising therapeutic target for human cervical cancer and a potential chemotherapy-sensitizing agent.

A prospective study was conducted to develop a better technique for ankle fusion. Eleven consecutive patients were treated using the tension-band technique for ankle fusion and underwent follow-up for a minimum of 2 years (range: 2-5 years). All 1 1 patients achieved solid fusion for a fusion rate of 1 00%. Average time to fusion was 3 months (range: 2-6 months). The indication for ankle fusion was intractable aching pain that could not be controlled by conservative methods. Two of 11 patients underwent surgery due to infected arthritis. After ankle fusion, there was no recurrence of infection during a 3-year follow-up period. The technique included osteotomy of the bimalleoli from the inside out, removal of articular cartilage and preserving wedge space for cancellous bone grafting, with or without staple stabilization, and external immobilization supplementation. The functional outcome in all 1 1 patients improved from unsatisfactory preoperatively to satisfactory at latest follow-up (P

Thirty-seven consecutive adult tibial shaft malunions which had not undergone surgical treatment were prospectively treated with reamed intramedullary nailing. Indications for this treatment modality included a malunion of a tibial shaft which had only been conservatively treated, lesion level fitting for traditional or locked reamed intramedullary nail fixation, less than 2 cm shortening, and without evidence of deep infection at present. The malunions were treated with fibulotomy, closed wedge tibial osteotomy, open reaming of the marrow cavity, stable reamed intramedullary nail stabilization with or without supplementation, and cancellous bone grafting. Thirty-four (92%) patients were followed up for at least 1 year (range 1.0-4.3 years), and all achieved a solid union. The union period was 5.8+/-0.8 months. Complications included 2 (6%) patients with deep infection and 1 (3%) with cortical perforation. However, all 3 patients recovered completely after adequate management. In conclusion, a reamed intramedullary nail is an ideal instrument for tibial shaft malunions in indicated cases. Good exposure of the bony segments to ream the marrow cavity precisely can avoid cortical perforation. Gentle dissection of the soft tissues may lower the infection rate. Concomitant cancellous bone grafting can improve the union rate.

We report an extremely rare case of Ewing's sarcoma (ES) of the humerus in a Chinese neonate. Plain radiography and magnetic resonance imaging showed extensive neoplastic involvement of the humeral diaphysis and adjacent soft tissues, confirmed on histology and immunohistochemistry as being due to ES. This is the first report of congenital ES in a long bone. Since ultrasound at 20 weeks gestation showed a normal fetal skeleton, the ES may have begun to develop in the late middle or third trimester.

We report a case of bronchial atresia associated with an epibronchial right pulmonary artery (ERPA) and an aberrant right middle lobe artery (ARMLA). CT showed a branching opacity, which was hyperintense on MR images, in the anterior segment of the right upper lobe with segmental hyperinflation and the ERPA. At surgery, the ARMLA was found to originate from the ERPA, crossing the anterior aspect of the right upper lobe bronchus. It is postulated that the ARMLA might have interfered with the normal bronchial development, leading to the development of segmental bronchial atresia.

Purpose: to report on unusual imaging presentations in renal transitional cell carcinoma (TCC) Material and Methods: Imaging studies of 140 cases of pathologically proven renal TCC were retrospectively studied with the focus on unusual presentations Results: Unusual imaging manifestations were found in 20 cases (14.3%). These findings were classified into 5 categories: perirenal abscesses or perirenal hematomas in 6 cases; parenchymal masses in 5; undue thickening of the hydronephrotic wall in 4; “tuberculoid” pyelograms in 3; and tumors with massive necrosis in 2 Conclusion: Deceptive imaging presentations may occur in renal TCC. Recognition of these presentations may help to prevent delay in diagnosis

We report a rare case of early-stage endometrial adenocarcinoma in a 22 year old nullipara with polycystic ovaries undergoing conservative treatment. Pretreatment evaluation including tumour grade, depth of myometrial invasion, tumour size, hormone receptor status and flow cytometric analysis indicated a favourable prognosis. The patient underwent repeat endometrial curettage and a 6 month period of therapy with megestrol acetate and tamoxifen. A combination contraceptive pill was then prescribed to ensure withdrawal of the menstrual cycle thereafter. Now, 1 year after the last curettage, there is no evidence of disease. During the treatment period, hysteroscopy allowed for a more precise approach in panoramically examining the tumour nest in the endometrial cavity, and the subsequent endometrial response to hormone therapy. Laparoscopy using bulldog clamps applied to the isthmic portion of the Fallopian tubes prevented i.p. spread of endometrial tissue from retrograde regurgitation during hysteroscopy. Laparoscopic ovarian electrocautery resulted in the reduction of abnormal hypervascularization on the surface of polycystic ovaries postoperatively but caused a peri-ovarian adhesion complication. It is interesting that this case posed a unique opportunity to demonstrate the tumour regression under the assistance of laparoscopy and hysteroscopy.

The clinical features and response to therapy of 32 Chinese patients with localised plasmacytoma are presented, and a comparison between extramedullary plasmacytoma (EMP) and solitary plasmacytoma of bone (SPB) is made. Twenty-two patients had SPB and ten had EMP, accounting for 9% of all of our plasma cell neoplasms. Both groups had a male predominance with a median age of 54 years for SPB and 63 years for EMP. The common sites of SPB included vertebral bodies (15) and the skull (4). Most EMPs occurred in the oronasopharynx (6) and paranasal sinuses (2). An M-protein was detected in eight patients with SPB and in six with EMP. Seventeen patients with SPB and seven with EMP received radiation therapy, and all achieved initial local control. The pattern of failure in 22 patients with SPB manifested as local recurrence in two, multiple bone metastases without bone marrow plasmacytosis in two, multiple EMP progression in two, and development of multiple myeloma (MM) in one. There were two local recurrences, one further solitary bone involvement and one MM conversion in the EMP group. Local recurrence or dissemination was associated with the appearance of M-protein or an increase in the M-protein level in both groups. There was no significant difference in M-protein status or incidence and patterns of failure between the two groups. Patients with EMP had a more favourable overall survival than those with SPB (P = 0.03). The 5 year disease-free survival rate was 79% for EMP and 58% for SPB (P = 0.53). Patients aged less than 60 years had a better overall survival in the SPB group, but location of tumour, presence of M-protein, radiation dose and chemotherapy did not influence prognosis in either group. Our results indicate that adequate local therapy can result in long-term survival with a low frequency of MM progression for patients with localised plasmacytomas, and both EMP and SPB appear to be similar in terms of frequency and patterns of failure.

A case of malignant fibrous histiocytoma (MFH) of the gastrocolic ligament is presented. It appeared as a huge, thin walled cystic tumour in the upper abdominal cavity on CT. Barium studies showed splaying of the stomach and transverse colon by the mass. 1 year after resection of the cystic tumour, recurrence occurred at the greater curvature of the stomach and in the liver, with a cystic appearance similar to the primary tumour. To our knowledge, the CT appearance of primary cystic MFH of the gastrocolic ligament has not been previously documented.

Background Scaphoid fractures are among the most common types of carpal bone injury; they can be easily overlooked in the acute stage. Scaphoid fractures detected in the subacute stage require a more meticulous and prompt approach, to prevent chronicity and regain wrist function. Methods The records of 30 patients were selected from 97 with scaphoid fractures surgically treated between 1994 and 2002. Fractures that were diagnosed between 2 weeks and 5 months (average, 2.2 months) after the injury were included. We report the fracture patterns and locations, as determined from radiographs, as well as the surgical methods used. The mean follow-up was 2.5 years. Results Oblique fractures (60%) were the most commonly overlooked fractures. Twenty-six patients (87%) underwent open surgery, and 23 (77%) required bone grafts. Percutaneous fixation was indicated for only four patients, whose fractures were reducible via either fluoroscopic or arthroscopic guidance. Osseous unions were achieved for 29 (97%) patients; these patients returned to their pre-injury level of activity. The average union time was 10.6 weeks. Conclusion Oblique-type scaphoid fractures are potentially unstable and may result in detrimental sequelae if overlooked in the acute stage. Accurate diagnosis is possible through critical skepticism and the meticulous scrutiny of radiographs. Prompt surgical intervention is associated with promising outcomes.

Mutation in UCH-L1 has been reported as a rare cause of autosomal dominant Parkinson's disease (PD). A S18Y polymorphism in the same gene has been associated with sporadic PD. We investigated the frequency of this polymorphism among the Han-Chinese ethnic population in a case–control study. A total of 600 patients with PD and 334 unrelated healthy controls were genotyped using PCR-restriction fragment length polymorphism analysis. We did not observe any difference in allele or genotype frequencies between the cases and the controls ( P > 0.05). Our results do not support a role for this variant in sporadic PD.

Mutations in the gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been recently linked with autosomal-dominant parkinsonism, and polymorphisms have been commonly associated with sporadic Parkinson's disease (PD). A p.2385GR variant has been reported as a risk factor for PD in Taiwan, Singapore and Japan. Herein, we have assessed the frequency of this polymorphism among the ethnic Han-Chinese population in a case-control study. A total of 600 patients with PD and 334 unrelated healthy controls were genotyped using PCR-restriction fragment length polymorphism analysis. Hardy-Weinberg equilibrium of each group was calculated, and differences in genotype frequencies between groups were assessed by the Chi-square test. In the PD cohort, 70 patients (11.7%) were heterozygous and 1 (0.2%) was homozygous for the p.2385GR variant. This was significantly more frequent than in the controls [3.3%, Odds ratio = 3.9, 95% confidence interval (CI) = 2.1-7.5, P0.01]. Clinically, the age of PD onset of the p.2385GR carriers was lower than the non-carriers (P = 0.01). Our study indicates that this LRRK2 p.2385GR substitution contributes to the development of PD in ethnic Han-Chinese population, which may play important implications for future study on molecular genetics and pathogenesis of PD.

Seidel locked nailing has been successfully used to treat a humeral shaft fracture or nonunion. However, if union fails despite this treatment, the next approach to try has not been well defined. We, therefore, developed a technique using a staple to enforce the local stability without removing the failed nail. The technique was very simple, and the outcome was always satisfactory.

A case of primary synovial sarcoma of the gastrocolic ligament is reported in a 37-year-old woman. CT showed an encapsulated intraabdominal cystic tumour with an amorphous solid component. Barium studies showed a mass at the gastrocolic ligament which elevated the gastric antrum and displaced the transverse colon downwards. This is the first report of synovial sarcoma formation in the gastrocolic ligament. This tumour may have originated from pluripotential mesenchyme.

Pulmonary lymphangioleiomyomatosis is a rare, progressive and fatal interstitial lung disease that affects women of child-bearing age. It is characterized by the nonneoplastic proliferation of atypical smooth muscle cells around lymphatics, venules, and bronchioles. Patients with pulmonary lymphangioleiomyomatosis most commonly present with exertional dyspnea and a cough. Pneumothorax is almost always found on the initial chest radiograph. We report a case of a 29-year-old woman who presented with abrupt right chest pain and progressive dyspnea. Physical examination in the emergency department was significantly diminished breath sounds over the right lung, and a chest X-ray revealed a right-sided pneumothorax. She required a chest tube for complete lung re-expansion. On the sixth day of admission, left-sided pneumothorax occurred and another chest tube was inserted. She underwent high-resolution computed tomography of the thorax with the findings of numerous cysts evenly distributed throughout the parenchyma of both lungs. Bilateral thoracotomy with lung biopsies and pleurodesis were performed and the surgical findings confirmed the presence of multiple, small, pink-colored cystic lesions on the surfaces of both lungs. Pathological examination showed the characteristic findings of pulmonary lymphangioleiomyomatosis.

Background Increasing evidence suggests that E-selectin contributes to tumour growth and metastasis, possibly by increasing angiogenesis and the adhesion of tumour cells to endothelial cells at distant sites. This study aimed to examine the relationship between preoperative levels of circulating soluble E-selectin and breast cancer. Methods Sixty-four consecutive women undergoing surgery for invasive breast cancer were studied prospectively. Venous blood samples were collected before the operation. A control group consisted of 16 patients with a benign breast tumour (eight with fibrocystic disease and eight with fibroadenoma). Serum concentrations of soluble E-selectin were measured by the quantitative sandwich enzyme immunoassay technique and compared with clinicopathological information. Results The mean(s.d.) serum level of soluble E-selectin in patients with invasive breast cancer was 73·7(20·9) ng/ml, compared with 36·3(5·6) ng/ml in the control group (P < 0·001). Furthermore, the serum levels of soluble E-selectin were significantly higher in women with oestrogen receptor-negative tumours (P = 0·001), poorly differentiated tumours (P < 0·001), more advanced primary tumour stage (P < 0·001), involved lymph nodes (P < 0·001), distant metastases (P < 0·001) and more advanced tumour node metastasis (TNM) stage (P < 0·001). On multivariate analysis, TNM stage (P < 0·001) was found to be an independent factor with regard to higher serum levels of soluble E-selectin. Conclusion Preoperative serum levels of soluble E-selectin might reflect the severity of invasive breast cancer; further evaluation is warranted.

We report a rare case of bilateral adrenocortical adenomas causing ACTH-independent Cushing's syndrome at different periods 9 yr apart. The subject, a 24-yr-old woman, in June 1989 had a typical Cushingoid appearance. Her baseline plasma cortisol levels did not show a diurnal rhythm and she had a very low baseline plasma ACTH level. Plasma cortisol levels could not be suppressed by overnight low-dose or two-day high-dose dexamethasone suppression test. Marked uptake of 131I-6beta-iodomethyl-19-norcholesterol (NP-59) was observed in the right adrenal gland. Abdominal computed tomography (CT) showed a right adrenal tumor. The right adrenal gland with adenoma was removed. The non-tumorous part of the adrenal cortex was atrophic. By April 1998, she had experienced a weight gain of more than 20 kg over a two-yr period. The baseline plasma cortisol levels were at the lower limit of the normal range with loss of diurnal rhythmicity. The baseline plasma ACTH levels were very low. Neither a two-day low-dose nor a two-day high-dose dexamethasone suppression test could suppress serum cortisol or urinary free cortisol levels. NP-59 adrenal scan revealed increased uptake of the left adrenal gland at 72 h after intravenous injection of the tracer. Abdominal CT and magnetic resonance imaging (MRI) all demonstrated a left adrenal mass. Left adrenalectomy was performed in June 1998; histological features showed a cortical adenoma and atrophic change in the non-tumorous part of the adrenal cortex. Elevated plasma ACTH levels after bilateral adrenalectomy could be suppressed with conventional corticosteroid replacement therapy and overnight low-dose dexamethasone suppression test.

Nonstructural 5A (NS5A) and the second envelope (E2) proteins of hepatitis C virus (HCV) have the potential to block interferon (IFN)-induced RNA-dependent protein kinase (PKR) and may therefore interfere with the response to IFN therapy, but controversy still exists regarding the relevance of this. This study aimed to assess whether mutations in these regions correlated with the response to combination therapy, IFN and ribavirin. Pretreatment parameters were analysed in 57 HCV-1b patients who had received IFN-alpha2b (3 or 5 MU three times weekly) and ribavirin (800-1200 mg per day) for 24 weeks. The amino acid sequences of the NS5A and PKR-eIF2alpha phosphorylation homology domain (E2-PePHD) were deduced from the corresponding coding sequence, which were determinated by direct sequencing of the HCV genome amplified by the polymerase chain reaction. Twenty (36%) patients achieved a sustained virological response (SVR). The mean number of amino acid substitutions in the NS5A-PKR binding domain (2209-2274), interferon sensitivity-determining region (ISDR) (2209-2248), and E2-PePHD sequence (659-670) in patients with and without SVR were 4.53 +/- 3.31 vs 2.83 +/- 1.78 (P = 0.094), 2.45 +/- 2.74 vs 1.03 +/- 1.32 (P = 0.042) and 0.25 +/- 0.70 vs 0.03 +/- 0.17 (P = 0.109), respectively. Patients with a mutant-type (>/= 4) NS5A-ISDR had a higher rate of SVR (six of nine, 67%) than those with wild-type (five of 22, 23%) (P = 0.038). Stepwise multiple logistic regression analysis of the factors (age, gender, viral load, cirrhosis rate, IFN dosage and amino acid substitutions) revealed that the mutation in NS5A-ISDR (>/= 4 vs < 4) was the only independent variable of treatment outcome. Our study showed that NS5A-ISDR mutations were correlated with the SVR to combination therapy in chronic HCV-1b patients in Taiwan.

Spinal cord compression due to extramedullary hematopoiesis is a well-known complication in a number of hematological diseases. Most of the patients present with progressive paraparesis due to the slow expansion of the extramedullary hematopoietic tissue. The authors report a case of chronic myeloproliferative disorder with spinal extramedullary hematopoiesis presenting with acute paraplegia. Chronic myeloproliferative disorder is an uncommon cause of spinal cord compression, especially when associated with acute paraplegia. The authors discuss the pathomechanism of this unusual presentation.

Thirty-six nonunions of the femoral shaft were treated by closed removal of previous nails, reaming of marrow cavity as widely as possible, and reinsertion of stable intramedullary nail. Indications included femoral shaft aseptic nonunions with inserted intramedullary nail, nonunions with a radiolucent line, without segmental bony defects, and less than 1 cm shortening. They were followed up for a median of 2.9 (1–6) years. Thirty-three nonunions healed uneventfully within a median period of 4 (3–8) months. Except for three persistent nonunions, no other significant complications occurred.

Antibiotic G0069A, produced by a Streptomyces strain isolated from a soil sample collected in Yunnan Province, China, has been verified as a clavam peptide. Determined by MTT assay, G0069A showed highly potent cytotoxicity to cancer cells with multidrug resistance. The IC50 values of G0069A to KB and KB/VCR cells were 0.60 and 0.46 mumol.L-1, and to MCF-7 and MCF-7/ADM cells were 1.4 and 1.2 mumol.L-1, respectively. G0069A displayed equally potent cytotoxicity to the parent cell lines and their resistant sublines. When administered by i.v. or i.p. route at tolerable doses, G0069A exhibited markedly inhibitory effect on the growth of sarcoma 180 and hepatoma 22 in mice. At dose level of 3 mg.kg-1, i.v., x3, sarcoma 180 and hepatoma 22 were suppressed by 87%(P0.01) and 72%(P0.01), respectively. The results indicate that G0069A is a beta-lactam antibiotic showing antitumor activity.

Extracapsular hip infected nonunion after stabilization with a sliding hip screw (SCS) is uncommon and a convincing treatment method has not yet been reported in the literature.Thirteen consecutive patients who sustained such a disability were treated with removal of SCS, local radical debridement, vancomycin powder with or without gentamicin solution application, re-insertion of a new SCS, and autogenous cancellous bone grafting. Postoperatively, ambulation with regulated weight bearing was encouraged as early as possible. Infectious microorganisms in 76% (10/13) of the lesion sites were oxacillin-resistant staphylococcus aureus (ORSA).Twelve patients were followed-up for at least 2 years (range, 2~6 years; median, 4 years) and all nonunions healed. The union rate was 100% (12/12) with a median union period of 4 months (range, 3~6 months). No wound infection recurred at the last follow-up. The satisfactory rate of hip function was 92% (11/12, P0.001).We, therefore, recommend this surgical procedure to treat all patients with a similar disability because of its high success rate and low complication rate.

We tested the hypothesis that in utero ethanol exposure results in changes in fetal and maternal adrenocorticotropin (ACTH) and cortisol during the third trimester equivalent, by using a chronically instrumented fetal sheep model.Pregnant ewes received saline or ethanol intravenously 3 consecutive days per week from day 109 to day 132 of gestation. Fetal and maternal blood samples were collected on days 118 and 132.Maternal and fetal ACTH and cortisol values increased on days 118 and 132 of gestation in response to ethanol infusions that created blood ethanol concentrations (BECs) that are easily achievable by human drinkers. Peak ACTH and cortisol values were detected 30 to 60 min after peak BECs were achieved.Chronic ethanol exposure during the third trimester equivalent in sheep resulted in repeated activation of the hypothalamus-pituitary-adrenal axis in both the mother and fetus. Temporally, the patterns of maternal and fetal responses to ethanol infusion were similar. We conclude that ovine maternal ethanol exposure during the third trimester equivalent increases fetal ACTH and cortisol concentrations, hormonal responses that may play a role in mediating alcohol-related birth defects.

Although the mechanisms that underlie fetal alcohol-induced neuronal loss have not been determined, hypoxia/hypoxemia has been considered a leading candidate. This study was designed to test the hypothesis that neuronal loss could occur in the developing brain in the absence of fetal hypoxemia.Three groups of pregnant sheep were used: a control group, a binge-drinking group, and a pair-fed group. The alcohol and pair-fed animals were anesthetized on day 113 of pregnancy, and the mothers and fetuses were instrumented with arterial and venous catheters. All animals were killed on day 133. Stereological cell counting techniques were used to estimate the total number of Purkinje cells in the fetal cerebellum.Peak maternal and fetal blood alcohol concentrations did not produce fetal hypoxemia. Nevertheless, there was a 25% loss of Purkinje cells of the cerebellum in the alcohol-exposed fetuses compared with that in the pair-fed controls. The loss of neurons was not accompanied by microencephaly or a concomitant decrease in either cerebellar weight or volume of the fetal cerebellum.Neuronal loss can be observed after alcohol exposure during the third trimester equivalent in fetal sheep in the absence of alcohol-induced hypoxemia. Furthermore, cell loss in the absence of deficits in gross brain weight or regional brain volume indicates that the lack of gross brain volume deficits from magnetic resonance imaging techniques is not a reliable indication that the brain is unaffected by the alcohol exposure.

The aim of this study was to investigate the value of chest sonography in the diagnosis and management of patients with chest radiograph opacities in an emergency department.Seventy-eight patients with acute chest complaints whose chest radiographs showed opacities underwent chest sonography. The initial diagnosis (based on clinical manifestations and the chest radiograph), the sonographic diagnosis (before any invasive procedures), and the final diagnosis were compared. The impact of chest sonography on the management of patients with chest opacities was also analyzed.The initial diagnosis was in concordance with the final diagnosis in 60 (77%) of the 78 patients, while the sonographic diagnosis was in concordance with the final diagnosis in 75 (96%) of the patients. Chest sonography therefore significantly increased the rate of correct diagnoses from 77% (95% confidence interval, 67-87%) to 96% (95% confidence interval, 92-100%; p0.0001). Sonography provided new information in 52 patients (67%): a different diagnosis from the initial diagnosis in 18 patients and additional diagnostic information in 34 patients. New information gained from sonography affected the management of 35 patients. Sonography also provided help in guiding 42 (70%) of 60 invasive diagnostic procedures and 22 (73%) of 30 invasive therapeutic procedures for which chest radiography and physical examination had failed to or were unsuitable to provide guidance. Overall, sonography assisted in the management of 64 (82%) of 78 patients. Sonography was of no benefit in 14 patients (18%).We conclude that chest sonography can complement chest radiography and is of value in the diagnosis and management of emergency department patients with acute chest diseases presenting as opacities on chest radiographs.

To estimate the prevalence of primary nocturnal enuresis (PNE) in Taiwanese children, and to examine factors associated with PNE and its severity.In all, 1683 questionnaires were sent to parents of schoolchildren aged 6-11 years randomly selected from three primary schools in Taipei City, Taiwan. The questionnaire was designed to collect information about the prevalence of and factors associated with PNE.Of the questionnaires distributed, 1176 (70%) were completed. PNE was reported in 92 (8%) of the children; nine (10%) of these children were wet3 nights per week. Factors associated with PNE included male gender, deep sleep, divorced parents or separated family and a positive family history of enuresis. Of these factors, only those children with deep sleep were more likely to have3 wet nights per week.The prevalence of and factors associated with PNE in Taiwan are similar to those reported in Western countries, but the percentage of children with severe enuresis is lower than in Sweden, France and Turkey. Deep sleepers are more likely to have severe enuresis.

Alcohol-induced zinc deficiency is one of the mechanisms proposed as a cause of developmental brain damage associated with fetal alcohol syndrome. It is known that alcohol exposure during the brain growth spurt period leads to cerebellar Purkinje cell loss. Therefore, this study examined whether zinc supplementation was capable of preventing alcohol-induced Purkinje cell loss in the cerebellar vermis in a neonatal rat model system.Sprague-Dawley rat pups were given alcohol (EtOH; 4.5 g/kg/day), zinc (Zn; 0.54 mg/ml diet; [10 times the regular diet Zn concentration]), or both from postnatal days (PD) 4 through 9 using the artificial-rearing paradigm. A gastrostomy control (GC) and a suckle control group (SC) also were included. All pups were killed on PD 10. Following perfusion, the cerebellar vermis was dissected and processed for stereological cell counting. The total number of Purkinje cells and the volume of the cerebellar vermis were determined.Alcohol produced a significant loss of Purkinje cells compared with that in the GC group (no EtOH and no Zn supplement). The zinc supplementation had no effect in attenuating alcohol-induced Purkinje cell loss in the cerebellar vermis. In fact, the serum zinc concentration data indicated higher zinc concentrations following either EtOH or Zn treatment. Interestingly, the GC group showed a significantly lower zinc concentration compared with the SC group, even though no significant difference in Purkinje cell numbers was observed between these two control groups.These findings indicate that alcohol exposure during the third trimester equivalent did not result in zinc deficiency in this neonatal rat model system, nor did zinc supplementation rescue the alcohol-induced Purkinje cell loss in the cerebellar vermis. These findings showed clearly that the serum zinc concentration was not correlated with Purkinje cell loss, suggesting that alcohol-induced loss of cerebellar Purkinje cells in this neonatal rat model system is independent of the availability of serum zinc.

The mechanisms by which maternal ethanol abuse during pregnancy causes neurodevelopmental injury in the fetus are not well understood. The purpose of this study was to use a chronically instrumented fetal sheep model system to determine if a binge pattern of ethanol exposure administered throughout the third trimester reduced fetal arterial partial pressure of oxygen (PaO2); a positive finding would support the hypothesis that fetal hypoxemia may play a role in mediating ethanol-related birth defects.Pregnant ewes received saline or 0.75, 1.25, 1.5, or 1.75 g/kg of ethanol intravenously over 1 hr beginning on day 109 of gestation (term = 145 days) for 3 consecutive days per week followed by 4 days without exposure. The fetuses were surgically instrumented on day 113, and experiments were performed on days 118 or 132, the 6th and the 12th ethanol exposure, respectively.Ethanol infusions resulted in peak blood ethanol concentrations of 80.8 +/- 6.5, 182.5 +/- 13.5, 224.4 +/- 13.9, and 260.6 +/- 20.0 mg/dl +/- SEM (maternal) and 70.0 +/- 5.9, 149.7 +/- 9.0, 216.9 +/- 14.0, and 233.3 +/- 19.8 mg/dl +/- SEM (fetal) in response to the 0.75, 1.25, 1.5, and 1.75 g/kg doses, respectively. Maternal and fetal heart rate and maternal blood pressure increased whereas fetal blood pressure decreased in a dose-dependent manner in response to ethanol infusions. Maternal and fetal arterial pH decreased and arterial partial pressures of carbon dioxide increased in response to ethanol infusions. Maternal PaO2 decreased whereas fetal PaO2 did not change in response to ethanol infusions.A binge ethanol exposure paradigm, three consecutive days per week throughout the third trimester at ethanol doses that created blood ethanol concentrations commonly achieved by human ethanol abusers, resulted in changes in maternal and fetal heart rate, changes in blood pressure, hypercapnea, acidemia, and maternal, but not fetal, hypoxemia. We conclude that in an ovine model system, ethanol doses that create blood ethanol concentrations as high as 260 mg/dl do not result in fetal hypoxemia. Remaining issues to address with this model system are whether neurodevelopmental injuries that are associated with maternal ethanol abuse are mediated by a reduction in fetal cerebral blood flow, fetal hypercapnea, or acidemia.

Using a modified AO tension band wiring technique to treat a patellar fracture has become popular and has achieved a high success rate. However, the technique of Kirschner wire insertion has not been considered in detail, which may migrate and consequently introduce fragments loss of reduction. A revised technique involving bending both ends of the Kirschner wires was prospectively studied. Sixty-eight consecutive patients were so treated, and 62 patients were followed-up for at least 2 years (range 2-6 years). All fractures healed with a union rate of 100% (62/62) and a union period of 2.5 +/- 0.5 months. Skin irritation was noted in 2 patients (3%). All patients achieved a satisfactory result. We therefore recommend this revised technique to treat all patellar fractures because of its high union rate and low complication rate.

Angiogenin (ANG), a potent inducer of neovascularization, is secreted by some types of human tumor cells and appears crucial for their growth. This study was designed with the aim to investigate any correlation between the serum angiogenin and the clinicopathological variables and furthermore evaluate the prognostic value of serum angiogenin in patients with breast cancer.Sixty-four consecutive patients with invasive breast cancer undergoing surgery were prospectively included and evaluated. Venous blood samples were collected before surgery. Sera were obtained by centrifugation and stored at -70 degrees C until assayed. The control group consisted of 16 patients with benign breast tumor (8 with fibrocystic disease and 8 with fibroadenoma). Serum concentration of angiogenin was measured by the quantitative sandwich enzyme immunoassay technique. The data on primary tumor staging, age, estrogen receptor, lymph node status, distant metastases and TNM staging were reviewed and recorded.The mean value of serum angiogenin in patients with invasive breast cancer was 2123.95 +/- 324.34 pg/ml and that of control group were 2108.16 +/- 398.20 pg/ml (fibrocystic disease) and 2010.27 +/- 318.40 pg/ml (fibroadenoma). The difference was not significant (p = 0.66). Furthermore, with univariate analysis, there were no significant differences in serum angiogenin levels between the subgroups of the above-mentioned clinicopathological variables.Serum angiogenin levels did not appear as a meaningful prognostic parameter for invasive breast cancer.

Congenital hepatic fibrosis (CHF) is associated with autosomal recessive polycystic kidney disease (ARPKD). Although cystic renal dysplasia (CRD) is the most common form of newborn cystic renal disease, this disorder of anomalous metanephric differentiation is only rarely found concurrent with CHF. Our literature review found only 13 sporadic and 12 familial non-syndromic cases of combined bilateral CRD and CHF reported outside Taiwan. We report the first domestic case, occurring in a fetus of 18 weeks' gestational age, which was the second pregnancy of a 24-year-old mother with a previous history of spontaneous abortion at 10 weeks' gestational age. Postmortem autopsy confirmed the concurrence of bilateral CRD and CHF without associated anomalies of other visceral organs and external appearance. This particular association must be differentiated from ARPKD and liver disease, in regard to ultrasonographic examination and genetic counseling.

We have quantified the expression of all 4 isoforms of vascular endothelial growth factor (VEGF) mRNA in non-small-cell lung cancer (NSCLC) using a new kinetic quantitative PCR method, real-time quantitative (RTQ) RT-PCR, and investigated the association between VEGF expression at the mRNA and protein levels and the clinicopathologic variables, tumor angiogenesis, patient survival and timing of relapse. Surgical tumor specimens from 72 NCSLC patients (37 squamous-cell carcinomas, 35 adenocarcinomas) were examined. Twenty-eight patients had stage I, 10 stage II and 34 stage IIIA or IIIB disease. Total VEGF mRNA (all 4 isoforms) was quantified by RTQ RT-PCR, while VEGF protein expression and microvessel number in tumors were assessed immunohistochemically. VEGF mRNA was detected in all 72 tumor samples at significantly higher levels than in adjacent normal tissue. Tumoral VEGF mRNA levels correlated strongly with the VEGF protein staining score and microvessel count. Adenocarcinomas showed significantly higher VEGF mRNA expression and a higher protein staining score than squamous-cell carcinomas. High tumoral VEGF mRNA expression was associated with advanced (IIIA or IIIB) tumor stage, lymph node metastasis, high tumoral microvessel counts, short patient survival (24 months) and early relapse (12 months), while a high VEGF protein staining score was associated with high tumoral microvessel counts, short patient survival and early relapse. Patients with high tumoral levels of both VEGF mRNA and protein had significantly shorter survival and earlier relapse. In multivariate analysis, the VEGF protein staining score and nodal status were the most important independent predictors of survival and recurrence. We conclude that RTQ RT-PCR is a sensitive method for detecting and quantifying VEGF mRNA expression in NSCLC and that the expression levels of total VEGF mRNA and protein in NSCLC are strongly associated with histologic type, tumor angiogenesis, survival and timing of relapse. High VEGF expression in adenocarcinomas may contribute to their greater metastatic potential.

Mesenchymal neoplasms of the gastrointestinal tract remain controversial in regard to both diagnostic criteria and prognostic factors. In order to investigate whether DNA ploidy in a single area of a tumor can be representative of the entire tumor, multiple samples from the same tumor were analyzed in 79 cases of gastrointestinal stromal tumors.Forty-three male and 36 female patients, aged 11 to 80 years with stromal tumors of the GI tract were selected. Flow cytometric DNA ploidy analysis was done on tissue cut from paraffin blocks by using the modified technique of Hedley et al.All 34 benign stromal tumors displayed a concordant diploid DNA content. Eighteen (40%) of the 45 malignant stromal tumors (13 low-grade, 5 high-grade) were diploid. Aneuploid and polyploid DNA stemlines were found in 10 cases (43.4%) of low-grade stromal tumors, and in 17 cases (77.2%) of high-grade stromal tumors. DNA polyploidy was identified in 21 (46.7%) of 45 malignant stromal tumors. Also, aneuploid populations were accompanied by diploid populations.DNA content correlated well with histologic category. Tumor aneuploidy was more frequently seen in tumors of advanced stage, but no relationship was seen between tumor stage and the presence of tumor heterogeneity. Differences in ploidy levels were thus not necessarily associated with apparent differences in histologic patterns. The mechanism responsible for regional differences in DNA ploidy in the same tumor remain unexplained. Several hypotheses are reviewed.

Idiopathic ventricular fibrillation (VF) is extremely rare in children who have not previously undergone cardiac surgery. Patients resuscitated from idiopathic VF remain at risk for recurrence. The use of an implantable cardioverter-defibrillator (ICD) effectively prevents such recurrences. We report the case of a 12-year-old girl who had a history of recurrent syncope and had survived an episode of VF. Serial studies after prolonged but successful resuscitation, including echocardiography, an electrocardiogram (ECG), and coronary angiography failed to reveal abnormal cardiac structures responsible for VF. No abnormal conduction pathways or abnormal early or late after depolarization were found on electrophysiologic study. The ST segments of the 12-lead ECG remained normal after procainamide challenge. The patient underwent ICD implantation 2 weeks after admission and syncope did not recur during a follow-up of 14 months. This report emphasizes that idiopathic VF may be responsible for syncope in children. ICD therapy prevents the recurrence of idiopathic VF and the associated risk of sudden death.

From January 1980 to February 1997, 19 cases, 8 males and 11 females, of choledochal cyst were diagnosed before one year old. The majority of patients were diagnosed by ultrasonography before 6 months old (15/19; 79%), including two diagnosed prenatally. According to Todani's classification, type Ia was the most common (74%), followed by type Ic (26%). Fourteen patients underwent Roux-en-Y choledocho- or hepatico-jejunostomy and cyst excision, 3 patients underwent Kasai operation, and I patient underwent external biliary drainage only. The remaining one patient with Trisomy 18 anomaly refused operation. Four of the 10 patients in whom liver histologic examinations were performed, had liver cirrhosis. The follow-up period of these patients ranged from 6 months to 9 years, with a mean of 4.1 years. We divided these 19 cases into 2 groups, according to the presence or absence of biliary atresia. In the 7 infants with biliary atresia (37%), all presented with jaundice and alcoholic stool. Two patients died due to delayed presentation and surgery, both had liver cirrhosis. One patient is living with liver cirrhosis. Another patient was lost to follow-up, but frequent cholangitis was noted till 8 months old. The remaining 3 patients are living and well. In the 12 without biliary atresia, 9 patients are living and well. Two patients died, one due to Trisomy 18 anomaly and the other with delayed surgery and liver cirrhosis. One case was lost to follow-up. In summary: 1-) a possibility of the association of biliary atresia in infants with choledochal cyst should be carefully searched and considered as a unique group; 2) ultrasonography is a good diagnostic tool in choledochal cyst during prenatal or infancy period; 3) the mortality cases were characterized by prolonged bile stasis, biliary cirrhosis, delayed surgery, or multiple anomalies; 4) surgery should be performed as early as possible for those with persistent jaundice and light colored stools.