Liquid chromatography tandem mass chromatography (LC-MS/MS) is an important hyphenated technique for quantitative analysis of drugs in biological fluids. Because of high sensitivity and selectivity, LC-MS/MS has been used for pharmacokinetic studies, metabolites identification in the plasma and urine. This manuscript gives comprehensive analytical review, focusing on chromatographic separation approaches (column packing materials, column length and mobile phase) as well as different acquisition modes (SIM, MRM) for quantitative analysis of glucocorticoids and stimulants. This review is not meant to be exhaustive but rather to provide a general overview for detection and confirmation of target drugs using LC-MS/MS and thus useful in the doping analysis, toxicological studies as well as in pharmaceutical analysis.

OBJECTIVETo survey the status of diagnosis and treatment of biliary tract cancer in Shanghai.

METHODSA clinical epidemiology investigation was carried out on 658 new cases of biliary duct cancers aged 35-74, that registered between June 1997 and May 2001 in urban Shanghai. Clinical findings were collected in 390 gallbladder cancer, 195 bile duct cancer and 73 ampullary cancer.

RESULTSBiliary tract cancers mainly occurred in elderly patients. Ratio of males to female was 1:2.61 in gallbladder cancer, while bile duct cancer and ampullary cancer were slightly more common in men. Association with gallstones was 68.5%, 43.1% and 22.4% for gallbladder cancer, bile duct cancer and ampullary cancer, respectively. Diagnostic accuracy rate of B-ultrasonography was 63.1% in gallbladder cancer. Incidental gallbladder cancer accounted for 20%, while stage IVA and IVB patients reached up to 43.6%. Misdiagnosis rate was still high in bile duct cancer and ampullary cancer, it was 19.1% and 47.1% respectively. In addition, most patients presented jaundice at diagnosis. 69 cases (18.2%) of gallbladder cancer, 50 cases (25.6%) of bile duct cancer and 54 cases (74%) of ampullary cancer underwent radical resection, the 1-, 3- and 5-year survival rates were 58.5%, 42.8% and 40.7%, 58%, 28.3% and 11.1%, 81.5%, 39.2% and 26.9%, respectively. 79 patients with bile duct cancer underwent palliative drainage, and most cases died within 1 year. Metal endo-prostheses or plastic stents were placed into the biliary tract in 38 patients. The median survival was about 7 months.

CONCLUSIONSIt is difficult to make early diagnosis of biliary tract cancers. Standardization of the operation for gallbladder cancer must be respected. Surgical exploration should be undertaken when a bile duct cancer is suspected and there are no contraindications to surgery. Pancreatoduodenectomy should be recommended for ampullary cancer.

Biliary Tract Neoplasms ; diagnosis ; epidemiology ; mortality ; therapy ; China ; epidemiology ; Data Collection ; Female ; Humans ; Male ; Survival Rate

OBJECTIVETo investigate the relationship between tea consumption, biliary tract cancers and gallstone disease.

METHODSA population-based case-control study was conducted in urban Shanghai from 1 June 1997 to 31 May 2001 involving interviews with 627 new cases of biliary tract cancers (including 368 cases of gallbladder cancer, 191 cases of extrahepatic bile duct cancer and 68 cases of cancer of the ampulla of Vater) aged 35 to 74 years and 959 population controls frequency-matched to cases by gender and age in five-year group. 1037 patients of gallstone disease were selected from the same hospital. All subjects were interviewed in person by trained interviewers by use of a structured questionnaire. Unconditional logistic regression analysis was used to calculate adjusted odds ratio (OR) and 95% confidence interval (CI).

RESULTSCompared with tea non-drinkers, current tea consumption was inversely associated with risk of gallbladder cancer, extrahepatic bile duct cancer and gallstone disease among females with OR of 0.57 (95% CI: 0.34-0.96), 0.53 (95% CI: 0.27-1.03) and 0.71 (95% CI: 0.51-0.99), respectively. OR declined with younger age at initiation of tea drinking and with longer duration of tea consumption (P for trend < 0.05). Among males, the corresponding OR were mostly below one, although not statistically significant.

CONCLUSIONTea consumption may decrease the risk of cancers of the gallbladder and extrahepatic bile duct among females. The protective effect appears to be independent of gallstone disease.

Adult ; Aged ; Bile Ducts, Extrahepatic ; Biliary Tract Neoplasms ; epidemiology ; etiology ; Case-Control Studies ; China ; epidemiology ; Female ; Flavonoids ; pharmacology ; Gallbladder Neoplasms ; epidemiology ; etiology ; Gallstones ; epidemiology ; etiology ; Humans ; Male ; Middle Aged ; Phenols ; pharmacology ; Polyphenols ; Protective Agents ; pharmacology ; Risk Factors ; Tea ; chemistry

PURPOSE: Partner and localizer of BRCA2 (PALB2) is a breast cancer susceptibility gene that plays an important role in DNA repair. This is the first study assessing the prevalence of PALB2 mutations in early-onset and familial breast/ovarian cancer patients from Pakistan. MATERIALS AND METHODS: PALB2 mutation screening was performed in 370 Pakistani patients with early-onset and familial breast/ovarian cancer, who were negative for BRCA1, BRCA2, TP53, CHEK2, and RAD51C mutations, using denaturing high-performance liquid chromatography analysis. Mutations were confirmed by DNA sequencing. Novel PALB2 alterations were analyzed for their potential effect on protein function or splicing using various in silico prediction tools. Three-hundred and seventy-two healthy controls were screened for the presence of the identified (potentially) functional mutations. RESULTS: A novel nonsense mutation, p.Y743*, was identified in one familial breast cancer patient (1/127, 0.8%). Besides, four in silico-predicted potentially functional mutations including three missense mutations and one 5' untranslated region mutation were identified: p.D498Y, novel p.G644R, novel p.E744K, and novel c.-134_-133delTCinsGGGT. The mutations p.Y743* and p.D498Y were identified in two familial patients diagnosed with unilateral or synchronous bilateral breast cancer at the ages of 29 and 39, respectively. The other mutations were identified in an early-onset (≤ 30 years of age) breast cancer patient each. All five mutations were absent in 372 healthy controls suggesting that they are disease associated. CONCLUSION: Our findings show that PALB2 mutations account for a small proportion of early-onset and hereditary breast/ovarian cancer cases in Pakistan.
5' Untranslated Regions ; Breast Neoplasms ; Chromatography, Liquid ; Codon, Nonsense ; Computer Simulation ; DNA Repair ; Germ-Line Mutation ; Humans ; Mass Screening ; Mutation, Missense ; Pakistan ; Prevalence ; Sequence Analysis, DNA

A multi-centred study was designed to collect dengue epidemiologic data from government and registered private hospitals/clinics and maintained archive of frozen specimens in bio-bank to be used for future dengue epidemic control program, and assess the epidemiology of dengue fever (DF) by evaluating biochemical and oxidative status of patients. ELISA IgM antibodies test was done to confirm DF. From August 2010 to December 2011, 101 confirmed blood samples of DF patients referred to pathology lab of Jinnah Hospital Lahore were subjected to the epidemiologic assessment by evaluating the biochemical and physiological indices and alterations of circulating antioxidants. Clinical features of DF patients and effect of fever on blood components and serum proteins of liver were recorded. The hospital stay in DF, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) showed significant difference. Significant increases in serum alanine amino transferase (ALT) (P=0.000), aspartate amino transferase (AST) (P=0.000), alkaline phosphatase (ALP) (P=0.000), malondialdehyde (MDA) along with significant decreases in total protein (TP) (P=0.000), reduced glutathione (GSH) (P=0.000), superoxide dismutase (SOD), catalase (CAT) (P=0.000), and sialic acid contents (P=0.016) were observed. A positive correlation existed between bound sialic acid levels, liver enzymes and circulating antioxidants (r=0.656, P=0.016). In the present study, alterations of circulating antioxidants in DF suggest that DF might be a metabolic response to an acute, self-limiting tropical viral infection, and a consequence of the viral inflammatory process.
Adult ; Antioxidants ; metabolism ; Biomarkers ; blood ; China ; Dengue ; classification ; diagnosis ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Immunoglobulin M ; metabolism ; Male ; Middle Aged ; Young Adult

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.