Anti-Bacterial Agents ; pharmacology ; therapeutic use ; Burkholderia pseudomallei ; drug effects ; isolation & purification ; Ceftazidime ; pharmacology ; therapeutic use ; Comorbidity ; Drug Resistance, Bacterial ; Humans ; Lymphadenitis ; physiopathology ; Male ; Mediastinal Diseases ; physiopathology ; Melioidosis ; etiology ; physiopathology ; Middle Aged

INTRODUCTIONSingapore was substantially affected by three 20th Century pandemics. This study describes the course of the pandemics, and the preventive measures adopted.

MATERIALS AND METHODSWe reviewed and researched a wide range of material including peer-reviewed journal articles, Ministry of Health reports, Straits Settlements reports and newspaper articles. Monthly mortality data were obtained from various official sources in Singapore.

RESULTSThe 1918 epidemic in Singapore occurred in 2 waves--June to July, and October to November--resulting in up to 3500 deaths. The 1957 epidemic occurred in May, and resulted in widespread morbidity, with 77,000 outpatient attendances in government clinics alone. The 1968 epidemic occurred in August and lasted a few weeks, with outpatient attendances increasing by more than 65%. The preventive measures instituted by the Singapore government during the pandemics included the closure of schools, promulgation of public health messages, setting up of influenza treatment centres, and screening at ports. Students, businessmen and healthcare workers were all severely affected by the pandemics.

CONCLUSIONSTropical cities should be prepared in case of a future pandemic. Some of the preventive measures used in previous pandemics may be applicable during the next pandemic.

Disease Outbreaks ; history ; statistics & numerical data ; History, 20th Century ; Humans ; Influenza, Human ; epidemiology ; history ; mortality ; Public Health ; history ; Singapore ; epidemiology

OBJECTIVETo summarize our experience in the diagnosis and treatment of malignant pancreatic endocrine tumour.

METHODSWe retrospectively reviewed 36 cases of malignant pancreatic endocrine tumours in our hospital from July 1987 to April 2002, and summarized its clinical features.

RESULTSLiver metastasis was the main malignant manifestation of malignant pancreatic endocrine tumours (incidence rate 72.2%). Removals of primary lesion and isolated hepatic metastatic lesion were means of curative therapy. Interventional chemotherapy was an important adjuvant treatment.

CONCLUSIONComprehensive therapy plays an important role in improving the prognosis of malignant pancreatic endocrine tumour.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Islet Cell ; diagnosis ; pathology ; therapy ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Gastrectomy ; Gastrinoma ; diagnosis ; pathology ; therapy ; Glucagonoma ; diagnosis ; pathology ; therapy ; Humans ; Insulinoma ; diagnosis ; pathology ; therapy ; Liver Neoplasms ; secondary ; therapy ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Pancreas ; surgery ; Pancreatectomy ; Pancreatic Neoplasms ; diagnosis ; pathology ; therapy ; Retrospective Studies

This study investigated the regulatory role of nerve growth factor (NGF) in sirtuin 1 (SIRT1) expression in cholestatic livers. We evaluated the expression of NGF and its cognate receptors in human livers with hepatolithiasis and the effects of NGF therapy on liver injury and hepatic SIRT1 expression in a bile duct ligation (BDL) mouse model. Histopathological and molecular analyses showed that the hepatocytes of human diseased livers expressed NGF, proNGF (a precursor of NGF), TrkA and p75NTR, whereas only p75NTR was upregulated in hepatolithiasis, compared with non-hepatolithiasis livers. In the BDL model without NGF therapy, p75NTR, but not TrkA antagonism, significantly deteriorated BDL-induced liver injury. By contrast, the hepatoprotective effect of NGF was abrogated only by TrkA and not by p75NTR antagonism in animals receiving NGF therapy. Intriguingly, a positive correlation between hepatic SIRT1 and NGF expression was found in human livers. In vitro studies demonstrated that NGF upregulated SIRT1 expression in mouse livers and human Huh-7 and rodent hepatocytes. Both NGF and proNGF induced protective effects against hydrogen peroxide-induced cytotoxicity in Huh-7 cells, whereas inhibition of TrkA and p75NTR activity prevented oxidative cell death. Mechanistically, NGF, but not proNGF, upregulated SIRT1 expression in human Huh-7 and rodent hepatocytes via nuclear factor (NF)-κB activity, whereas NGF-induced phosphoinositide-3 kinase/Akt, extracellular signal–regulated kinase and NF-κB signaling and SIRT1 activity were involved in its hepatoprotective effects against oxidative injury. These findings suggest that pharmacological manipulation of the NGF/SIRT1 axis might serve as a novel approach for the treatment of cholestatic disease.
Animals ; Bile Ducts ; Cell Death ; Cholestasis ; Hepatocytes ; Humans ; Hydrogen ; In Vitro Techniques ; Ligation ; Liver ; Mice ; Nerve Growth Factor ; Phosphotransferases ; Rodentia ; Sirtuin 1

BACKGROUNDPatients with congenital scoliosis often also have intraspinal abnormalities and other organ defects, and few studies of the effects of congenital scoliosis on cardiac function and structure have been published.

METHODSA total of 215 adolescent patients with congenital scoliosis (average age, 13.58 years) underwent preoperative echocardiography and were then assigned to subgroups according to apex vertebral rotation, side of convexity, curvature severity in the coronal and sagittal planes, type of deformity, and sex. Differences between the subgroups were compared by independent-samples t test or a one-factor analysis of variance.

RESULTSWe observed statistically significant differences between patients with right-sided scoliosis curvature and those with left-sided scoliosis curvature, respectively, in left ventricular inner diameter at end-diastole ((39.39 +/- 4.66) mm vs (41.74 +/- 4.90) mm), left ventricular inner diameter at end-systole ((24.80 +/- 3.45) mm vs (25.92 +/- 3.07) mm), interventricular septum thickness at end-diastole ((5.66 +/- 0.98) mm vs (5.98 +/- 1.03) mm), and posterior wall of left ventricle at end-diastole ((5.61 +/- 0.98) mm vs (6.06 +/- 1.20) mm). When the patients were evaluated by coronal plane Cobb angle, significant differences were found between those with Cobb angle of 40 degrees - 80 degrees and of > 80 degrees in left ventricular inner diameter at end-diastole ((40.97 +/- 5.06) mm vs (38.98 +/- 4.45) mm) and left ventricular inner diameter at end-systole ((25.53 +/- 3.39) mm vs (24.36 +/- 3.14) mm), respectively. When the patients were evaluated by sagittal plane Cobb angle (< 20 degrees, group 1; 20 degrees - 40 degrees, group 2; > 40 degrees, group 3), significant differences were found in right ventricular diameter between those with Cobb angle of < 20 degrees and of 20 degrees - 40 degrees ((18.27 +/- 3.66) mm vs (16.54 +/- 3.57) mm) and in diameter of aortic root between those with Cobb angle of 20 degrees - 40 degrees and of > 40 degrees ((23.83 +/- 3.39) mm vs (24.90 +/- 3.30) mm), respectively. No significant differences were found in ejection fraction and fractional shortening between patients according to apex vertebral rotation, side of convexity, coronal plane and sagittal plane Cobb angles, type of deformity, or sex.

CONCLUSIONSCongenital scoliosis influences cardiac structure, but not function.

Adolescent ; Child ; Congenital Abnormalities ; physiopathology ; Echocardiography ; methods ; Female ; Heart ; anatomy & histology ; diagnostic imaging ; physiology ; Humans ; Male ; Radiography ; Retrospective Studies ; Scoliosis ; physiopathology ; Young Adult

Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence, partial adherence, and in reducing relapse in BD. Various long-acting injectable (LAI) antipsychotics are available, including fluphenazine decanoate, haloperidol decanoate, olanzapine pamoate, risperidone microspheres, paliperidone palmitate, and aripiprazole monohydrate. Due to the increasing number of BD patients receiving LAI antipsychotics, treatment guidelines have been developed. However, the clinical applicability of LAI antipsychotics remains a global cause for concern, particularly in Asian countries. Expert physicians from Taiwan participated in a consensus meeting, which was held to review key areas based on both current literature and clinical practice. The purpose of this meeting was to generate a practical and implementable set of recommendations for LAI antipsychotic use to treat BD; target patient groups, dosage, administration, and adverse effects were considered. Experts recommended using LAI antipsychotics in patients with schizophrenia, rapid cycling BD, BD I, and bipolar-type schizoaffective disorder. LAI antipsychotic use was recommended in BD patients with the following characteristics: multiple episodes and low adherence; seldom yet serious episodes; low adherence potential per a physician's clinical judgment; preference for injectable agents over oral agents; and multiple oral agent users still experiencing residual symptoms.
Antipsychotic Agents* ; Asian Continental Ancestry Group ; Bipolar Disorder* ; Consensus* ; Fluphenazine ; Haloperidol ; Humans ; Judgment ; Microspheres ; Patient Compliance ; Psychotic Disorders ; Recurrence ; Risperidone ; Schizophrenia ; Taiwan ; Aripiprazole ; Paliperidone Palmitate

Background/Aims: Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). Conclusions HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.

Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein. Moreover, treatment with either a specific inhibitor of SHP-1 or SHP-1-targeted siRNA reduced the apoptotic effects of nintedanib, which validates the role of SHP-1 in nintedanib-mediated apoptosis. Furthermore, nintedanib-induced apoptosis was attenuated in TNBC cells expressing SHP-1 mutants with constantly open conformations, suggesting that the autoinhibitory mechanism of SHP-1 attenuated the effects of nintedanib. Importantly, nintedanib significantly inhibited tumor growth via the SHP-1/p-STAT3 pathway. Clinically, SHP-1 levels were downregulated, whereas p-STAT3 was upregulated in tumor tissues, and SHP-1 transcripts were associated with improved disease-free survival in TNBC patients. Our findings revealed that nintedanib induces TNBC apoptosis by acting as a SHP-1 agonist, suggesting that targeting STAT3 by enhancing SHP-1 expression could be a viable therapeutic strategy against TNBC.
Apoptosis* ; Breast Neoplasms ; Disease-Free Survival ; Humans ; Protein-Tyrosine Kinases* ; RNA, Small Interfering ; Triple Negative Breast Neoplasms* ; Tyrosine*

Adolescent ; Child ; Female ; Humans ; Male ; Marfan Syndrome ; complications ; diagnostic imaging ; Radiography ; Scoliosis ; diagnostic imaging ; surgery