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- Characterization of Liver Function Parameter Alterations After Transjugular Intrahepatic Portosystemic Shunt Creation and Association With Early Mortality. [JOURNAL ARTICLE]
- AJR Am J Roentgenol 2014 Dec; 203(6):1363-1370.
OBJECTIVE. The purpose of this article is to characterize the temporal evolution and clinical impact of laboratory liver function parameters after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS. In this single-institution retrospective study, 157 patients (98 men and 59 women; median age, 55 years) underwent TIPS between 2000 and 2012 and had 1-month hepatobiliary laboratory follow-up. Medical record review was used to compare baseline, peak, and low bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and international normalized ratio (INR) levels within 30 days after TIPS in surviving and dying patients to assess laboratory responses to shunt creation. RESULTS. TIPSs were created with a hemodynamic success rate of 98%, with median pressure gradient reduction of 13 mm Hg. Ninety-day mortality was 21%. Hepatobiliary laboratory values showed significant increases in the days after TIPS compared with baseline levels (bilirubin, 1.6 vs 3.5 mg/dL; AST, 49 vs 149 U/L; ALT, 26 vs 90 U/L; alkaline phosphatase, 97 vs 177 U/L; and INR, 1.5 vs 2.0; p < 0.05 in all cases). Patients surviving to 90 days experienced statistically significant but transient laboratory value elevations-up to twofold over baseline-within days of TIPS, whereas patients dying within 90 days experienced three-to fourfold increases over a longer period that did not return to baseline. Differences in laboratory evolution were statistically significant in surviving versus dying patients. CONCLUSION. TIPS results in acute transient elevation of hepatobiliary enzymes, which may be more pronounced in patients with early mortality. An exaggerated laboratory elevation in excess of threefold greater than baseline or a prolonged increase exceeding 1 week may herald poorer clinical outcome.
- Severity markers in severe leptospirosis: a cohort study. [JOURNAL ARTICLE]
- Eur J Clin Microbiol Infect Dis 2014 Nov 21.
We aimed to evaluate parameters for their value as severity markers in hospitalized leptospirosis patients. We recruited 47 informed adult consenting patients and assessed a number of clinical, hematological, biochemical, and biological variables. Patients were sorted according to severity based on fatality or the requirement of mechanical ventilation or dialysis; the parameters studied were compared between groups on inclusion and the next day. Beside septic shock presentation or a high severity score (Simplified Acute Physiology Score; SAPS II), increased lactate, total bilirubin, lipase, and AST/ALT ratio or a decreased cytokines IL-10/TNF-α ratio were all significantly associated with severity. The gene expression of the IL-1 receptor antagonist IL-1ra, IL-1α, and the long pentraxin PTX-3 were also transcribed at higher levels in most severe cases. Patients could rapidly improve or deteriorate, highlighting the need for a new assessment the next day. Our results add to the limited body of knowledge about severity markers in leptospirosis. They also suggest that patients should be reassessed the next day before being possibly discharged from the hospital. Further studies are needed in order to confirm relevant and reliable prognostic parameters in leptospirosis that would be helpful for the purpose of triage.
- In vivo antimalarial activity and toxicological effects of methanolic extract of Cocos nucifera (Dwarf red variety) husk fibre. [Journal Article]
- J Integr Med 2014 Nov; 12(6):504-11.
Phytochemical constituents as well as antimalarial and toxicity potentials of the methanolic extract of the husk fibre of Dwarf Red variety of Cocos nucifera were evaluated in this study.The dried powdered husk fibre was exhaustively extracted with hexane, ethyl acetate and methanol successively and the methanolic extract was screened for flavonoids, phenolics, tannins, alkaloids, steroids, triterpenes, phlobatannins, anthraquinones and glycosides. A 4-day suppressive antimalarial test was carried out using Plasmodium berghei NK65-infected mice, to which the extract was administered at doses of 31.25, 62.5, 125, 250 and 500 mg/kg body weight (BW). Toxicity of the extract was evaluated in rats using selected hematological parameters and organ function indices after orally administering doses of 25, 50 and 100 mg/kg BW for 14 d.Phytochemical analysis revealed the presence of alkaloids, tannins, phenolics, saponins, glycosides, steroids and anthraquinones in the extract. Moreover, the extract reduced parasitemia by 39.2% and 45.8% at doses of 250 and 500 mg/kg BW respectively on day 8 post-inoculation. Various hematological parameters evaluated were not significantly altered (P>0.05) at all doses of the extract, except red blood cell count which was significantly elevated (P<0.05) at 100 mg/kg BW. The extract significantly increased (P<0.05) urea, creatinine, cholesterol, high-density lipoprotein-cholesterol and bilirubin concentrations in the serum as well as atherogenic index, while it reduced albumin concentration significantly (P<0.05) at higher doses compared to the controls. Alanine aminotransferase activity was reduced in the liver and heart significantly (P<0.05) but was increased in the serum significantly (P<0.05) at higher doses of the extract compared to the controls.The results suggest that methanolic extract of the Dwarf red variety has partial antimalarial activity at higher doses, but is capable of impairing normal kidney and liver function as well as predisposing subjects to cardiovascular diseases.
- Heme-regulated eIF2α kinase plays a crucial role in protecting erythroid cells against Pb-induced hemolytic stress. [JOURNAL ARTICLE]
- Chem Res Toxicol 2014 Nov 20.
Lead (Pb) is a heavy metal with considerable environmental contamination. It is toxic to diverse cells, and has been reported to cause a wide array of detrimental health problems including neurological disorders and anemia. In light of the mechanisms underlying Pb-induced anemia, the current understandings is still limited, in spite of efforts for years. Our previous studies recognized a protective role for the heme-regulated eIF2α kinase (Hri) in erythroid cells against oxidative stress exerted by arsenic and cadmium. Whether Hri is involved in Pb-induced hemolytic stress has not been scrutinized. In the current study, to more stringently address this question, we looked into erythropoiesis upon Pb(NO3)2 exposure by using an in vivo mouse model and ex vivo cultured E14.5 fetal liver (FL) cells. Diagnostic of hemolytic anemia, decreased red cell count, reduced hemoglobin (Hb) concentration and elevated bilirubin level were observed in Hri knockout (Ko) mice only, upon low-dose Pb administration. Significantly different from Ko mice, Wild type (Wt) mice did not develop hemolytic anemia. Enforced extramedullary and medullary erythropoiesis was found in Ko mice with Pb exposure. However, anemia was not compensated in Hri-deficient mice, as in vivo and ex vivo results manifested that expanded Hri-null erythroid precursors experienced blocked differentiation and enhanced apoptosis, leading to ineffective erythropoiesis under Pb exposure. Additionally, Pb treatment also promoted hepcidin expression and consequentially increased splenic iron storage, resulting in restrained iron availability for erythropoiesis. All considered, Hri-null erythroid precursors were prone to Pb-induced hemolytic stress. Hri deficiency gave rise to ineffective erythropoiesis and reduced iron availability for erythropoiesis under Pb stimulation, and these events together exacerbated Pb-induced hemolytic anemia. It is thus conceivable that this study delineated an indispensable function of Hri in maintaining red cell membrane integrity and guiding erythroid cell differentiation under Pb exposure. Our findings therefore deciphered a crucial role for Hri in protecting erythroid cells against Pb-induced toxicity.
- Phytochemical and therapeutic evaluation of leaf and in vitro derived callus and shoot of Solanum trilobatum. [JOURNAL ARTICLE]
- Pak J Pharm Sci 2014 Nov; 27(6 Suppl):2101-2107.
This study focuses on the phytochemical properties and the anti-hepatocarcinogenic effects of the leaf and in vitro-derived callus and shoot extracts of Solanum trilobatum. In the leaf, callus and shoot, the presence of sugar, proteins, alkaloids, flavonoids, saponins, tananins, cardiacglycoside, terpenoid and lipids was established by preliminary phytochemical screening. Surface-sterilized explants (0.5-1.0 cm) were placed on the MS basal medium supplemented with different concentrations of 2,4-dichlorophenoxyacetic acid (0.45, 2.26, 4.52, 11.31 and 12.56μ M), naphthylacetic acid (NAA; 0.54, 1.34, 2.69, 5.37, 13.43 and 26.85μM) and 6-benzylaminopurine (BA; 0.44, 1.11, 2.22, 4.44, 8.88 and 13.32μM) for callus induction. Explants from node and callus culture were inoculated on the MS basal medium supplemented with varying concentrations of BA (0.44-22.20 μM) and NAA (0.54-10.74μM) for shoot multiplication. Rats were divided into five groups and administered with diethyl nitrosamine (DEN) and DEN (200mg/kg bwt) intraperitoneally along with methanol leaf and in vitro-derived callus and shoot extracts (250mg/kg bwt) orally for 3 months. A significant deviation (P<0.05) in marker enzymes such as alanine transaminase, aspartate transaminase, lactate dehydrogenase and total bilirubin was found in rats administered with DEN. The liver tissue was used for the analysis of glutathione reductase, lipid peroxidation, glutathione peroxidase, glutathione S-transferase, superoxide dismutase and catalase. DEN administration caused a significant elevation in serum enzymes and total bilirubin. Moreover, antioxidant enzymes were drastically inhibited with significant reduction in glutathione and increased lipid per oxidation. Increased glutathione level and reduced lipid peroxidation were also evident in S. trilobatum-treated rats. However, crude S. trilobatum and in vitro-derived callus and shoot extracts offered better protection against free radical toxicity induced by DEN.
- Clinical Features and Risk Factors for Atazanavir (ATV)-Associated Urolithiasis: A Case-Control Study. [JOURNAL ARTICLE]
- PLoS One 2014; 9(11):e112836.
Clinical features and risk factors for atazanavir (ATV)-associated urolithiasis have not been fully investigated.We reviewed all cases of ATV-containing urolithiasis identified by infrared spectrophotometry among HIV-infected patients over a 5-year period to describe their clinical features and outcome. A case-control study was performed to identify risk factors associated with ATV-associated urolithiasis using univariate and multivariate logistic regression analyses.30 cases of ATV-associated urolithiasis were analyzed. Patients were mostly men (87%), median age: 45.5 years, median CD4 cell count: 443 cells/µL and 97% had plasma HIV RNA level <50 cp/mL. Median time between the initiation of ATV-containing regimen and the diagnosis of urolithiasis was 3.1 years. Patients presented with flank pain in 90% and macroscopic hematuria in 82.6%, 34% had renal dysfunction and 44.8% needed ureteroscopic treatment. In univariate analysis, chronic hepatitis C, a history of urolithiasis, prior use of indinavir, ATV duration, undetectable plasma HIV RNA, use of ritonavir as a booster and serum free bilirubin level were associated with ATV-urolithiasis. Multivariate models retained serum free bilirubin level (OR: 2.31, p<0.02) and either ATV duration (OR: = 1.42, p = <0.03) or a history of urolithiasis (OR = 4.79, p<0.02) when adjusting on serum free bilirubin level as risk factors associated with urolithiasis.ATV-containing urolithiasis are associated with frank clinical symptoms and may require surgical intervention. A high serum bilirubin level, a long exposure to ATV and a history of urolithiasis are risk factors for this rare adverse event.
- A Case of Crimean-Congo Hemorrhagic Fever Complicated with Acute Pancreatitis. [JOURNAL ARTICLE]
- Vector Borne Zoonotic Dis 2014 Nov; 14(11):827-829.
Abstract Background: Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease characterized by nonspecific symptoms like fever, myalgia, severe headache, nausea, vomiting, diarrhea, and abdominal pain. It can result in various complications during the course of the disease due to the diffuse endothelial injury involved in the pathogenesis of CCHF. Objectives: Here we present a patient with CCHF complicated by acute pancreatitis, including pleural and intra-abdominal effusions. Case report: A 70-year-old patient was referred to our hospital from an endemic area with the suspicion of CCHF. The physical examination of the patient revealed high fever (38°C), somnolence, and petechial eruption. The diagnosis of case was confirmed with positive reverse transcriptase polymerase chain reaction (RT-PCR). The viral load of the patient was 4×10(9) copies/mL. On the fifth day of admission, upper abdominal pain, scleral ichter, and abdominal distention developed. The patient had abdominal tenderness with guarding. The laboratory tests revealed an amylase level of 1740 U/L (28-100), lipase level of 583 U/L (13-60), and total bilirubin level of 3.75 mg/dL (<0.3). The diagnosis of acute pancreatitis was confirmed with radiological findings. Conclusions: Until now, atypical presentations of CCHF have been reported in some case reports, but not acute pancreatitis. To the best of our knowledge, this is the first case of acute pancreatitis in the literature seen in the course of CCHF.
- Importance of Hyperbilirubinemia in Differentiation of Primary and Secondary Hemophagocytic Lymphohistiocytosis in Pediatric Cases. [JOURNAL ARTICLE]
- Mediterr J Hematol Infect Dis 2014; 6(1):e2014067.
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper-inflammatory disease. It is difficult to differentiate between primary and secondary HLH based on clinical findings at the onset of disease. We aimed to find parameters that can help to differentiate primary and secondary HLH at initial diagnosis especially for physicians working in developing countries.We retrospectively analyzed data of 38 HLH patients who were admitted to the Pediatric Hematology Department of Gaziantep University between January 2009 and December 2013.Of 38 patients, 20 were defined as primary, and 18 were secondary HLH. The average age of primary and secondary HLH patients was 31±9 and 81±14 months, respectively (p=0.03). We found consanguinity rates significantly higher in primary HLH patients compared to secondary HLH patients (p=0.03). We found that total and direct bilirubin levels significantly increased in primary HLH patients compared to secondary HLH patients (p=0.006, p=0.044). Also, CRP levels were found markedly increased in secondary HLH patients compared to primary ones (p=0.017).We showed that cholestasis and hyperbilirubinemia findings of HLH patients at the initial diagnosis should be considered in favor of primary HLH, and an increased level of CRP should be considered in favor of secondary HLH.
- Excellent Biochemical Response to Polychemotherapy with Nab-Paclitaxel/Gemcitabine in an 82-Year-Old Female with Metastatic Breast Cancer. [JOURNAL ARTICLE]
- Case Rep Oncol 2014 9; 7(3):638-642.
We report the case of an 82-year-old female diagnosed with HER2-negative, hormone receptor (HR)-positive metastatic breast cancer. Upon biochemical disease progression of the initially HR-receptor positive disease under anti-hormonal treatment with tamoxifen and letrozole, she received combination chemotherapy with paclitaxel/gemcitabine. Due to her suffering from severe toxicity, therapy was switched to nab-paclitaxel/gemcitabine. From April 22, 2013, to July 15, 2013, the patient received 5 cycles of nab-paclitaxel/gemcitabine as a 30-min infusion every 3 weeks, with excellent biochemical responses to treatment. Tumor marker levels as well as bilirubin were reduced to baseline levels. Chemotherapy with nab-paclitaxel/gemcitabine was well tolerated. At a follow-up visit immediately after the end of chemotherapy, the patient reported well-being and presented with a Karnofsky performance status (KPS) of 100%. At the last follow-up in October 2013, she was alive with multiple metastatic sites in the liver and bone metastases in the spine without risk of fracture and a KPS of 90%. She has received palliative single agent chemotherapy with capecitabine (14/7 regimen, 1,500 mg b.i.d.) since August 2013 and continued to show a good biochemical treatment response at the last follow-up in October 2013. Since August 2013, the patient has also received denosumab (120 mg sc, q4w) for her metastatic bone disease. As of July 2014, treatment has not been changed and the patient reports her well-being.
- Hepatoprotective and antioxidant activities of extracts from Salvia¿Nelumbinis naturalis against nonalcoholic steatohepatitis induced by methionine- and choline-deficient diet in mice. [JOURNAL ARTICLE]
- J Transl Med 2014 Nov 19; 12(1):315.
BackgroundNonalcoholic steatohepatitis (NASH), the advanced stage of nonalcoholic fatty liver disease that is characterized by both steatosis and severe injury in liver, still lacks efficient treatment. The traditional Chinese formula Salvia¿Nelumbinis naturalis (SNN) is effectively applied to improve the symptoms of nonalcoholic simple fatty liver (NAFL) patients. Previous studies have confirmed that SNN could reduce the liver lipid deposition and serum transaminases of NAFL experimental models. This study aims to determine whether SNN is effective for murine NASH model and investigate the underlying pharmacological mechanisms.MethodsC57BL/6 J mice were fed with methionine- and choline-deficient (MCD) diet for six weeks to induce NASH. Simultaneously, SNN or saline was intragastrically administered daily to the mice in the SNN or model group, respectively. A standard diet was given to the control mice. Serum biochemical indices and tumor necrosis factor-¿ were measured. Liver histopathology was observed, and the contents of triglycerides and lipid peroxide malondialdehyde (MDA) in liver homogenates were evaluated. The hepatic expression and/or activation of genes associated with inflammation, apoptosis, and oxidative stress were determined by quantitative RT-PCR or Western blot analysis.ResultsThe prominent liver steatosis displayed in the NASH model was prevented by SNN. The liver injury of NASH mice was obviously manifested by the increased levels of serum transaminases and bilirubin, as well as the lobular inflammation, elevated pro-inflammatory cytokines, and upregulated apoptosis in liver tissues. SNN administration improved the aforementioned pathological changes. The increased hepatic levels of MDA and cytochrome P450 2E1 of the model confirmed the unregulated balance of oxidative stress. The hepatic expression of nuclear factor erythroid 2-related factor 2 and its target genes decreased, whereas c-Jun N-terminal kinase activation in the model mice increased. Treating the mice with SNN significantly improved oxidative stress-related harmful factors.ConclusionsThis study shows that SNN can protect the liver from severe steatosis and damage induced by MCD diet, which suggests the potential use of SNN on the treatment of NASH patient. The results also indicate that improving the hepatic antioxidant capability of the liver may contribute to the underlying hepatoprotective mechanism.