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Sample records for adult primary liver

  1. Treatment Options for Adult Primary Liver Cancer

    MedlinePlus

    ... Cancer Prevention Liver Cancer Screening Research Adult Primary Liver Cancer Treatment (PDQ®)–Patient Version General Information About Adult Primary Liver Cancer Go to Health Professional Version Key Points ...

  2. Treatment Option Overview (Adult Primary Liver Cancer)

    MedlinePlus

    ... Cancer Prevention Liver Cancer Screening Research Adult Primary Liver Cancer Treatment (PDQ®)–Patient Version General Information About Adult Primary Liver Cancer Go to Health Professional Version Key Points ...

  3. Stages of Adult Primary Liver Cancer

    MedlinePlus

    ... Cancer Prevention Liver Cancer Screening Research Adult Primary Liver Cancer Treatment (PDQ®)–Patient Version General Information About Adult Primary Liver Cancer Go to Health Professional Version Key Points ...

  4. General Information about Adult Primary Liver Cancer

    MedlinePlus

    ... Cancer Prevention Liver Cancer Screening Research Adult Primary Liver Cancer Treatment (PDQ®)–Patient Version General Information About Adult Primary Liver Cancer Go to Health Professional Version Key Points ...

  5. PET-CT in Determining the Radioembolization Dose Delivered to Patients With Liver Metastasis, Primary Liver Cancer, or Biliary Cancer

    ClinicalTrials.gov

    2017-01-24

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Stage D Adult Primary Liver Cancer (BCLC); Unspecified Adult Solid Tumor, Protocol Specific

  6. Isolation and cultivation of adult primary bovine hepatocytes from abattoir derived liver

    PubMed Central

    Ehrhardt, Sonja; Schmicke, Marion

    2016-01-01

    The aim was to establish a cell culture of adult primary bovine hepatocytes obtained from liver following slaughter and to cultivate the cells in a sandwich culture. Cells and medium samples were taken after separation of cells (day 0), during monolayer (days 1, 2 and 3) and during sandwich culture (days 1, 2, 3, 4, 7, 10 and 14). The mRNA expression of BAX, BCL2L, FAS, IGF-1 and GHR1A was measured as well as urea and LDH. Hepatocytes were obtained by using a two-step collagenase perfusion and were purified thereafter by density gradient centrifugation. The viability was 68.2 ± 9.5 %. In sandwich culture, cells have a typical polygonal hepatocyte-like shape, build cell-cell contacts, and show irregularity of cell borders suggesting bile canaliculi generation. The BAX mRNA expression increased on day 1 as well but decreased steadily until day 3 and remained constant for 14 days. Urea- and LDH-concentrations increased from day 4 to day 7. In conclusion, we found that it is possible to gather viable primary hepatocytes from adult bovine liver after slaughter, and that cells gathered this way show typical morphologies, urea-production and low LDH-leakage especially at day 4 in a sandwich system. PMID:28275320

  7. Primary tumors of the liver.

    PubMed Central

    Anderson, B. B.; Ukah, F.; Tette, A.; Villaflor, S. G.; Koh, D.; Seton, P.

    1992-01-01

    Primary tumors of the liver that are of clinical significance are rare. Ninety-five percent of such lesions when encountered will be malignant and only 5% will be benign. Malignant primary hepatic lesions represent 2% to 3% of primary cancers encountered in the United States. Hepatocellular carcinoma constitutes 90% of malignant liver primaries in the adult. Seventy-five percent of cases are associated with cirrhosis of the liver and patients with hepatitis B infection have a 33- to 200-fold excess risk for this malignancy. Cholangiocarcinoma represents 5% to 10% of hepatic primary malignancies while hepatoblastoma is distinctly uncommon in adults. Treatment is primarily surgical, and resectability is limited by the presence of cirrhosis and spread of the tumor within and outside of the liver. Of the benign liver tumors, the liver cell adenoma seem to be associated with oral contraception and have a proclivity for intraperitoneal hemorrhage, especially during pregnancy. Focal nodular hyperplasia is a tumor-like condition that also may be associated with oral contraception. This article describes five cases, two of which had quite unique presentations. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 PMID:1602511

  8. Sorafenib Tosylate in Treating Patients With Liver Cancer Who Have Undergone a Liver Transplant

    ClinicalTrials.gov

    2015-03-25

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer

  9. Liver Disease and Adult Vaccination

    MedlinePlus

    ... Vaccination Recommendations Adult Vaccination Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet ... critical for people with health conditions such as liver disease. If you have chronic liver disease, talk ...

  10. Brain tumor - primary - adults

    MedlinePlus

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  11. 3-Tesla MRI Response to TACE in HCC (Liver Cancer)

    ClinicalTrials.gov

    2016-08-22

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Stage A Adult Primary Liver Cancer (BCLC); Stage B Adult Primary Liver Cancer (BCLC)

  12. Prevalence and factors associated with the presence of non alcoholic fatty liver disease in an apparently healthy adult population in primary care units

    PubMed Central

    Caballería, Llorenç; Auladell, Ma Antonia; Torán, Pere; Miranda, Dolores; Aznar, Jesús; Pera, Guillem; Gil, Dolors; Muñoz, Laura; Planas, Jaume; Canut, Santiago; Bernad, Jesús; Aubà, Josep; Pizarro, Gregorio; Aizpurua, Miren Maite; Altaba, Anna; Tibau, Albert

    2007-01-01

    Background Fatty liver disease is characterized by the accumulation of fat vacuoles inside of the hepatocytes. Non alcoholic fatty liver is associated with obesity, type 2 diabetes, dyslipemia, the intake of certain drugs and with the so-called metabolic syndrome. However, there is little information on the clinical relevance of this disorder as a healthcare problem in the general population, since the studies published generally include a limited number of patients and the diagnosis is established on the basis of clear biochemical alterations and liver biopsy. Methods/Design The aim of the study is the prevalence of non-alcoholic fatty liver disease in a general adult population by hepatic ultrasonography. A population-based, descriptive, transversal, multicentre study. Eighteen primary care centres of the north of Barcelona and the Maresme Areas of Healthcare Management attending an urban and semi-urban population of 360.000 inhabitants. A randomized sample of 786 subjects of 15 years or older were selected from the population and assigned to the participating centres according to the Primary Care Information System (SIAP): This population is practically the same as the general population of the area. The following determinations will be carried out in all the participants: hepatic ultrasonography to detect fatty liver, a questionnaire concerning liver diseases, alcohol intake, smoking and drug use, physical examination including abdominal perimeter and body mass index and biochemical analysis including liver function tests and parameters related to the metabolic syndrome and the HAIR score. Ultrasonographic diagnosis of fatty liver will be made according to established criteria (American Gastroenterology Association) and diagnosis of metabolic syndrome according to the criteria of the European Group for the Study of Insulin Resistance. Discussion This study will attempt to determine the prevalence of non alcoholic fatty liver disease, as well as, the factors

  13. [Primary cancer of the liver].

    PubMed

    Orozco, H; Mercado, M A

    1997-01-01

    The epidemiologic and pathogenic aspects of primary hepatic malignancies are discussed. The role of viruses in the etiology of the disease is stressed. Imageology methods have a preponderant role for diagnosis and treatment options. Liver resection has a one years survival between 60 and 80% and a five years survival of 20 to 40%. A good surgical results is expected for tumors with no more than 5 cm in diameter, encapsulated and without vascular invasion non-cirrhotic livers, large tumors can also be removed. Surgical resection margin should be of 1 cm. For cirrhotic livers, a good liver function is needed (Child A-B) and no safe major resection can be done. History of bleeding portal hypertension has a negative role in the outcome. Liver transplantation should be limited to selected case, in which the tumors are small and asymptomatic (incidental). For larger tumors, long term results are not good with invariable recurrency of the tumor.

  14. Split liver transplantation in adults

    PubMed Central

    Hashimoto, Koji; Fujiki, Masato; Quintini, Cristiano; Aucejo, Federico N; Uso, Teresa Diago; Kelly, Dympna M; Eghtesad, Bijan; Fung, John J; Miller, Charles M

    2016-01-01

    Split liver transplantation (SLT), while widely accepted in pediatrics, remains underutilized in adults. Advancements in surgical techniques and donor-recipient matching, however, have allowed expansion of SLT from utilization of the right trisegment graft to now include use of the hemiliver graft as well. Despite less favorable outcomes in the early experience, better outcomes have been reported by experienced centers and have further validated the feasibility of SLT. Importantly, more than two decades of experience have identified key requirements for successful SLT in adults. When these requirements are met, SLT can achieve outcomes equivalent to those achieved with other types of liver transplantation for adults. However, substantial challenges, such as surgical techniques, logistics, and ethics, persist as ongoing barriers to further expansion of this highly complex procedure. This review outlines the current state of SLT in adults, focusing on donor and recipient selection based on physiology, surgical techniques, surgical outcomes, and ethical issues. PMID:27672272

  15. Improving the diagnostic criteria for primary liver graft non-function in adults utilizing standard and transportable laboratory parameters. An outcome based analysis.

    PubMed

    Al-Freah, Mohammad A B; McPhail, Mark J W; Dionigi, Elena; Foxton, Matthew R; Auzinger, Georg; Rela, Mohamed; Wendon, Julia A; O'Grady, John G; Heneghan, Michael A; Heaton, Nigel D; Bernal, William

    2017-02-15

    Current diagnostic criteria for primary non-function (PNF) of liver grafts are based on clinical experience rather than statistical methods. A retrospective, single centre study was conducted of all adults (n=1,286) who underwent primary liver transplant 2000-2008 in our centre. Laboratory variable during the first post-liver transplant week were analysed. Forty two patients (3.7%) had 2-week graft failure. Transplant albumin, day-1 AST, day-1 lactate, day-3 bilirubin, day-3 INR and day-7 AST were independently associated with PNF on multivariate logistic regression. PNF score =(0.000280*D1AST)+(0.361*D1 Lactate)+(0.00884*D3 Bilirubin)+(0.940*D 3 INR)+(0.00153*D7 AST)-(0.0972*TxAlbumin)-4.5503. ROC analysis showed the model AUROC of 0.912 (0.889 -0.932) was superior to the current United Kingdom (UK) PNF criteria of 0.669 (0.634-0.704, p<0.0001). When applied to a validation cohort (n=386, 34.4% patients) the model had AUROC of 0.831 (0.789 -0.867) compared to the UK EGD criteria of 0.674 (0.624-0.721). The new model performed well after exclusion of patients with marginal grafts and when modified to include variables from the first three post-LT days only (AUROC of 0.818, 0.776-0.856, p=0.001). This model is superior to the current UK PNF criteria and is based on statistical methods. The model is also applicable to recipients of all types of grafts (marginal and non-marginal). This article is protected by copyright. All rights reserved.

  16. A PROSPECTIVE RANDOMIZED TRIAL OF TACROLIMUS AND PREDNISONE VERSUS TACROLIMUS, PREDNISONE AND MYCOPHENOLATE MOFETIL IN PRIMARY ADULT LIVER TRANSPLANTATION: A SINGLE CENTER REPORT1

    PubMed Central

    Jain, A.; Kashyap, R.; Dodson, F.; Kramer, D.; Hamad, I.; Khan, A.; Eghestad, B.; Starzl, T.E.; Fung, J.J.

    2010-01-01

    Background Tacrolimus (TAC) and mycophenolate mofetil (MMF) are currently approved immunosuppressants for prevention of rejection in liver transplantation (LTx). They have different modes of action and toxicity profiles, but the efficacy and safety of MMF in primary liver transplantation with TAC has not been determined. Methods An Institutional Review Board-approved, open-label, single-center, prospective randomized trial was initiated to study the efficacy and toxicity of TAC and steroids (double-drug therapy (D)) versus TAC, steroids, and MMF (triple-drug therapy (T)) in primary adult LTx recipients. Both groups of patients were started on the same doses of TAC and steroids. Patients randomized to T also received 1 gm MMF twice a day. Results Between August 1995 and May 1998, 350 patients were enrolled at a single center-175 in the D and 175 in the T groups. All patients were followed until May 1998, with a mean follow-up of 33.8±9.1 months. Using an intention-to-treat analysis, the 1-, 2-, 3-, and 4-year patient survival was 85.1%, 81.6%, 78.6%, and 75.8%, respectively, for D and 87.4%, 85.4%, 81.3%, and 79.9%, respectively, for T. The 4-year graft survival was 70% for D and 72.1% for T. Although the rate of acute rejection in the first 3 months was significantly lower for T than for D (28% for triple vs. 38.9% for double, P=0.03), the overall rate of rejection for T at the end of 1 year was not significantly lower than for the D (38.9% triple vs. 45.2% double). The median time to the first episode of rejection was 14 days for D versus 24 days for T (P=0.008). During the study period, 38 of 175 patients in D received MMF to control ongoing acute rejection, nephrotoxicity, and/or neurotoxicity. On the other hand, 103 patients in the T discontinued MMF for infection, myelosuppression, and/or gastrointestinal disturbances. The need for corticosteroids was less after 6 months for T and the perioperative need for dialysis was lower with use of MMF. Conclusion This

  17. [PRIMARY BILIARY LIVER CIRRHOSIS: MODERN CONCEPTS].

    PubMed

    Tsimmerman, Ya S

    2015-01-01

    Modern data on primary biliary liver cirrhosis are presented including the definition, prevalence, possible etiological factors, and detailed description of pathogenesis (autoimmune mechanisms, intrahepatic cholestasis, hereditary predisposition, environmental factors) and clinical picture. Also considered are complications and concomitant diseases, methods of laboratory, instrumental and morphological diagnostics, approaches to medicamental treatment and its effectiveness, indications for liver transplantation.

  18. [Multiple primary malignant tumors involving the liver].

    PubMed

    Tiszlavicz, L

    1991-11-17

    In the autopsy material of the Department of Pathology of Albert Szent-Györgyi Medical University 167 primary liver cancers were observed in 30 years, from which 13 patients (7.8%) had also other primary malignancies. The tumour-associations were mainly synchronously, there was strong male predominance. In 9 cases the hepatocellular carcinoma originated in cirrhotic liver. The most frequent extrahepatic tumours were found in the lungs (5 cases), smoking was among the anamnestic data.

  19. A liver lesion in primary sclerosing cholangitis

    PubMed Central

    Biswas, Sujata; Rajoriya, Neil; Wang, Lai Mun; Collier, Jane

    2015-01-01

    Primary sclerosing cholangitis is associated with an increased risk of cholangiocarcinoma; appropriate surveillance should be undertaken for this. Our case illustrates an unexpected liver lesion in such a patient, which would not have been detected with imaging alone. In suspected cancer, if a patient is not a candidate for liver resection, liver biopsy should be considered in case there is a treatment option for an alternative cause of the liver lesion. This is a careful decision to be made due to the risk of tumour seeding compromising cure and needs to be discussed via the hepatobiliary multidisciplinary team. PMID:25827915

  20. Evidence for epithelial-mesenchymal transitions in adult liver cells.

    PubMed

    Sicklick, Jason K; Choi, Steve S; Bustamante, Marcia; McCall, Shannon J; Pérez, Elizabeth Hernández; Huang, Jiawen; Li, Yin-Xiong; Rojkind, Marcos; Diehl, Anna Mae

    2006-10-01

    Both myofibroblastic hepatic stellate cells (HSC) and hepatic epithelial progenitors accumulate in damaged livers. In some injured organs, the ability to distinguish between fibroblastic and epithelial cells is sometimes difficult because cells undergo epithelial-mesenchymal transitions (EMT). During EMT, cells coexpress epithelial and mesenchymal cell markers. To determine whether EMT occurs in adult liver cells, we analyzed the expression profile of primary HSC, two HSC lines, and hepatic epithelial progenitors. As expected, all HSC expressed HSC markers. Surprisingly, these markers were also expressed by epithelial progenitors. In addition, one HSC line expressed typical epithelial progenitor mRNAs, and these epithelial markers were inducible in the second HSC line. In normal and damaged livers, small ductular-type cells stained positive for an HSC marker. In conclusion, HSC and hepatic epithelial progenitors both coexpress epithelial and mesenchymal markers, providing evidence that EMT occurs in adult liver cells.

  1. Diagnosis of Primary Cancer of the Liver

    PubMed Central

    Kew, M. C.; Dos Santos, H. A.; Sherlock, Sheila

    1971-01-01

    The diagnosis of primary cancer of the liver was reviewed in 75 patients. A definitive diagnosis was made during life in 63% and in a further 20% this condition was suspected though histological confirmation was obtained only at necropsy. The most common presenting complaints were abdominal pain and weight loss and the most frequent findings hepatomegaly and ascites. Less than one-half of the patients were jaundiced and when present it was usually mild. An arterial bruit was heard over the liver in 25% of the patients. A sudden and unexplained deterioration in a patient known to have cirrhosis or haemochromatosis should raise the possibility of a primary hepatic tumour; this occurred in 24% of our patients. Alpha-fetoprotein was found in the serum of 11 out of 18 cases. The presence of a mass in the liver was frequently confirmed by liver scan, portal venography, or hepatic arteriography, but these showed no features diagnostic of a primary tumour. Liver scan also proved useful in localizing the lesion for biopsy purposes. Definitive diagnosis is dependent on the histological demonstration of the features of the tumour. This can frequently be achieved by percutaneous needle biopsy, which was positive in 38 out of 57 patients. Wedge biopsies were positive in a further nine patients. PMID:5124443

  2. Time spent in hospital after liver transplantation: Effects of primary liver disease and comorbidity

    PubMed Central

    Tovikkai, Chutwichai; Charman, Susan C; Praseedom, Raaj K; Gimson, Alexander E; van der Meulen, Jan

    2016-01-01

    AIM To explore the effect of primary liver disease and comorbidities on transplant length of stay (TLOS) and LOS in later admissions in the first two years after liver transplantation (LLOS). METHODS A linked United Kingdom Liver Transplant Audit - Hospital Episode Statistics database of patients who received a first adult liver transplant between 1997 and 2010 in England was analysed. Patients who died within the first two years were excluded from the primary analysis, but a sensitivity analysis was also performed including all patients. Multivariable linear regression was used to evaluate the impact of primary liver disease and comorbidities on TLOS and LLOS. RESULTS In 3772 patients, the mean (95%CI) TLOS was 24.8 (24.2 to 25.5) d, and the mean LLOS was 24.2 (22.9 to 25.5) d. Compared to patients with cancer, we found that the largest difference in TLOS was seen for acute hepatic failure group (6.1 d; 2.8 to 9.4) and the largest increase in LLOS was seen for other liver disease group (14.8 d; 8.1 to 21.5). Patients with cardiovascular disease had 8.5 d (5.7 to 11.3) longer TLOS and 6.0 d (0.2 to 11.9) longer LLOS, compare to those without. Patients with congestive cardiac failure had 7.6 d longer TLOS than those without. Other comorbidities did not significantly increase TLOS nor LLOS. CONCLUSION The time patients spent in hospital varied according to their primary liver disease and some comorbidities. Time spent in hospital of patients with cancer was relatively short compared to most other indications. Cardiovascular disease and congestive cardiac failure were the comorbidities with a strong impact on increased LOS. PMID:28058226

  3. BMS-247550 in Treating Patients With Liver or Gallbladder Cancer

    ClinicalTrials.gov

    2014-05-13

    Adult Primary Cholangiocellular Carcinoma; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  4. [Multiple primary malignant tumors involving the liver].

    PubMed

    Tiszlavicz, L; Tasnádi, T

    1993-01-31

    In the Department of Pathology of the Albert Szent-Györgyi Medical University in Szeged during the last 30 years 1770 (19.4% of the cancers) primary malignant lung tumours were observed in autopsy material, from which 86 patients (4.9%) had other malignancies as well. In 81 cases other extrapulmonary and in 5 cases other primary lung tumours were observed. The male predominance in these cases was significant. All of the patients were heavy smokers. Amongst these synchronous tumour-associations the most frequent extrapulmonary tumours arose in the urogenital tract, in the head and neck, relatively frequently also in the breast, liver, stomach, intestine and thyroid. These cases caused diagnostic dilemmas both for the clinician and even for the pathologist. Several signs help to distinguish a new primary tumour from a metastasis. Multiplicity itself does not mean poorer prognosis. Each cancer should possibly receive adequate treatment.

  5. Primary brain tumours in adults.

    PubMed

    Ricard, Damien; Idbaih, Ahmed; Ducray, François; Lahutte, Marion; Hoang-Xuan, Khê; Delattre, Jean-Yves

    2012-05-26

    Important advances have been made in the understanding and management of adult gliomas and primary CNS lymphomas--the two most common primary brain tumours. Progress in imaging has led to a better analysis of the nature and grade of these tumours. Findings from large phase 3 studies have yielded some standard treatments for gliomas, and have confirmed the prognostic value of specific molecular alterations. High-throughput methods that enable genome-wide analysis of tumours have improved the knowledge of tumour biology, which should lead to a better classification of gliomas and pave the way for so-called targeted therapy trials. Primary CNS lymphomas are a group of rare non-Hodgkin lymphomas. High-dose methotrexate-based regimens increase survival, but the standards of care and the place of whole-brain radiotherapy remain unclear, and are likely to depend on the age of the patient. The focus now is on the development of new polychemotherapy regimens to reduce or defer whole-brain radiotherapy and its delayed complications.

  6. Acute liver failure caused by hemophagocytic lymphohistiocytosis in adults

    PubMed Central

    Lin, Shide; Li, Ying; Long, Jun; Liu, Qichuan; Yang, Fangwan; He, Yihuai

    2016-01-01

    Abstract Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare condition that can be caused by a primary or acquired disorder of uncontrolled immune response. Liver injury is a common complication of HLH; however, HLH presenting as acute liver failure (ALF) has rarely been reported in adults. Case summary: A 34-year-old man was admitted to our hospital with nausea and fatigue persisting for 2 weeks and jaundice for 1 week. He had hyperthermia at the onset of disease. At admission, he had severe liver injury with unknown etiology. The laboratory data showed that he had hyperferritinemia, thrombocytopenia, anemia, hypertriglyceridemia, and hypofibrinogenemia. Finally, a bone marrow biopsy revealed hemophagocytic cells, and he was diagnosed with HLH. The patient was treated with prednisone and plasma exchange. However, the liver function of the patient deteriorated, and he finally died of multiorgan failure. Conclusions: Reports of adult patients with ALF caused by HLH have increased, and HLH should be suspected in patients with ALF of indeterminate cause. Although the efficacy of the treatment strategy recommended by the HLH 2004 remains to be confirmed in adult patients with ALF caused by HLH, early diagnosis and prompt combined treatment with steroids and cyclosporin A or etoposide should be emphasized. PMID:27893685

  7. Management of adults with paediatric-onset chronic liver disease: strategic issues for transition care.

    PubMed

    Vajro, Pietro; Ferrante, Lorenza; Lenta, Selvaggia; Mandato, Claudia; Persico, Marcello

    2014-04-01

    Advances in the management of children with chronic liver disease have enabled many to survive into adulthood with or without their native livers, so that the most common of these conditions are becoming increasingly common in adult hepatology practice. Because the aetiologies of chronic liver disease in children may vary significantly from those in adulthood, adults with paediatric-onset chronic liver disease may often present with clinical manifestations unfamiliar to their adulthood physician. Transition of medical care to adult practice requires that the adulthood medical staff (primary physicians and subspecialists) have a comprehensive knowledge of childhood liver disease and their implications, and of the differences in caring for these patients. Pending still unavailable Scientific Society guidelines, this article examines causes, presentation modes, evaluation, management, and complications of the main paediatric-onset chronic liver diseases, and discusses key issues to aid in planning a program of transition from paediatric to adult patients.

  8. Radio Frequency Ablation for Primary Liver Cancer

    PubMed Central

    2004-01-01

    organizations for health technology assessments, including the Canadian Coordinating Office for Health Technology Assessment (CCOHTA) and the International Network of Agencies for Health Technology Assessment (INAHTA), were scanned for previous systematic reviews on RFA. The Cochrane Library Database was also scanned. The most recent systematic review examined the literature up to October 2003. Five previous health technology assessments were found. To update the international systematic reviews, the Medical Advisory Secretariat systematically reviewed the literature from January 1, 2003 to the third week of April 2004. Peer-reviewed literature from EMBASE, MEDLINE (including in-process and other nonindexed citations) and the Cochrane Library Database were searched for the following search terms: Catheter ablation Radiofrequency or radio-frequency or radio frequency or RFA or RFTA Liver neoplasms or liver cancer or hepatocellular or hepatocellular or hepatic Cancer The inclusion criteria were as follows: Population: patients with primary hepatocellular carcinoma Procedure: RFA used as the only treatment (not as an adjunct) Language: publication in English Published health technology assessments, guidelines, and peer-reviewed literature (abstracts and in-progress manuscripts) Outcomes: therapeutic response (% complete ablation), mortality, survival, and tumour recurrence Grey literature, where relevant, was also reviewed. Summary of Findings The Medical Advisory Secretariat included 5 previous health technology assessments from 2002 to 2004 and 9 peer-reviewed studies from January 2003 to April 2004 in its review. The health technology assessments suggested that RFA is as safe and effective for treating up to 3 or 4 small (< 4 to 5 cm), unresectable liver tumours in the short term (2 years). One small randomized controlled trial (RCT) that compared RFA with percutaneous ethanol injection (PEI), another ablative technique, suggested that RFA is at least as safe and effective for

  9. Primary Hepatic Osteosarcoma: A Rare Cause of Primary Liver Tumor

    PubMed Central

    Tamang, Tsering Gyalpo Lama; Shuster, Marina; Chandra, Abhinav B.

    2016-01-01

    INTRODUCTION Extraosseous osteosarcomas are rare, accounting for approximately 4% of all osteosarcomas. A literature review yields very few cases of osteosarcoma primarily arising from the hepatic parenchyma. CASE REPORT This report describes a case of a man in his 50s with a history of hepatitis C and cirrhosis who presented with 5 days of progressive right upper quadrant pain. Magnetic resonance imaging of the abdomen and pelvis demonstrated a 4.4 cm × 4.8 cm × 4.8 cm right hepatic lobe mass with a large area of necrosis and peripheral enhancement. The subsequent liver biopsy showed few cores of tumor composed of fibroblastic malignant cells producing lace-like osteoid matrix. Osteosarcomatous foci in other parts of the body were excluded by performing extensive physical examination, radiologic imaging, and biopsy. Hence, a primary osteosarcoma was diagnosed. The patient underwent portal vein embolization in preparation for a surgical resection of the right liver lobe. He was admitted six weeks after the embolization for dyspnea and abdominal distension and expired due to abdominal hematoma and pulmonary embolism. CONCLUSION Based on the rarity, lack of consensus in treatment, and dismal prognosis, extraosseous osteosarcoma should be considered a separate entity from osseous osteosarcoma. More data and research are needed in this rare and understudied malignancy. PMID:27081321

  10. Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer

    ClinicalTrials.gov

    2017-03-08

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Advanced Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma

  11. Liver regeneration after living donor transplantation: adult-to-adult living donor liver transplantation cohort study.

    PubMed

    Olthoff, Kim M; Emond, Jean C; Shearon, Tempie H; Everson, Greg; Baker, Talia B; Fisher, Robert A; Freise, Chris E; Gillespie, Brenda W; Everhart, James E

    2015-01-01

    Adult-to-adult living donors and recipients were studied to characterize patterns of liver growth and identify associated factors in a multicenter study. Three hundred and fifty donors and 353 recipients in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) receiving transplants between March 2003 and February 2010 were included. Potential predictors of 3-month liver volume included total and standard liver volumes (TLV and SLV), Model for End-Stage Liver Disease (MELD) score (in recipients), the remnant and graft size, remnant-to-donor and graft-to-recipient weight ratios (RDWR and GRWR), remnant/TLV, and graft/SLV. Among donors, 3-month absolute growth was 676 ± 251 g (mean ± SD), and percentage reconstitution was 80% ± 13%. Among recipients, GRWR was 1.3% ± 0.4% (8 < 0.8%). Graft weight was 60% ± 13% of SLV. Three-month absolute growth was 549 ± 267 g, and percentage reconstitution was 93% ± 18%. Predictors of greater 3-month liver volume included larger patient size (donors and recipients), larger graft volume (recipients), and larger TLV (donors). Donors with the smallest remnant/TLV ratios had larger than expected growth but also had higher postoperative bilirubin and international normalized ratio at 7 and 30 days. In a combined donor-recipient analysis, donors had smaller 3-month liver volumes than recipients adjusted for patient size, remnant or graft volume, and TLV or SLV (P = 0.004). Recipient graft failure in the first 90 days was predicted by poor graft function at day 7 (HR = 4.50, P = 0.001) but not by GRWR or graft fraction (P > 0.90 for each). Both donors and recipients had rapid yet incomplete restoration of tissue mass in the first 3 months, and this confirmed previous reports. Recipients achieved a greater percentage of expected total volume. Patient size and recipient graft volume significantly influenced 3-month volumes. Importantly, donor liver volume is a

  12. Surgical treatment of double primary liver cancer

    PubMed Central

    Li, Aijun; Ma, Senlin; Pawlik, Timothy; Wu, Bin; Yang, Xiaoyu; Cui, Longjiu; Wu, Mengchao

    2016-01-01

    Abstract Double primary liver cancer (DPLC) is a special type of clinical situation. As such, a detailed analysis of the surgical management and prognosis of patients with DPLC is lacking. The objective of the current study was to define the management and outcome of patients undergoing surgery for DPLC at a major hepatobiliary center. A total of 87 patients treated by surgical resection at the Eastern Hepatobiliary Surgery Hospital from January 1st, 2007 to October 31st, 2013 who had DPLC demonstrated by final pathological diagnosis were identified. Among these, 50 patients had complete clinical and prognostic data. Demographic and tumor characteristics as well as the prognosis were analyzed. The proportion of hepatitis B surface antigen (HBsAg) (+) and hepatitis B virus e antigen (HBeAg) (+), HBsAg (+), and HBeAg (−) hepatocirrhosis in all patients was 21.84%, 67.82%, and 63.22%, respectively. Incidental findings accounted for 58.62% of patients; among those who had symptoms, the main symptom was abdominal pain (31.03%). Nonanatomic wedge resection was the main operative approach (62.07%). Postoperatively, the main complications included seroperitoneum (11.49%), hypoproteinemia (10.34%), and pleural effusion (8.05%). Factors associated with disease-free survival (DFS) included intrahepatic cholangiocarcinoma (ICC) tumor size (P = 0.002) and use of postoperative prophylactic transcatheter arterial chemoembolization (TACE) treatment (P = 0.015). Meanwhile, hepatocellular carcinoma (HCC) size (P = 0.045), ICC size (P < 0.001), and liver function (including aspartate aminotransferase [P = 0.001] and r-glutamyl transferase [P < 0.001]) were associated with overall survival (OS). Hepatitis B virus (HBV)-related hepatitis or cirrhosis is also an important factor in the pathogenesis of DPLC and surgical treatment is safe for it with low complication rates. In addition, it is effective to prolong DFS that DPLC patients undergo postoperative

  13. Autoimmune hepatitis-primary biliary cirrhosis concurrent with biliary stricture after liver transplantation.

    PubMed

    Kang, Yong-Zhen; Sun, Xiao-Ye; Liu, Yi-He; Shen, Zhong-Yang

    2015-02-21

    Although the development of de novo autoimmune liver disease after liver transplantation (LT) has been described in both children and adults, autoimmune hepatitis (AIH)-primary biliary cirrhosis (PBC) overlap syndrome has rarely been seen in liver transplant recipients. Here, we report a 50-year-old man who underwent LT for decompensated liver disease secondary to alcoholic steatohepatitis. His liver function tests became markedly abnormal 8 years after LT. Standard autoimmune serological tests were positive for anti-nuclear and anti-mitochondrial antibodies, and a marked biochemical response was observed to a regimen consisting of prednisone and ursodeoxycholic acid added to maintain immunosuppressant tacrolimus. Liver biopsy showed moderate bile duct lesions and periportal lymphocytes infiltrating along with light fibrosis, which confirmed the diagnosis of AIH-PBC overlap syndrome. We believe that this may be a case of post-LT de novo AIH-PBC overlap syndrome; a novel type of autoimmune overlap syndrome.

  14. Primary gastrointestinal stromal tumor of the liver: A case report

    PubMed Central

    Luo, Xiao-Li; Liu, Dan; Yang, Jian-Jun; Zheng, Min-Wen; Zhang, Jing; Zhou, Xiao-Dong

    2009-01-01

    We report a case of primary gastrointestinal stromal tumor (GIST) of the liver. A 17-year-old man with a solid mass in the anterior segment of the right liver was asymptomatic with negative laboratory examinations with the exception of positive HBV. Contrast-enhanced ultrasound (CEUS) revealed a hypervascular lesion in the arterial phase and hypoechoic features during the portal and late phases. However, enhanced spiral computed tomography (CT) showed hypoattenuation in all three phases. Following biopsy, immunohistochemical evaluation demonstrated positive CD117. Different imaging features of primary GISTs of the liver are due to pathological properties and different working systems between CEUS and enhanced spiral CT. PMID:19653356

  15. Primary pure choriocarcinoma of the liver.

    PubMed

    Fernández Alonso, J; Sáez, C; Pérez, P; Montaño, A; Japón, M A

    1992-04-01

    We report a pure choriocarcinoma of the liver studied at necropsy. The tumour was diagnosed ante-mortem and treated by chemotherapy with no satisfactory response. Previous cases of hepatic choriocarcinoma are reviewed and criteria to diagnose this extragonadal neoplasm are recommended.

  16. Primary care of adults with developmental disabilities

    PubMed Central

    Sullivan, William F.; Berg, Joseph M.; Bradley, Elspeth; Cheetham, Tom; Denton, Richard; Heng, John; Hennen, Brian; Joyce, David; Kelly, Maureen; Korossy, Marika; Lunsky, Yona; McMillan, Shirley

    2011-01-01

    Abstract Objective To update the 2006 Canadian guidelines for primary care of adults with developmental disabilities (DD) and to make practical recommendations based on current knowledge to address the particular health issues of adults with DD. Quality of evidence Knowledgeable health care providers participating in a colloquium and a subsequent working group discussed and agreed on revisions to the 2006 guidelines based on a comprehensive review of publications, feedback gained from users of the guidelines, and personal clinical experiences. Most of the available evidence in this area of care is from expert opinion or published consensus statements (level III). Main message Adults with DD have complex health issues, many of them differing from those of the general population. Good primary care identifies the particular health issues faced by adults with DD to improve their quality of life, to improve their access to health care, and to prevent suffering, morbidity, and premature death. These guidelines synthesize general, physical, behavioural, and mental health issues of adults with DD that primary care providers should be aware of, and they present recommendations for screening and management based on current knowledge that practitioners can apply. Because of interacting biologic, psychoaffective, and social factors that contribute to the health and well-being of adults with DD, these guidelines emphasize involving caregivers, adapting procedures when appropriate, and seeking input from a range of health professionals when available. Ethical care is also emphasized. The guidelines are formulated within an ethical framework that pays attention to issues such as informed consent and the assessment of health benefits in relation to risks of harm. Conclusion Implementation of the guidelines proposed here would improve the health of adults with DD and would minimize disparities in health and health care between adults with DD and those in the general population

  17. Arterial conduits for hepatic artery revascularisation in adult liver transplantation.

    PubMed

    Muralidharan, Vijayaragavan; Imber, Charles; Leelaudomlipi, Surasak; Gunson, Bridget K; Buckels, John A C; Mirza, Darius F; Mayer, A David; Bramhall, Simon R

    2004-05-01

    Arterial complications after orthotopic liver transplantation (OLT), including hepatic artery thrombosis (HAT), are important causes of early graft failure. The use of an arterial conduit is an accepted alternative to the utilisation of native recipient hepatic artery for specific indications. This study aims to determine the efficacy of arterial conduits and the outcome in OLT. We retrospectively reviewed 1,575 cadaveric adult OLTs and identified those in which an arterial conduit was used for hepatic revascularisation. Data on the primary disease, indication for using arterial conduit, type of vascular graft, operative technique and outcome were obtained. Thirty-six (2.3%) patients underwent OLT in which arterial conduits were used for hepatic artery (HA) revascularisation. Six of these were performed on the primary transplant, while the rest (n=30) were performed in patients undergoing re-transplantation, including six who had developed hepatic artery aneurysms. The incidence of arterial conduits was 0.4% (6/1,426 cases) in all primary OLTs and 20.1% (30/149 cases) in all re-transplants. Twenty-nine procedures utilised iliac artery grafts from the same donor as the liver, six used iliac artery grafts from a different donor, and a single patient underwent a polytetrafluoroethylene (PTFE) graft. Two techniques were used: infra-renal aorto-hepatic artery conduit and interposition between the donor and recipient native HAs, or branches of the HAs. The 30-day mortality rate for operations using an arterial conduit was 30.6%. Three conduits thrombosed at 9, 25 and 155 months, respectively, but one liver graft survived without re-transplantation. The arterial conduits had 1- and 5-year patency rates of 88.5% and 80.8%. The 1- and 5-year patient survival rates were 66.7% and 44%. We can thus conclude that an arterial conduit is a viable alternative option for hepatic revascularisation in both primary and re-transplantation. Despite a lower patency rate than that of

  18. Radioembolization for primary and metastatic liver cancer

    PubMed Central

    Memon, Khairuddin; Lewandowski, Robert J; Kulik, Laura; Riaz, Ahsun; Mulcahy, Mary F; Salem, Riad

    2011-01-01

    The incidence of hepatocellular carcinoma is increasing. Most patients present beyond potentially curative options and are usually affected by underlying cirrhosis. In this scenario, trans-arterial therapies, such as radioembolization, are rapidly gaining acceptance as a potential therapy for hepatocellular carcinoma and liver metastases. Radioembolization is a catheter-based liver-directed therapy that involves injection of micron-sized embolic particles loaded with a radioisotope by use of percutaneous transarterial techniques. Cancer cells are preferentially supplied by arterial blood and normal hepatocytes by portal venous blood; radioembolization therefore specifically targets tumor cells with a high dose of lethal radiation and spares healthy hepatocytes. The antitumor effect mostly comes from radiation rather than embolization. The most commonly used radioisotope is Yttrium-90. The commercially available devices are TheraSphere® (glass-based) and SIR-Sphere® (resin-based). The procedure is performed on outpatient basis. The incidence of complications is generally less than other locoregional therapies and may include nausea, fatigue, abdominal pain, hepatic dysfunction, biliary injury, fibrosis, radiation pneumonitis, gastrointestinal ulcers and vascular injury. However, these can be avoided by meticulous pretreatment assessment, careful patient selection and adequate dosimetry. This article focuses on both the technical and clinical aspects of radioembolization with emphasis on patient selection, uses and complications. PMID:21939859

  19. Adult human liver mesenchymal progenitor cells express phenylalanine hydroxylase.

    PubMed

    Baruteau, Julien; Nyabi, Omar; Najimi, Mustapha; Fauvart, Maarten; Sokal, Etienne

    2014-09-01

    Phenylketonuria (PKU) is one of the most prevalent inherited metabolic diseases and is accountable for a severe encephalopathy by progressive intoxication of the brain by phenylalanine. This results from an ineffective L-phenylalanine hydroxylase enzyme (PAH) due to a mutated phenylalanine hydroxylase (PAH) gene. Neonatal screening programs allow an early dietetic treatment with restrictive phenylalanine intake. This diet prevents most of the neuropsychological disabilities but remains challenging for lifelong compliance. Adult-derived human liver progenitor cells (ADHLPC) are a pool of precursors that can differentiate into hepatocytes. We aim to study PAH expression and PAH activity in a differenciated ADHLPC. ADHLPC were isolated from human hepatocyte primary culture of two different donors and differenciated under specific culture conditions. We demonstrated the high expression of PAH and a large increase of PAH activity in differenciated LPC. The age of the donor, the cellular viability after liver digestion and cryopreservation affects PAH activity. ADHLPC might therefore be considered as a suitable source for cell therapy in PKU.

  20. Oncogenic role of the Notch pathway in primary liver cancer

    PubMed Central

    LU, JIE; XIA, YUJING; CHEN, KAN; ZHENG, YUANYUAN; WANG, JIANRONG; LU, WENXIA; YIN, QIN; WANG, FAN; ZHOU, YINGQUN; GUO, CHUANYONG

    2016-01-01

    Primary liver cancer, which includes hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and fibrolamellar HCC, is one of the most common malignancies and the third leading cause of cancer-associated mortality, worldwide. Despite the development of novel therapies, the prognosis of liver cancer patients remains extremely poor. Thus, investigation of the genetic background and molecular mechanisms underlying the development and progression of this disease has gained significant attention. The Notch signaling pathway is a crucial determinant of cell fate during development and disease in several organs. In the liver, Notch signaling is involved in biliary tree development and tubulogenesis, and is also significant in the development of HCC and ICC. These findings suggest that the modulation of Notch pathway activity may have therapeutic relevance. The present review summarizes Notch signaling during HCC and ICC development and discusses the findings of recent studies regarding Notch expression, which reveal novel insights into its function in liver cancer progression. PMID:27347091

  1. Ablation techniques for primary and metastatic liver tumors

    PubMed Central

    Ryan, Michael J; Willatt, Jonathon; Majdalany, Bill S; Kielar, Ania Z; Chong, Suzanne; Ruma, Julie A; Pandya, Amit

    2016-01-01

    Ablative treatment methods have emerged as safe and effective therapies for patients with primary and secondary liver tumors who are not surgical candidates at the time of diagnosis. This article reviews the current literature and describes the techniques, complications and results for radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation. PMID:26839642

  2. Colorectal Liver Metastasis, Primary Gallbladder Carcinoma and Myelofibrosis Present Simultaneously in a Liver Resection Specimen

    PubMed Central

    Gray, Sophie A.; Raber, Menno H.; Provoost, Esther; Toes, Gert-Jan; Klaase, Joost M.

    2015-01-01

    Myelofibrosis and gallbladder carcinoma are both very rare diseases. This case report describes a patient with a history of myelofibrosis and colorectal carcinoma who was diagnosed with colorectal liver metastases. Surgery was performed to remove the metastases, and on site, the gallbladder was removed because of involvement in one of the liver lesions. After pathological examination, a primary gallbladder carcinoma and myelofibrosis were found in addition to the liver metastases. The combination of diseases was not likely to be interconnected but rather an unlucky course of events for the patient. PMID:26600770

  3. Critical care issues in adult liver transplantation

    PubMed Central

    Gopal, Palepu B.; Kapoor, Dharmesh; Raya, Ravichandra; Subrahmanyam, M.; Juneja, Deven; Sukanya, B.

    2009-01-01

    Over the last decade, liver transplantation has become an operational reality in our part of the world. As a result, clinicians working in an intensive care unit are more likely to be exposed to these patients in the immediate postoperative period, and thus, it is important that they have a working knowledge of the common complications, when they are likely to occur, and how to deal with them. The main focus of this review is to address the variety of critical care issues in liver transplant recipients and to impress upon the need to provide favorable circumstances for the new liver to start functioning and maintain the function of other organs to aid in this process. PMID:20040807

  4. Erlotinib in Treating Patients With Unresectable Liver, Bile Duct, or Gallbladder Cancer

    ClinicalTrials.gov

    2013-06-03

    Adult Primary Cholangiocellular Carcinoma; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  5. Liver Progenitors Isolated from Adult Healthy Mouse Liver Efficiently Differentiate to Functional Hepatocytes In Vitro and Repopulate Liver Tissue.

    PubMed

    Tanimizu, Naoki; Ichinohe, Norihisa; Ishii, Masayuki; Kino, Junichi; Mizuguchi, Toru; Hirata, Koichi; Mitaka, Toshihiro

    2016-12-01

    It has been proposed that tissue stem cells supply multiple epithelial cells in mature tissues and organs. However, it is unclear whether tissue stem cells generally contribute to cellular turnover in normal healthy organs. Here, we show that liver progenitors distinct from bipotent liver stem/progenitor cells (LPCs) persistently exist in mouse livers and potentially contribute to tissue maintenance. We found that, in addition to LPCs isolated as EpCAM(+) cells, liver progenitors were enriched in CD45(-) TER119(-) CD31(-) EpCAM(-) ICAM-1(+) fraction isolated from late-fetal and postnatal livers. ICAM-1(+) liver progenitors were abundant by 4 weeks (4W) after birth. Although their number decreased with age, ICAM-1(+) liver progenitors existed in livers beyond that stage. We established liver progenitor clones derived from ICAM-1(+) cells between 1 and 20W and found that those clones efficiently differentiated into mature hepatocytes (MHs), which secreted albumin, eliminated ammonium ion, stored glycogen, and showed cytochrome P450 activity. Even after long-term culture, those clones kept potential to differentiate to MHs. When ICAM-1(+) clones were transplanted into nude mice after retrorsine treatment and 70% partial hepatectomy, donor cells were incorporated into liver plates and expressed hepatocyte nuclear factor 4α, CCAAT/enhancer binding protein α, and carbamoylphosphate synthetase I. Moreover, after short-term treatment with oncostatin M, ICAM-1(+) clones could efficiently repopulate the recipient liver tissues. Our results indicate that liver progenitors that can efficiently differentiate to MHs exist in normal adult livers. Those liver progenitors could be an important source of new MHs for tissue maintenance and repair in vivo, and for regenerative medicine ex vivo. Stem Cells 2016;34:2889-2901.

  6. Prognosis of adult patients transplanted with liver grafts < 35% of their standard liver volume.

    PubMed

    Ikegami, Toshihiko; Masuda, Yuichi; Ohno, Yasunari; Mita, Atsushi; Kobayashi, Akira; Urata, Koichi; Nakazawa, Yuichi; Miwa, Shirou; Hashikura, Yasuhiko; Miyagawa, Shinichi

    2009-11-01

    We have previously reported that a graft volume (GV) > 30% of the recipient's standard liver volume (SLV) can meet the recipient's metabolic demands. Here we report our experience with adult-to-adult living donor liver transplantation using left side grafts < 35% of the recipient's SLV. Of 143 adult living donor liver transplants, 13 auxiliary partial orthotopic liver transplants, 8 right side grafts, and 2 retransplantation cases were excluded. The resulting 120 cases were divided into 2 groups: group S consisted of 33 patients who received liver grafts < 35% of their SLV, and group L consisted of 87 patients who received liver grafts > or = 35% of their SLV. Patient characteristics, postoperative liver function, duration of hospital stay, and recipient survival rates were compared between the 2 groups. There were no significant differences between groups in recipient or donor background characteristics. The mean GV/SLV ratio of group S was 31.8%, whereas that of group L was 42.5%. There were no significant differences in the postoperative serum total bilirubin levels, prothrombin time international normalized ratio, daily ascites volume, or duration of postoperative hospital stay between the groups. The 1- and 5-year survival rates in group S were 80.7% and 64.2%, respectively, whereas those of group L were 90.8% and 84.9%, respectively, with no significant difference between groups. In conclusion, graft size was not considered to be the only cause of so-called small-for-size graft syndrome, and left side grafting appears to be the procedure of choice for adult-to-adult living donor liver transplantation because of the lower risk to donors in comparison with right lobe grafting.

  7. Laparoscopic combined colorectal and liver resections for primary colorectal cancer with synchronous liver metastases

    PubMed Central

    Takorov, Ivelin; Lukanova, Tsonka; Atanasov, Boiko; Dzharov, Georgi; Djurkov, Ventzeslav; Odisseeva, Evelina; Vladov, Nikola

    2016-01-01

    Backgrounds/Aims Synchronous liver metastases (SLMs) are found in 15-25% of patients at the time of diagnosis with colorectal cancer, which is limited to the liver in 30% of patients. Surgical resection is the most effective and potentially curative therapy for metastatic colorectal carcinoma (CRC) of the liver. The comparison of simultaneous resection of primary CRC and synchronous liver metastases with staged resections is the subject of debate with respect to morbidity. Laparoscopic surgery improves postoperative recovery, diminishes postoperative pain, reduces wound infections, shortens hospitalization, and yields superior cosmetic results, without compromising the oncological outcome. The aim of this study is therefore to evaluate our initial experience with simultaneous laparoscopic resection of primary CRC and SLM. Methods Currently, laparoscopic resection of primary CRC is performed in more than 53% of all patients in our surgical department. Twenty-six patients with primary CRC and a clinical diagnosis of SLM underwent combined laparoscopic colorectal and liver surgery. Six of them underwent laparoscopic colorectal resection combined with major laparoscopic liver resection. Results The surgical approaches were total laparoscopic (25 patients) or hybrid technique (1 patients). The incision created for the extraction of the specimen varied between 5 and 8cm. The median operation time was 223 minutes (100 to 415 min.) with a total blood loss of 180 ml (100-300 ml). Postoperative hospital stay was 6.8 days (6-14 days). Postoperative complications were observed in 6 patients (22.2%). Conclusions Simultaneous laparoscopic colorectal and liver resection appears to be safe, feasible, and with satisfying short-term results in selected patients with CRC and SLM. PMID:28261695

  8. In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells

    PubMed Central

    Ramachandran, Sarada Devi; Schirmer, Katharina; Münst, Bernhard; Heinz, Stefan; Ghafoory, Shahrouz; Wölfl, Stefan; Simon-Keller, Katja; Marx, Alexander; Øie, Cristina Ionica; Ebert, Matthias P.; Walles, Heike

    2015-01-01

    In this study we used differentiated adult human upcyte® cells for the in vitro generation of liver organoids. Upcyte® cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte® process). Proliferating upcyte® cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte® cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel™, they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions. PMID:26488607

  9. Primary carnitine deficiency in a male adult.

    PubMed

    Karmaniolas, Konstantinos; Ioannidis, Panagiotis; Liatis, Stavros; Dalamanga, Maria; Papalambros, Theoharis; Migdalis, Ilias

    2002-01-01

    The case is described of a 36 year-old man who presented with progressive proximal muscle weakness and weight loss. His serum creatine phosphokinase (CPK) levels were markedly elevated. The muscle biopsy showed lipid storage myopathy. The muscle carnitine concentration was extremely low (5.6% of normal levels), establishing the diagnosis of myopathic carnitine deficiency. The disorder was considered as primary because there were no indications of any other identifiable condition which could result in a secondary carnitine deficiency. The patient was treated with oral L-carnitine (2 g per day) and showed rapid improvement. Primary myopathic carnitine deficiency is a curable disorder and therefore it should always be considered as a potential diagnosis in cases of myopathy in young adults.

  10. Fetal and adult liver stem cells for liver regeneration and tissue engineering.

    PubMed

    Fiegel, H C; Lange, Claudia; Kneser, U; Lambrecht, W; Zander, A R; Rogiers, X; Kluth, D

    2006-01-01

    For the development of innovative cell-based liver directed therapies, e.g. liver tissue engineering, the use of stem cells might be very attractive to overcome the limitation of donor liver tissue. Liver specific differentiation of embryonic, fetal or adult stem cells is currently under investigation. Different types of fetal liver (stem) cells during development were identified, and their advantageous growth potential and bipotential differentiation capacity were shown. However, ethical and legal issues have to be addressed before using fetal cells. Use of adult stem cells is clinically established, e.g. transplantation of hematopoietic stem cells. Other bone marrow derived liver stem cells might be mesenchymal stem cells (MSC). However, the transdifferentiation potential is still in question due to the observation of cellular fusion in several in vivo experiments. In vitro experiments revealed a crucial role of the environment (e.g. growth factors and extracellular matrix) for specific differentiation of stem cells. Co-cultured liver cells also seemed to be important for hepatic gene expression of MSC. For successful liver cell transplantation, a novel approach of tissue engineering by orthotopic transplantation of gel-immobilized cells could be promising, providing optimal environment for the injected cells. Moreover, an orthotopic tissue engineering approach using bipotential stem cells could lead to a repopulation of the recipients liver with healthy liver and biliary cells, thus providing both hepatic functions and biliary excretion. Future studies have to investigate, which stem cell and environmental conditions would be most suitable for the use of stem cells for liver regeneration or tissue engineering approaches.

  11. Locally ablative therapies for primary and metastatic liver cancer.

    PubMed

    Li, David; Kang, Josephine; Madoff, David C

    2014-08-01

    Locally ablative therapies have an increasing role in the effective multidisciplinary approach towards the treatment of both primary and metastatic liver tumors. In patients who are not considered surgical candidates and have low volume disease, these therapies have now become established into consensus practice guidelines. A large range of therapeutic options exist including percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, percutaneous laser ablation (PLA), irreversible electroporation (IRE), stereotactic body radiation therapy (SBRT) and high intensity focused ultrasound (HIFU); each having benefits and drawbacks. The greatest body of evidence supporting clinical utility in the liver currently exists for RFA, with PEI having fallen out of favor. MWA, IRE, SBRT and HIFU are relatively nascent technologies, and outcomes data supporting their use is promising. Future directions of ablative therapies include tandem approaches to improve efficacy in the treatment of liver tumors.

  12. Innumerable Liver Masses in a Patient with Autoimmune Hepatitis and Primary Sclerosing Cholangitis Overlap Syndrome.

    PubMed

    Gharibpoor, Alireza; Mansour-Ghanaei, Fariborz; Sadeghi, Mahbobe; Gharibpoor, Faeze; Joukar, Farahnaz; Mavaddati, Sara

    2017-02-07

    BACKGROUND In patients with the diagnosis of autoimmune hepatitis (AIH), the presence of cholestatic features raise the possibility of an overlap syndrome with primary sclerosing cholangitis (PSC). Here, we present a unique case with AIH-PSC overlap syndrome and innumerable liver masses. CASE REPORT A 26-year-old man presented with generalized icterus. Based on the serological findings of hypergamainmunoglobulinemia and positive anti-nuclear antibody tests, together with an abnormal cholangiogram, he was diagnosed with overlap syndrome (AIH-PSC). Liver imaging revealed innumerable liver masses with a benign appearance in the pathological evaluation. To rule out the colon abnormalities that usually coexist with such liver masses, colonoscopy was performed and showed no significant changes. The liver masses were nonmalignant and were resolved after immunosuppressant therapy. CONCLUSIONS Because AIH-PSC overlap syndrome is rare, it is suggested that radiological evaluation of the biliary tree should be performed routinely in adults diagnosed with AIH to reduce the missed diagnosis of overlap syndrome and liver masses.

  13. Primary biliary cirrhosis in the era of liver transplantation.

    PubMed

    Raczyńska, Joanna; Habior, Andrzej; Pączek, Leszek; Foroncewicz, Bartosz; Pawełas, Andrzej; Mucha, Krzysztof

    2014-09-29

    Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver, characterized by the presence of antimitochondrial antibodies (AMA) and progressive immune-mediated destruction of biliary ductules, which lead to cirrhosis. Theories of the PBC etiopathogenesis assume that the disease develops secondarily as an improper immunological reaction to undefined environmental and/or infectious factors in genetically predisposed individuals. Ursodeoxycholic acid (UDCA) is the only drug recommended to treat PBC; it delays the progression of liver disease, but remains only a symptomatic treatment. In the advanced stage of PBC, the treatment of choice is liver transplantation (LTx). Nowadays, PBC is the third indication for LTx, after viral-related and alcoholic liver cirrhosis. Unfortunately, PBC recurs in 21-37% of patients at 10 years after LTx, and in 43% at 15 years after LTx, with the median time to recurrence of 3-5.5 years. Diagnosis of recurrent PBC (rPBC) is based on the liver histopathology. Although various risk factors of rPBC have been investigated, the cause of the recurrence is not clear. There is no specific treatment of rPBC. Together with immunosuppression after LTx, UDCA remains the treatment of choice. New diagnostic technologies (e.g., genomics, proteomics, cell-based therapy, and clinical study of the rPBC patients) may be helpful in understanding the pathogenesis of PBC and the development of new treatment modalities.

  14. [Autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome in adults: report of three cases].

    PubMed

    Santos, Oscar Mauricio; Muñoz Ortiz, Edison; Pérez, Camilo; Restrepo, Juan Carlos

    2012-04-01

    Overlap syndromes are cases of liver diseases that share clinical, serological, histological and radiological criteria of autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). No definitions have been fully established and therefore there is no solid evidence on the diagnosis and treatment. This article presents the cases of three adult patients with overlapping features of AIH and PSC. Orthotopic liver transplantation was considered the best therapeutic alternative due to advanced disease progression in one patient, while medical treatment was provided in the remaining two patients.

  15. Imaging of Primary Liver Carcinosarcoma Scintigraphically; A Case Report

    PubMed Central

    Abdulrezzak, Ümmühan; Kula, Mustafa; Erdoğan, Zeynep; Tutuş, Ahmet

    2014-01-01

    Primary liver carcinosarcoma is a very rare disease. There have been only a few cases described to date, none of which has been imaged by bone scintigraphy. A 69-year-old man who developed right back pain and weight loss was admitted to our hospital. Tenderness of the right upper abdomen, hepatomegaly, and a giant mass were the main physical examination signs. Abdominal ultrasonography showed a large lobulated heterogeneous echogenic solid mass with multiple cystic areas of varying size and a highly echogenic region that had posterior acoustic shadowing within the mass in the right lobe of the liver. Labeled erythrocyte imaging and 99mTc-nanocolloid liver-spleen scan were performed to exclude hemangioma, showing a large intrahepatic photon deficient area. 99mTc-methylene diphosphonate (MDP) bone scintigraphy revealed heterogeneous, irregular and dense activity accumulation thought to be osteoblastic activity in the liver mass. Postsurgical pathological diagnosis revealed “carcinosarcoma”. Conflict of interest:None declared. PMID:24653934

  16. Salvage Liver Transplantation Leads to Poorer Outcome in Hepatocellular Carcinoma Compared with Primary Liver Transplantation

    PubMed Central

    Shan, Yuhua; Huang, Lifeng; Xia, Qiang

    2017-01-01

    Hepatocellular carcinoma is the most common liver malignancy. Salvage liver transplantation (SLT) is viewed as a feasible cure for recurrence of HCC after resectomy, but the effect is under dispute. A retrospective study examined data at Renji Hospital for 239 transplants from January 2006 to December 2015, including 211 who received primary liver transplantation (PLT) and 28 who underwent SLT. A multivariable cox regression model was employed to pick out relative factors to overall survival (OS) and recurrence free survival (RFS). Propensity score matching (PSM) was used to balance the bias. Both OS and RFS were worse in SLT group than in PLT group, especially for those patients within Milan criteria. Our study demonstrates that SLT bears higher risk of recurrence and death than PLT, indicating that SLT should be given a more careful thought at performance. PMID:28294176

  17. Orthotopic liver transplantation in an adult with situs inversus: an easy way to fit the liver.

    PubMed

    Hoyos, Sergio; Guzmán, Carlos; Correa, Gonzalo; Restrepo, Juan Carlos; Franco, Hernán; Cárdenas, Andrés

    2006-01-01

    Situs inversus (SI) is a rare congenital disorder with a complete mirror image of thoracic and abdominal organs. In adults with SI and decompensated cirrhosis experience with liver transplantation is limited. Orthotopic liver transplantation (OLT) in an adult with cirrhosis using a technique where the recipient liver was placed using a 90-degree rotation of the graft was previously reported by Klintmalm et al, however no other reports using this technique have been described. We report a case of a 41 year-old man with situs inversus and decompensated cirrhosis who successfully underwent OLT using this technique. The donor liver was rotated 90-degrees towards the left and easily fitted into the recipients'fossa with the left lobe pointing toward the left lower quadrant. The patient had an uneventful recovery and has been followed for 21 months without any complications. This technique has the advantage of preventing compromise of the size of the donor liver, permits an easy reconstruction of vascular and biliary tree and in this case was associated with an excellent outcome.

  18. Innumerable Liver Masses in a Patient with Autoimmune Hepatitis and Primary Sclerosing Cholangitis Overlap Syndrome

    PubMed Central

    Gharibpoor, Alireza; Mansour-Ghanaei, Fariborz; Sadeghi, Mahbobe; Gharibpoor, Faeze; Joukar, Farahnaz; Mavaddati, Sara

    2017-01-01

    Patient: Male, 26 Final Diagnosis: AIH-PSC overlap syndrome Symptoms: Palpable liver more than 5 cm below the costal margin and both firm and nodular • 8-kg weight loss during the last 2 months • clay-colored stool • dark urine • general fatigue • generalized icterus • light abdominal tenderness in the right upper quadrant with isolated hepatomegaly • loss of appetite • neither spider angioma nor stigmata • no clinical evidence of ascites or lymphadenopathy • non-specific abdominal discomfort • normoactive bowel sound • pruritus Medication: — Clinical Procedure: Lab tests • MRCP • Pathological analysis Specialty: Gastroenterology and Hepatology Objective: Challenging differential diagnosis Background: In patients with the diagnosis of autoimmune hepatitis (AIH), the presence of cholestatic features raise the possibility of an overlap syndrome with primary sclerosing cholangitis (PSC). Here, we present a unique case with AIH-PSC overlap syndrome and innumerable liver masses. Case Report: A 26-year-old man presented with generalized icterus. Based on the serological findings of hypergamainmunoglobulinemia and positive anti-nuclear antibody tests, together with an abnormal cholangiogram, he was diagnosed with overlap syndrome (AIH-PSC). Liver imaging revealed innumerable liver masses with a benign appearance in the pathological evaluation. To rule out the colon abnormalities that usually coexist with such liver masses, colonoscopy was performed and showed no significant changes. The liver masses were nonmalignant and were resolved after immunosuppressant therapy. Conclusions: Because AIH-PSC overlap syndrome is rare, it is suggested that radiological evaluation of the biliary tree should be performed routinely in adults diagnosed with AIH to reduce the missed diagnosis of overlap syndrome and liver masses. PMID:28167813

  19. Congenital hepatic fibrosis, liver cell carcinoma and adult polycystic kidneys.

    PubMed

    Manes, J L; Kissane, J M; Valdes, A J

    1977-06-01

    In reviewing the literature, we found no liver cell carcinoma (LCC) or well-documented adult polycystic kidneys (APK) associated with congenital hepatic fibrosis (CHF). We report a 69-year-old man with CHF, LCC, APK, duplication cyst of distal portion of stomach, two calcified splenic artery aneurysms, myocardial fibrosis and muscular hypertrophy of esophagus. The LCC was grossly predunculated and microscopically showed prominent fibrosis and hyaline intracytoplasmic inclusions in the tumor cells.

  20. [Adult-onset Still's disease with liver failure requiring liver transplantation].

    PubMed

    Terán, Alvaro; Casafont, Fernando; Fábrega, Emilio; Martínez-Taboada, Víctor Manuel; Rodríguez-Valverde, Vicente; Pons-Romero, Fernando

    2009-12-01

    We present the case of a 23-year-old man with fever of unknown origin, who developed acute liver failure 2 months after symptom onset, requiring an urgent liver transplantation. The diagnosis of adult-onset Still's disease was established after the reappearance of symptoms after transplantation, and high doses of corticosteroids were used to control disease activity. Subsequently, given the impossibility of tapering the steroid dose, interleukin-1 receptor blocking treatment was started with satisfactory outcome. We also review the published literature.

  1. Open-Porous Hydroxyapatite Scaffolds for Three-Dimensional Culture of Human Adult Liver Cells.

    PubMed

    Finoli, Anthony; Schmelzer, Eva; Over, Patrick; Nettleship, Ian; Gerlach, Joerg C

    2016-01-01

    Liver cell culture within three-dimensional structures provides an improved culture system for various applications in basic research, pharmacological screening, and implantable or extracorporeal liver support. Biodegradable calcium-based scaffolds in such systems could enhance liver cell functionality by providing endothelial and hepatic cell support through locally elevated calcium levels, increased surface area for cell attachment, and allowing three-dimensional tissue restructuring. Open-porous hydroxyapatite scaffolds were fabricated and seeded with primary adult human liver cells, which were embedded within or without gels of extracellular matrix protein collagen-1 or hyaluronan. Metabolic functions were assessed after 5, 15, and 28 days. Longer-term cultures exhibited highest cell numbers and liver specific gene expression when cultured on hydroxyapatite scaffolds in collagen-1. Endothelial gene expression was induced in cells cultured on scaffolds without extracellular matrix proteins. Hydroxyapatite induced gene expression for cytokeratin-19 when cells were cultured in collagen-1 gel while culture in hyaluronan increased cytokeratin-19 gene expression independent of the use of scaffold in long-term culture. The implementation of hydroxyapatite composites with extracellular matrices affected liver cell cultures and cell differentiation depending on the type of matrix protein and the presence of a scaffold. The hydroxyapatite scaffolds enable scale-up of hepatic three-dimensional culture models for regenerative medicine applications.

  2. Open-Porous Hydroxyapatite Scaffolds for Three-Dimensional Culture of Human Adult Liver Cells

    PubMed Central

    Schmelzer, Eva; Over, Patrick; Nettleship, Ian; Gerlach, Joerg C.

    2016-01-01

    Liver cell culture within three-dimensional structures provides an improved culture system for various applications in basic research, pharmacological screening, and implantable or extracorporeal liver support. Biodegradable calcium-based scaffolds in such systems could enhance liver cell functionality by providing endothelial and hepatic cell support through locally elevated calcium levels, increased surface area for cell attachment, and allowing three-dimensional tissue restructuring. Open-porous hydroxyapatite scaffolds were fabricated and seeded with primary adult human liver cells, which were embedded within or without gels of extracellular matrix protein collagen-1 or hyaluronan. Metabolic functions were assessed after 5, 15, and 28 days. Longer-term cultures exhibited highest cell numbers and liver specific gene expression when cultured on hydroxyapatite scaffolds in collagen-1. Endothelial gene expression was induced in cells cultured on scaffolds without extracellular matrix proteins. Hydroxyapatite induced gene expression for cytokeratin-19 when cells were cultured in collagen-1 gel while culture in hyaluronan increased cytokeratin-19 gene expression independent of the use of scaffold in long-term culture. The implementation of hydroxyapatite composites with extracellular matrices affected liver cell cultures and cell differentiation depending on the type of matrix protein and the presence of a scaffold. The hydroxyapatite scaffolds enable scale-up of hepatic three-dimensional culture models for regenerative medicine applications. PMID:27403430

  3. The immunopathology of liver granulomas in primary biliary cirrhosis.

    PubMed

    You, Zhengrui; Wang, Qixia; Bian, Zhaolian; Liu, Yuan; Han, Xiaofeng; Peng, Yanshen; Shen, Lei; Chen, Xiaoyu; Qiu, Dekai; Selmi, Carlo; Gershwin, M Eric; Ma, Xiong

    2012-09-01

    Liver granulomas and elevated serum IgM are commonly observed in patients with primary biliary cirrhosis (PBC) but their pathogenetic significance remains largely unknown. To address this issue we performed an extensive immunostaining and colocalization study of markers associated with dendritic cells and IgM in a large cohort of tissue samples from PBC and control livers as well as from non-hepatic granulomatous diseases. First, the classical dendritic cell CD11c marker is highly expressed and more sensitive than classical hematoxylin-eosin staining in detecting granulomas associated with PBC and other conditions. Second, PBC cases with CD11c-positive granulomas have significantly higher serum IgM levels and earlier disease stages. Third, granulomas from PBC and other diseases demonstrate markers of dendritic cell immaturity, i.e. CD11b, reduced MHC II, IL-23, CCR7 and CD83 expression, and elevated C1q expression. Lastly, B cells and IgM-positive plasma cells are largely represented around PBC granulomas along with macrophages. In conclusion, our comprehensive immunohistochemical study suggests that dendritic cells are key to the pathogenesis of granulomas, regardless of their origin. More specifically, PBC liver granulomas may result from the interaction between immature dendritic cells and IgM.

  4. Adult Embryonal Sarcoma of the Liver: Management of a Massive Liver Tumor

    PubMed Central

    Roudenko, Alexandra; El Hussein, Siba; Rizer, Magda

    2016-01-01

    Undifferentiated embryonal sarcomas of the liver are extremely rare cases in adults. We report the case of a 30-year-old male who presented with early satiety and abdominal pain due to a massive tumor originating from the left liver and occupying the entire epigastrium. The patient underwent bland embolization in an attempt to decrease the size of the tumor. He then underwent a formal left hepatectomy with resection of liver segments 2, 3, and 4. Extrahepatic inflow control of the portal vein and hepatic artery was performed prior to parenchymal transection. No Pringle maneuver was required. Pathology analysis showed a 45 cm tumor consistent with an undifferentiated embryonal sarcoma and negative microscopic margins. The epidemiology, treatment, and prognosis of this unusual cancer presentation are reviewed. PMID:27895954

  5. Pharmacologic therapy for nonalcoholic fatty liver disease in adults.

    PubMed

    Malinowski, Scott S; Byrd, Jennifer S; Bell, Allison M; Wofford, Marion R; Riche, Daniel M

    2013-02-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of triglycerides in hepatocytes in the absence of excessive alcohol intake, ranging in severity from simple steatosis to nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis can ultimately progress to cirrhosis and hepatocellular carcinoma. NAFLD is associated with cardiometabolic risk factors and is the most common chronic liver disease among adults in the Western Hemisphere. Although simple steatosis is generally considered a self-limiting disease, evidence suggests an increased risk of cardiovascular disease, and, less conclusively, mortality, among individuals with NAFLD and/or NASH. The current standard of care for the treatment of patients with NAFLD focuses on lifestyle interventions, particularly diet and exercise. There is a lack of consensus regarding the most effective and appropriate pharmacologic therapy. A PubMed search was conducted using the medical subject heading terms "fatty liver" and "steatohepatitis." This review focuses on the current pharmacologic options available for treating adults with NAFLD and/or NASH. Continued investigation of drugs or combinations that improve NAFLD progression is crucial. Clinicians, particularly pharmacists, must take an active role in identification and appropriate selection of pharmacotherapy for NAFLD.

  6. Immunolocalization of putative human liver progenitor cells in livers from patients with end-stage primary biliary cirrhosis and sclerosing cholangitis using the monoclonal antibody OV-6.

    PubMed

    Crosby, H A; Hubscher, S; Fabris, L; Joplin, R; Sell, S; Kelly, D; Strain, A J

    1998-03-01

    The term oval cell describes small cells with oval nuclei that arise in the periphery of the portal tracts in rat models of hepatocarcinogenesis and injury and can differentiate into either hepatocytes or bile duct cells, ie, are bipotential. The presence of such cells in human liver is controversial. Here, immunolocalization of OV-6 and two biliary markers, cytokeratin 19 (CK-19) and human epithelial antigen 125 (HEA-125) is compared in normal adult human livers and in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) liver sections. CK-19 and HEA-125 stained bile ducts and ductules in normal liver as well as proliferating ductular structures in diseased livers. OV-6 did not label ducts or ductules in normal liver, but in PBC and PSC stained numerous proliferating ductular and periductular cells and lobular hepatocytes. In PBC, discrete OV-6-positive cells with a mature biliary-cell-like morphology were seen integrated into some intact bile ducts as well as occasional small immature oval-like cells. In addition, in PSC, hepatocytes in regenerating lobules were also strongly stained with OV-6, and on close inspection, in both PBC and PSC, oval cells and small hepatocytes at the margins of the lobules were strongly labeled. In contrast to the rat liver, OV-6 and CK-19 staining did not always co-localize. It is proposed that the small OV-6-positive oval cells are analogous to those seen in rat models and may represent human liver progenitor cells that may differentiate into OV-6-positive ductal cells or lobular hepatocytes.

  7. Primary liver cells cultured on carbon nanotube substrates for liver tissue engineering and drug discovery applications.

    PubMed

    Che Abdullah, Che Azurahanim; Azad, Chihye Lewis; Ovalle-Robles, Raquel; Fang, Shaoli; Lima, Marcio D; Lepró, Xavier; Collins, Steve; Baughman, Ray H; Dalton, Alan B; Plant, Nick J; Sear, Richard P

    2014-07-09

    Here, we explore the use of two- and three-dimensional scaffolds of multiwalled-carbon nanotubes (MWNTs) for hepatocyte cell culture. Our objective is to study the use of these scaffolds in liver tissue engineering and drug discovery. In our experiments, primary rat hepatocytes, the parenchymal (main functional) cell type in the liver, were cultured on aligned nanogrooved MWNT sheets, MWNT yarns, or standard 2-dimensional culture conditions as a control. We find comparable cell viability between all three culture conditions but enhanced production of the hepatocyte-specific marker albumin for cells cultured on MWNTs. The basal activity of two clinically relevant cytochrome P450 enzymes, CYP1A2 and CYP3A4, are similar on all substrates, but we find enhanced induction of CYP1A2 for cells on the MWNT sheets. Our data thus supports the use of these substrates for applications including tissue engineering and enhancing liver-specific functions, as well as in in vitro model systems with enhanced predictive capability in drug discovery and development.

  8. Adult Living Donor Liver Transplantation Across ABO-Incompatibility.

    PubMed

    Lee, Chen-Fang; Cheng, Chih-Hsien; Wang, Yu-Chao; Soong, Ruey-Shyang; Wu, Tsung-Han; Chou, Hong-Shiue; Wu, Ting-Jung; Chan, Kun-Ming; Lee, Ching-Song; Lee, Wei-Chen

    2015-10-01

    The objective of this study was to evaluate the results of adult ABO-incompatible living donor liver transplantation (LDLT).ABO-incompatible LDLT is an aggressive treatment that crosses the blood-typing barrier for saving lives from liver diseases. Although graft and patient survival have been improved recently by various treatments, the results of adult ABO-incompatible LDLT require further evaluation.Two regimens were designed based on isoagglutinin IgG and IgM titers and the time course of immunological reactions at this institute. When isoagglutinin IgG and IgM titers were ≤64, liver transplantation was directly performed and rituximab (375 mg/m) was administrated on postoperative day 1 (regimen I). When isoagglutinin titers were >64, rituximab (375 mg/m) was administered preoperatively with or without plasmapheresis and boosted on postoperative day 1 (regimen II). Immunosuppression was achieved by administration of mycophenolate mofetil, tacrolimus, and steroids.Forty-six adult ABO-incompatible and 340 ABO-compatible LDLTs were performed from 2006 to 2013. The Model for End-Stage Liver Disease scores for ABO-incompatible recipients ranged from 7 to 40, with a median of 14. The graft-to-recipient weight ratio ranged from 0.61% to 1.61% with a median of 0.91%. The 1-, 3-, and 5-year survival rates were 81.7%, 75.7%, and 71.0%, respectively, for ABO-incompatible LDLT recipients, compared to 81.0%, 75.2%, and 71.5% for ABO-C recipients (P = 0.912). The biliary complication rate was higher in ABO-incompatible LDLT recipients than in the ABO-compatible recipients (50.0% vs 29.7%, P = 0.009).In the rituximab era, the blood type barrier can be crossed to achieve adult ABO-incompatible LDLT with survival rates comparable to those of ABO-compatible LDLT, but with more biliary complications.

  9. Diagnosis of Liver Involvement in Primary Sjögren Syndrome

    PubMed Central

    Zeron, Pilar Brito; Retamozo, Soledad; Bové, Albert; Kostov, Belchin Adriyanov; Sisó, Antoni

    2013-01-01

    Liver involvement was one of the first extraglandular manifestations to be reported in patients with primary Sjögren syndrome (SS). In the 1990s, a study of liver involvement in patients with primary SS integrated the evaluation of clinical signs of liver disease, liver function and a complete panel of autoantibodies. Recent developments in the field of hepatic and viral diseases have significantly changed the diagnostic approach to liver involvement in SS. The most recent studies have shown that, after eliminating hepatotoxic drugs and fatty liver disease, the two main causes of liver disease in primary SS are chronic viral infections and autoimmune liver diseases. The differential diagnosis of liver disease in primary SS (viral vs autoimmune) is clinically important, since the two processes require different therapeutic approaches and have different prognoses. With respect to viral infections, chronic HCV infection is the main cause of liver involvement in SS patients from the Mediterranean area, while chronic HBV infection may be the main cause of liver involvement in SS patients from Asian countries. After eliminating viral hepatitis, primary biliary cirrhosis (PBC) should be considered the main cause of liver disease in primary SS. PBC-related SS patients may have a broad spectrum of abnormalities of the liver, including having no clinical or analytical data suggestive of liver disease. Autoimmune hepatitis (AIH) is the second most frequently found autoimmune liver disease to be associated with SS (all reported cases are type I), and nearly 10% of these patients have an AIH-PBC overlap. Finally, IgG4-related disease must be investigated in patients with SS presenting with sclerosing cholangitis, especially when autoimmune pancreatitis or retroperitoneal fibrosis are also present. PMID:26355632

  10. Percutaneous Endovascular Treatment of Hepatic Artery Stenosis in Adult and Pediatric Patients After Liver Transplantation

    SciTech Connect

    Maruzzelli, Luigi; Miraglia, Roberto Caruso, Settimo; Milazzo, Mariapina; Mamone, Giuseppe; Gruttadauria, Salvatore; Spada, Marco; Luca, Angelo; Gridelli, Bruno

    2010-12-15

    The purpose of this study was to evaluate the efficacy of percutaneous endovascular techniques for the treatment of hepatic artery stenosis (HAS) occurring after liver transplantation (LT) in adult and pediatrics patients. From February 2003 to March 2009, 25 patients (15 adults and 10 children) whose developed HAS after LT were referred to our interventional radiology unit. Technical success was achieved in 96% (24 of 25) of patients. Percutaneous transluminal angioplasty (PTA) was performed in 13 patients (7 children), and stenting was performed in 11 patients (2 children). After the procedure, all patients were followed-up with liver function tests, Doppler ultrasound, and/or computed tomography. Mean follow-up was 15.8 months (range 5 days to 58 months). Acute hepatic artery thrombosis occurred immediately after stent deployment in 2 patients and was successfully treated with local thrombolysis. One patient developed severe HA spasm, which reverted after 24 h. After the procedure, mean trans-stenotic pressure gradient decreased from 30.5 to 6.2 mmHg. Kaplan-Meyer curve of HA primary patency was 77% at 1 and 2 years. During the follow-up period, 5 patients (20%) had recurrent stenosis, and 2 patients (8.3%) had late thrombosis. Two of 7 patients with stenosis/thrombosis underwent surgical revascularization (n = 1) and liver retransplantation (n = 1). Six (25%) patients died during follow-up, but overall mortality was not significantly different when comparing patients having patent hepatic arteries with those having recurrent stenosis/thrombosis. There were no significant differences in recurrent stenosis/thrombosis and mortality comparing patients treated by PTA versus stenting and comparing adult versus pediatric status. Percutaneous interventional treatment of HAS in LT recipients is safe and effective and decreases the need for surgical revascularization and liver retransplantation. However, the beneficial effects for survival are not clear, probably because

  11. Primary Care Providers' HIV Prevention Practices Among Older Adults

    PubMed Central

    Davis, Tracy; Teaster, Pamela B.; Thornton, Alice; Watkins, John F.; Alexander, Linda; Zanjani, Faika

    2016-01-01

    Purpose To explore primary care providers' HIV prevention practices for older adults. Primary care providers' perceptions and awareness were explored to understand factors that affect their provision of HIV prevention materials and HIV screening for older adults. Design and Method Data were collected through 24 semistructured interviews with primary care providers (i.e., physicians, physician assistants, and nurse practitioners) who see patients older than 50 years. Results Results reveal facilitators and barriers of HIV prevention for older adults among primary care providers and understanding of providers' HIV prevention practices and behaviors. Individual, patient, institutional, and societal factors influenced HIV prevention practices among participants, for example, provider training and work experience, lack of time, discomfort in discussing HIV/AIDS with older adults, stigma, and ageism were contributing factors. Furthermore, factors specific to primary and secondary HIV prevention were identified, for instance, the presence of sexually transmitted infections influenced providers' secondary prevention practices. Implications HIV disease, while preventable, is increasing among older adults. These findings inform future research and interventions aimed at increasing HIV prevention practices in primary care settings for patients older than 50. PMID:25736425

  12. [Primary graft failure as the result of unsuspected severe steatosis in the donor liver].

    PubMed

    García Ureña, M A; Moreno González, E; Colina Ruíz-Delgado, F; Jiménez Romero, C; García García, I; González-Pinto, I; Loinaz Segurola, C

    1998-10-01

    Primary non-function is an serious complication after orthotopic liver transplantation. A relationship between the severity of fatty infiltration in the donor liver and immediate graft function has been described. We present two cases of primary non-function, attributable to the presence of severe steatosis in the donor liver. They were two recipients with a deteriorated clinical status before liver transplantation. In both cases, liver fatty infiltration was not suspected because of the macroscopic aspect of the donor liver at procurement. In time 0 biopsies, hematoxyllin-eosin stained sections evaluated the degree of severity of the fatty infiltration as moderate (30-60% of hepatocytes involved), while the Sudan stained sections revealed more degree of severity (more than 60%). We believe that in case of moderate steatosis in liver donor the graft may be considered when it is not associated to another known risk factors as poor medical status of recipient and retransplantation.

  13. Comparison of histidine-tryptophan-ketoglutarate solution (HTK) and University of Wisconsin solution (UW) in adult liver transplantation.

    PubMed

    Mangus, Richard S; Tector, A Joseph; Agarwal, Avinash; Vianna, Rodrigo; Murdock, Phillip; Fridell, Jonathan A

    2006-02-01

    Histidine-tryptophan-ketoglutarate solution (HTK) and University of Wisconsin solution (UW) have been shown to have similar outcomes in cadaveric kidney, pancreas, and liver transplantation. Our institution changed from UW to HTK as the primary preservation solution for liver, kidney and pancreas transplantation. This study compares the perioperative and first year outcomes of liver transplantation using UW or HTK. Primary use of HTK began on May 1, 2003. We reviewed the records of all adult liver transplant recipients from July 1, 2002 to December 31, 2004. Recipients were compared based on organ preservation solution (UW n = 204, HTK n = 174). Outcomes included 1-, 6- and 12-month graft and patient survival and 1-, 7-, 14-, and 30-day liver function and serum creatinine. During the entire study period, the two groups were managed similarly in operative technique, immunosuppressive regimens, and donor liver criteria. Over 30 months, 378 adult patients underwent liver transplantation. There were no significant differences between UW and HTK in 1-, 6-, or 12-month graft or patient survival. The HTK group had a higher day 1 median AST, ALT, and total bilirubin, but the two groups were similar thereafter. An anticipated difference in infused volume between UW and HTK was demonstrated. In conclusion, to our knowledge, this is the first reported large case series from North America comparing HTK and UW in liver transplantation with 2- to 12-month follow-up. There were no significant differences between HTK and UW in this population when comparing 1 month graft function and first-year graft and patient survival.

  14. Primary Liver Abscess with Anterior Abdominal Wall Extension Caused by Mycobacterium tuberculosis Complex

    PubMed Central

    Kandekar, Rahul Vilas; Tiwari, Ajeet Ramamani; Kadam, Rahul; Adhikari, Devbrata Radhikamohan

    2016-01-01

    Tubercular liver abscess is generally secondary to some other primary foci in the body, most notably pulmonary and gastrointestinal system. To find primary tubercular liver abscess is rare, with prevalence of 0.34% in patients with hepatic tuberculosis. Abscess tracking into abdominal wall from spinal and para spinal tuberculosis is known, however primary liver tuberculosis rupturing into anterior abdominal wall has been reported only twice in literature. We report a case of 43-year-old female with direct invasion of the anterior abdominal wall from an isolated tubercular parenchymal liver abscess, caused by Mycobacterium tuberculosis complex, diagnosed primarily on smear for Acid Fast Bacilli (AFB), imaging and isolated by culture and BACTEC MGIT 960 KIT. We discuss here the diagnostic dilemma, management and outcome of primary tubercular liver parenchymal abscess with direct invasion into anterior abdominal wall. PMID:28050433

  15. On 4-hydroxyphenylpyruvate dioxygenase of adult frog liver.

    PubMed

    Lindstedt, S; Odelhög, B; Rundgren, M

    1982-01-01

    1. It has been reported that 4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27) activity in the liver from Rana esculenta is present only after autolysis of trypsin digestion, which releases a heat-and acid-stable inhibitor of low molecular mass. 2. Attempts to demonstrate similar effects with the liver enzyme from adult Rana pipiens were unsuccessful. Trypsin had only an inhibitory effect on the enzyme activity in crude extracts. 3. Both untreated and trypsin-treated enzyme had a molecular mass of about 100,000 daltons as determined by gel filtration. The pI was around pH 4.6. One pH-optimum between pH 7 and 8 was observed. 4. At pH 7.5 and 37 degrees C the basal enzyme activity was 1.3 mumol/min per g of protein. It was increased six-fold by a reductant in the presence of catalase. Fe2+ (50 muM) increased the activity further 1.6-fold when the reaction was carried out in Tris-HCl buffer, but not in potassium phosphate buffer. 5. The Km for 4-hydroxyphenylpyruvate was 50 muM and the Vmax was around 10 mumol/min per g of soluble protein with reductively activated enzyme. 6. Substrate inhibition was observed above 20 muM concentrations of 4-hydroxyphenylpyruvate.

  16. Metabolic aspects of adult patients with nonalcoholic fatty liver disease

    PubMed Central

    Abenavoli, Ludovico; Milic, Natasa; Di Renzo, Laura; Preveden, Tomislav; Medić-Stojanoska, Milica; De Lorenzo, Antonino

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome (MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance (IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD. PMID:27610012

  17. Adult-to-adult living donor liver transplantation: Operative techniques to optimize the recipient's outcome

    PubMed Central

    Koh, Peng Soon; Chan, See Ching

    2017-01-01

    Adult-to-adult living donor liver transplantation (LDLT) is widely accepted today with good outcomes and safety reported worldwide for both donor and recipient. Nonetheless, it remained a highly demanding technical and complex surgery if undertaken. The last two decades have seen an increased in adult-to-adult LDLT following our first report of right lobe LDLT in overcoming graft size limitation in adults. In this article, we discussed the operative techniques and challenges of adult right lobe LDLT incorporating the middle hepatic vein, which is practiced in our center for the recipient operation. The various issues and challenges faced by the transplant surgeon in ensuring good recipient outcome are explored and discussed here as well. Hence, it is important to understand that a successful recipient operation is dependent of multifactorial events starting at the preoperative stage of planning, understanding the intraoperative technical challenges and the physiology of flow modulation that goes hand-in-hand with the operation. Therefore, one needs to arm oneself with all the possible knowledge in overcoming these technical challenges and the ability to be flexible and adaptable during LDLT by tailoring the needs of each patient individually. PMID:28250667

  18. Treatment of Adult Primary Alveolar Proteinosis.

    PubMed

    Rodríguez Portal, José Antonio

    2015-07-01

    Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of surfactant-like lipoproteinaceous material in the distal air spaces and terminal bronchi, which may lead to impaired gas exchange. This accumulation of surfactant is due to decreased clearance by the alveolar macrophages. Its primary, most common form, is currently considered an autoimmune disease. Better knowledge of the causes of PAP have led to the emergence of alternatives to whole lung lavage, although this is still considered the treatment of choice. Most studies are case series, often with limited patient numbers, so the level of evidence is low. Since the severity of presentation and clinical course are variable, not all patients will require treatment. Due to the low level of evidence, some objective criteria based on expert opinion have been arbitrarily proposed in an attempt to define in which patients it is best to initiate treatment.

  19. Primary Tubercular Liver Abscess Complicated by Tubercular Meningitis in Portal Cavernoma Cholangiopathy

    PubMed Central

    Choksi, Dhaval; Poddar, Prateik; Shah, Kaivan; Ingle, Meghraj; Sawant, Prabha

    2016-01-01

    While hepatic tuberculosis is rare, primary tubercular liver abscess (TLA) is a rarer condition even in endemic countries such as India. Liver abscess in portal cavernoma cholangiopathy (PCC) is predominantly pyogenic. A 14-year-old girl was found to have PCC with multiple liver abscesses. Persistent fever and development of neurological symptoms prompted further evaluation, and she was found to have primary TLA complicated by tubercular meningitis. We report a rare case of primary TLA complicated by tubercular meningitis in asymptomatic PCC. PMID:28119947

  20. Refractory Adult Primary Autoimmune Neutropenia that Responded to Alemtuzumab.

    PubMed

    Neerukonda, Anu R; Lan, Fengshuo; Gabig, Theodore; Saraya, Takeshi

    2016-01-01

    Primary autoimmune neutropenia (P-AIN) is an extremely rare disease. The most effective treatment for primary P-AIN is a granulocyte colony-stimulating factor; however, no curative treatment has been reported. We herein report a case of an adult P-AIN patient with a relatively mild medical history (irrespective of the severe neutropenia) who showed a sustained hematological response over seventeen months after the initiation of treatment with subcutaneous Alemtuzumab.

  1. Employment of adult mammalian primary cells in toxicology: In vivo and in vitro genotoxic effects of environmentally significant N-nitrosodialkylamines in cells of the liver, lung, and kidney

    SciTech Connect

    Pool, B.L.; Brendler, S.Y.; Liegibel, U.M.; Schmezer, P. ); Tompa, A. )

    1990-01-01

    This report focuses on the use of freshly isolated primary mammalian cells from different tissues and organs of the rat for the rapid and efficient analysis of toxic and genotoxic chemicals. The cells are either treated in vitro or they are isolated from treated animals. Viability by trypan blue exclusion and DNA damage as single-strand breaks are monitored in either case. Therefore, it is possible to compare in vitro and in vivo results directly. N-nitrosamines with unique organ-specific modes in carcinogenesis were studied in vitro using hepatocytes derived from three species (rat, hamster, and pig) and in rat lung and kidney cells. The sensitive detection of all carcinogenic nitrosamines was achieved, although a pattern of cell-specific activation was not observable. The new modification of the in vivo approach allowed the sensitive detection of NDMA genotoxicity in hepatic and in extrahepatic tissues. It is important to point out that the method is an efficient tool for toxicokinetic studies with genotoxic carcinogens in vivo.

  2. Primary liver tumors in beagle dogs exposed by inhalation to aerosols of plutonium-238 dioxide.

    PubMed Central

    Gillett, N. A.; Muggenburg, B. A.; Mewhinney, J. A.; Hahn, F. F.; Seiler, F. A.; Boecker, B. B.; McClellan, R. O.

    1988-01-01

    Primary liver tumors developed in Beagle dogs exposed by inhalation to aerosols of 238PuO2. Initial deposition of 238PuO2 in the respiratory tract was followed by translocation of a portion of the 238Pu to the liver and skeleton, which resulted in a large dose commitment and tumor risk to all three tissues. In a population of 144 dogs exposed to 238PuO2, 112 dogs died or were killed 4000 days after 238Pu exposure, 100 dogs had osteosarcoma, and 28 dogs had lung cancers. At increasing times after exposure, however, liver lesions have become more pronounced. Ten primary liver tumors in nine animals were diagnosed in the dogs dying before 4000 days after exposure. An additional five primary liver tumors in three dogs occurred in 9 animals killed after 4000 days after exposure. The majority of these tumors have been fibrosarcomas. The liver tumors were usually not the cause of death, and rarely metastasized. The occurrence of liver tumors in this study indicates that 238Pu is an effective hepatic carcinogen. Liver carcinogenesis is assuming an increasing importance in this study at late times after inhalation exposure. These results suggest that the liver may be an important organ at risk for the development of neoplasia in humans at time periods long after inhalation of 238Pu. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:3142267

  3. Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease

    PubMed Central

    Bell, Catherine C.; Hendriks, Delilah F. G.; Moro, Sabrina M. L.; Ellis, Ewa; Walsh, Joanne; Renblom, Anna; Fredriksson Puigvert, Lisa; Dankers, Anita C. A.; Jacobs, Frank; Snoeys, Jan; Sison-Young, Rowena L.; Jenkins, Rosalind E.; Nordling, Åsa; Mkrtchian, Souren; Park, B. Kevin; Kitteringham, Neil R.; Goldring, Christopher E. P.; Lauschke, Volker M.; Ingelman-Sundberg, Magnus

    2016-01-01

    Liver biology and function, drug-induced liver injury (DILI) and liver diseases are difficult to study using current in vitro models such as primary human hepatocyte (PHH) monolayer cultures, as their rapid de-differentiation restricts their usefulness substantially. Thus, we have developed and extensively characterized an easily scalable 3D PHH spheroid system in chemically-defined, serum-free conditions. Using whole proteome analyses, we found that PHH spheroids cultured this way were similar to the liver in vivo and even retained their inter-individual variability. Furthermore, PHH spheroids remained phenotypically stable and retained morphology, viability, and hepatocyte-specific functions for culture periods of at least 5 weeks. We show that under chronic exposure, the sensitivity of the hepatocytes drastically increased and toxicity of a set of hepatotoxins was detected at clinically relevant concentrations. An interesting example was the chronic toxicity of fialuridine for which hepatotoxicity was mimicked after repeated-dosing in the PHH spheroid model, not possible to detect using previous in vitro systems. Additionally, we provide proof-of-principle that PHH spheroids can reflect liver pathologies such as cholestasis, steatosis and viral hepatitis. Combined, our results demonstrate that the PHH spheroid system presented here constitutes a versatile and promising in vitro system to study liver function, liver diseases, drug targets and long-term DILI. PMID:27143246

  4. Adult to adult right lobe living donor liver transplantation: does biological relationship matter?

    PubMed Central

    Zhang, Wei; Tan, Yifei; Shen, Shu; Jiang, Li; Yan, Lunan; Yang, Jiayin; Li, Bo; Wen, Tianfu; Zeng, Yong; Wang, WenTao; Xu, Mingqing

    2017-01-01

    Abstract The influence of the biological relationship between the donor and the recipient is rarely discussed in living donor liver transplantation (LDLT), although it is believed to be an important risk factor in other types of organ transplantations. A total of 272 consecutive patients undergoing adult to adult right lobe LDLT were retrospectively analyzed and stratified into a nonbiologically related (NBR) group (69 patients) and a biologically related (BR) group (203 patients). The preoperative data and postoperative outcomes of both recipients and donors were evaluated. More than two-thirds of the recipients had histories of HBV infection, and hepatocellular carcinoma (HCC) was the main reason for the patients undergoing LDLT in both groups. The percentage of female donors in the NBR group was more than the percentage in the BR group (P = 0.000). There were no differences between the groups in postoperative laboratory testing or daily immunosuppression dose, and the complication rates in both the recipient and donor surgeries showed no significant differences. For patients with benign diseases, the cumulative 1-, 3-, 5-, and 10-year survival rate were 92.9% in the 4 periods in the NBR group and 89.1%, 87.6%, 83.7%, and 83.7%, respectively, in BR group, while for the patients diagnosed as HCC, if patients exceeding the Milan criteria were involved, the 5-year survival rate was 41.2%, compared to 82% for patients within the Milan criteria, which was nearly the same as for those with the benign disease. In conclusion, our findings suggested that the biological relationship between the donor and the recipient in adult to adult LDLT was not associated with the short- and long-term outcomes of recipients diagnosed with benign liver diseases and early stage HCC. Moreover, the criteria for patients diagnosed with HCC to undergo LDLT should be restrictively selected. PMID:28121912

  5. Primary Liver Sinusoidal Non-Hodgkin's Lymphoma Presenting as Acute Liver Failure

    PubMed Central

    Nagral, Aabha; Jhaveri, Ajay; Kalthoonical, Vilesh; Bhat, Ganapathi; Mahajan, Pravin; Borges, Anita

    2015-01-01

    We describe a case of a middle-aged woman, who presented to us with fever, anorexia, abdominal distension from a massive hepatomegaly, low hemoglobin, and acute liver failure. A liver biopsy revealed B cell non-Hodgkin's lymphoma predominantly in the sinusoids with CD10, CD20, and Bcl-2 positive on immunohistochemistry. She initially responded well to chemotherapy but succumbed 6 months later to the recurrence of disease. Sinusoidal non-Hodgkin's lymphoma of the liver should be considered in the differential diagnosis of a patient with large hepatomegaly presenting with acute liver failure. PMID:26900276

  6. Use of liposome encapsulated hemoglobin as an oxygen carrier for fetal and adult rat liver cell culture.

    PubMed

    Montagne, Kevin; Huang, Hongyun; Ohara, Keikou; Matsumoto, Kunio; Mizuno, Atsushi; Ohta, Katsuji; Sakai, Yasuyuki

    2011-11-01

    Engineering liver tissue constructs with sufficient cell mass for transplantation implies culturing large numbers of hepatocytes in a reduced volume; however, providing sufficient oxygen to dense cell cultures is still not feasible using only conventional culture medium. Liposome-encapsulated hemoglobin (LEH), an oxygen-carrying blood substitute originally designed for short-term perfusion, may be a good candidate as an oxygen carrier to cultured liver cells. In this study, we investigated the feasibility of maintaining long term hepatocyte cultures using LEH. Primary fetal and adult rat liver cells were directly exposed to LEH for 6 to 14 days in static culture or in a perfused flat plate bioreactor. The functions and viability of adult rat hepatocytes exposed to LEH were not adversely affected in static monolayer culture and were even improved in the bioreactor. However, some cytotoxicity of LEH was observed with fetal rat liver cells after 4 days of culture. LEH, though a suitable oxygen carrier for long-term culture of mature hepatocytes, is not suitable in its present form for perfusing fetal hepatocyte cultures in direct contact with the liposomes; either the LEH will have to be made less toxic or a more sophisticated bioreactor that prevents the direct contact between hepatocytes and perfusates will have to be designed if fetal cells are to be used for liver tissue engineering.

  7. Outcomes Among Older Adult Liver Transplantation Recipients in the Model of End Stage Liver Disease (MELD) Era

    PubMed Central

    Malinis, Maricar F.; Chen, Shu; Allore, Heather G.; Quagliarello, Vincent J.

    2014-01-01

    Background Since 2002, the Model of End Stage Liver Disease (MELD) score has been the basis of the liver transplant (LT) allocation system. Among older adult LT recipients, short-term outcomes in the MELD era were comparable to the pre-MELD era, but long-term outcomes remain unclear. Material/Methods This is a retrospective cohort study using the UNOS data on patients age ≥50 years who underwent primary LT from February 27, 2002 until October 31, 2011. Results A total of 35,686 recipients met inclusion criteria. The cohort was divided into 5-year interval age groups. Five-year over-all survival rates for ages 50–54, 55–59, 60–64, 65–69, and 70+ were 72.2%, 71.6%, 69.5%, 65.0%, and 57.5%, respectively. Five-year graft survival rates after adjusting for death as competing risk for ages 50–54, 55–59,60–64, 65–69 and 70+ were 85.8%, 87.3%, 89.6%, 89.1% and 88.9%, respectively. By Cox proportional hazard modeling, age ≥60, increasing MELD, donor age ≥60, hepatitis C, hepatocellular carcinoma (HCC), dialysis and impaired pre-transplant functional status (FS) were associated with increased 5-year mortality. Using Fine and Gray sub-proportional hazard modeling adjusted for death as competing risk, 5-year graft failure was associated with donor age ≥60, increasing MELD, hepatitis C, HCC, and impaired pre-transplant FS. Conclusions Among older LT recipients in the MELD era, long-term graft survival after adjusting for death as competing risk was improved with increasing age, while over-all survival was worse. Donor age, hepatitis C, and pre-transplant FS represent potentially modifiable risk factors that could influence long-term graft and patient survival. PMID:25256592

  8. Interactions of silver nanoparticles with primary mouse fibroblasts and liver cells

    SciTech Connect

    Arora, S.; Jain, J.; Rajwade, J.M.; Paknikar, K.M.

    2009-05-01

    Primary cells are ideal for in vitro toxicity studies since they closely resemble tissue environment. Here, we report a detailed study on the in vitro interactions of 7-20 nm spherical silver nanoparticles (SNP) with primary fibroblasts and primary liver cells isolated from Swiss albino mice. The intended use of silver nanoparticles is in the form of a topical antimicrobial gel formulation for the treatment of burns and wounds. Upon exposure to SNP for 24 h, morphology of primary fibroblasts and primary liver cells remained unaltered up to 25 {mu}g/mL and 100 {mu}g/mL SNP, respectively, although with minor decrease in confluence. IC{sub 50} values for primary fibroblasts and primary liver cells as revealed by XTT assay were 61 {mu}g/mL and 449 {mu}g/mL, respectively. Ultra-thin sections of primary cells exposed to 1/2 IC{sub 50} SNP for 24 h, visualized under Transmission electron microscope showed the presence of dark, electron dense, spherical aggregates inside the mitochondria, and cytoplasm, probably representing the intracellular SNP. When the cells were challenged with {approx} 1/2 IC{sub 50} concentration of SNP (i.e. 30 {mu}g/mL and 225 {mu}g/mL for primary fibroblasts and primary liver cells, respectively), enhancement of GSH ({approx} 1.2 fold) and depletion of lipid peroxidation ({approx} 1.4 fold) were seen in primary fibroblasts which probably protect the cells from functional damage. In case of primary liver cells; increased levels of SOD ({approx} 1.4 fold) and GSH ({approx} 1.1 fold) as compared to unexposed cells were observed. Caspase-3 activity assay indicated that the SNP concentrations required for the onset of apoptosis were found to be much lower (3.12 {mu}g/mL in primary fibroblasts, 12.5 {mu}g/mL in primary liver cells) than the necrotic concentration (100 {mu}g/mL in primary fibroblasts, 500 {mu}g/mL in primary liver cells). These observations were confirmed by CLSM studies by exposure of cells to 1/2 IC{sub 50} SNP (resulting in apoptosis

  9. Gut-liver axis: an immune link between celiac disease and primary biliary cirrhosis.

    PubMed

    Volta, Umberto; Caio, Giacomo; Tovoli, Francesco; De Giorgio, Roberto

    2013-03-01

    The association between celiac disease and primary biliary cirrhosis is well established. The breakdown of gut-liver axis equilibrium plays a central role in the development of immune disorders involving the small bowel and liver. In celiac disease, immunologically active molecules generated from the cross-linking between tissue transglutaminase and food/bacterial antigens reach the liver through the portal circulation owing to the increased intestinal permeability. A molecular mimicry between bacterial antigens and the pyruvate dehydrogenase E2 component, recognized by antimitochondrial autoantibodies, may have a role in primary biliary cirrhosis pathogenesis. An aberrant intestinal T lymphocyte homing to the liver may contribute to trigger immune hepatic damage. Both celiac disease and primary biliary cirrhosis share several features, including a higher prevalence in females, autoimmune comorbidities and specific autoantibodies. Reciprocal screening for both diseases is recommended, as an early diagnosis with the appropriate treatment can improve the outcome of these patients.

  10. Cancer Stem Cells in Primary Liver Cancers: Pathological Concepts and Imaging Findings

    PubMed Central

    Joo, Ijin; Kim, Haeryoung

    2015-01-01

    There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth. Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes. Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations. In this article, we reviewed the recent concepts of CSCs in the development of primary liver cancers, focusing on their pathological and radiological findings. Awareness of the pathological concepts and imaging findings of primary liver cancers with features of CSCs is critical for accurate diagnosis, prediction of outcome, and appropriate treatment options for patients. PMID:25598674

  11. Immature mice are more susceptible than adult mice to acetaminophen-induced acute liver injury

    PubMed Central

    Lu, Yan; Zhang, Cheng; Chen, Yuan-Hua; Wang, Hua; Zhang, Zhi-Hui; Chen, Xi; Xu, De-Xiang

    2017-01-01

    Acetaminophen (APAP) overdose induces acute liver injury. The aim of the present study was to analyze the difference of susceptibility between immature and adult mice to APAP-induced acute liver injury. Weanling immature and adult mice were injected with APAP (300 mg/kg). As expected, immature mice were more susceptible than adult mice to APAP-induced acute liver injury. APAP-evoked hepatic c-Jun N-terminal kinase phosphorylation was stronger in immature mice than in adult mice. Hepatic receptor-interacting protein (RIP)1 was obviously activated at APAP-exposed immature and adult mice. Interestingly, hepatic RIP3 activation was more obvious in APAP-treated immature mice than adult mice. Although there was no difference on hepatic GSH metabolic enzymes between immature and adult mice, immature mice were more susceptible than adult mice to APAP-induced hepatic GSH depletion. Of interest, immature mice expressed a much higher level of hepatic Cyp2e1 and Cyp3a11 mRNAs than adult mice. Correspondingly, immature mice expressed a higher level of hepatic CYP2E1, the key drug metabolic enzyme that metabolized APAP into the reactive metabolite NAPQI. These results suggest that a higher level of hepatic drug metabolic enzymes in immature mice than adult mice might contribute to the difference of susceptibility to APAP-induced acute liver injury. PMID:28205631

  12. Primary care for adults on the autism spectrum.

    PubMed

    Nicolaidis, Christina; Kripke, Clarissa Calliope; Raymaker, Dora

    2014-09-01

    Autism spectrum disorder (ASD) is defined by differences in social communication and restricted, repetitive patterns of behavior, interests, or activities. Skills and challenges can change depending on environmental stimuli, supports, and stressors. Quality of life can be improved by the use of accommodations, assistive technologies, therapies to improve adaptive function or communication, caregiver training, acceptance, access, and inclusion. This article focuses on the identification of ASD in adults, referrals for services, the recognition of associated conditions, strategies and accommodations to facilitate effective primary care services, and ethical issues related to caring for autistic adults.

  13. Primary adenosquamous carcinoma of the liver: a case report

    PubMed Central

    Nam, Kyung Han; Kim, Ji Yeon

    2016-01-01

    Adenosquamous carcinoma of the liver is a rare variant of cholangiocarcinoma. It is known to be a highly aggressive tumor with a poor prognosis, but its pathogenesis remains unclear owing to limited data in the literature. We report a case of 56-year-old woman who presented with a 1-week history of epigastric pain. Magnetic resonance imaging revealed a 6.5-cm ill-defined mass with low signal intensity in the left lobe of the liver, which was suspicious of cholangiocarcinoma. The patient underwent left hemihepatectomy. Microscopically, the tumor consisted of malignant glandular and squamous components and staged as pT2aN1. Despite postoperative chemoradiation, the patient had recurrence 8 months after surgery. PMID:28081592

  14. Non-Invasive Assessment of Liver Fibrosis Progression and Prognosis in Primary Biliary Cholangitis.

    PubMed

    Poupon, Raoul

    2015-01-01

    PBC (formerly known as primary biliary cirrhosis and now named primary biliary cholangitis) is a disease with a wide range of severity and variable rate of progression. The diagnosis of advanced liver fibrosis/cirrhosis portends an increased risk of liver-related morbidity and mortality. Because of its invasiveness, liver biopsy tends to be replaced by non-invasive tools for assessing liver fibrosis, making prognosis and optimising risk stratification for selection of patients, requiring new medical approaches. Many direct or indirect biomarkers have been found to correlate with the severity of liver fibrosis in PBC. They are easy to use but lack sensitivity and reproducibility in individuals with early stage disease. Three main radiologic approaches are currently proposed to assess liver fibrosis: vibration controlled transient elastography (VCTE), acoustic radiation force impulse and magnetic resonance elastography. Data using VCTE are available only for the longitudinal evaluation of liver fibrosis and prognosis in PBC. VCTE outperformed all other non-invasive current surrogate markers of liver fibrosis in PBC. Because of its high acceptability and its ability to predict hepatic decompensation, VCTE could be a useful tool to help allocate cirrhotic patients into different categories of risk. None of the radiologic and serum markers have a perfect accuracy in studies so far published. Concordance between VCTE and serum biomarkers is a prerequisite for a correct prognosis assessment in individuals in clinical practice.

  15. Cross-modal synaptic plasticity in adult primary sensory cortices.

    PubMed

    Lee, Hey-Kyoung; Whitt, Jessica L

    2015-12-01

    Sensory loss leads to widespread adaptation of brain circuits to allow an organism to navigate its environment with its remaining senses, which is broadly referred to as cross-modal plasticity. Such adaptation can be observed even in the primary sensory cortices, and falls into two distinct categories: recruitment of the deprived sensory cortex for processing the remaining senses, which we term 'cross-modal recruitment', and experience-dependent refinement of the spared sensory cortices referred to as 'compensatory plasticity.' Here we will review recent studies demonstrating that cortical adaptation to sensory loss involves LTP/LTD and homeostatic synaptic plasticity. Cross-modal synaptic plasticity is observed in adults, hence cross-modal sensory deprivation may be an effective way to promote plasticity in adult primary sensory cortices.

  16. Isolated intestinal transplants vs. liver-intestinal transplants in adult patients in the United States: 22 yr of OPTN data.

    PubMed

    Desai, Chirag S; Gruessner, Angelika C; Khan, Khalid M; Fishbein, Thomas M; Jie, Tun; Rodriguez Rilo, Horacio L; Gruessner, Rainer W G

    2012-01-01

    We examined the outcomes of adult intestinal transplants (ITx); isolated ITx vs. liver-intestinal transplants (L-ITx) were compared using the UNOS database (1987-2009). Of 759 ITx transplants in 687 patients, 463 (61%) were isolated and 296 (39%) were L-ITx. Patient survival for primary isolated ITx at one, three, and five yr was 84%, 66.7%, and 54.2%; and primary L-ITx was, 67%, 53.3%, and 46% (p = 0.0005). Primary isolated ITx graft survival at one, three, and five yr was 80.7%, 57.6%, 42.8%; primary L-ITx was 64.1%, 51%, 44.1% (p = 0.0003 at one, three yr, Wilcoxon test). For retransplants (n = 72), patient and graft survival for isolated ITx (n = 41) at five yr was 40% in era 1 (1987-2000) and 16% in era 2 (p = 0.47); for retransplanted L-ITx (n = 31), it improved from 14% to 64% in era 2 (p = 0.01). Cox regression: creatinine >1.3 mg/dL and pre-transplant hospitalization were negative predictors for outcome of both; bilirubin >1.3 mg/dL was a negative predictor for isolated ITx and donor age >40 yr for L-ITx. Isolated ITx should be considered prior to liver disease for adults with intestinal failure; L-ITx is preferable for retransplantation.

  17. Organoids from adult liver and pancreas: Stem cell biology and biomedical utility.

    PubMed

    Hindley, Christopher J; Cordero-Espinoza, Lucía; Huch, Meritxell

    2016-12-15

    The liver and pancreas are critical organs maintaining whole body metabolism. Historically, the expansion of adult-derived cells from these organs in vitro has proven challenging and this in turn has hampered studies of liver and pancreas stem cell biology, as well as being a roadblock to disease modelling and cell replacement therapies for pathologies in these organs. Recently, defined culture conditions have been described which allow the in vitro culture and manipulation of adult-derived liver and pancreatic material. Here we review these systems and assess their physiological relevance, as well as their potential utility in biomedicine.

  18. Fulminant hepatic failure from primary hepatic lymphoma: successful treatment with orthotopic liver transplantation and chemotherapy.

    PubMed

    Cameron, Andrew M; Truty, Jadwiga; Truell, Jeff; Lassman, Charles; Zimmerman, Michael A; Kelly, Burnett S; Farmer, Douglas G; Hiatt, Jonathan R; Ghobrial, Rafik; Busuttil, Ronald W

    2005-10-15

    Systemic lymphomas may involve the liver but rarely cause fulminant hepatic failure (FHF). Acute liver failure from primary hepatic lymphoma (PHL) is even less common with most patients succumbing to the sequelae of FHF before the correct diagnosis is made. We report a patient who underwent successful orthotopic liver transplant (OLT) and chemotherapy for FHF secondary to PHL. This previously-well male developed profound coagulopathy and encephalopathy 6 weeks after the onset of jaundice and fatigue. Workup failed to reveal the underlying cause of his liver failure and the patient soon required urgent OLT. Pathologic evaluation of his explanted liver revealed a malignant T-cell rich, large B-cell non-Hodgkin's lymphoma with widespread hepatocellular necrosis. The patient made an excellent clinical recovery and is undergoing CHOP-Rituxan chemotherapy. This scenario demonstrates that lymphoma should be considered in the differential diagnosis of FHF without clear etiology because of the potential for intervention with transplant and chemotherapy.

  19. Prognostic significance of B7-H4 expression in matched primary pancreatic cancer and liver metastases

    PubMed Central

    Qian, Yun; Sang, Yiwen; Wang, Frederick X.C.; Hong, Bo; Wang, Qi; Zhou, Xinhui; Weng, Tianhao; Wu, Zhigang; Zheng, Min; Zhang, Hong; Yao, Hangping

    2016-01-01

    Liver metastasis development in pancreatic cancer patients is common and confers a poor prognosis. Clinical relevance of biomarker analysis in metastatic tissue is necessary. B7-H4 has an inhibitory effect on T cell mediated response and may be involved in tumor development. Although B7-H4 expression has been detected in pancreatic cancer, its expression in liver metastases from pancreatic cancer is still unknown. In this study, overall 43 pancreatic cancer liver metastases (with matched primaries in 15/43 cases) and 57 pancreatic cancer cases without liver metastases or other distant metastases were analyzed for their expression of B7-H4 by immunohistochemistry. Survival curves and log-rank tests were used to test the association of B7-H4 expression with survival. B7-H4 was highly expressed in 28 (65.1%) of the 43 liver metastases and 9 (60.0%) of the 15 matched primary tumors. The expression of B7-H4 in liver metastases was significantly higher than in the matched primary tumors (p < 0.05). Patients with high B7-H4 expression in their primary pancreatic cancer had higher risk of developing liver metastases (p < 0.05). In univariate analysis, B7-H4 expression was significantly associated with the risk of death (p < 0.05). And the multivariate analysis identified that B7-H4 was an independent prognostic indicator (p < 0.05). Our results revealed B7-H4 to be associated with poor prognosis in patients with pancreatic cancer liver metastasis. B7-H4 may promote pancreatic cancer metastasis and was promising to be a potential prognostic indicator of pancreatic cancer. PMID:27750217

  20. Primary Hepatic Amyloidosis Presenting as Acute-on-Chronic Liver Failure

    PubMed Central

    Rangegowda, Devaraja; Vyas, Tanmay; Kulkarni, Anand; Grover, Shrruti; Mahiwall, Rakhi; Sarin, Shiv Kumar

    2017-01-01

    Systemic amyloidosis of amyloid light chain associated protein (AL), also called primary amyloidosis, frequently involves the liver, but rarely causes clinically apparent liver disease. The more common presentation is with acute renal failure. Hepatomegaly and mild elevation of alkaline phosphatase are the most common clinical and biochemical findings, respectively. We report a case of systemic amyloidosis of AL that clinically presented as acute-on-chronic liver failure and resulted in a fatal clinical course in a 56-year-old man. PMID:28286788

  1. Production of Exocytic Vesicular Antigens by Primary Liver Cell Cultures

    DTIC Science & Technology

    1990-05-08

    filtration to the measurement of the binding of phenol red by human serum protein. J. Chromatogr. 10: 68-71. 44. Lehninger , A . L . 1978. Biochemistry: The...34~’ ~I*.1 wa.’o.W J msX~ Ser-ce. OkeUwa ’o IUWtmM ODXC.U AMd A4W L215; . bX JV ~ Su" l IMA. A0l.6. VA A = &V 10 .401C3 aHA AM~ ~ ~ P&.Jd= Ajgt.I o .JJ’,t...with HBSS- EGTA [ 101, and centrifuged at 10OXg, 4" C for 4 min. The pellet of relatively pure liver cells was then washed a final time in L -15A

  2. Expression pattern of thymosin beta 4 in the adult human liver

    PubMed Central

    Nemolato, S.; Van Eyken, P.; Cabras, T.; Cau, F.; Fanari, M.U.; Locci, A.; Fanni, D.; Gerosa, C.; Messana, I.; Castagnola, M.; Faa, G.

    2011-01-01

    Thymosin beta-4 (Tβ4) is a member of beta-thymosins, a family of small peptides involved in polymerization of G-actin, and in many critical biological processes including apoptosis, cell migration, angiogenesis, and fibrosis. Previous studies in the newborn liver did not reveal any significant reactivity for Tβ4 during the intrauterine life. The aim of the present study was to investigate by immunohistochemistry Tβ4 expression in the adult normal liver. Thirty-five human liver samples, including 11 needle liver biopsies and 24 liver specimens obtained at autopsy, in which no pathological change was detected at the histological examination, were immunostained utilizing an anti-Tβ4 commercial antibody. Tβ4 was detected in the hepatocytes of all adult normal livers examined. A zonation of Tβ4 expression was evident in the vast majority of cases. Immunostaining was preferentially detected in zone 3, while a minor degree of reactivity was detected in periportal hepatocytes (zone 1). At higher power, Tβ4-reactive granules appeared mainly localized at the biliary pole of hepatocytes. In cases with a strong immunostaining, even perinuclear areas and the sinusoidal pole of hepatocytes appeared interested by immunoreactivity for Tβ4. The current work first evidences a strong diffuse expression of Tβ4 in the adult human liver, and adds hepatocytes to the list of human cells able to synthesize large amounts of Tβ4 in adulthood. Moreover, Tβ4 should be added to the liver proteins characterized by a zonate expression pattern, in a descending gradient from the terminal vein to the periportal areas of the liver acinus. Identifying the intimate role played by this peptide intracellularly and extracellularly, in physiology and in different liver diseases, is a major challenge for future research focusing on Tβ4. PMID:22073372

  3. Primary Colonic Eosinophilia and Eosinophilic Colitis in Adults.

    PubMed

    Turner, Kevin O; Sinkre, Richa A; Neumann, William L; Genta, Robert M

    2017-02-01

    The normal content of eosinophils in the adult colon and the criteria for the histopathologic diagnosis of eosinophilic colitis remain undefined. This study aimed at: (1) establishing the numbers of eosinophils in the normal adult colon; and (2) proposing a clinicopathologic framework for the diagnosis of primary colonic eosinophilia and eosinophilic colitis. To accomplish these goals, we counted the eosinophils in the right, transverse, and left colon of 159 adults with normal colonic histology. Using a database of 1.2 million patients with colonic biopsies, we extracted all adults with a diagnosis of colonic eosinophilia. We reviewed the slides from all cases and captured demographic, clinical, and pathologic data, including information about eosinophilia in other organs. We then compared the clinical manifestations of the study patients (those with no identifiable cause of eosinophilia) to those of patients with other types of colitis. The normal eosinophil counts (per mm) were 55.7±23.4 in the right, 41.0±18.6 in the transverse, and 28.6±17.2 in the left colon. Of the 194 study patients (eosinophil counts 166-5050/mm), 63 were asymptomatic and had a normal colonoscopy. Diarrhea and abdominal pain were the commonest indications for colonoscopy (38% and 27%, respectively) among the 131 patients who had symptoms, endoscopic abnormalities, or both. Neither clinical manifestations nor endoscopic appearance were sufficiently characteristic to elicit the suspicion of colonic eosinophilia. In conclusion, primary colonic eosinophilia was extremely rare in this series (<1 in 6000 patients); one third of these patients were asymptomatic. Their clinical manifestations were not distinctive and could not have led clinicians to suspect this condition; one third of the patients were asymptomatic. We suggest that regularly reporting high colonic eosinophilia may result in increased opportunities for clinicopathologic studies that might lead to a better definition of this

  4. Laparoscopic Nephroureterectomy for Adult Patient with Primary Obstructive Megaureter

    PubMed Central

    Makiyama, Kazuhide; Ohtake, Shinji; Yamanaka, Hiroyuki; Sano, Futoshi; Nakaigawa, Noboru; Kubota, Yoshinobu

    2013-01-01

    A 29-year-old female with a complaint of abdominal distension was referred to our hospital. She had a history of being treated for pyelonephritis three times. By computed tomography and retrograde pyelography, she was diagnosed with adult left primary megaureter. Her left renal function was severely deteriorated. She hoped for surgical intervention before becoming pregnant. Laparoscopic nephroureterectomy for megaureters seems to be difficult due to the large size. By sucking urine from an inserted ureteral catheter and setting trocar positions, we successfully performed laparoscopic nephroureterectomy for megaureter. PMID:24455395

  5. Rapid development of advanced liver fibrosis after acquisition of hepatitis C infection during primary HIV infection.

    PubMed

    Osinusi, Anu; Kleiner, David; Wood, Brad; Polis, Michael; Masur, Henry; Kottilil, Shyam

    2009-06-01

    We report the first reported case of a 61-year-old MSM who was diagnosed with syphilis, primary HIV infection, and acute hepatitis C (HCV) within the same time period who rapidly developed significant liver fibrosis within 6 months of acquisition of both infections. It has been well described that individuals with primary HIV infection have an increase in activated CD8+ T cells, which causes a state of immune activation as was evident in this patient. Acquisition of HCV during this time could have further skewed this response resulting in massive hepatocyte destruction, inflammation, and subsequent liver fibrosis. Recent literature suggest that MSM with primary HIV infection have higher rates of acquisition of HCV than other HIV-positive cohorts and HCV acquisition can occur very soon after acquiring HIV. This case of rapid hepatic fibrosis progression coupled with the increasing incidence of HCV in individuals with primary HIV infection demonstrates a need for this phenomenon to be studied more extensively.

  6. Expression of Yes-associated protein modulates Survivin expression in primary liver malignancies.

    PubMed

    Bai, Haibo; Gayyed, Mariana F; Lam-Himlin, Dora M; Klein, Alison P; Nayar, Suresh K; Xu, Yang; Khan, Mehtab; Argani, Pedram; Pan, Duojia; Anders, Robert A

    2012-09-01

    Hepatocellular carcinoma and intrahepatic cholangiocarcinoma account for 95% of primary liver cancer. For each of these malignancies, the outcome is dismal; incidence is rapidly increasing, and mechanistic understanding is limited. We observed abnormal proliferation of both biliary epithelium and hepatocytes in mice after genetic manipulation of Yes-associated protein, a transcription coactivator. Here, we comprehensively documented Yes-associated protein expression in the human liver and primary liver cancers. We showed that nuclear Yes-associated protein expression is significantly increased in human intrahepatic cholangiocarcinoma and hepatocellular carcinoma. We found that increased Yes-associated protein levels in hepatocellular carcinoma are due to multiple mechanisms including gene amplification and transcriptional and posttranscriptional regulation. Survivin, a member of the inhibitors-of-apoptosis protein family, has been reported as an independent prognostic factor for poor survival in both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. We found that nuclear Yes-associated protein expression correlates significantly with nuclear Survivin expression for both intrahepatic cholangiocarcinoma and hepatocellular carcinoma. Furthermore, using mice engineered to conditionally overexpress Yes-associated protein in the liver, we found that Survivin messenger RNA expression depends upon Yes-associated protein levels. Our findings suggested that Yes-associated protein contributes to primary liver tumorigenesis and likely mediates its oncogenic effects through modulating Survivin expression.

  7. Selective Internal Radiation Therapy (SIRT) as Conversion Therapy for Unresectable Primary Liver Malignancies

    PubMed Central

    Cucchetti, Alessandro; Cappelli, Alberta; Ercolani, Giorgio; Mosconi, Cristina; Cescon, Matteo; Golfieri, Rita; Pinna, Antonio Daniele

    2016-01-01

    Background Many patients with primary liver cancers are not candidates for surgery, and systemic therapies are seldom effective. Selective internal radiation therapy (SIRT) has been shown to obtain partial and even complete response in unresectable primary tumors. As a “side effect”, SIRT can induce contra-lateral liver hypertrophy. Tumor response to SIRT can be sufficient to allow disengagement from normal vital structures whose involvement is the cause of the initial unresectability. The contra-lateral hypertrophy can thereby increase the future liver remnant (FLR) volume to over the safe threshold so that extended hepatectomy can be performed. Summary A review of the available literature was performed to assess the tumor response and liver hypertrophy that can be expected after SIRT, in order to delineate whether SIRTcan play a role in conversion therapy for resectability of primary liver malignancies. Key Message Available data suggest that SIRT in unresectable hepatocellular and cholangiocellular carcinomas can provide a considerable down-sizing of the tumors to possibly allow resection. Hypertrophy of the contra-lateral lobe represents a favorable collateral effect that can help in achieving safer subsequent major hepatectomy. In patients whose FLR volume represents the only surgical concern, portal vein embolization remains the treatment of choice. PMID:27781202

  8. Adult mouse model of early hepatocellular carcinoma promoted by alcoholic liver disease

    PubMed Central

    Ambade, Aditya; Satishchandran, Abhishek; Gyongyosi, Benedek; Lowe, Patrick; Szabo, Gyongyi

    2016-01-01

    AIM: To establish a mouse model of alcohol-driven hepatocellular carcinoma (HCC) that develops in livers with alcoholic liver disease (ALD). METHODS: Adult C57BL/6 male mice received multiple doses of chemical carcinogen diethyl nitrosamine (DEN) followed by 7 wk of 4% Lieber-DeCarli diet. Serum alanine aminotransferase (ALT), alpha fetoprotein (AFP) and liver Cyp2e1 were assessed. Expression of F4/80, CD68 for macrophages and Ly6G, MPO, E-selectin for neutrophils was measured. Macrophage polarization was determined by IL-1β/iNOS (M1) and Arg-1/IL-10/CD163/CD206 (M2) expression. Liver steatosis and fibrosis were measured by oil-red-O and Sirius red staining respectively. HCC development was monitored by magnetic resonance imaging, confirmed by histology. Cellular proliferation was assessed by proliferating cell nuclear antigen (PCNA). RESULTS: Alcohol-DEN mice showed higher ALTs than pair fed-DEN mice throughout the alcohol feeding without weight gain. Alcohol feeding resulted in increased ALT, liver steatosis and inflammation compared to pair-fed controls. Alcohol-DEN mice had reduced steatosis and increased fibrosis indicating advanced liver disease. Molecular characterization showed highest levels of both neutrophil and macrophage markers in alcohol-DEN livers. Importantly, M2 macrophages were predominantly higher in alcohol-DEN livers. Magnetic resonance imaging revealed increased numbers of intrahepatic cysts and liver histology confirmed the presence of early HCC in alcohol-DEN mice compared to all other groups. This correlated with increased serum alpha-fetoprotein, a marker of HCC, in alcohol-DEN mice. PCNA immunostaining revealed significantly increased hepatocyte proliferation in livers from alcohol-DEN compared to pair fed-DEN or alcohol-fed mice. CONCLUSION: We describe a new 12-wk HCC model in adult mice that develops in livers with alcoholic hepatitis and defines ALD as co-factor in HCC. PMID:27122661

  9. New physiologically-relevant liver tissue model based on hierarchically cocultured primary rat hepatocytes with liver endothelial cells.

    PubMed

    Xiao, Wenjin; Perry, Guillaume; Komori, Kikuo; Sakai, Yasuyuki

    2015-11-01

    To develop an in vitro liver tissue equivalent, hepatocytes should be cocultured with liver non-parenchymal cells to mimic the in vivo physiological microenvironments. In this work, we describe a physiologically-relevant liver tissue model by hierarchically organizing layers of primary rat hepatocytes and human liver sinusoidal endothelial cells (TMNK-1) on an oxygen-permeable polydimethylsiloxane (PDMS) membrane, which facilitates direct oxygenation by diffusion through the membrane. This in vivo-mimicking hierarchical coculture was obtained by simply proceeding the overlay of TMNK-1 cells on the hepatocyte layer re-formed on the collagen immobilized PDMS membranes. The comparison of hepatic functionalities was achieved between coculture and sandwich culture with Matrigel, in the presence and absence of direct oxygenation. A complete double-layered structure of functional liver cells with vertical contact between hepatocytes and TMNK-1 was successfully constructed in the coculture with direct oxygen supply and was well-maintained for 14 days. The hepatocytes in this hierarchical culture exhibited improved survival, functional bile canaliculi formation, cellular level polarization and maintenance of metabolic activities including Cyp1A1/2 activity and albumin production. By contrast, the two cell populations formed discontinuous monolayers on the same surfaces in the non-oxygen-permeable cultures. These results demonstrate that (i) the direct oxygenation through the PDMS membranes enables very simple formation of a hierarchical structure consisting of a hepatocyte layer and a layer of TMNK-1 and (ii) we may include other non-parenchymal cells in this format easily, which can be widely applicable to other epithelial organs.

  10. Living related liver transplantation in adults: first year experience at the University of Liège.

    PubMed

    Detry, O; De Roover, A; Delwaide, J; Coimbra, C; Kaba, A; Joris, J; Damas, P; Meurisse, M; Honoré, P

    2004-04-01

    Living related liver transplantation (LRLT) in adult recipients has been recently developed to overcome the organ donor shortage, but LRLT leaves the healthy donors at risk of serious post-operative complications, or even death. The aim of this paper is to report the prospective evaluation of the initial experience of adult LRLT at the University of Liège. From March 2002 till March 2003, in a consecutive series of 35 adult liver transplantations, five recipients (mean age: 51 years) underwent LRLT, including one retransplantation. Indications for transplantation were autoimmune hepatitis, hepatitis B virus related cirrhosis with hepatocarcinoma (two cases), hepatitis C virus related cirrhosis with hepatocarcinoma, and ischemic intrahepatic bile duct necrosis 10 years after primary liver transplantation. Mean age of the donors was 34 years (range: 21-53 years). All donation cases were intra familial at first degree. The right lobe was used as a graft in four cases and the left lobe in one case. All right lobe donors developed transient hyperbilirubinemia and hypocoagulation for 4 to 6 days. No severe complication (transfusion, bile duct fistula, reintervention, rehospitalization) nor significant long-term sequelae were observed in the donors. In the recipients, graft function was immediate, and there was no small-for-size syndrome. One recipient developed biliary fistula treated by reoperation. One recipient died from invasive aspergillosis 11 days after the procedure. The four other recipients were alive without recurrence of the disease at follow-up. This report confirmed that LRLT may be a valuable alternative to cadaveric liver transplantation in the era of organ donor shortage. However, even if there was no severe complication for the donors in our preliminary experience, LRLT puts healthy living donors at risk of significant morbidity and even death.

  11. Totally laparoscopic associating liver tourniquet and portal vein occlusion for staged hepatectomy combined with simultaneous left hemicolectomy for bilateral liver metastases of the primary colon cancer

    PubMed Central

    Xu, Hong-wei; Li, Hong-yu; Liu, Fei; Wei, Yong-gang; Li, Bo

    2017-01-01

    Abstract Background: Resection of the liver is often limited to the insufficient future liver remnant (FLR). To address this problem, the modification surgical technique “associating liver tourniquet and portal vein occlusion for staged hepatectomy” (ALTPS) was developed and led to quick hypertrophy in a short interval. In some colorectal cancer patients with multiple and bilobar metastases, the resection of the primary is often protracted immensely to the unpredictable postoperative complications for whom is to be treated with a liver-first approach. To overcome this problem, a simultaneous resection of the primary tumor and totally laparoscopic ALTPS for bilateral liver metastases of the primary colon cancer were performed. Case summary: A 63-year-old female patient with left colon cancer and synchronous bilateral colorectal liver metastases underwent a totally laparoscopic ALTPS and simultaneous left hemicolectomy because of the small FLR. The operative times were 460 minutes for the first stage and 240 minutes for the second stage without the need for blood transfusions. The recoveries after the first and the second operations were uneventful, and the patient was discharged on postoperative day 11 of the second stage operation. Conclusion: Our case shows the totally laparoscopic ALTPS and simultaneous left hemicolectomy at step 1 for bilobar liver metastases of the primary colon cancer with no severe postoperative complications. If a resection of the primary tumor does not compromise the split procedure, the combination of pure laparoscopic ALTPS and primary resection is feasible and safe. PMID:28296776

  12. Incidence and mortality of primary liver cancer in England and Wales: Changing patterns and ethnic variations

    PubMed Central

    Ladep, Nimzing G; Khan, Shahid A; Crossey, Mary ME; Thillainayagam, Andrew V; Taylor-Robinson, Simon D; Toledano, Mireille B

    2014-01-01

    AIM: To explore recent trends, modes of diagnosis, ethnic distribution and the mortality to incidence ratio of primary liver cancer by subtypes in England and Wales. METHODS: We obtained incidence (1979-2008) and mortality (1968-2008) data for primary liver cancer for England and Wales and calculated age-standardised incidence and mortality rates. Trends in age-standardised mortality (ASMR) and incidence (ASIR) rates and basis of diagnosis of primary liver cancer and subcategories: hepatocellular carcinoma, intrahepatic bile duct and unspecified liver tumours, were analysed over the study period. Changes in guidelines for the diagnosis of primary liver cancer (PLC) may impact changing trends in the rates that may be obtained. We thus explored changes in the mode of diagnosis as reported to cancer registries. Furthermore, we examined the distribution of these tumours by ethnicity. Most of the statistical manipulations of these data was carried out in Microsoft excel® (Seattle, Washington, United Sttaes). Additional epidemiological statistics were done in Epi Info software (Atlanta, GA, United Sttaes). To define patterns of change over time, we evaluated trends in ASMR and ASIR of PLC and intrahepatic bile duct carcinoma (IHBD) using a least squares regression line fitted to the natural logarithm of the mortality and incidence rates. We estimated the patterns of survival over subsequent 5 and 10 years using complement of mortality to incidence ratio (1-MIR). RESULTS: Age-standardised mortality rate of primary liver cancer increased in both sexes: from 2.56 and 1.29/100000 in 1968 to 5.10 and 2.63/100000 in 2008 for men and women respectively. The use of histology for diagnostic confirmation of primary liver cancer increased from 35.7% of registered cases in 1993 to plateau at about 50% during 2005 to 2008. Reliance on cytology as a basis of diagnosis has maintained a downward trend throughout the study period. Although approximately 30% of the PLC registrations had

  13. c-MET expression in primary and liver metastases in uveal melanoma.

    PubMed

    Gardner, Faithlore P; Serie, Daniel J; Salomao, Diva R; Wu, Kevin J; Markovic, Svetomir N; Pulido, Jose S; Joseph, Richard W

    2014-12-01

    There is a pressing need for effective therapies to treat uveal melanoma. Agents that inhibit the c-MET pathway have shown promise in multiple malignancies that overexpress c-MET. Herein, we assess c-MET expression in both primary uveal melanoma and liver metastases of uveal melanoma and evaluate the association of c-MET expression with clinical and pathologic variables. We have retrospectively identified tumor samples from primary and liver metastases of uveal melanoma from 1 January 1990 to 1 January 2012. We utilized immunohistochemistry to assess c-MET expression, and two pathologists quantified c-MET expression using an H-score (product of the intensity of staining and percentage of positive cells). The Mann-Whitney U-test, Pearson's correlation, and Cox model were used as appropriate. Thirty-nine of 40 (98%) primary tumors and nine of 10 (90%) metastatic liver lesions expressed c-MET (H-score range 0-300). There was a strong association between the percentage of positive cells and the intensity of c-MET expression (P=0.007). We found no association between c-MET H-score and clinicopathologic variables such as age, sex, or stage. c-MET expression was significantly higher in metastatic compared with primary tumors (median H-score 190 vs. 30, P=0.022). c-MET is expressed in the vast majority of primary and liver metastases of uveal melanomas; however, c-MET expression did not associate with pathologic features in our cohort. Metastatic lesions have higher expression of c-MET expression than primary tumors. Clinical trials involving c-MET inhibitors deserve further study in patients with uveal melanoma in both the adjuvant and metastatic setting.

  14. Primary gastrointestinal stromal tumor of the liver: A case report and review of the literature

    PubMed Central

    Cheng, Xiaobin; Chen, Dong; Chen, Wenbin; Sheng, Qinsong

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors located in the alimentary tract. A small portion of GISTs are observed in extra-gastrointestinal regions, primarily in the omentum, mesentery and retroperioneum, and these types of GISTs are referred to as extra-gastrointestinal stromal tumors. The present study reports of a patient with unique primary liver GIST. The patient underwent en bloc resection and post-operative administration of imatinib, and subsequently experienced a good prognosis. The present case is followed by a brief review of reported cases of liver GISTs identified in the literature. The literature revealed that primary liver GISTs are usually large in size and possess a high mitotic index, which contributes to malignant characterization, thus classifying these tumors as high-risk. En bloc resection remains the mainstay of treatment for resectable primary liver GISTs. However, the prognosis of these patients is not favorable. Perioperative administration of imatinib may be useful to a certain extent, and interventional therapy, including radiofrequency ablation, should be considered. PMID:27698856

  15. Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

    PubMed Central

    Croft, Ashley M; Herxheimer, Andrew

    2002-01-01

    Background Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. Presentation We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs) may be related to the development of severe or prolonged adverse reactions to mefloquine. Implications We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. Testing Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis. PMID:11914150

  16. Comparison of hepatic-like cell production from human embryonic stem cells and adult liver progenitor cells: CAR transduction activates a battery of detoxification genes.

    PubMed

    Funakoshi, Natalie; Duret, Cédric; Pascussi, Jean-Marc; Blanc, Pierre; Maurel, Patrick; Daujat-Chavanieu, Martine; Gerbal-Chaloin, Sabine

    2011-09-01

    In vitro production of human hepatocytes is of primary importance in basic research, pharmacotoxicology and biotherapy of liver diseases. We have developed a protocol of differentiation of human embryonic stem cells (ES) towards hepatocyte-like cells (ES-Hep). Using a set of human adult markers including CAAT/enhancer binding protein (C/EBPalpha), hepatocyte nuclear factor 4/7 ratio (HNF4alpha1/HNF4alpha7), cytochrome P450 7A1 (CYP7A1), CYP3A4 and constitutive androstane receptor (CAR), and fetal markers including alpha-fetoprotein, CYP3A7 and glutathione S-transferase P1, we analyzed the expression of a panel of 41 genes in ES-Hep comparatively with human adult primary hepatocytes, adult and fetal liver. The data revealed that after 21 days of differentiation, ES-Hep are representative of fetal hepatocytes at less than 20 weeks of gestation. The glucocorticoid receptor pathway was functional in ES-Hep. Extending protocols of differentiation to 4 weeks did not improve cell maturation. When compared with hepatocyte-like cells derived from adult liver non parenchymal epithelial (NPE) cells (NPE-Hep), ES-Hep expressed several adult and fetal liver makers at much greater levels (at least one order of magnitude), consistent with greater expression of liver-enriched transcription factors Forkhead box A2, C/EBPalpha, HNF4alpha and HNF6. It therefore seems that ES-Hep reach a better level of differentiation than NPE-Hep and that these cells use different lineage pathways towards the hepatic phenotype. Finally we showed that lentivirus-mediated expression of xenoreceptor CAR in ES-Hep induced the expression of several detoxification genes including CYP2B6, CYP2C9, CYP3A4, UDP-glycosyltransferase 1A1, solute carriers 21A6, as well as biotransformation of midazolam, a CYP3A4-specific substrate.

  17. The evaluation of saphenofemoral insufficiency in primary adult varicocele.

    PubMed

    Koyuncu, Hakan; Ergenoglu, Mehmet; Yencilek, Faruk; Gulcan, Nilay; Tasdelen, Neslihan; Yencilek, Esin; Sarica, Kemal

    2011-01-01

    The aim of this study was to evaluate the possible relationship between varicocele and saphenofemoral insufficiency in patients diagnosed with primary varicocele. A total of 70 patients with the primary diagnosis of varicocele were included into the study. A total of 30 age-matched healthy adults were also included in the study as a control group. Varicocele was diagnosed by palpation and observation of each spermatic cord in standing position before and during a valsalva maneuver. Additionally, scrotal Doppler and lower extremity venous Doppler ultrasonography were performed. Patients who were with spermatic varicose vein larger than 3.0 mm were included in the study group as a varicocele patient. At the lower extremity venous Doppler ultrasonography, a retrograde flow lasting longer than 0.5 seconds during normal breathing or at the valsalva maneuver was considered to be meaningful for saphenofemoral junction insufficiency. Thirty-six (51.35%) patients had insufficiency in saphenofemoral junction in the study group (6 [8.5%] bilateral, 30 [42.85%] unilateral) whereas 8 (26.6%) had insufficiency in the control group (2 [6.6%] bilateral, 6 [20%] unilateral insufficiency). The patients with primary varicocele had a statistically significant (P = .02) higher rate of venous insufficiency in their saphenofemoral junctions when compared with the control group. In the present study, the rate of saphenofemoral insufficiency has been found to be statistically higher in patients with primary varicocele compared with healthy men. Depending on the common presence of valvular insufficiency, we believe that the presence of varicocele should be investigated in the young population suffering from saphenofemoral junction insufficiency.

  18. Genotyping diagnosis of alpha-1 antitrypsin deficiency in Saudi adults with liver cirrhosis

    PubMed Central

    Al-Jameil, Noura; Hassan, Amina A.; Buhairan, Ahlam; Hassanato, Rana; Isac, Sree R.; Al-Otaiby, Maram; Al-Maarik, Basmah; Al-Ajeyan, Iman

    2017-01-01

    Abstract The acute phase protein alpha-1 antitrypsin (AAT) is mainly produced in liver cells. AAT deficiency affects the lungs and liver. We conducted a case-control study to define a valuable method for the proper diagnosis of alpha-1 antitrypsin deficiency (AATD), as well as the association of liver cirrhosis with AATD in Saudi adults. Blood samples from 300 liver cirrhosis patients and 400 controls were analyzed according to serum AAT concentration, phenotyping, and genotyping. Nephelometry was used for AAT quantification, isoelectric focusing electrophoresis was used for phenotyping detection, and real-time PCR was used for genotyping to determine the Z and S deficiency alleles. This study highlights the accuracy of using genotyping in addition to AAT quantification, since this technique has proven to be successful in the diagnosis of AATD for 100% of our cases. A significant deviation in AAT genotypes frequencies from the Hardy–Weinberg equilibrium in the adult cirrhosis group occurred due to a higher observed frequency than expected for the Pi ZZ homozygous genotype. Pi ZZ in adults may be considered as the risk factor for liver cirrhosis. However, we could not establish this relationship for heterozygous AATD genotypes (such as Pi MZ and Pi SZ). PMID:28178162

  19. Risk factors associated with non-alcoholic fatty liver disease in subjects from primary care units. A case-control study

    PubMed Central

    Caballería, Llorenç; Auladell, Ma Antonia; Torán, Pere; Pera, Guillem; Miranda, Dolores; Alumà, Alba; Casas, José Dario; Muñoz, Laura; Sanchez, Carmen; Tibau, Albert; Birules, Marti; Canut, Santiago; Bernad, Jesús; Aubà, Josep; Aizpurua, Miren Maite; Alcaraz, Enriqueta

    2008-01-01

    Background Non alcoholic fatty liver disease (NAFL) consists in the accumulation of fat vacuoles in the cytoplasm of hepatocytes. Many etiologic factors are associated with NAFL, such as, the metabolic syndrome factors, medications, bariatric surgery, nutritional disorders. However, very little information is available on the clinical relevance of this disorder as a health problem in the general population. Methods and design The aim of the study is establish the risk factors most frequently associated with NAFL in a general adult population assigned to the primary care units and to investigate the relationship between each component of the metabolic syndrome and the risk of having a NAFL. A population based case-control, observational and multicenter study will be carried out in 18 primary care units from the "Area de Gestión del Barcelonés Nord y Maresme" (Barcelona) attending a population of 360,000 inhabitants and will include 326 cases and 370 controls. Cases are defined as all subjects fulfilling the inclusion criteria and with evidence of fatty liver in an abdominal ultrasonography performed for any reason. One control will be randomly selected for each case from the population, matched for age, gender and primary care center. Controls with fatty liver or other liver diseases will be excluded. All cases and controls will be asked about previous hepatic diseases, consumption of alcohol, smoking and drugs, and a physical examination, biochemical analyses including liver function tests, the different components of the metabolic syndrome and the HAIR score will also be performed. Paired controls will also undergo an abdominal ultrasonography. Discussion This study will attempt to determine the factors most frequently associated with the presence of NAFL investigate the relationship between the metabolic syndrome and the risk of fatty liver and study the influence of the different primary care professionals in avoiding the evolution of the disease. PMID

  20. Primary graft dysfunction of the liver: definitions, diagnostic criteria and risk factors.

    PubMed

    Neves, Douglas Bastos; Rusi, Marcela Balbo; Diaz, Luiz Gustavo Guedes; Salvalaggio, Paolo

    2016-01-01

    Primary graft dysfunction is a multifactorial syndrome with great impact on liver transplantation outcomes. This review article was based on studies published between January 1980 and June 2015 and retrieved from PubMed database using the following search terms: "primary graft dysfunction", "early allograft dysfunction", "primary non-function" and "liver transplantation". Graft dysfunction describes different grades of graft ischemia-reperfusion injury and can manifest as early allograft dysfunction or primary graft non-function, its most severe form. Donor-, surgery- and recipient-related factors have been associated with this syndrome. Primary graft dysfunction definition, diagnostic criteria and risk factors differ between studies. RESUMO A disfunção primária do enxerto hepático é uma síndrome multifatorial com grande impacto no resultado do transplante de fígado. Foi realizada uma ampla revisão da literatura, consultando a base de dados PubMed, em busca de estudos publicados entre janeiro de 1980 e junho de 2015. Os termos descritivos utilizados foram: "primary graft dysfunction", "early allograft dysfunction", "primary non-function" e "liver transplantation". A disfunção traduz graus diferentes da lesão de isquemia e reperfusão do órgão, e pode se manifestar como disfunção precoce ou, na forma mais grave, pelo não funcionamento primário do enxerto. Fatores relacionados ao doador, ao transplante e ao receptor contribuem para essa síndrome. Existem definições diferentes na literatura quanto ao diagnóstico e aos fatores de risco associados à disfunção primária.

  1. Undifferentiated (embryonal) sarcoma of liver in adult: A case report

    PubMed Central

    Dai, Chao-Liu; Xu, Feng; Shu, Hong; Xu, Yong-Qing; Huang, Yong

    2005-01-01

    We report a case of undifferentiated (embryonal) sarcoma of the liver (UESL), which showed cystic formation in a 20-year-old man with no prior history of any hepatitis or liver cirrhosis. He was admitted with abdominal pain and a palpable epigastric mass. The physical examination findings were unremarkable except for a tenderness mass and the results of routine laboratory studies were all within normal limits. Abdominal ultrasound and computed tomography (CT) both showed a cystic mass in the left hepatic lobe. Subsequently, the patient underwent a tumor excision and another two times of hepatectomy because of tumor recurrence. Immunohistochemical study results showed that the tumor cells were positive for vimentin, alpha-1-antichymotrypsin (AACT) and desmin staining, and negative for alpha-fetoprotein (AFP), and eosinophilic hyaline globules in the cytoplasm of some giant cells were strongly positive for periodic acid-Schiff (PAS) staining. The pathological diagnosis was UESL. The patient is still alive with no tumor recurrence for four months. PMID:15682496

  2. Primary sinusoidal lymphoma of the liver revealed by autoimmune hemolytic anemia.

    PubMed

    Pouderoux, P; Gris, J C; Pignodel, C; Joujoux, J M; Schved, J F; Balmes, J L

    1997-01-01

    Primary liver lymphomas usually present with the clinical picture of a liver tumor, and are characterized by a predominantly portal invasion by lymphoid cells of the B-cell phenotype. We report a case of primary sinusoidal lymphoma of the liver, in a 36 year-old male patient, revealed by homogeneous hepatosplenomegaly and infiltration of liver sinusoids by morphologically normal lymphocytes, without destruction of the parenchyma. Immunohistochemistry in paraffin-embedded tissue sections was positive for the pan T-cell marker MTI, weakly positive for UCHLI, and negative for CD3, and B-cell markers were negative; these findings were consistent with the diagnosis of T-cell lymphoma. The clinical, histological and immunological presentation of this lymphoma was similar to that of hepatosplenic gamma delta T-cell lymphoma. Autoimmune hemolytic anaemia preceded the lymphoma. Despite chemotherapy, the patient died 24 months after the initial presentation in the leukemic phase. A better understanding of this exceptional but characteristic entity is required for an accurate and early diagnosis.

  3. Primary Diffuse Large B-Cell Lymphoma of the Liver in a Patient with Sjogren Syndrome

    PubMed Central

    Gorodetskiy, Vadim; Klapper, Wolfram; Probatova, Natalya; Vasilyev, Vladimir

    2016-01-01

    Sjögren's syndrome (SS) has the highest incidence of malignant lymphoproliferative disorders transformation among autoimmune diseases. We present a case of extranodal high grade lymphoma of the liver in a 52-year-old patient with long history of SS. Lymphoma manifested with sharp significant pain in the right hypochondrium, weakness, and profuse night sweats. Contrast-enhanced computed tomography scan (CT-scan) of the abdomen revealed multiple low density foci with homogeneous structure and clear contours in both lobes of the liver. Histologically, proliferation of medium sized lymphoma cells with round-oval and slightly irregular nuclei with fine chromatin was shown. Immunohistochemical and molecular features of the tumors allowed diagnosis of diffuse large B-cell lymphoma (DLBCL). To exclude secondary liver lesion by non-Hodgkin lymphoma, chest and small pelvis CT-scan, endoscopy of upper and lower gastrointestinal tract and study of bone marrow were performed. After 8 cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), the complete remission was achieved, which persists after 45 months of follow-up. Primary hepatic lymphomas are extremely rare, and previously only low-grade hepatic lymphomas have been described in SS. To our knowledge, the patient described here represents the first reported case of DLBCL with primary liver involvement in SS. PMID:26998372

  4. Retroperitoneal and intrahepatic metastasis from primary clear cell carcinoma of the liver

    PubMed Central

    Xiong, Junjie; He, Du; Hu, Weiming; Liu, Xubao

    2017-01-01

    Abstract Background: Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide and the incidence is increasing as a result of growing hepatitis B and C virus infections. Primary clear cell carcinoma of the liver (PCCCL) is a rare subgroup of primary HCC, which has low metastatic potential and infrequently reported in literature. Retroperitoneal and intrahepatic metastasis of PCCCL has not been reported previously. Case Summary: Here, we present a 55-year-old male with retroperitoneal and intrahepatic metastasis of PCCCL who is managed with surgical method and transcatheter arterial chemoembolization (TACE) at our institution. When the patient is followed up in 16 months after surgery and TACE, he is alive without any extrahepatic metastasis and abnomal liver function. Conclusion: We concluded that surgical resection of retroperitoneal metastasis and TACE of the intrahepatic tumors provided an appropriate strategy for the patient with unresectable PCCCL accompanied with extra-hepatic metastasis. PMID:28328858

  5. Helper-dependent adenoviral vectors for liver-directed gene therapy of primary hyperoxaluria type 1

    PubMed Central

    Castello, Raffaele; Borzone, Roberta; D’Aria, Stefania; Annunziata, Patrizia; Piccolo, Pasquale; Brunetti-Pierri, Nicola

    2015-01-01

    Primary hyperoxaluria type 1 (PH1) is an inborn error of liver metabolism due to deficiency of the peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT) which catalyzes conversion of glyoxylate into glycine. AGT deficiency results in overproduction of oxalate which ultimately leads to end-stage renal disease and death. Organ transplantation as either preemptive liver transplantation or combined liver/kidney transplantation is the only available therapy to prevent disease progression. Gene therapy is an attractive option to provide an alternative treatment for PH1. Towards this goal, we investigated helper-dependent adenoviral (HDAd) vectors for liver-directed gene therapy of PH1. Compared to saline controls, AGT-deficient mice injected with an HDAd encoding the AGT under the control of a liver-specific promoter showed a significant reduction of hyperoxaluria and less increase of urinary oxalate following challenge with Ethylene Glycol (EG), a precursor of glyoxylate. These studies may thus pave the way to clinical application of HDAd for PH1 gene therapy. PMID:26609667

  6. Helper-dependent adenoviral vectors for liver-directed gene therapy of primary hyperoxaluria type 1.

    PubMed

    Castello, R; Borzone, R; D'Aria, S; Annunziata, P; Piccolo, P; Brunetti-Pierri, N

    2016-02-01

    Primary hyperoxaluria type 1 (PH1) is an inborn error of liver metabolism due to deficiency of the peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT), which catalyzes conversion of glyoxylate into glycine. AGT deficiency results in overproduction of oxalate that ultimately leads to end-stage renal disease and death. Organ transplantation as either preemptive liver transplantation or combined liver/kidney transplantation is the only available therapy to prevent disease progression. Gene therapy is an attractive option to provide an alternative treatment for PH1. Toward this goal, we investigated helper-dependent adenoviral (HDAd) vectors for liver-directed gene therapy of PH1. Compared with saline controls, AGT-deficient mice injected with an HDAd encoding the AGT under the control of a liver-specific promoter showed a significant reduction of hyperoxaluria and less increase of urinary oxalate following challenge with ethylene glycol, a precursor of glyoxylate. These studies may thus pave the way to clinical application of HDAd for PH1 gene therapy.

  7. Phenotyping and auto-antibody production by liver-infiltrating B cells in primary sclerosing cholangitis and primary biliary cholangitis.

    PubMed

    Chung, Brian K; Guevel, Bardia T; Reynolds, Gary M; Gupta Udatha, D B R K; Henriksen, Eva Kristine Klemsdal; Stamataki, Zania; Hirschfield, Gideon M; Karlsen, Tom Hemming; Liaskou, Evaggelia

    2017-02-01

    Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are immune-mediated biliary diseases that demonstrate prominent and restricted genetic association with human leukocyte antigen (HLA) alleles. In PBC, anti-mitochondrial antibodies (AMA) are specific and used as diagnostic biomarkers. PSC-relevant auto-antibodies remain controversial despite a distinct HLA association that mirrors archetypical auto-antigen driven disorders. Herein, we compared antibody-secreting B cells (ASCs) in PSC and PBC liver explants to determine if liver-infiltrating ASCs represent an opportune and novel source of disease-relevant auto-antibodies. Using enzymatic digestion and mechanical disruption, liver mononuclear cells (LIMCs) were isolated from fresh PSC and PBC explants and plasmablast (CD19+CD27+CD38(hi)CD138-) and plasma cell (CD19+CD27+CD38(hi)CD138+) ASCs were enumerated by flow cytometry. We observed 45-fold fewer plasma cells in PSC explants (n = 9) compared to PBC samples (n = 5, p < 0.01) and 10-fold fewer IgA-, IgG- and IgM-positive ASCs (p < 0.05). Liver-infiltrating ASCs from PSC and PBC explants were functional and produced similar concentrations of IgA, IgG and IgM following 2 weeks of culture. Antibody production by PBC ASCs (n = 3) was disease-specific as AMA to pyruvate dehydrogenase complex E2 subunit (PDC-E2) was detected by immunostaining, immunoblotting and ELISA. Antibody profiling of PSC supernatants (n = 9) using full-length recombinant human protein arrays (Cambridge Protein Arrays) revealed reactivities to nucleolar protein 3 (5/9) and hematopoietic cell-specific Lyn substrate 1 (3/9). Array analysis of PBC supernatants (n = 3) detected reactivities to PDC-E2 and hexokinase 1 (3/3). In conclusion, we detected unique frequencies of liver-infiltrating ASCs in PSC and PBC and in so doing, highlight a feasible approach for understanding disease-relevant antibodies in PSC.

  8. Phase I-II study of isotopic immunoglobulin therapy for primary liver cancer

    SciTech Connect

    Ettinger, D.S.; Order, S.E.; Wharam, M.D.; Parker, M.K.; Klein, J.L.; Leichner, P.K.

    1982-02-01

    A phase I-II study of isotopic immunoglobulin therapy was performed in 18 patients with primary liver cancer; 14 were evaluable for toxicity. The patients received a dose of 37-157 millicuries of 131I-labeled antibody. The dose-limiting factor appears to be hematologic toxicity, especially thrombocytopenia. An objective antitumor effect was seen in six of nine patients who were evaluable for response. Present results suggest that further clinical studies with isotopic immunoglobulin are indicated.

  9. Positron emission tomography / computerized tomography evaluation of primary Hodgkin's disease of liver.

    PubMed

    Gota, V S; Purandare, N C; Gujral, S; Shah, S; Nair, R; Rangarajan, V

    2009-01-01

    Occurrence of primary Hodgkin's lymphoma (PHL) of the liver is extremely rare. We report on a case of a 60-year-old male who presented with liver mass and B-symptomatology. Hepatoma or hepatic metastasis from a gastrointestinal primary was initially suspected. Tumor markers like AFP, CEA, Total PSA, and CA-19.9 were within normal limits. Positron Emission Tomography / Computerized Tomography (PET/CT) revealed a large hepatic lesion and a nodal mass in the porta hepatis. A liver biopsy was consistent with Hodgkin's lymphoma. There was complete regression of the hepatic lesion and evidence of shrinkage of the nodal mass following four cycles of chemotherapy. 18F Fluro -de-oxy Glucose (FDG) PET / CT in this case helped in establishing a primary hepatic lymphoma by demonstrating the absence of pathologically hypermetabolic foci in any other nodes or organs. PET / CT scan is a useful adjunct to conventional imaging and histopathology, not only to establish the initial diagnosis, but also to monitor treatment response in PHL.

  10. The Correlation between NK Cell and Liver Function in Patients with Primary Hepatocellular Carcinoma

    PubMed Central

    Zeng, Xiao-Hui; Min, Lu

    2014-01-01

    Background/Aims This study aimed to detect the expression of natural killer (NK) cell receptor natural killer group 2D (NKG2D) in the peripheral blood of patients with primary hepatocellular carcinoma and to discuss the correlation between NK cell cytotoxicity and liver function. Methods The number of NK cells and the expression of NK cell receptor NKG2D in peripheral blood were determined by flow cytometry in patients with primary hepatocellular carcinoma, hepatitis B cirrhosis, chronic hepatitis B, and healthy controls. Results When compared with patients in the healthy and the chronic hepatitis B groups, the primary hepatocellular carcinoma group showed significant decreases in all parameters, including the cytotoxicity of NK cells on K562 cells, expression rate of NKG2D in NK cells, number of NKG2D+ NK cells, expression level of NKG2D, and number of NK cells (p<0.05). The activity of NK cells showed a positive correlation, whereas the Child-Pugh scores in the primary hepatocellular carcinoma and the hepatitis B cirrhosis groups showed a negative correlation with all parameters detected above. Conclusions The decrease of NK cell activity in patients with primary hepatocellular carcinoma is closely related to their lower expression of NKG2D. Liver function affects the expression of NKG2D and the activity of NK cells. PMID:24827627

  11. The role of focal liver ablation in the treatment of unresectable primary and secondary malignant liver tumors.

    PubMed

    Gannon, Christopher J; Curley, Steven A

    2005-10-01

    Surgical resection is often the first-line treatment option for primary and select metastatic hepatic malignancies. A minority of patients with hepatocellular carcinoma undergo potentially curative resection. Similarly, patients with liver-only metastasis are candidates for resection less than 15% of the time because of bilobar disease in which resection would sacrifice too great a volume of hepatic parenchyma, tumor proximity to major vascular or biliary structures thus preventing adequate margins, or unfavorable tumor biology. Ablative techniques directed at tumor elimination while minimizing injury to the surrounding functional hepatic parenchyma may be offered to select patients with unresectable cancers. Radiofrequency ablation, percutaneous ethanol injection, transarterial chemoembolization, cryoablation, microwave coagulation, and laser-induced interstitial thermotherapy all offer potential local tumor control and occasionally achieve long-term disease-free survival. This review focuses on the indications, anticipated benefits, and limitations of these ablative techniques.

  12. The association between MMF and risk of progressive renal dysfunction and death in adult liver transplant recipients with HCV.

    PubMed

    Lake, John; Patel, Dharmesh; David, Kristin; Richwine, Jason; Morris, Jonathan

    2009-01-01

    The impact of a three-drug regimen including mycophenolate mofetil (MMF) vs. a two-drug (no MMF) regimen on progressive renal dysfunction (PRD) in liver transplant recipients with hepatitis C virus (HCV) infection has not been well described. Adults with HCV who received a primary liver transplant between January 1, 2000 and December. 31, 2005 and were discharged from the hospital on a three-drug regimen [CNI+MMF+steroids (S)] (n = 4 946) were compared with those discharged on two-drug regimen (CNI+S) (n = 3 884). Time to PRD (defined by a post-transplant 25% decline in estimated GFR, based on the four-variable MDRD equation) and recipient death were evaluated using Kaplan-Meier analysis. Cox proportional hazards regression was used to estimate the risk for post-transplant PRD and death after controlling for baseline characteristics and extended steroid use. The two groups were similar in baseline characteristics. The percentage of recipients on three- vs. two-drug regimen without PRD was higher, 36.8% vs. 31.9%, (p < 0.001), at three yrs post-transplant; three-drug therapy was associated with a 6% lower adjusted risk of PRD. The death rate and adjusted risk for death was lower for recipients on a three- vs. two-drug regimen. Liver transplant recipients with HCV on a MMF-containing regimen are at a lower risk for PRD and death compared with recipients on a regimen not including MMF.

  13. Repeated-dose liver micronucleus test of 4,4'-methylenedianiline using young adult rats.

    PubMed

    Sanada, Hisakazu; Koyama, Naomi; Wako, Yumi; Kawasako, Kazufumi; Hamada, Shuichi

    2015-03-01

    Liver micronucleus (MN) tests using partial hepatectomized rats or juvenile rats have been shown to be useful for the detection of hepatic carcinogens. Moreover, Narumi et al. established the repeated-dose liver MN test using young adult rats for integration into general toxicity. In the present study, in order to examine the usefulness of the repeated-dose liver MN test, we investigated MN induction with a 14 or 28 day treatment protocol using young adult rats treated with 4,4′-methylenedianiline (MDA), a known hepatic carcinogen. MDA dose-dependently induced micronuclei in hepatocytes in 14- and 28-day repeated-dose tests. However, although statistically significant increases in micronuclei were observed in bone marrow cells at two dose levels in the 14-day study, there was no dose response and no increases in micronuclei in the 28-day study. These results indicate that the evaluation of genotoxic effects using hepatocytes is effective in cases where chromosomal aberrations are not clearly detectable in bone marrow cells. Moreover, the repeated-dose liver MN test allows evaluation at a dose below the maximum tolerable dose, which is required for the conventional MN test because micronucleated hepatocytes accumulate. The repeated-dose liver MN test employed in the present study can be integrated into the spectrum of general toxicity tests without further procedural modifications.

  14. Immunogenicity of inactivated seasonal influenza vaccine in adult and pediatric liver transplant recipients over two seasons.

    PubMed

    Suzuki, Michio; Torii, Yuka; Kawada, Jun-ichi; Kimura, Hiroshi; Kamei, Hideya; Onishi, Yasuharu; Kaneko, Kenitiro; Ando, Hisami; Kiuchi, Tetsuya; Ito, Yoshinori

    2013-10-01

    Immunological responses to influenza vaccination administered to liver transplantation recipients are not fully elucidated. To compare inactivated influenza vaccine's immunogenicity between adult and pediatric recipients, 16 adult and 15 pediatric living donor liver transplantation recipients in the 2010-11 influenza season, and 53 adult and 21 pediatric recipients in the 2011-12 season, were investigated. Seroprotection rates (hemagglutinin-inhibition [HI] antibody titer 1:40) were 50-94% to all three antigens among adults and 27-80% among children in both seasons. Seroconversion rates (fourfold or more HI antibody rise) were 32-56% among adults and 13-67% among children in both seasons. No significant differences were observed between the two groups. In addition, 20/53 adult and 13/21 pediatric recipients received a vaccine containing identical antigens in both of these seasons. Geometric mean titer fold increases of all three antigens in adult recipients were significantly lower than those in recipients who had not received a preceding vaccination. In contrast, in pediatric recipients, there were no significant differences between the groups who had and had not received preceding vaccinations. The number of patients with rejection did not differ significantly between the two groups (0/53 vs. 1/21) in the 2011-12 season. The incidence of influenza after vaccination was significantly different between adult and pediatric recipients (0/16 vs. 5/15 in 2010-11 and 0/53 vs. 3/21 in 2011-12, respectively). Overall, there were no significant differences in antibody responses between adult and pediatric groups. Influenza infection was more frequent in pediatric recipients. Long-term response to preceding vaccinations appeared to be insufficient in both groups.

  15. Serial volumetric assessment of large for size liver grafts after whole cadaveric liver transplant in adults: do large liver grafts shrink in size?

    PubMed Central

    Bekheit, Mohamed; Rajakannu, Muthukumarassamy; Bucur, Petru; Adam, Rene; SaCunha, Antonio; Castaing, Denis; Cherqui, Daniel; Vibert, Eric

    2015-01-01

    Background After whole graft orthotopic liver transplantation (OLT), adaptation of the large grafts' volume to recipient weight is widely accepted despite the paucity of evidence on this subject. Methods Thirty nine patients with GRWR > 2.5% were included in this study and subsequently divided into two groups with 3 ≥ GRWR > 3%. Patients had CT scans at three predetermined time points after OLT used for measuring the liver volume. The objective of this study is to evaluate the volumetric changes of whole large liver grafts after adult OLT. Results At LT, the mean graft recipient body weight ratio (GRWR) was 3.1 ± 0.4%. The mean liver weight was 1881 ± 68 g at LT, 2014 ± 99 ml at one week, 1725 ± 126 ml at 3 months, and 1632 ± 117 (ml) at >6 months. There is an initial increase at 1 week after LT and a subsequent decrease of liver volume on later measurements. None of the late volume measurements were significantly different from the initial graft volume at liver transplant in pair wise comparisons ANOVA repeated measures (p > 0.05). Similarly, the mean GRWR did not change significantly between the initial calculation at transplantation date and the subsequent measurements during the different study time points (F = 0.04, p = 0.96) with a mean of 3.1% (95% CI = 2.2–4.2). AUC ROC discriminated a cutoff of 3% for the initial GRWR above which grafts tend to decrease in size over time (c statistics = 0.74, p = 0.036). In a Clustered ANOVA repeated measures, there was no significant difference in the changes of liver volume between both groups. However, patients with GRWR > 3 showed a trend towards a latent reduction in volume over the tracing period. There was a tendency, but none significant; towards a higher bilirubin, AST, ALT levels over the first postoperative days in recipients with GRWR > 3. Conclusion Large grafts do not significantly decrease in size. Nonetheless, grafts weighing >3% of the GRWR show a different trend

  16. A Novel Virulence Gene in Klebsiella pneumoniae Strains Causing Primary Liver Abscess and Septic Metastatic Complications

    PubMed Central

    Fang, Chi-Tai; Chuang, Yi-Ping; Shun, Chia-Tung; Chang, Shan-Chwen; Wang, Jin-Town

    2004-01-01

    Primary Klebsiella pneumoniae liver abscess complicated with metastatic meningitis or endophthalmitis is a globally emerging infectious disease. Its pathogenic mechanism remains unclear. The bacterial virulence factors were explored by comparing clinical isolates. Differences in mucoviscosity were observed between strains that caused primary liver abscess (invasive) and those that did not (noninvasive). Hypermucoviscosity correlated with a high serum resistance and was more prevalent in invasive strains (52/53 vs. 9/52; P < 0.0001). Transposon mutagenesis identified candidate virulence genes. A novel 1.2-kb locus, magA, which encoded a 43-kD outer membrane protein, was significantly more prevalent in invasive strains (52/53 vs. 14/52; P < 0.0001). The wild-type strain produced a mucoviscous exopolysaccharide web, actively proliferated in nonimmune human serum, resisted phagocytosis, and caused liver microabscess and meningitis in mice. However, magA− mutants lost the exopolysaccharide web and became extremely serum sensitive, phagocytosis susceptible, and avirulent to mice. Virulence was restored by complementation using a magA-containing plasmid. We conclude that magA fits molecular Koch's postulates as a virulence gene. Thus, this locus can be used as a marker for the rapid diagnosis and for tracing the source of this emerging infectious disease. PMID:14993253

  17. Carcinoid Heart Disease without Liver Involvement Caused by a Primary Ovarian Carcinoid Tumour.

    PubMed

    Agarwal, Chirag; Goel, Sunny; Stern, Eric; Warner, Richard; Castillo, Javier; Croft, Lori; Lavine, Ronald; Zacks, Jerome

    2015-07-01

    Carcinoid heart disease, caused by primary ovarian carcinoid tumour, is a rare form of valvular heart disease. This form of heart disease usually presents with symptoms of right-sided valvular dysfunction, ultimately leading to right-sided heart failure. This entity is unique as it develops in the absence of liver metastasis. We report a case of 75 year-old woman with primary ovarian carcinoid tumour who presented with symptoms of severe right-sided heart failure and successfully underwent pulmonic and tricuspid valve replacement along with a right ventricular (RV) outflow patch enlargement. This patient later underwent uneventful resection of the primary ovarian carcinoid tumour, with complete resolution of her symptoms.

  18. Immunohistochemical evidence of disease recurrence after liver transplantation for primary biliary cirrhosis.

    PubMed

    Van de Water, J; Gerson, L B; Ferrell, L D; Lake, J R; Coppel, R L; Batts, K P; Wiesner, R H; Gershwin, M E

    1996-11-01

    Whether primary biliary cirrhosis (PBC) recurs after liver transplantation has remained an interesting and controversial issue; rejection, viral hepatitis, and drug effects all may mimic recurrent PBC histologically and biochemically. Furthermore, reliable clinical criteria for PBC recurrence are lacking. In this study, the issue of disease recurrence using a well-characterized monoclonal antibody (MAb), C355.1, that reacts with the immunodominant mitochondrial autoantigen of PBC (pyruvate dehydrogenase complex [PDC-E2]) was addressed. When used in an immunohistochemical assay, C355.1 produces intense apical staining of bile duct epithelium specifically in liver sections of patients with PBC and may be the earliest known marker of PBC. Immunohistochemical and histological analysis of serial liver biopsy specimens of 67 patients pre- and post-orthotopic liver transplantation (OLT), including 38 patients with PBC and 29 non-PBC liver disease controls, was performed. Sections were stained with MAb C355.1 or the control MAb C315 and analyzed to determine whether there was a recurrence of apical reactivity in the bile ducts of the posttransplantation biopsy specimens. The immunohistochemical staining was correlated with the histological findings and serum biochemistries at the time of the biopsy. Our data indicate that a significant number of patients who underwent transplantation for PBC (28 of 38) but not controls (0 of 29) develop a staining pattern of liver bile duct epithelium with MAb C355.1 that is indistinguishable from the pretransplantation pattern. Of the 28 patients with this apical staining pattern, 8 were characterized histologically as possible recurrent PBC, 2 as chronic rejection, 2 as acute rejection, 9 as nonspecific changes, 4 as normal or near normal, and 3 had other histological changes. Only 50% of the patients with apical C355.1 staining had liver enzyme levels suggestive of cholestasis. Thus, there appears to be immunohistochemical evidence that

  19. The 14-day repeated dose liver micronucleus test with methapyrilene hydrochloride using young adult rats.

    PubMed

    Inoue, Kenji; Ochi, Akimu; Koda, Akira; Wako, Yumi; Kawasako, Kazufumi; Doi, Takaaki

    2015-03-01

    The repeated dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect genotoxic hepatocarcinogens that can be integrated into a general toxicity study. The assay methods were thoroughly validated by 19 Japanese facilities. Methapyrilene hydrochloride (MP), known to be a non-genotoxic hepatocarcinogen, was examined in the present study. MP was dosed orally at 10, 30 and 100mg/kg/day to 6-week-old male Crl:CD (SD) rats daily for 14 days. Treatment with MP resulted in an increase in micronucleated hepatocytes (MNHEPs) with a dosage of only 100mg/kg/day. At this dose level, cytotoxicity followed by regenerative cell growth was noted in the liver. These findings suggest that MP may induce clastogenic effects indirectly on the liver or hepatotoxicity of MP followed by regeneration may cause increase in spontaneous incidence of MNHEPs.

  20. Child-to-Adult Liver Transplantation With Donation After Cardiac Death Donors: Three Case Reports.

    PubMed

    Hu, Liangshuo; Liu, Xuemin; Zhang, Xiaogang; Yu, Liang; Sha, Huanchen; Zhou, Ying; Tian, Min; Shi, Jianhua; Wang, Wanli; Liu, Chang; Guo, Kun; Lv, Yi; Wang, Bo

    2016-02-01

    Development of organ transplantation is restricted by the discrepancy between the lack of donors and increasing number of patients. The outcome of pediatric donors transplanted into adult recipients especially with donation after circulatory death (DCD) pattern has not been well studied. The aim of this paper is to describe our experience of 3 successful DCD donor child-to-adult liver transplantations lately. Three DCD donors were separately 7, 5, and 8 years old. The ratio between donor graft weight and recipient body weight was 1.42%, 1.00%, and 1.33%, respectively. Ratio between the volume of donor liver and the expected liver volume was 0.65, 0.46, and 0.60. Splenectomy was undertaken for the second recipient according to the portal vein pressure (PVP) which was observed during the operation. Two out of 3 of the recipients suffered with acute kidney injury and got recovered after renal replacement therapy. The first recipient also went through early allograft dysfunction and upper gastrointestinal bleeding. The hospital course of the third recipient was uneventful. After 1 year of follow-up visit, the first and second recipients maintain good quality of life and liver function. The third patient was followed up for 5 months until now and recovered well. DCD child-to-adult liver transplantation should only be used for comparatively matched donor and recipient. PVP should be monitored during the operation. The short-term efficacy is good, but long-term follow-up and clinical study with large sample evaluation are still needed.

  1. Liver transplantation in a patient with primary antiphospholipid syndrome and Budd-Chiari syndrome.

    PubMed

    Reshetnyak, Tatiana M; Seredavkina, Natalia V; Satybaldyeva, Maria A; Nasonov, Evgeniy L; Reshetnyak, Vasiliy I

    2015-09-08

    The antiphospholipid syndrome (APS) is an acquired thrombophilic disorder in which autoantibodies are produced to a variety of phospholipids determinants of cell membranes or phospholipid binding proteins. There are few reports about association between antiphospholipid antibodies and development of Budd-Chiari syndrome (BCS). We report the case of BCS development in young Russian male with primary APS. The patient underwent orthotopic liver transplantation on August 26, 2012. At present time his state is good, the blood flow in the liver restored and its function is not impaired. We report about the first time the successful use of dabigatran etexilate for prolonged anticoagulation therapy in APS patient with BCS. In addition patient is managed with immunosuppressive drugs.

  2. Liver transplantation in a patient with primary antiphospholipid syndrome and Budd-Chiari syndrome

    PubMed Central

    Reshetnyak, Tatiana M; Seredavkina, Natalia V; Satybaldyeva, Maria A; Nasonov, Evgeniy L; Reshetnyak, Vasiliy I

    2015-01-01

    The antiphospholipid syndrome (APS) is an acquired thrombophilic disorder in which autoantibodies are produced to a variety of phospholipids determinants of cell membranes or phospholipid binding proteins. There are few reports about association between antiphospholipid antibodies and development of Budd-Chiari syndrome (BCS). We report the case of BCS development in young Russian male with primary APS. The patient underwent orthotopic liver transplantation on August 26, 2012. At present time his state is good, the blood flow in the liver restored and its function is not impaired. We report about the first time the successful use of dabigatran etexilate for prolonged anticoagulation therapy in APS patient with BCS. In addition patient is managed with immunosuppressive drugs. PMID:26380049

  3. Combined liver-kidney transplantation in a child with primary hyperoxaluria.

    PubMed

    Polinsky, M S; Dunn, S; Kaiser, B A; Schulman, S L; Wolfson, B J; Elfenbein, I B; Baluarte, H J

    1991-05-01

    A 3.5-year-old boy presented with end-stage renal disease and bilateral nephrocalcinosis. Renal biopsy demonstrated marked parenchymal calcium oxalate deposition and a diagnosis of primary hyperoxaluria (PH) was made. Following 2 years of hemodialysis he received two renal allografts which were lost at 7 and 11 months, respectively, due to biopsy-proven recurrent oxalosis. Combined liver-kidney transplantation was then performed, after which renal and hepatic function initially stabilized. The patient died on the 28th postoperative day, of infectious complications and progressive respiratory insufficiency. However, comparisons between the patterns of urinary oxalate excretion noted after the isolated renal and liver-kidney transplants indicated that, following the latter, successful biochemical correction of the enzyme defect responsible for type 1 PH had occurred.

  4. A Monte Carlo approach to assessing 147Pm in the liver of the adult phantom.

    PubMed

    Bhati, S

    1993-06-01

    A low-background phoswich detector is used to detect small amounts of 147Pm--a pure beta-emitting nuclide--present in the liver of an occupational worker. The assessment was based on the measurement of bremsstrahlung radiation produced by the beta particles in the tissue. Computer programs based on Monte Carlo techniques for photon transport have been developed to calculate the response of an external phoswich detector to 1) a 147Pm point source embedded in tissue-equivalent slabs of various thicknesses; and 2) various source distributions of 147Pm in the liver of an adult phantom. The goal is to theoretically calibrate the phoswich detector for each source distribution and to study the variation of maxima of the spectra with the depth of the source in the adult phantom liver and tissue-equivalent slabs. The initial bremsstrahlung photon distribution of 147Pm in water has been computed using Wyard's and Pratt's methods. These calculations have been compared with experimental measurements using Perspex acrylic sheet slabs. Good agreements have been noted when the initial bremsstrahlung spectrum is obtained by using Wyard's method. These results find applications in monitoring the liver burdens in occupational workers handling 147Pm-based radioluminous paints.

  5. Epinephrine and phenylephrine pretreatments for preventing postreperfusion syndrome during adult liver transplantation.

    PubMed

    Ryu, Ho-Geol; Jung, Chul-Woo; Lee, Hyung-Chul; Cho, Youn-Joung

    2012-12-01

    Acute hypotension after reperfusion of the liver graft occurs frequently during liver transplantation. A randomized, prospective trial was performed to test the effects of epinephrine and phenylephrine pretreatments for attenuating postreperfusion syndrome (PRS). Ninety-three adult liver recipients were randomly allocated to receive an intravenous bolus of 10 μg of epinephrine, 100 μg of phenylephrine, or normal saline (the control group) at the time of graft reperfusion. The occurrence of PRS, the use of vasoactive drugs, and the postoperative courses were compared. The epinephrine and phenylephrine groups showed PRS less frequently (39% and 48%) than the control group (77%, P = 0.006) as well as higher mean arterial pressures (MAPs) immediately after reperfusion (P < 0.05). An overshoot of MAP was observed in one-third of the pretreated patients with minimal heart rate changes. Only 2 patients in each pretreatment group showed an increase in MAP that was greater than 20% of the baseline value. The intraoperative epinephrine and dopamine requirements were significantly lower in both pretreatment groups. Perioperative laboratory data, postoperative stays, and in-hospital mortality rates were similar for the 3 groups. In conclusion, pretreatment with 10 μg of epinephrine or 100 μg of phenylephrine significantly reduces the occurrence of PRS and vasopressor requirements without immediate or delayed adverse effects in adult liver transplantation.

  6. Does Lysosomial Acid Lipase Reduction Play a Role in Adult Non-Alcoholic Fatty Liver Disease?

    PubMed Central

    Baratta, Francesco; Pastori, Daniele; Polimeni, Licia; Tozzi, Giulia; Violi, Francesco; Angelico, Francesco; Del Ben, Maria

    2015-01-01

    Lysosomal Acid Lipase (LAL) is a key enzyme involved in lipid metabolism, responsible for hydrolysing the cholesteryl esters and triglycerides. Wolman Disease represents the early onset phenotype of LAL deficiency rapidly leading to death. Cholesterol Ester Storage Disease is a late onset phenotype that occurs with fatty liver, elevated aminotransferase levels, hepatomegaly and dyslipidaemia, the latter characterized by elevated LDL-C and low HDL-C. The natural history and the clinical manifestations of the LAL deficiency in adults are not well defined, and the diagnosis is often incidental. LAL deficiency has been suggested as an under-recognized cause of dyslipidaemia and fatty liver. Therefore, LAL activity may be reduced also in non-obese patients presenting non-alcoholic fatty liver disease (NAFLD), unexplained persistently elevated liver transaminases or with elevation in LDL cholesterol. In these patients, it could be indicated to test LAL activity. So far, very few studies have been performed to assess LAL activity in representative samples of normal subjects or patients with NAFLD. Moreover, no large study has been carried out in adult subjects with NAFLD or cryptogenic cirrhosis. PMID:26602919

  7. Plasma selenium levels and nonalcoholic fatty liver disease in Chinese adults: a cross-sectional analysis

    PubMed Central

    Yang, Zhen; Yan, Chonghuai; Liu, Gang; Niu, Yixin; Zhang, Weiwei; Lu, Shuai; Li, Xiaoyong; Zhang, Hongmei; Ning, Guang; Fan, Jiangao; Qin, Li; Su, Qing

    2016-01-01

    Selenium exposure can induce liver insulin resistance and increased liver triglyceride concentrations in animals, which may link to an increased risk of nonalcoholic fatty liver disease (NAFLD). However, epidemiological studies investigating the association between elevated plasma selenium levels and NAFLD were not available. We aimed to investigate the association of selenium levels with the prevalence of NAFLD in Chinese adults. This was a cross-sectional study of 8550 Chinese adults aged 40 yr or older in Shanghai, China. A questionnaire, anthropometric measurements, and laboratory tests were conducted. NAFLD was diagnosed by hepatic ultrasound after the exclusion of alcohol abuse and other liver diseases. Plasma selenium concentration was assessed by inductively coupled plasma mass spectroscopy. The median concentration of plasma selenium was 213.0 μg/L. Elevated plasma selenium levels were associated with higher triglycerides, LDL-cholesterol, fasting plasma glucose, post-loading plasma glucose, A1c, HOMA-IR, as well as ALT, AST and γ-GT (all P < 0.05). The odds ratios were substantially higher for NAFLD (OR = 1.54, 95% CI 1.13–2.18) in the highest selenium quartile compared with those in the lowest quartile, after adjustment for potential cofounder. The results of this study provided epidemiological evidence that increased plasma selenium level is associated with elevated prevalence of NAFLD. PMID:27853246

  8. Does Lysosomial Acid Lipase Reduction Play a Role in Adult Non-Alcoholic Fatty Liver Disease?

    PubMed

    Baratta, Francesco; Pastori, Daniele; Polimeni, Licia; Tozzi, Giulia; Violi, Francesco; Angelico, Francesco; Del Ben, Maria

    2015-11-25

    Lysosomal Acid Lipase (LAL) is a key enzyme involved in lipid metabolism, responsible for hydrolysing the cholesteryl esters and triglycerides. Wolman Disease represents the early onset phenotype of LAL deficiency rapidly leading to death. Cholesterol Ester Storage Disease is a late onset phenotype that occurs with fatty liver, elevated aminotransferase levels, hepatomegaly and dyslipidaemia, the latter characterized by elevated LDL-C and low HDL-C. The natural history and the clinical manifestations of the LAL deficiency in adults are not well defined, and the diagnosis is often incidental. LAL deficiency has been suggested as an under-recognized cause of dyslipidaemia and fatty liver. Therefore, LAL activity may be reduced also in non-obese patients presenting non-alcoholic fatty liver disease (NAFLD), unexplained persistently elevated liver transaminases or with elevation in LDL cholesterol. In these patients, it could be indicated to test LAL activity. So far, very few studies have been performed to assess LAL activity in representative samples of normal subjects or patients with NAFLD. Moreover, no large study has been carried out in adult subjects with NAFLD or cryptogenic cirrhosis.

  9. Hepatic resection for giant haemangioma in a patient with a contemporaneous adult polycystic liver disease.

    PubMed

    Levi Sandri, G B; Lai, Q; Melandro, F; Guglielmo, N; Garofalo, M; Morabito, V; Cirelli, C; Lucatelli, P; Di Laudo, M; Rossi, M; Berloco, P B

    2012-01-01

    Hepatic resection for giant haemangioma in a patient with a contemporaneous adult polycystic liver disease. According to Gigot classification, and to the characteristics of haemangioma surgery in these patients can be considered safe. We report the case of a 55 year-old man affected by an adult polycystic liver disease (PCLD) and a contemporaneous symptomatic haemangioma of the III segment. At the preoperative imaging scans, APCLD was classified in a type II grading according to Gigot classification. The patient underwent surgery: a wedge resection of the III segment with the exportation of the haemangioma and a fenestration of a large cyst placed in the VIII segment were performed. Post-operative course was regular and the patient was discharged uneventfully in post-operative 9th day, with a total regress of the initial symptoms. APCLD and haemangioma are two benign conditions that do not require surgery except if they cause important symptoms, such as pain. The good clinical conditions of the patient, the moderate gravity of the APCLD and the particular exofitic localisation of the cavernous haemangioma gave us the possibility to make a safe surgery for the patient. To the best of our knowledge, this is the first case reported in literature in which a liver resection for haemangioma in patient with APCLD was performed. In conclusion, liver resection for haemangioma is not contraindicated, mainly if it is symptomatic, even in the contemporaneous presence of an APCLD.

  10. Simultaneous resection of primary colorectal cancer and synchronous liver metastases: a population-based study

    PubMed Central

    Nanji, Sulaiman; Mackillop, William J.; Wei, Xuejiao; Booth, Christopher M.

    2017-01-01

    Background Simultaneous resection of primary colorectal cancer (CRC) and synchronous liver metastases (LM) is gaining interest. We describe management and outcomes of patients undergoing simultaneous resection in the general population. Methods All patients with CRC who underwent surgical resection of LM between 2002 and 2009 were identified using the population-based Ontario Cancer Registry and linked electronic treatment records. Synchronous disease was defined as having resection of CRCLM within 12 weeks of surgery for the primary tumour. Results During the study period, 1310 patients underwent resection of CRCLM. Of these, 226 (17%) patients had synchronous disease; 100 (44%) had a simultaneous resection and 126 (56%) had a staged resection. For the simultaneous and the staged groups, the mean number of liver lesions resected was 1.6 and 2.3, respectively (p < 0.001); the mean size of the largest lesion was 3.1 and 4.8 cm, respectively (p < 0.001); and the major hepatic resection rate was 21% and 79%, respectively (p < 0.001). Postoperative mortality for simultaneous cases at 90 days was less than 5%. Five-year overall survival and cancer-specific survival for patients with simultaneous resection was 36% (95% confidence interval [CI] 26%–45%) and 37% (95% CI 25%–50%), respectively. Simultaneous resections are common in the general population. A more conservative approach is being adopted for simultaneous resections by limiting the extent of liver resection. Postoperative mortality and long-term survival in this patient population is similar to that reported in other contemporary series. Conclusion Compared with a staged approach, patients undergoing simultaneous resections had fewer and smaller liver metastases and underwent less aggressive resections. One-third of these patients achieved long-term survival. PMID:28234215

  11. Multi-cellular 3D human primary liver cell culture elevates metabolic activity under fluidic flow.

    PubMed

    Esch, Mandy B; Prot, Jean-Matthieu; Wang, Ying I; Miller, Paula; Llamas-Vidales, Jose Ricardo; Naughton, Brian A; Applegate, Dawn R; Shuler, Michael L

    2015-05-21

    We have developed a low-cost liver cell culture device that creates fluidic flow over a 3D primary liver cell culture that consists of multiple liver cell types, including hepatocytes and non-parenchymal cells (fibroblasts, stellate cells, and Kupffer cells). We tested the performance of the cell culture under fluidic flow for 14 days, finding that hepatocytes produced albumin and urea at elevated levels compared to static cultures. Hepatocytes also responded with induction of P450 (CYP1A1 and CYP3A4) enzyme activity when challenged with P450 inducers, although we did not find significant differences between static and fluidic cultures. Non-parenchymal cells were similarly responsive, producing interleukin 8 (IL-8) when challenged with 10 μM bacterial lipoprotein (LPS). To create the fluidic flow in an inexpensive manner, we used a rocking platform that tilts the cell culture devices at angles between ±12°, resulting in a periodically changing hydrostatic pressure drop between reservoirs and the accompanying periodically changing fluidic flow (average flow rate of 650 μL min(-1), and a maximum shear stress of 0.64 dyne cm(-2)). The increase in metabolic activity is consistent with the hypothesis that, similar to unidirectional fluidic flow, primary liver cell cultures increase their metabolic activity in response to fluidic flow periodically changes direction. Since fluidic flow that changes direction periodically drastically changes the behavior of other cells types that are shear sensitive, our findings support the theory that the increase in hepatic metabolic activity associated with fluidic flow is either activated by mechanisms other than shear sensing (for example increased opportunities for gas and metabolite exchange), or that it follows a shear sensing mechanism that does not depend on the direction of shear. Our mode of device operation allows us to evaluate drugs under fluidic cell culture conditions and at low device manufacturing and operation

  12. Prevalence and predictors of change in adult-child primary caregivers.

    PubMed

    Szinovacz, Maximiliane E; Davey, Adam

    2013-01-01

    Family caregiving research is increasingly contextual and dynamic, but few studies have examined prevalence and predictors of change in primary caregivers, those with the most frequent contact with healthcare professionals. We identified prevalence and predictors of 2-year change in primary adult-child caregivers. Data pooled from the 1992-2000 waves of the Health and Retirement Study (HRS) represent 1,068 parent-level care occasions and 3,616 child-level occasions. There is considerable 2-year stability in primary adult-child caregivers. Parents are more prone to experience a change in adult-child primary caregivers if they live by themselves and if they have more sons and daughters. As far as the adult children are concerned, daughters and children living closer to parents are more likely to remain primary caregivers. Results suggest that change in primary caregivers is more strongly associated with available alternatives and gender norms than burden and competing obligations.

  13. Deep sexual dimorphism in adult medaka fish liver highlighted by multi-omic approach

    PubMed Central

    Qiao, Qin; Le Manach, Séverine; Sotton, Benoit; Huet, Hélène; Duvernois-Berthet, Evelyne; Paris, Alain; Duval, Charlotte; Ponger, Loïc; Marie, Arul; Blond, Alain; Mathéron, Lucrèce; Vinh, Joelle; Bolbach, Gérard; Djediat, Chakib; Bernard, Cécile; Edery, Marc; Marie, Benjamin

    2016-01-01

    Sexual dimorphism describes the features that discriminate between the two sexes at various biological levels. Especially, during the reproductive phase, the liver is one of the most sexually dimorphic organs, because of different metabolic demands between the two sexes. The liver is a key organ that plays fundamental roles in various physiological processes, including digestion, energetic metabolism, xenobiotic detoxification, biosynthesis of serum proteins, and also in endocrine or immune response. The sex-dimorphism of the liver is particularly obvious in oviparous animals, as the female liver is the main organ for the synthesis of oocyte constituents. In this work, we are interested in identifying molecular sexual dimorphism in the liver of adult medaka fish and their sex-variation in response to hepatotoxic exposures. By developing an integrative approach combining histology and different high-throughput omic investigations (metabolomics, proteomics and transcriptomics), we were able to globally depict the strong sexual dimorphism that concerns various cellular and molecular processes of hepatocytes comprising protein synthesis, amino acid, lipid and polysaccharide metabolism, along with steroidogenesis and detoxification. The results of this work imply noticeable repercussions on the biology of oviparous organisms environmentally exposed to chemical or toxin issues. PMID:27561897

  14. Deep sexual dimorphism in adult medaka fish liver highlighted by multi-omic approach.

    PubMed

    Qiao, Qin; Le Manach, Séverine; Sotton, Benoit; Huet, Hélène; Duvernois-Berthet, Evelyne; Paris, Alain; Duval, Charlotte; Ponger, Loïc; Marie, Arul; Blond, Alain; Mathéron, Lucrèce; Vinh, Joelle; Bolbach, Gérard; Djediat, Chakib; Bernard, Cécile; Edery, Marc; Marie, Benjamin

    2016-08-26

    Sexual dimorphism describes the features that discriminate between the two sexes at various biological levels. Especially, during the reproductive phase, the liver is one of the most sexually dimorphic organs, because of different metabolic demands between the two sexes. The liver is a key organ that plays fundamental roles in various physiological processes, including digestion, energetic metabolism, xenobiotic detoxification, biosynthesis of serum proteins, and also in endocrine or immune response. The sex-dimorphism of the liver is particularly obvious in oviparous animals, as the female liver is the main organ for the synthesis of oocyte constituents. In this work, we are interested in identifying molecular sexual dimorphism in the liver of adult medaka fish and their sex-variation in response to hepatotoxic exposures. By developing an integrative approach combining histology and different high-throughput omic investigations (metabolomics, proteomics and transcriptomics), we were able to globally depict the strong sexual dimorphism that concerns various cellular and molecular processes of hepatocytes comprising protein synthesis, amino acid, lipid and polysaccharide metabolism, along with steroidogenesis and detoxification. The results of this work imply noticeable repercussions on the biology of oviparous organisms environmentally exposed to chemical or toxin issues.

  15. Practice guidelines for the pathological diagnosis of primary liver cancer: 2015 update

    PubMed Central

    Cong, Wen-Ming; Bu, Hong; Chen, Jie; Dong, Hui; Zhu, Yu-Yao; Feng, Long-Hai; Chen, Jun; Committee, Guideline

    2016-01-01

    In 2010, a panel of Chinese pathologists reported the first expert consensus for the pathological diagnosis of primary liver cancers to address the many contradictions and inconsistencies in the pathological characteristics and diagnostic criteria for PLC. Since then considerable clinicopathological studies have been conducted globally, prompting us to update the practice guidelines for the pathological diagnosis of PLC. In April 18, 2014, a Guideline Committee consisting of 40 specialists from seven Chinese Societies (including Chinese Society of Liver Cancer, Chinese Anti-Cancer Association; Liver Cancer Study Group, Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Pathology, Chinese Anti-Cancer Association; Digestive Disease Group, Chinese Society of Pathology, Chinese Medical Association; Chinese Society of Surgery, Chinese Medical Association; Chinese Society of Clinical Oncology, Chinese Anti-Cancer Association; Pathological Group of Hepatobiliary Tumor and Liver Transplantation, Chinese Society of Pathology, Chinese Medical Association) was created for the formulation of the first guidelines for the standardization of the pathological diagnosis of PLC, mainly focusing on the following topics: gross specimen sampling, concepts and diagnostic criteria of small hepatocellular carcinoma (SHCC), microvascular invasion (MVI), satellite nodules, and immunohistochemical and molecular diagnosis. The present updated guidelines are reflective of current clinicopathological studies, and include a novel 7-point baseline sampling protocol, which stipulate that at least four tissue specimens should be sampled at the junction of the tumor and adjacent liver tissues in a 1:1 ratio at the 12, 3, 6 and 9 o’clock reference positions. For the purposes of molecular pathological examination, at least one specimen should be sampled at the intratumoral zone, but more specimens should be sampled for tumors harboring different textures or colors

  16. Primary liver cancer and food-based toxins. A Swaziland review.

    PubMed

    McGlashan, N D

    1982-01-01

    This review brings together evidence on the scientific unfolding of the relationship between primary liver cancer and food based toxins with particular reference to Swaziland. Growth of knowledge of the geographic patterns of the disease has been paralleled by development in other disciplines, notably agriculture and toxicology, of understanding of the occurrence and mode of action of natural hepatotoxins in the dietary environment of people in southern Africa. Areas for further enquiry are highlighted but the agriculturally advantageous side-effects of policies aimed to reduce mycotoxin ingestion in Swaziland are already unequivocal.

  17. Priorities for young adults when accessing UK primary care: literature review.

    PubMed

    Davey, Antoinette; Carter, Mary; Campbell, John L

    2013-10-01

    This literature review focuses on what matters to young adults when they access primary care services in the United Kingdom. Patients' access to and experience of primary care services differs across age groups. Existing research has largely focused on the needs and experiences of children, adolescents, and adults. There is some evidence to suggest the views of young adults (aged 18-25 years) that may differ from the views of other age groups, and research has not previously reported specifically on the views of this group of the population. The literature was reviewed to identify the views and priorities of young UK adults regarding primary healthcare provision, and furthermore, to identify those related topics that would benefit from further research. Relevant academic publications and grey literature published from 2000 onwards was reviewed and synthesised. We identified and reported emerging themes that were of importance to young adults in respect of the UK primary care provision. A total of 19 papers met our inclusion criteria. Young adults access primary care services less frequently than other age groups; this may be because of their experience of primary care throughout childhood and adolescence. Five aspects of primary care provision emerged as being of importance to young adults--the accessibility and availability of services, the confidentiality of health-related information, issues relating to communication with healthcare professionals, continuity of care, and behaviours and attitudes expressed towards young adults by healthcare professionals. There is a lack of focus of current research on the expectations, needs, and primary healthcare experiences of young adults. Young adults may hold views that are distinct from other age groups. Further research is needed to better understand the needs of a young adult population as their needs may impact the future use of services.

  18. Nurse Practitioner Primary Care Competencies in Specialty Areas: Adult, Family, Gerontological, Pediatric, and Women's Health.

    ERIC Educational Resources Information Center

    Crabtree, M. Katherine; Stanley, Joan; Werner, Kathryn E.; Schmid, Emily

    This document presents the nurse practitioner primary care competencies that a national panel of representatives of nine national organizations of the five primary care nurse practitioner specialties--adult, family, gerontological, pediatric, and women's health--identified as necessary for entry-level primary care nurse practitioners. Section 1…

  19. Non-alcoholic fatty liver disease in obese adults: clinical aspects and current management strategies.

    PubMed

    Pallayova, M; Taheri, S

    2014-10-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder whose prevalence is strongly linked to the current epidemic of obesity in many western countries. The prevalence of NAFLD is two to four times higher in populations with pre-existing metabolic comorbidities than in the general population. The diagnosis of primary NAFLD involves establishing the presence of hepatic steatosis or steatohepatitis by imaging or histology, along with establishing the non-alcoholic nature of the disease process and excluding competing aetiologies for hepatic steatosis. Among the indirect serum biomarkers, the NAFLD fibrosis score can help to identify patients with NAFLD and with higher likelihood of having fibrosis or cirrhosis. A liver biopsy should be considered in NAFLD patients at increased risk for steatohepatitis/advanced fibrosis and in cases where a liver biopsy is necessary to exclude co-existing chronic liver diseases and other aetiologies for hepatic steatosis. The treatment and management recommendations for obesity-associated NAFLD are aimed towards weight reduction. The currently available interventions employed to promote weight loss and improve the metabolic responses in NAFLD include lifestyle modification, pharmacotherapy and bariatric surgery.

  20. A search for the primary abnormality in adult-onset type II citrullinemia

    SciTech Connect

    Kobayashi, Keiko; Shaheen, Nazma; Saheki, Takeyori ); Kumashiro, Ryukichi; Tanikawa, Kyuichi ); O'Brien, W.E.; Beaudet, A.L. )

    1993-11-01

    Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia in human beings. Type II citrullinemia is found in most patients with adult-onset citrullinemia in Japan, and ASS deficiency is found specifically in the liver. Previous studies have shown that the decrease of hepatic ASS activity is caused by a decrease in enzyme protein with normal kinetic properties and that there were no apparent abnormalities in the amount, translational activity, and gross structure of hepatic ASS mRNA. In the present work, the authors show by sequencing analysis that there was no mutation in the ASS mRNA from two patients with type II citrullinemia. The authors also report RFLP analysis of a consanguineous family with type II citrullinemia, by using three DNA polymorphisms located within the ASS gene locus. In spite of having consanguineous parents, the patient was not a homozygous haplotype for the ASS gene. The RFLP analysis of 16 affected patients from consanguineous parents showed that 5 of 16 patients had the heterozygous pattern for one of the three DNA probes and that the frequency of the heterozygous haplotype was not different from the control frequency. These results suggest that the primary defect of type II citrullinemia is not within the ASS gene locus. 29 refs., 1 fig., 3 tabs.

  1. Donor Safety in Adult-Adult Living Donor Liver Transplantation: A Single-Center Experience of 356 Cases

    PubMed Central

    Meng, Haipeng; Yang, Jiayin; Yan, Lunan

    2016-01-01

    Background As an important means to tackle the worldwide shortage of liver grafts, adult-adult living donor liver transplantation (A-ALDLT) is the most massive operation a healthy person could undergo, so donor safety is of prime importance. However, most previous research focused on recipients, while complications in donors have not been fully described or investigated. Material/Methods To investigate donor safety in terms of postoperative complications, the clinical data of 356 A-ALDLT donors in our center from January 2002 to September 2015 were retrospectively analyzed. These patients were divided into a pre-2008 group (before January 2008) and a post-2008 group (after January 2008). Donor safety was evaluated with regard to the type, frequency, and severity of postoperative complications. Results There were no donor deaths in our center during this period. The overall complication rate was 23.0% (82/356). The proportion of Clavien I, II, III, and IV complications was 51.2% (42/82), 25.6% (21/82), 22.0% (18/82), and 1.2% (1/82), respectively. In all the donors, the incidence of Clavien I, II, III, and IV complications was 11.8% (42/356), 5.9% (21/356), 5.1% (18/356), and 0.3% (1/356), respectively. The overall complication rate in the post-2008 group was significantly lower than that in the pre-2008 group (18.1% (41/227) vs. 32.6% (42/129), P<0.01). Biliary complications were the most common, with an incidence of 8.4% (30/356). Conclusions The risk to A-ALDLT donors is controllable and acceptable with improvement in preoperative assessment and liver surgery. PMID:27178367

  2. In vitro culture of isolated primary hepatocytes and stem cell-derived hepatocyte-like cells for liver regeneration.

    PubMed

    Hu, Chenxia; Li, Lanjuan

    2015-08-01

    Various liver diseases result in terminal hepatic failure, and liver transplantation, cell transplantation and artificial liver support systems are emerging as effective therapies for severe hepatic disease. However, all of these treatments are limited by organ or cell resources, so developing a sufficient number of functional hepatocytes for liver regeneration is a priority. Liver regeneration is a complex process regulated by growth factors (GFs), cytokines, transcription factors (TFs), hormones, oxidative stress products, metabolic networks, and microRNA. It is well-known that the function of isolated primary hepatocytes is hard to maintain; when cultured in vitro, these cells readily undergo dedifferentiation, causing them to lose hepatocyte function. For this reason, most studies focus on inducing stem cells, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), hepatic progenitor cells (HPCs), and mesenchymal stem cells (MSCs), to differentiate into hepatocyte-like cells (HLCs) in vitro. In this review, we mainly focus on the nature of the liver regeneration process and discuss how to maintain and enhance in vitro hepatic function of isolated primary hepatocytes or stem cell-derived HLCs for liver regeneration. In this way, hepatocytes or HLCs may be applied for clinical use for the treatment of terminal liver diseases and may prolong the survival time of patients in the near future.

  3. Obesity and the extent of liver damage among adult New Zealanders: findings from a national survey

    PubMed Central

    Miller, J. C.; Gray, A. R.; Schultz, M.; Mann, J. I.; Parnell, W. R.

    2015-01-01

    Summary Objective Non‐alcoholic fatty liver disease (NAFLD), defined as excessive fat accumulation in hepatocytes when no other pathologic causes are present, is an increasingly common obesity‐related disorder. We sought to describe the prevalence of elevated liver enzymes, a marker of liver damage, among New Zealand adults, and high‐risk subgroups including those with an elevated body mass index and those with pre‐diabetes or diabetes, to gain a better understanding of the burden of liver disease. Methods A total of 4,721 New Zealanders aged 15+ years participated in a nationally representative nutrition survey. Liver enzymes, alanine transaminase (ALT) and gamma glutamyl transpeptidase (GGT) were measured in serum. Results were available for 3,035 participants, of whom 10.8% were Māori and 4.5% Pacific. Results Overall, the prevalence of elevated ALT and elevated GGT was 13.1% (95% confidence interval [CI]: 11.2 – 15.0) and 13.7% (95% CI: 12.0 – 15.4), respectively. Odds ratios for an elevated ALT or GGT markedly increased with increasing body mass index. Men with obesity had the highest elevated ALT prevalence (28.5%; 95% CI: 21.7–35.4), and women with diabetes had the highest elevated GGT prevalence (36.5%; 95% CI: 26.0–47.0). Adding alcohol consumption categories to each of the adjusted models did not meaningfully change any results, although for women, heavy alcohol consumption was associated with an elevated GGT (overall p = 0.03). Conclusions Obesity‐related liver disease is likely to increasingly burden the New Zealand health sector and contribute to health disparities unless effective obesity treatment and prevention measures are given high priority. © 2015 The Authors. Obesity Science & Practice published by John Wiley & Sons Ltd, World Obesity and The Obesity Society. PMID:27774250

  4. Combined Detection of Serum IL-10, IL-17, and CXCL10 Predicts Acute Rejection Following Adult Liver Transplantation

    PubMed Central

    Kim, Nayoung; Yoon, Young-In; Yoo, Hyun Ju; Tak, Eunyoung; Ahn, Chul-Soo; Song, Gi-Won; Lee, Sung-Gyu; Hwang, Shin

    2016-01-01

    Discovery of non-invasive diagnostic and predictive biomarkers for acute rejection in liver transplant patients would help to ensure the preservation of liver function in the graft, eventually contributing to improved graft and patient survival. We evaluated selected cytokines and chemokines in the sera from liver transplant patients as potential biomarkers for acute rejection, and found that the combined detection of IL-10, IL-17, and CXCL10 at 1-2 weeks post-operation could predict acute rejection following adult liver transplantation with 97% specificity and 94% sensitivity. PMID:27498551

  5. From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

    NASA Astrophysics Data System (ADS)

    Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

    2005-05-01

    Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

  6. Study of Silymarin and Vitamin E Protective Effects on Silver Nanoparticle Toxicity on Mice Liver Primary Cell Culture.

    PubMed

    Faedmaleki, Firouz; Shirazi, Farshad H; Ejtemaeimehr, Shahram; Anjarani, Soghra; Salarian, Amir-Ahmad; Ahmadi Ashtiani, Hamidreza; Rastegar, Hossein

    2016-02-01

    Nanotechnology is a most promising field for generating new applications in medicine, although, only few nano products are currently in use for medical purposes. A most prominent nanoproduct is nanosilver. Nano-silver has biological properties which are significant for consumer products, food technology, textiles, and medical applications (e.g. wound care products, implantable medical devices, in diagnosis, drug delivery, and imaging). For their antibacterial activity, silver nanoparticles (Ag NPs) are largely used in various commercially available products. The use of nano-silver is becoming more and more widespread in medicine and related applications, and due to its increasing exposure, toxicological and environmental issues need to be raised. Cytotoxicity induced by silver nanoparticles (AgNPs) and the role that oxidative stress plays in this process were demonstrated in human hepatoma cells AgNPs agglomerated in the cytoplasm and nuclei of treated cells, and they induced intracellular oxidative stress. AgNP reduced ATP content of the cell and caused damage to mitochondria and increased production of reactive oxygen species (ROS) in a dose-dependent manner. Silymarin was known as a hepatoprotective agent that is used in the treatment of hepatic diseases including viral hepatitis, alcoholic liver diseases, Amanita mushroom poisoning, liver cirrhosis, toxic and drug-induced liver diseases. It promotes protein synthesis, helps in regenerating liver tissue, controls inflammation, enhances glucuronidation, and protects against glutathione depletion. Vitamin E is a well-known antioxidant and has hepatoprotective effect in liver diseases. In this study, we investigated the cytotoxic effects of Ag NPs on primary liver cells of mice. Cell viability (cytotoxicity) was examined with MTT assay after primary liver cells of mice exposure to AgNPs at 1, 10, 50, 100, 150, 200, 400 ppm for 24h. AgNPs caused a concentration- dependent decrease of cell viability (IC50 value = 121

  7. Repair of liver mediated by adult mouse liver neuro-glia antigen 2-positive progenitor cell transplantation in a mouse model of cirrhosis

    PubMed Central

    Zhang, Hongyu; Siegel, Christopher T.; Shuai, Ling; Lai, Jiejuan; Zeng, Linli; Zhang, Yujun; Lai, Xiangdong; Bie, Ping; Bai, Lianhua

    2016-01-01

    NG2-expressing cells are a population of periportal vascular stem/progenitors (MLpvNG2+ cells) that were isolated from healthy adult mouse liver by using a “Percoll-Plate-Wait” procedure. We demonstrated that isolated cells are able to restore liver function after transplantation into a cirrhotic liver, and co-localized with the pericyte marker (immunohistochemistry: PDGFR-β) and CK19. Cells were positive for: stem cell (Sca-1, CD133, Dlk) and liver stem cell markers (EpCAM, CD14, CD24, CD49f); and negative for: hematopoietic (CD34, CD45) and endothelial markers (CD31, vWf, von Willebrand factor). Cells were transplanted (1 × 106 cells) in mice with diethylnitrosamine-induced cirrhosis at week 6. Cells showed increased hepatic associated gene expression of alpha-fetoprotein (AFP), Albumin (Alb), Glucose-6-phosphatase (G6Pc), SRY (sex determining region Y)-box 9 (Sox9), hepatic nuclear factors (HNF1a, HNF1β, HNF3β, HNF4α, HNF6, Epithelial cell adhesion molecule (EpCAM), Leucine-rich repeated-containing G-protein coupled receptor 5-positive (Lgr5) and Tyrosine aminotransferase (TAT). Cells showed decreased fibrogenesis, hepatic stellate cell infiltration, Kupffer cells and inflammatory cytokines. Liver function markers improved. In a cirrhotic liver environment, cells could differentiate into hepatic lineages. In addition, grafted MLpvNG2+ cells could mobilize endogenous stem/progenitors to participate in liver repair. These results suggest that MLpvNG2+ cells may be novel adult liver progenitors that participate in liver regeneration. PMID:26905303

  8. Patterns and Predictors of Sexual Function After Liver Donation: the Adult to Adult Living Donor Liver Transplantation Cohort Study (A2ALL)

    PubMed Central

    DiMartini, AF.; Dew, MA.; Butt, Z.; Simpson, MA.; Ladner, DP.; Smith, AR.; Hill-Callahan, P.; Gillespie, BW.

    2015-01-01

    Although sexual functioning is an important facet of living donor quality of life, it has not received extensive evaluation in this population. Using data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study, we examined donor sexual functioning across the donation process from the predonation evaluation to 3 months and 1 year postdonation. Donors (n=208) and a comparison group of non-donors (n=155) completed self-reported surveys with specific questions on sexual desire, satisfaction, orgasm, and (for men) erectile function. Across the three time points, donor sexual functioning was lower at the evaluation phase and 3 months postdonation than at one year postdonation. In the early recovery period, abdominal pain was associated with difficulty reaching orgasm (OR = 3.98, 95% CI 1.30–12.16), concerns over appearance with lower sexual desire (OR = 4.14, 95% CI 1.02–16.79), and not feeling back to normal was associated with dissatisfaction with sexual life (OR 3.58, 95% CI 1.43–8.99). Efforts to educate donors before the surgery and prepare them for the early recovery phase may improve recovery and reduce distress regarding sexual functioning. PMID:25779554

  9. Enhancing Primary Health Care Services for Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Melville, C. A.; Finlayson, J.; Cooper, S.-A.; Allan, L.; Robinson, N.; Burns, E.; Martin, G.; Morrison, J.

    2005-01-01

    Primary health care teams have an important part to play in addressing the health inequalities and high levels of unmet health needs experienced by people with intellectual disabilities (ID). Practice nurses have an expanding role within primary health care teams. However, no previous studies have measured their attitudes, knowledge, training…

  10. The liver is a common non-exocrine target in primary Sjögren's syndrome: A retrospective review

    PubMed Central

    Kaplan, Mariana J; Ike, Robert W

    2002-01-01

    Background The autoimmune destruction of exocrine glands that defines primary Sjögren's syndrome (1°SS) often extends to non-exocrine organs including the liver. We aimed to determine the prevalence of liver disease in patients with 1°SS and to evaluate the association of this complication with other non-exocrine features and serologic markers of autoimmunity and systemic inflammation. Methods We reviewed 115 charts of patients with 1°SS and further analyzed the 73 cases that fulfilled the European Epidemiology Center Criteria, seeking evidence for clinical and subclinical liver disease. Results Liver function tests had been determined in 59 of the 73 patients. Of those, 29 patients (49.1%) had abnormal liver function tests including 20.3% with clinically overt hepatic disease. Liver disease was the most common non-exocrine feature in this cohort. Risk factors for abnormal liver function tests were distributed similarly between the patients with and without liver disease. In 60% of patients with abnormal liver function tests no explanation for this complication was found except for 1°SS. Liver involvement was significantly more common in 1°SS patients who also had evidence of lung, kidney and hematological abnormalities. Patients with abnormal liver function tests were also more likely to have an elevated sedimentation rate and a positive anti-ENA during the course of their disease. Conclusion Liver involvement is a common complication in 1°SS. Its presence correlates with systemic disease. We consider that this complication should be routinely sought in patients with 1°SS, especially when a positive anti-ENA or evidence of systemic inflammation is found. PMID:12230633

  11. Explanted diseased livers - a possible source of metabolic competent primary human hepatocytes.

    PubMed

    Kleine, Moritz; Riemer, Marc; Krech, Till; DeTemple, Daphne; Jäger, Mark D; Lehner, Frank; Manns, Michael P; Klempnauer, Jürgen; Borlak, Jürgen; Bektas, Hueseyin; Vondran, Florian W R

    2014-01-01

    Being an integral part of basic, translational and clinical research, the demand for primary human hepatocytes (PHH) is continuously growing while the availability of tissue resection material for the isolation of metabolically competent PHH remains limited. To overcome current shortcomings, this study evaluated the use of explanted diseased organs from liver transplantation patients as a potential source of PHH. Therefore, PHH were isolated from resected surgical specimens (Rx-group; n = 60) and explanted diseased livers obtained from graft recipients with low labMELD-score (Ex-group; n = 5). Using established protocols PHH were subsequently cultured for a period of 7 days. The viability and metabolic competence of cultured PHH was assessed by the following parameters: morphology and cell count (CyQuant assay), albumin synthesis, urea production, AST-leakage, and phase I and II metabolism. Both groups were compared in terms of cell yield and metabolic function, and results were correlated with clinical parameters of tissue donors. Notably, cellular yields and viabilities were comparable between the Rx- and Ex-group and were 5.3±0.5 and 2.9±0.7×106 cells/g liver tissue with 84.3±1.3 and 76.0±8.6% viability, respectively. Moreover, PHH isolated from the Rx- or Ex-group did not differ in regards to loss of cell number in culture, albumin synthesis, urea production, AST-leakage, and phase I and II metabolism (measured by the 7-ethoxycoumarin-O-deethylase and uracil-5'-diphosphate-glucuronyltransferase activity). Likewise, basal transcript expressions of the CYP monooxygenases 1A1, 2C8 and 3A4 were comparable as was their induction when treated with a cocktail that consisted of 3-methylcholantren, rifampicin and phenobarbital, with increased expression of CYP 1A1 and 3A4 mRNA while transcript expression of CYP 2C8 was only marginally changed. In conclusion, the use of explanted diseased livers obtained from recipients with low labMELD-score might represent

  12. Primary clear cell carcinoma in the liver: CT and MRI findings

    PubMed Central

    Liu, Qing-Yu; Li, Hai-Gang; Gao, Ming; Lin, Xiao-Feng; Li, Yong; Chen, Jian-Yu

    2011-01-01

    AIM: To retrospectively analyze the computed tomography (CT) and magnetic resonance imaging (MRI) appearances of primary clear cell carcinoma of the liver (PCCCL) and compare the imaging appearances of PCCCL and common type hepatocellular carcinoma (CHCC) to determine whether any differences exist between the two groups. METHODS: Twenty cases with pathologically proven PCCCL and 127 cases with CHCC in the Second Affiliated Hospital of Sun Yat-sen University were included in this study. CT or MRI images from these patients were retrospectively analyzed. The following imaging findings were reviewed: the presence of liver cirrhosis, tumor size, the enhancement pattern on dynamic contrast scanning, the presence of pseudo capsules, tumor rupture, portal vein thrombosis and lymph node metastasis. RESULTS: Both PCCCL and CHCC were prone to occur in patients with liver cirrhosis, the association rate of liver cirrhosis was 80.0% and 78.7%, respectively (P > 0.05). The mean sizes of PCCCL and CHCC tumors were (7.28 ± 4.25) cm and (6.96 ± 3.98) cm, respectively. Small HCCs were found in 25.0% (5/20) of PCCCL and 19.7% (25/127) of CHCC cases. No significant differences in mean size and ratio of small HCCs were found between the two groups (P = 0.658 and 0.803, respectively). Compared with CHCC patients, PCCCL patients were more prone to form pseudo capsules (49.6% vs 75.0%, P = 0.034). Tumor rupture, typical HCC enhancement patterns and portal vein tumor thrombosis were detected in 15.0% (3/20), 72.2% (13/18) and 20.0% (4/20) of patients with PCCCL and 3.1% (4/127), 83.6% (97/116) and 17.3% (22/127) of patients with CHCC, respectively. There were no significant differences between the two groups (all P > 0.05). No patients with PCCCL and 2.4% (3/127) of patients with CHCC showed signs of lymph node metastasis (P > 0.05). CONCLUSION: The imaging characteristics of PCCCL are similar to those of CHCC and could be useful for differentiating these from other liver tumors (such

  13. Preoperative Thromboelastometry as a Predictor of Transfusion Requirements during Adult Living Donor Liver Transplantation

    PubMed Central

    Fayed, Nirmeen; Mourad, Wessam; Yassen, Khaled; Görlinger, Klaus

    2015-01-01

    Background The ability to predict transfusion requirements may improve perioperative bleeding management as an integral part of a patient blood management program. Therefore, the aim of our study was to evaluate preoperative thromboelastometry as a predictor of transfusion requirements for adult living donor liver transplant recipients. Methods The correlation between preoperative thromboelastometry variables in 100 adult living donor liver transplant recipients and intraoperative blood transfusion requirements was examined by univariate and multivariate linear regression analysis. Thresholds of thromboelastometric parameters for prediction of packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, and cryoprecipitate transfusion requirements were determined with receiver operating characteristics analysis. The attending anesthetists were blinded to the preoperative thromboelastometric analysis. However, a thromboelastometry-guided transfusion algorithm with predefined trigger values was used intraoperatively. The transfusion triggers in this algorithm did not change during the study period. Results Univariate analysis confirmed significant correlations between PRBCs, FFP, platelets or cryoprecipitate transfusion requirements and most thromboelastometric variables. Backward stepwise logistic regression indicated that EXTEM coagulation time (CT), maximum clot firmness (MCF) and INTEM CT, clot formation time (CFT) and MCF are independent predictors for PRBC transfusion. EXTEM CT, CFT and FIBTEM MCF are independent predictors for FFP transfusion. Only EXTEM and INTEM MCF were independent predictors of platelet transfusion. EXTEM CFT and MCF, INTEM CT, CFT and MCF as well as FIBTEM MCF are independent predictors for cryoprecipitate transfusion. Thromboelastometry-based regression equation accounted for 63% of PRBC, 83% of FFP, 61% of cryoprecipitate, and 44% of platelet transfusion requirements. Conclusion Preoperative thromboelastometric analysis is

  14. Lack of correlation between hepatitis B virus infection and the increasing incidence of primary liver cancer in Sweden.

    PubMed

    Kaczynski, J; Hansson, G; Norkrans, G; Wallerstedt, S

    1991-01-01

    The incidence of primary carcinoma of the liver in Sweden has been reported to increase. In order to study the role of chronic hepatitis B virus (HBV) infection for liver cancer development 40 cases with hepatocellular carcinoma (HCC) were examined for the presence of HBV surface antigen and HBV core antigen in the cancer and in the surrounding non-neoplastic liver tissue. It was not possible to demonstrate a single case with tissue HBV antigen, indicating that HBV plays a minor role in the etiology of HCC in Sweden and thus does not seem to be responsible for the increasing incidence of this cancer.

  15. Left lobe living donor liver transplantation in adults: What is the safety limit?

    PubMed

    Ikegami, Toru; Yoshizumi, Tomoharu; Sakata, Kazuhito; Uchiyama, Hideaki; Harimoto, Norifumi; Harada, Noboru; Itoh, Shinji; Nagatsu, Akihisa; Soejima, Yuji; Maehara, Yoshihiko

    2016-12-01

    Small-for-size syndrome (SFSS) is the most significant cause of graft loss after living donor liver transplantation (LDLT), especially after left lobe (LL) LDLT in adults. The safety limit of applying LL-LDLT in adults without severe SFSS with a high rate of lethality needs to be determined. A total of 207 LL-LDLTs in adults since September 2005 were evaluated to analyze the risk factors for severe SFSS, defined as a serum total bilirubin concentration of ≥20.0 mg/dL after LDLT. Although there were no significant differences in cumulative graft survival after LDLT between medium grafts (graft volume [GV] to standard liver volume [SLV] ratio ≥ 40.0%), small grafts (35.0% ≤ GV/SLV < 40.0%), and extra small grafts (GV/SLV < 35.0%), patients with severe SFSS showed a significantly lower 5-year graft survival rate than those without (42.9% versus 94.3%, respectively; P < 0.001). Multivariate analysis for severe SFSS after LL-LDLT showed that donor age of ≥48 years (P = 0.01), Model for End-Stage Liver Disease (MELD) score of ≥ 19 (P < 0.01), and end portal venous pressure of ≥19 mm Hg (P = 0.04) were the significant and independent factors for severe SFSS after LL-LDLT. Within such high-risk subgroups of patients with a donor age of ≥48 years or MELD score of ≥ 19 before LDLT, operative blood loss volume of ≥8.0 L was a risk factor for severe SFSS. LL-LDLT in adults could be indicated and provide acceptable outcomes for the combinations of donors aged < 48 years and recipients with a MELD score of <19. Smaller grafts might yield acceptable outcomes in appropriately selected donor-recipient combinations. Liver Transplantation 22 1666-1675 2016 AASLD.

  16. Risk and prognosis of adult primary immune thrombocytopenia.

    PubMed

    Frederiksen, Henrik; Christiansen, Christian Fynbo; Nørgaard, Mette

    2012-04-01

    Adult immune thrombocytopenia was previously considered a benign disease affecting young people and with a low risk of severe bleeding. This view was challenged by studies published during the past decade, as the median age of adult immune thrombocytopenia patients has been found to be 55-60 years and the incidence increases with age. Recent studies reported that mortality and morbidity are increased compared with the general population. In this review, we describe patient-specific factors associated with the outcome of disease, the clinical course of immune thrombocytopenia including the potential adverse impact of some treatments and finally the overall prognosis.

  17. Trichloroethylene exposure reduces liver injury in a mouse model of primary biliary cholangitis.

    PubMed

    Ray, Jessica L; Kopec, Anna K; Joshi, Nikita; Cline-Fedewa, Holly; Lash, Lawrence H; Williams, Kurt J; Leung, Patrick S; Gershwin, M Eric; Luyendyk, James P

    2017-01-23

    Trichloroethylene (TCE) is a persistent environmental contaminant proposed to contribute to autoimmune disease. Experimental studies in lupus-prone MRL(+/+) mice have suggested that TCE exposure can trigger autoimmune hepatitis. The vast majority of studies examining the connection between TCE and autoimmunity utilize this model, and the impact of TCE exposure in other established models of autoimmune liver disease is not known. We tested the hypothesis that TCE exposure exacerbates experimental hepatic autoimmunity in dominant negative transforming growth factor beta receptor type II (dnTGFBRII) mice, which develop serological and histological features resembling human primary biliary cholangitis. Female 8-week-old wild-type and dnTGFBRII mice were exposed to TCE (0.5 mg/ml) or vehicle (1% ethoxylated castor oil) in the drinking water for 12 or 22 weeks. Liver histopathology in 20- and 30-week-old wild-type mice was unremarkable irrespective of treatment. Mild portal inflammation was observed in vehicle-exposed 20-week-old dnTGFBRII mice and was not exacerbated by TCE exposure. Vehicle-exposed 30-week-old dnTGFBRII mice developed anti-mitochondrial antibodies, marked hepatic inflammation with necrosis, and hepatic accumulation of both B and T lymphocytes. To our surprise, TCE exposure dramatically reduced hepatic parenchymal inflammation and injury in 30-week-old dnTGFBRII mice, reflected by changes in hepatic proinflammatory gene expression, serum chemistry, and histopathology. Interestingly, TCE did not affect hepatic B cell accumulation or induction of the anti-inflammatory cytokine IL10. These data indicate that TCE exposure reduces autoimmune liver injury in female dnTGFBRII mice and suggests that the precise effect of environmental chemicals in autoimmunity depends on the experimental model.

  18. Reducing Liver Fat by Low Carbohydrate Caloric Restriction Targets Hepatic Glucose Production in Non-Diabetic Obese Adults with Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Yu, Haoyong; Jia, Weiping; Guo, ZengKui

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) impairs liver functions, the organ responsible for the regulation of endogenous glucose production and thus plays a key role in glycemic homeostasis. Therefore, interventions designed to normalize liver fat content are needed to improve glucose metabolism in patients affected by NAFLD such as obesity. Objective: this investigation is designed to determine the effects of caloric restriction on hepatic and peripheral glucose metabolism in obese humans with NAFLD. Methods: eight non-diabetic obese adults were restricted for daily energy intake (800 kcal) and low carbohydrate (<10%) for 8 weeks. Body compositions, liver fat and hepatic glucose production (HGP) and peripheral glucose disposal before and after the intervention were determined. Results: the caloric restriction reduced liver fat content by 2/3 (p = 0.004). Abdominal subcutaneous and visceral fat, body weight, BMI, waist circumference and fasting plasma triglyceride and free fatty acid concentrations all significantly decreased (p < 0.05). The suppression of post-load HGP was improved by 22% (p = 0.002) whereas glucose disposal was not affected (p = 0.3). Fasting glucose remained unchanged and the changes in the 2-hour plasma glucose and insulin concentration were modest and statistically insignificant (p > 0.05). Liver fat is the only independent variable highly correlated to HGP after the removal of confounders. Conclusion: NAFLD impairs HGP but not peripheral glucose disposal; low carbohydrate caloric restriction effectively lowers liver fat which appears to directly correct the HGP impairment. PMID:25411646

  19. The changing role of surgery in the treatment of primary liver cancer.

    PubMed

    Tang, Z Y; Yu, Y Q; Zhou, X D

    1986-01-01

    For decades, the role of surgery in the treatment of primary liver cancer (PLC) was important but limited. However, a comparison of pathologically proven PLC during the three periods 1958-1966, 1967-1975, and 1976-1984 revealed that as a result of alpha fetoprotein (AFP) serosurvey, changing concepts in surgical oncology, and introduction of new surgical modalities, the role of surgery has become greater. The increasing proportion of subclinical PLC (0, 7.2, and 21.2%) has favored the increasing series resection rate (16.1, 34.7, and 39.6%) and palliative surgery (13.7, 17.0, and 29.8%). The results indicated that early resection, reoperation for subclinical recurrence, resection of huge PLC in stages, and combination of palliative surgery other than resection might be responsible for the increasing 5-year survival rate (1.7, 7.1, and 19.5%) in the entire series.

  20. [The prospective research of risk factors of primary liver cancer in Nanhui County, Shanghai].

    PubMed

    Yu, S Z; Chen, W; Li, J

    1995-02-01

    Based on a prospective study including a population size of eighty thousand in Nanhui County, the risk factors of primary liver cancer in Nanhui County were found as follows: history of hepatitis (OR 1.03, 95%CL 1.02-1.04), the length of drinking pond & ditch water (OR 1.16, 95% CL 1.02-1.32) and the length of drinking river water (OR 1.25, 95% CL 1.09-1.43). The length of drinking shallow well water (OR 0.65, 95% CL 0.59-0.73) and deep well water (including tap water, OR 0.20, 95% CL 0.16-0.25) seemed to be the protective factors of PLC. These data are useful for PLC prevention and to identify the high-risk individuals in Nanhui County.

  1. Hepatitis B virus and primary liver cancer on Chongming Island, People's Republic of China.

    PubMed

    Tu, J T; Gao, R N; Zhang, D H; Gu, B C

    1985-12-01

    Data on potential risk factors for primary liver cancer (PLC), including hepatitis B virus (HBV) infection, contaminated drinking water, maize consumption, and use of tobacco and alcohol were collected from 12,222 males over 40 years of age living on Chongming Island, a high-risk area for PLC. During the first 3 years of follow-up (1980-82), 70 deaths from this disease occurred among study subjects. Preliminary results indicate that HBV carriers were 6.7 times more likely to die of PLC than were noncarriers (P less than .05). No association was found between PLC and alcohol consumption. More data are needed for evaluation of the relationships between cigarette smoking, maize consumption, contaminated drinking water, and PLC on Chongming Island.

  2. [A population-based case control study of primary liver cancer in Fusui].

    PubMed

    Zhang, M D

    1993-02-01

    A population-based case control study of primary liver cancer (PLC) was undertaken in Fusui County, Guangxi Autonomous Region. Ninety-nine PLC cases and 99 age-sex-matched controls were surveyed for their general conditions, life style features, dietary habits, types of drinking water and family history. Cases and controls were well distributed in nationality, education, marital status and annual income per person. Conditional logistic regression results showed that HBV infection, drinking pond-ditch water, family history and total alcohol intake were the risk factors of PLC with the relative risks 5.330 (2.502-11.35), 3.703 (1.251-10.96), 2.881 (1.289-6.441), 1.002 (1.000-1.004), respectively. And antibody of HBV surface antigen is protective factor with the relative risk of 0.418 (0.210-0.834).

  3. Primarily screening and analyzing ESTs differentially expressed in rats’ primary liver cancer

    PubMed Central

    Liu, Dandan; Zhi, Lijuan; Ma, Mingxia; Qiao, Dan; Wang, Meijuan; Wang, Yawei; Jin, Baijie; Li, Anqi; Liu, Guting; Zhang, Yiqing; Song, Yanyan

    2013-01-01

    Objective To screen and analyze key express sequence tags (ESTs) which were differentially displayed in every period of SD rats’ primary hepatic carcinoma and reveal the molecular mechanism of carcinogenesis. Methods Using diethylnitrosamine (DENA) as a cancerigenic agent, animal models with different phases of primary hepatic cancer were constructed in SD rats. Rats were respectively sacrificed at d 14, d 28, d 56, d 77, d 105 and d 112 after the rats received DENA by gavage, then the livers were harvested. One part of the livers was classified according to their pathological changes, while the other was reserved for molecular mechanism studies on hepatocarcinogenesis. The differentially expressed genes were isolated from both normal and morbid tissues by mRNA differential display technique (DDRT-PCR). After the fragments were sequenced, bioinformatics were used to analyze the results. Results Twelve differentially expressed cDNA fragments were obtained. Nine fragments had the homology with known cDNA clones, especially EST-7 was similar to BN/SsNHsdMCW mitochondrion gene and the identity was 100% which suggested EST-7 may be the part of BN/SsNHsdMCW mitochondrion gene. In contrast, other three fragments (EST-1, EST-3 and EST-5) had extremely low identity to any genes registered in GENBANK databases. Conclusions BN/SsNHsdMCW mitochondrion gene was expressed in different periods of hepatocarcinogenesis. Moreover, EST-1, EST-3 and EST-5 were suggested to contribute to the development of rat hepatocarcinogenesis, and thus may be candidates of new targets of oncogenes or cancer suppressor genes. PMID:23372344

  4. Primary Care for Adults with Down Syndrome: Adherence to Preventive Healthcare Recommendations

    ERIC Educational Resources Information Center

    Jensen, K. M.; Taylor, L. C.; Davis, M. M.

    2013-01-01

    Background: Due to significant medical improvements, persons with Down syndrome now live well into adulthood. Consequently, primary care for adults with Down syndrome needs to incorporate routine care with screening for condition-specific comorbidities. This study seeks to evaluate the adherence of primary care physicians to age- and…

  5. Guideline for primary care management of headache in adults

    PubMed Central

    Becker, Werner J.; Findlay, Ted; Moga, Carmen; Scott, N. Ann; Harstall, Christa; Taenzer, Paul

    2015-01-01

    Abstract Objective To increase the use of evidence-informed approaches to diagnosis, investigation, and treatment of headache for patients in primary care. Quality of evidence A comprehensive search was conducted for relevant guidelines and systematic reviews published between January 2000 and May 2011. The guidelines were critically appraised using the AGREE (Appraisal of Guidelines for Research and Evaluation) tool, and the 6 highest-quality guidelines were used as seed guidelines for the guideline adaptation process. Main message A multidisciplinary guideline development group of primary care providers and other specialists crafted 91 specific recommendations using a consensus process. The recommendations cover diagnosis, investigation, and management of migraine, tension-type, medication-overuse, and cluster headache. Conclusion A clinical practice guideline for the Canadian health care context was created using a guideline adaptation process to assist multidisciplinary primary care practitioners in providing evidence-informed care for patients with headache. PMID:26273080

  6. Vascular complications after adult living donor liver transplantation: Evaluation with ultrasonography

    PubMed Central

    Ma, Lin; Lu, Qiang; Luo, Yan

    2016-01-01

    Living donor liver transplantation (LDLT) has been widely used to treat end-stage liver disease with improvement in surgical technology and the application of new immunosuppressants. Vascular complications after liver transplantation remain a major threat to the survival of recipients. LDLT recipients are more likely to develop vascular complications because of their complex vascular reconstruction and the slender vessels. Early diagnosis and treatment are critical for the survival of graft and recipients. As a non-invasive, cost-effective and non-radioactive method with bedside availability, conventional gray-scale and Doppler ultrasonography play important roles in identifying vascular complications in the early postoperative period and during the follow-up. Recently, with the detailed vascular tracing and perfusion visualization, contrast-enhanced ultrasound (CEUS) has significantly improved the diagnosis of postoperative vascular complications. This review focuses on the role of conventional gray-scale ultrasound, Doppler ultrasound and CEUS for early diagnosis of vascular complications after adult LDLT. PMID:26819527

  7. Toxicity Effect of Silver Nanoparticles on Mice Liver Primary Cell Culture and HepG2 Cell Line.

    PubMed

    Faedmaleki, Firouz; H Shirazi, Farshad; Salarian, Amir-Ahmad; Ahmadi Ashtiani, Hamidreza; Rastegar, Hossein

    2014-01-01

    Nano-silver (AgNP) has biological properties which are significant for consumer products, food technology, textiles and medical applications (e.g. wound care products, implantable medical devices, in diagnosis, drug delivery, and imaging). For their antibacterial activity, silver nanoparticles are largely used in various commercially available products. Thus, the use of nano-silver is becoming more and more widespread in medicine. In this study we investigated the cytotoxic effects of AgNPs on liver primary cells of mice, as well as the human liver HepG2 cell. Cell viability was examined with MTT assay after HepG2 cells exposure to AgNPs at 1, 2, 3, 4, 5, 7.5, 10 ppm compared to mice primary liver cells at 1, 10, 50, 100, 150, 200, 400 ppm for 24h. AgNPs caused a concentration-dependent decrease of cell viability in both cells. IC50 value of 2.764 ppm (µg/mL) was calculated in HepG2 cell line and IC50 value of 121.7 ppm (µg/mL) was calculated in primary liver cells of mice. The results of this experiment indicated that silver nanoparticles had cytotoxic effects on HepG2 cell line and primary liver cells of mice. The results illustrated that nano-silver had 44 times stronger inhibitory effect on the growth of cancerous cells (HepG2 cell line) compared to the normal cells (primary liver cells of mice). which might further justify AgNPs as a cytotoxic agents and a potential anticancer candidate which needs further studies in this regard.

  8. Adult Living Donor Liver Transplantation with ABO-Incompatible Grafts: A German Single Center Experience

    PubMed Central

    Goralczyk, Armin D.; Obed, Aiman; Schnitzbauer, Andreas; Doenecke, Axel; Tsui, Tung Yu; Scherer, Marcus N.; Ramadori, Giuliano; Lorf, Thomas

    2009-01-01

    Adult living donor liver transplantations (ALDLTs) across the ABO blood group barrier have been reported in Asia, North Americas, and Europe, but not yet in Germany. Several strategies have been established to overcome the detrimental effects that are attached with such a disparity between donor and host, but no gold standard has yet emerged. Here, we present the first experiences with three ABO-incompatible adult living donor liver transplantations in Germany applying different immunosuppressive strategies. Four patient-donor couples were considered for ABO-incompatible ALDLT. In these patients, resident ABO blood group antibodies (isoagglutinins) were depleted by plasmapheresis or immunoadsorption and replenishment was inhibited by splenectomy and/or B-cell-targeted immunosuppression. Despite different treatments ALDLT could safely be performed in three patients and all patients had good initial graft function without signs for antibody-mediated rejection (AMR). Two patients had long-term graft survival with stable graft function. We thus propose the feasibility of ABO-incompatible ALDLT with these protocols and advocate further expansion of ABO incompatible ALDLT in multicenter trials to improve efficacy and safety. PMID:20148072

  9. ABO-Incompatible Adult Living Donor Liver Transplantation Under the Desensitization Protocol With Rituximab.

    PubMed

    Song, G-W; Lee, S-G; Hwang, S; Kim, K-H; Ahn, C-S; Moon, D-B; Ha, T-Y; Jung, D-H; Park, G-C; Kim, W-J; Sin, M-H; Yoon, Y-I; Kang, W-H; Kim, S-H; Tak, E-Y

    2016-01-01

    ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the largest single-center experience of ABO-incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in-hospital mortality. The cumulative 3-year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO-compatible group (n = 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody-mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized.

  10. Primary Afferent Synapses on Developing and Adult Renshaw Cells

    PubMed Central

    Mentis, George Z.; Siembab, Valerie C.; Zerda, Ricardo; O’Donovan, Michael J.; Alvarez, Francisco J.

    2010-01-01

    The mechanisms that diversify adult interneurons from a few pools of embryonic neurons are unknown. Renshaw cells, Ia inhibitory interneurons (IaINs), and possibly other types of mammalian spinal interneurons have common embryonic origins within the V1 group. However, in contrast to IaINs and other V1-derived interneurons, adult Renshaw cells receive motor axon synapses and lack proprioceptive inputs. Here, we investigated how this specific pattern of connectivity emerges during the development of Renshaw cells. Tract tracing and immunocytochemical markers [parvalbumin and vesicular glutamate transporter 1 (VGLUT1)] showed that most embryonic (embryonic day 18) Renshaw cells lack dorsal root inputs, but more than half received dorsal root synapses by postnatal day 0 (P0) and this input spread to all Renshaw cells by P10–P15. Electrophysiological recordings in neonates indicated that this input is functional and evokes Renshaw cell firing. VGLUT1-IR bouton density on Renshaw cells increased until P15 but thereafter decreased because of limited synapse proliferation coupled with the enlargement of Renshaw cell dendrites. In parallel, Renshaw cell postsynaptic densities apposed to VGLUT1-IR synapses became smaller in adult compared with P15. In contrast, vesicular acetylcholine transporter-IR motor axon synapses contact embryonic Renshaw cells and proliferate postnatally matching Renshaw cell growth. Like other V1 neurons, Renshaw cells are thus competent to receive sensory synapses. However, after P15, these sensory inputs appear deselected through arrested proliferation and synapse weakening. Thus, Renshaw cells shift from integrating sensory and motor inputs in neonates to predominantly motor inputs in adult. Similar synaptic weight shifts on interneurons may be involved in the maturation of motor reflexes and locomotor circuitry. PMID:17182780

  11. Primary afferent synapses on developing and adult Renshaw cells.

    PubMed

    Mentis, George Z; Siembab, Valerie C; Zerda, Ricardo; O'Donovan, Michael J; Alvarez, Francisco J

    2006-12-20

    The mechanisms that diversify adult interneurons from a few pools of embryonic neurons are unknown. Renshaw cells, Ia inhibitory interneurons (IaINs), and possibly other types of mammalian spinal interneurons have common embryonic origins within the V1 group. However, in contrast to IaINs and other V1-derived interneurons, adult Renshaw cells receive motor axon synapses and lack proprioceptive inputs. Here, we investigated how this specific pattern of connectivity emerges during the development of Renshaw cells. Tract tracing and immunocytochemical markers [parvalbumin and vesicular glutamate transporter 1 (VGLUT1)] showed that most embryonic (embryonic day 18) Renshaw cells lack dorsal root inputs, but more than half received dorsal root synapses by postnatal day 0 (P0) and this input spread to all Renshaw cells by P10-P15. Electrophysiological recordings in neonates indicated that this input is functional and evokes Renshaw cell firing. VGLUT1-IR bouton density on Renshaw cells increased until P15 but thereafter decreased because of limited synapse proliferation coupled with the enlargement of Renshaw cell dendrites. In parallel, Renshaw cell postsynaptic densities apposed to VGLUT1-IR synapses became smaller in adult compared with P15. In contrast, vesicular acetylcholine transporter-IR motor axon synapses contact embryonic Renshaw cells and proliferate postnatally matching Renshaw cell growth. Like other V1 neurons, Renshaw cells are thus competent to receive sensory synapses. However, after P15, these sensory inputs appear deselected through arrested proliferation and synapse weakening. Thus, Renshaw cells shift from integrating sensory and motor inputs in neonates to predominantly motor inputs in adult. Similar synaptic weight shifts on interneurons may be involved in the maturation of motor reflexes and locomotor circuitry.

  12. Omega-3-enriched lipid emulsion for liver salvage in parenteral nutrition-induced cholestasis in the adult patient.

    PubMed

    Jurewitsch, Brian; Gardiner, Geoffrey; Naccarato, Mark; Jeejeebhoy, Khursheed N

    2011-05-01

    The intrahepatic cholestasis attributed to parenteral nutrition (PN) in the adult patient is relatively rare and usually occurs in patients receiving long-term PN. This article reports the first case of an adult patient with cholestatic PN-associated liver disease without sepsis who received almost all her nutrition requirements through PN. Administration of an ω-3-enriched lipid emulsion added to the PN regimen reversed cholestasis and demonstrated histologic improvement on serial liver biopsy. The patient had failed to respond to other modalities of treatment for this condition and was deeply jaundiced. Liver biochemistry profiles returned to baseline, and follow-up liver biopsy showed that cholestasis had resolved and that the only residual changes were mild portal inflammation with no histochemical or ultrastructural progression. The PN regimen for the patient was restored to provide total estimated energy requirements and remains the principle source of the patient's nutrition to date.

  13. Improving nutritional support for adults in primary and secondary care.

    PubMed

    Cartwright, Andrea

    There has been serious concern about the nutritional care provided in some secondary and primary care settings. As a result, best practice, benchmarking initiatives and nutritional guidance have been issued by government and non-government agencies. This article helps nurses to synthesise these initiatives and improve their knowledge of nutritional care.

  14. Comparison between psychosocial long-term outcomes of recipients and donors after adult-to-adult living donor liver transplantation.

    PubMed

    Noma, Shun'ichi; Hayashi, Akiko; Uehara, Minako; Uemoto, Shinji; Murai, Toshiya

    2011-01-01

    The purpose of this study was to examine psychosocial states of recipients and donors several years after living donor liver transplantation (LDLT) and to find out the pre-transplant predictors of desirable post-transplant psychosocial states. The recipients and donors of adult-to-adult LDLT at Kyoto University Hospital, Japan, from November 2001 through July 2003 were interviewed and examined by means of questionnaires about anxiety, depression, and quality of life (QOL), and the participants were evaluated by the same test batteries sent by mail three to five yr after LDLT. Twenty-seven pairs of recipients and donors, 13 recipients, and three donors participated in this study. The recipients and the donors had a decline in social QOL. The main predictor of psychosocial states of the recipients was the length of wait for LDLT, and the predictors of the donors were family or support system availability and recipients' depressive states at LDLT. The donors who were spouses of the recipients had better QOL than other donors. It might be better to perform LDLT as soon as possible once LDLT has been judged to be necessary, and the relative who is on close terms with the recipient should be selected as donor.

  15. Protocol for Isolation of Primary Human Hepatocytes and Corresponding Major Populations of Non-parenchymal Liver Cells.

    PubMed

    Kegel, Victoria; Deharde, Daniela; Pfeiffer, Elisa; Zeilinger, Katrin; Seehofer, Daniel; Damm, Georg

    2016-03-30

    Beside parenchymal hepatocytes, the liver consists of non-parenchymal cells (NPC) namely Kupffer cells (KC), liver endothelial cells (LEC) and hepatic Stellate cells (HSC). Two-dimensional (2D) culture of primary human hepatocyte (PHH) is still considered as the "gold standard" for in vitro testing of drug metabolism and hepatotoxicity. It is well-known that the 2D monoculture of PHH suffers from dedifferentiation and loss of function. Recently it was shown that hepatic NPC play a central role in liver (patho-) physiology and the maintenance of PHH functions. Current research focuses on the reconstruction of in vivo tissue architecture by 3D- and co-culture models to overcome the limitations of 2D monocultures. Previously we published a method to isolate human liver cells and investigated the suitability of these cells for their use in cell cultures in Experimental Biology and Medicine(1). Based on the broad interest in this technique the aim of this article was to provide a more detailed protocol for the liver cell isolation process including a video, which will allow an easy reproduction of this technique. Human liver cells were isolated from human liver tissue samples of surgical interventions by a two-step EGTA/collagenase P perfusion technique. PHH were separated from the NPC by an initial centrifugation at 50 x g. Density gradient centrifugation steps were used for removal of dead cells. Individual liver cell populations were isolated from the enriched NPC fraction using specific cell properties and cell sorting procedures. Beside the PHH isolation we were able to separate KC, LEC and HSC for further cultivation. Taken together, the presented protocol allows the isolation of PHH and NPC in high quality and quantity from one donor tissue sample. The access to purified liver cell populations could allow the creation of in vivo like human liver models.

  16. What is the best strategy for investigating abnormal liver function tests in primary care? Implications from a prospective study

    PubMed Central

    Lilford, Richard J; Bentham, Louise M; Armstrong, Matthew J; Neuberger, James; Girling, Alan J

    2013-01-01

    Objective Evaluation of predictive value of liver function tests (LFTs) for the detection of liver-related disease in primary care. Design A prospective observational study. Setting 11 UK primary care practices. Participants Patients (n=1290) with an abnormal eight-panel LFT (but no previously diagnosed liver disease). Main outcome measures Patients were investigated by recording clinical features, and repeating LFTs, specific tests for individual liver diseases, and abdominal ultrasound scan. Patients were characterised as having: hepatocellular disease; biliary disease; tumours of the hepato-biliary system and none of the above. The relationship between LFT results and disease categories was evaluated by stepwise regression and logistic discrimination, with adjustment for demographic and clinical factors. True and False Positives generated by all possible LFT combinations were compared with a view towards optimising the choice of analytes in the routine LFT panel. Results Regression methods showed that alanine aminotransferase (ALT) was associated with hepatocellular disease (32 patients), while alkaline phosphatase (ALP) was associated with biliary disease (12 patients) and tumours of the hepatobiliary system (9 patients). A restricted panel of ALT and ALP was an efficient choice of analytes, comparing favourably with the complete panel of eight analytes, provided that 48 False Positives can be tolerated to obtain one additional True Positive. Repeating a complete panel in response to an abnormal reading is not the optimal strategy. Conclusions The LFT panel can be restricted to ALT and ALP when the purpose of testing is to exclude liver disease in primary care. PMID:23794594

  17. De novo autoimmune hepatitis following liver transplantation for primary biliary cirrhosis: an unusual cause of late grafts dysfunction.

    PubMed

    Ennaifer, Rym; Ayadi, Hend; Romdhane, Haifa; Cheikh, Meriem; Mestiri, Hafedh; Khalfallah, Taher; Hadj, Najet Bel

    2015-01-01

    De novo autoimmune hepatitis (AIH) is a rare disorder first described in 1998. It occurs in patients who underwent liver transplantation for a different etiology. We present the case of a 56-year-old woman who was diagnosed with primary biliary cirrhosis and had liver transplantation for refractory pruritis. Seven years after transplantation, she presented alterations in the hepatic profile with hypertransaminasemia, elevated alkaline phosphatase and gamma-glutamyl-transferase. Her liver functions test also showed elevated IgG levels. Serum autoantibodies were negative except for antimitochondrial antibodies. Histological findings indicated features of AIH without bile duct damage or loss. She had a pretreatment AIH score of 13 points and a post treatment score of 15 points according to the International AIH Group. The patient was treated effectively with prednisolone and her liver function and globulin levels rapidly returned to normal.

  18. Primary lymphoma of the liver in a patient with acquired immune deficiency syndrome and chronic hepatitis B.

    PubMed

    Lisker-Melman, M; Pittaluga, S; Pluda, J M; Kleiner, D E; Thompson, P; Martin, P; Yarchoan, R; Di Bisceglie, A M

    1989-11-01

    We describe the case of a homosexual man with asymptomatic infection with human immunodeficiency virus and hepatitis B virus who developed primary hepatic lymphoma. The lymphoma presented with rapid enlargement of the liver, and ultrasound examination revealed multiple hypoechoic lesions within the liver. Histological examination of the liver showed massive replacement by lymphomatous tissue, as well as changes of chronic active hepatitis B. Immunohistochemical stains for hepatitis B surface and core antigens were strongly positive in almost all hepatocytes, but not in tumor tissue. Whereas the occurrence of lymphoma probably is related to HIV infection, possible interactions between hepatitis B virus and HIV infection are discussed. Thus, the presence of mass lesions within the liver in a patient with HIV infection should raise the possibility of hepatic lymphoma even if there is no evidence of generalized lymphadenopathy.

  19. EROD induction in microsomes and primary hepatocyte cultures prepared from individual double-crested cormorant embryo livers

    SciTech Connect

    Davis, J.A.; Fry, D.M.; Wilson, B.W.

    1994-12-31

    Double-crested cormorants (Phalacrocorax auritus) are being studied as a high trophic level indicator species for toxic contamination in San Francisco Bay and other locations on the California coast. In 1993, median ethoxyresorufin-o-deethylase (EROD) activities in embryo liver microsomes sampled from San Francisco Bay colonies were 4.2-fold and 2.3-fold higher than two coastal locations. In 1994 cormorant embryo livers from these same locations were again analyzed for liver microsomal EROD activity. In addition, basal and maximal EROD activity were measured in primary hepatocyte cultures from portions of the same livers used for microsomal EROD analysis to determine whether factors other than contaminant burdens in the egg contribute to the observed differences in activity. Differences in basal activity and induction capacity among the populations are discussed in the context of the hypothesis that polluted habitats select for increased metabolic capacity in affected populations.

  20. Risk Factors for Intractable Ascites After Adult-to-Adult Living Donor Liver Transplantation Using Left Lobe

    PubMed Central

    Matsudaira, Shinichi; Ishizaki, Yoichi; Yoshimoto, Jiro; Fujiwara, Noriko; Kawasaki, Seiji

    2017-01-01

    Background Intractable ascites is one of the causes of graft loss after adult-to-adult living donor liver transplantation (LDLT) using a small graft. Identification of factors associated with increasing posttransplant ascites has important implications for prevention and treatment. Methods All 59 consecutive adult patients who underwent left lobe LDLT without portal inflow modulation between October 2002 and February 2016 were prospectively enrolled. Factors associated with the average daily amount of ascites for 2 weeks after LDLT were assessed. Results The median daily amount of ascites during the 2 weeks was 1052 mL (range, 52-3480 mL). Although 16 of the 59 patients developed intractable ascites, exceeding 1500 mL daily (massive ascites group), the remaining 43 patients produced less than 1500 mL of ascites daily (nonmassive ascites group). The presence of pretransplant ascites (P = 0.001), albumin (P = 0.011), albumin/globulin ratio (P = 0.026), cold ischemia time (P = 0.004), operation time (P = 0.022), and pretransplant portal vein pressure (PVP) (P = 0.047) differed significantly between the 2 groups. Neither posttransplant PVP nor portal vein flow differed between the 2 groups. The variables associated with intractable ascites that remained significant after logistic regression analysis were pretransplant PVP (P = 0.047) and cold ischemia time (P = 0.049). After appropriate fluid resuscitation for intractable ascites, 58 (98%) of the 59 recipients were discharged from hospital after removal of the indwelling drains. Conclusions It is important to shorten the scold ischemia time to reduce massive ascites after LDLT. Pretransplant portal hypertension is more closely associated with ascites production than posttransplant hemodynamic status. PMID:28361122

  1. Primary primitive neuroectodermal tumour of the kidney in adults.

    PubMed

    Verma, Ritu; Singhal, Mitali; Pandey, Rakesh

    2013-03-04

    Primitive neuroectodermal tumour (PNET) is a neural crest tumour derived from neuroectoderm. Renal PNET is a very rare tumour occurring during childhood or adolescence. We report two cases of PNET involving kidney in adults. Presenting signs and symptoms include abdominal/flank pain and/or haematuria. Microscopy reveals the tumour consisted of small round cells with round nuclei and scant cytoplasm. Diagnosis was confirmed by immunohistochemistry with diffuse membranous positivity of tumour cells with CD99. As these tumours have an aggressive clinical course with rapid death in many reported cases, it is important to differentiate them from other small round-cell tumours.

  2. Genomic gain of the PRL-3 gene may represent poor prognosis of primary colorectal cancer, and associate with liver metastasis.

    PubMed

    Nakayama, N; Yamashita, K; Tanaka, T; Kawamata, H; Ooki, A; Sato, T; Nakamura, T; Watanabe, M

    2016-01-01

    PRL-3 genomic copy number is increased in colorectal cancer (CRC), and PRL-3 expression is closely associated with lymph node and liver metastasis of CRC. However, the clinical significance of PRL-3 genomic gain for CRC remains obscure. Here, PRL-3 genomic status in 109 primary CRC tumors and in 44 CRC tumors that had metastasized to the liver, was quantified using real time PCR. Association of PRL-3 genomic status with clinicopathological factors and prognosis was assessed in detail. PRL-3 genomic gain was identified in 31 primary CRC (27.4 %) and was more frequently seen in stage III than in stage II (p = 0.025). Among the clinicopathological factors assessed, PRL-3 genomic gain was significantly associated with poorly differentiated histology (p = 0.0039). Moreover, CRC patients with PRL-3 genomic gain exhibited poorer prognosis than those with no gain in stage II-IV CRC (p = 0.017). PRL-3 genomic gain was identified in 18 (41 %) of the liver metastasis tumors, and this frequency of gain was significantly increased as compared to that of the corresponding primary CRCs (11 %) (p = 0.001). Our findings suggested that PRL-3 genomic gain may represent an aggressive phenotype of primary CRC, and may associate with liver metastasis.

  3. Trends in the incidence of primary liver cancer in Central Uganda, 1960–1980 and 1991–2005

    PubMed Central

    Ocama, P; Nambooze, S; Opio, C K; Shiels, M S; Wabinga, H R; Kirk, G D

    2009-01-01

    Primary liver cancer (PLC) incidence trends from Africa are unknown. Using Kampala Cancer Registry data from 1960 to 1980 and 1991 to 2005, we identified 771 PLCs. Although rates were stable among men, PLC incidence among women increased >50%. Investigations of viral hepatitis, aflatoxin, obesity, and human immunodeficiency virus (HIV) may help to explain the increasing incidence of hepatocellular carcinomas (HCCs). PMID:19174820

  4. HLA-G and classical HLA class I expression in primary colorectal cancer and associated liver metastases.

    PubMed

    Swets, Marloes; König, Marion H; Zaalberg, Anniek; Dekker-Ensink, Neeltje G; Gelderblom, Hans; van de Velde, Cornelis J H; van den Elsen, Peter J; Kuppen, Peter J K

    2016-09-01

    De novo expression of HLA-G has been demonstrated in colorectal cancer. HLA-G, amongst others, inhibits natural killer cell function, contributing to host immune defense evasion. Another mechanism to escape anti-tumor immunity is loss of HLA class I. Therefore, we determined HLA-G and HLA class I expression on primary colorectal tumors and associated liver metastases, in order to get insight in the metastasizing process regarding escaping anti-tumor immunity. HLA-G expression was evaluated using three mAbs; 4H84, MEM-G/1 and MEM-G/2. In total 81 colorectal cancer patients were evaluated. Formalin-fixed paraffin-embedded tissue sections of primary tumors and associated liver metastases, were immunohistochemically stained. A concordance between expression or loss/downregulation in the primary tumor and associated liver metastasis regarding HLA class I expression was observed in 80% of the cases. In contrast with the hypothesis of escaping NK cell-killing, we demonstrated for each HLA-G detecting mAbs used in this study, that the majority of the primary tumors that positively stained for HLA-G did not express HLA-G in the associated liver metastasis. Furthermore, we revealed the existence of non-specific binding and in addition we found that the different epitopes of HLA-G detected by 4H84, MEM-G/1 and MEM-G/2 mAbs were expressed differentially in colorectal tumor tissues.

  5. Nonalcoholic fatty liver disease and carotid artery atherosclerosis in children and adults: a meta-analysis.

    PubMed

    Madan, Shivank A; John, Febin; Pyrsopoulos, Nikolaos; Pitchumoni, Capecomorin S

    2015-11-01

    Observational studies suggest that nonalcoholic fatty liver disease (NAFLD) is associated with increased carotid intimal medial thickness (C-IMT) and carotid plaques in both children and adults. We carried out a meta-analysis to evaluate the relationship between NAFLD and carotid atherosclerosis measured as C-IMT and carotid plaque prevalence. Medline (Ovid), PubMed, Web of Science, and CINAHL databases were searched from 1946 to September 2014, complemented with a manual review of references of the published articles for studies that compared C-IMT or carotid plaque prevalence in adults and children. Results were pooled using both fixed and random effects models. Of the studies identified, 20 were suitable for testing the effect of NAFLD on C-IMT in adults, 13 for testing the effect of NAFLD on carotid plaque prevalence in adults, and five for testing the effect of NAFLD on C-IMT in the pediatric population. The pooled data from 20 studies (19,274 adult participants: NAFLD=8652, controls=10,622) showed significantly increased C-IMT in patients with NAFLD, compared with controls without NAFLD, according to both fixed [standardized mean difference (SMD)=0.251, 95% confidence interval (CI): 0.220-0.282, P<0.001] and random effects models (SMD=0.944, 95% CI: 0.728-1.160, P<0.001). NAFLD was also found to be associated with a higher carotid artery plaque prevalence when compared with controls, according to both fixed (OR=1.273, 95% CI=1.162-1.394, P<0.001) and random effects models (OR=1.769, 95% CI: 1.213-2.581, P=0.003), on pooling of 13 studies (14,445 adult participants: NAFLD=5399 and controls=9046). Analysis of pooled data from five studies in the pediatric population (1121 pediatric participants: NAFLD=312 and controls=809) also found NAFLD to be associated with significantly increased C-IMT according to fixed (SMD=0.995, 95% CI: 0.840-1.150, P<0.001) and random effects models (1.083, 95% CI: 0.457-1.709, P=0.001). NAFLD is associated with increased C-IMT in

  6. Serum cell death biomarkers for prediction of liver fibrosis and poor prognosis in primary biliary cirrhosis.

    PubMed

    Sekiguchi, Tomohiro; Umemura, Takeji; Fujimori, Naoyuki; Shibata, Soichiro; Ichikawa, Yuki; Kimura, Takefumi; Joshita, Satoru; Komatsu, Michiharu; Matsumoto, Akihiro; Tanaka, Eiji; Ota, Masao

    2015-01-01

    The development of simple, noninvasive markers of liver fibrosis is urgently needed for primary biliary cirrhosis (PBC). This study examined the ability of several serum biomarkers of cell death to estimate fibrosis and prognosis in PBC. A cohort of 130 patients with biopsy-proven PBC and 90 healthy subjects were enrolled. We assessed the utility of the M30 ELISA, which detects caspase-cleaved cytokeratin-18 (CK-18) fragments and is representative of apoptotic cell death, as well as the M65 and newly developed M65 Epideath (M65ED) ELISAs, which detect total CK-18 as indicators of overall cell death, in predicting clinically relevant fibrosis stage. All 3 cell death biomarkers were significantly higher in patients with PBC than in healthy controls and were significantly correlated with fibrosis stage. The areas under the receiver operating characteristic curve for the M65 and M65ED assays for differentiation among significant fibrosis, severe fibrosis, and cirrhosis were 0.66 and 0.76, 0.66 and 0.73, and 0.74 and 0.82, respectively. In multivariate analysis, high M65ED (hazard ratio 6.13; 95% confidence interval 1.18-31.69; P = 0.031) and severe fibrosis (hazard ratio 7.45; 95% confidence interval 1.82-30.51; P = 0.005) were independently associated with liver-related death, transplantation, or decompensation. High serum M65ED was also significantly associated with poor outcome in PBC (log-rank test; P = 0.001). Noninvasive cell death biomarkers appear to be clinically useful in predicting fibrosis in PBC. Moreover, the M65ED assay may represent a new surrogate marker of adverse disease outcome.

  7. Capacity for intracellular pH compensation during hypercapnia in white sturgeon primary liver cells.

    PubMed

    Huynh, Khuong Tuyen; Baker, Daniel W; Harris, Robert; Church, John; Brauner, Colin J

    2011-10-01

    Fish, exposed to elevated water CO(2), experience a rapid elevation in blood CO(2) (hypercapnia), resulting in acidification of both intra- and extra-cellular compartments. White sturgeon, Acipenser transmontanus, are exceptionally CO(2) tolerant and can regulate tissue intracellular pH (pH(i)) in the presence of a pronounced hypercapnic acidosis (preferential pH(i) regulation). In this study, pH(i) regulatory capacity of sturgeon liver cells in primary culture was examined to assess the suitability of employing this in vitro system to understand in vivo CO(2) tolerance in sturgeon. Using the pH-sensitive fluoroprobe BCECF, real-time changes in resting pH(i) and rates of pH(i) recovery were investigated during exposure to hypercapnia (3 and 6% CO(2)) in the absence and presence of additional acid loads induced by (20 mM) ammonium prepulse. During short-term (10 min) exposure to hypercapnia (3 and 6% CO(2)), sturgeon cells were acidified and no pH(i) compensation was observed. However, when exposure to 6% CO(2) was extended to over 19 h, the CO(2)-induced intracellular acidosis was partially compensated by a pH(i) increase of over 0.2 pH unit despite the sustained extracellular acidosis, indicative of a capacity for preferential pH(i) regulation in vitro. Since this capacity in sturgeon liver is present both in vivo and in vitro, the transmembrane transporters involved may be the same. Therefore, cell culture may be a suitable tool to identify the transporters (i.e., the cellular mechanisms underlying in vivo CO(2) tolerance) in white sturgeon and possibly in other hypercapnia-tolerant species.

  8. Adult-Derived Human Liver Stem/Progenitor Cells Infused 3 Days Postsurgery Improve Liver Regeneration in a Mouse Model of Extended Hepatectomy.

    PubMed

    Herrero, Astrid; Prigent, Julie; Lombard, Catherine; Rosseels, Valérie; Daujat-Chavanieu, Martine; Breckpot, Karine; Najimi, Mustapha; Deblandre, Gisèle; Sokal, Etienne M

    2017-02-16

    There is growing evidence that cell therapy constitutes a promising strategy for liver regenerative medicine. In the setting of hepatic cancer treatments, cell therapy could prove a useful therapeutic approach for managing the acute liver failure that occurs following extended hepatectomy. In this study, we examined the influence of delivering adult-derived human liver stem/progenitor cells (ADHLSCs) at two different early time points in an immunodeficient mouse model (Rag2-/-IL2Rγ-/-) that had undergone a 70% hepatectomy procedure. The hepatic mesenchymal cells were intrasplenically infused either immediately after surgery (n = 26) or following a critical 3-day period (n = 26). We evaluated the cells' capacity to engraft at day 1 and day 7 following transplantation by means of human Alu qPCR quantification, along with histological assessment of human albumin and α-smooth muscle actin. In addition, cell proliferation (anti-mouse and human Ki-67 staining) and murine liver weight were measured in order to evaluate liver regeneration. At day 1 posttransplantation, the ratio of human to mouse cells was similar in both groups, whereas 1 week posttransplantation this ratio was significantly improved (p < 0.016) in mice receiving ADHLSC injection at day 3 posthepatectomy (1.7%), compared to those injected at the time of surgery (1%). On the basis of liver weight, mouse liver regeneration was more extensive 1 week posttransplantation in mice transplanted with ADHLSCs (+65.3%) compared to that of mice from the sham vehicle group (+42.7%). In conclusion, infusing ADHLSCs 3 days after extensive hepatectomy improves the cell engraftment and murine hepatic tissue regeneration, thereby confirming that ADHLSCs could be a promising cell source for liver cell therapy and hepatic tissue repair.

  9. Environmental factors associated with primary care access among urban older adults.

    PubMed

    Ryvicker, Miriam; Gallo, William T; Fahs, Marianne C

    2012-09-01

    Disparities in primary care access and quality impede optimal chronic illness prevention and management for older adults. Although research has shown associations between neighborhood attributes and health, little is known about how these factors - in particular, the primary care infrastructure - inform older adults' primary care use. Using geographic data on primary care physician supply and surveys from 1260 senior center attendees in New York City, we examined factors that facilitate and hinder primary care use for individuals living in service areas with different supply levels. Supply quartiles varied in primary care use (visit within the past 12 months), racial and socio-economic composition, and perceived neighborhood safety and social cohesion. Primary care use did not differ significantly after controlling for compositional factors. Individuals who used a community clinic or hospital outpatient department for most of their care were less likely to have had a primary care visit than those who used a private doctor's office. Stratified multivariate models showed that within the lowest-supply quartile, public transit users had a higher odds of primary care use than non-transit users. Moreover, a higher score on the perceived neighborhood social cohesion scale was associated with a higher odds of primary care use. Within the second-lowest quartile, nonwhites had a lower odds of primary care use compared to whites. Different patterns of disadvantage in primary care access exist that may be associated with - but not fully explained by - local primary care supply. In lower-supply areas, racial disparities and inadequate primary care infrastructure hinder access to care. However, accessibility and elder-friendliness of public transit, as well as efforts to improve social cohesion and support, may facilitate primary care access for individuals living in low-supply areas.

  10. Molecular characteristics of circulating tumor cells resemble the liver metastasis more closely than the primary tumor in metastatic colorectal cancer

    PubMed Central

    Onstenk, Wendy; Sieuwerts, Anieta M.; Mostert, Bianca; Lalmahomed, Zarina; Bolt-de Vries, Joan B.; van Galen, Anne; Smid, Marcel; Kraan, Jaco; Van, Mai; de Weerd, Vanja; Ramírez-Moreno, Raquel; Biermann, Katharina; Verhoef, Cornelis; Grünhagen, Dirk J.; IJzermans, Jan N.M.; Gratama, Jan W.; Martens, John W.M.; Foekens, John A.; Sleijfer, Stefan

    2016-01-01

    Background CTCs are a promising alternative for metastatic tissue biopsies for use in precision medicine approaches. We investigated to what extent the molecular characteristics of circulating tumor cells (CTCs) resemble the liver metastasis and/or the primary tumor from patients with metastatic colorectal cancer (mCRC). Results The CTC profiles were concordant with the liver metastasis in 17/23 patients (74%) and with the primary tumor in 13 patients (57%). The CTCs better resembled the liver metastasis in 13 patients (57%), and the primary tumor in five patients (22%). The strength of the correlations was not associated with clinical parameters. Nine genes (CDH1, CDH17, CDX1, CEACAM5, FABP1, FCGBP, IGFBP3, IGFBP4, and MAPT) displayed significant differential expressions, all of which were downregulated, in CTCs compared to the tissues in the 23 patients. Patients and Methods Patients were retrospectively selected from a prospective study. Using the CellSearch System, CTCs were enumerated and isolated just prior to liver metastasectomy. A panel of 25 CTC-specific genes was measured by RT-qPCR in matching CTCs, primary tumors, and liver metastases. Spearman correlation coefficients were calculated and considered as continuous variables with r=1 representing absolute concordance and r= -1 representing absolute discordance. A cut-off of r>0.1 was applied in order to consider profiles to be concordant. Conclusions In the majority of the patients, CTCs reflected the molecular characteristics of metastatic cells better than the primary tumors. Genes involved in cell adhesion and epithelial-to-mesenchymal transition were downregulated in the CTCs. Our results support the use of CTC characterization as a liquid biopsy for precision medicine. PMID:27340863

  11. Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease

    PubMed Central

    Schwimmer, J B; Newton, K P; Awai, H I; Choi, L J; Garcia, M A; Ellis, L L; Vanderwall, K; Fontanesi, J

    2013-01-01

    Background Screening overweight and obese children for non-alcoholic fatty liver disease (NAFLD) is recommended by paediatric and endocrinology societies. However, gastroenterology societies have called for more data before making a formal recommendation. Aim To determine whether the detection of suspected NAFLD in overweight and obese children through screening in primary care and referral to paediatric gastroenterology resulted in a correct diagnosis of NAFLD. Methods Information generated in the clinical evaluation of 347 children identified with suspected NAFLD through screening in primary care and referral to paediatric gastroenterology was captured prospectively. Diagnostic outcomes were reported. The diagnostic performance of two times the upper limit of normal (ULN) for alanine aminotransferase (ALT) was assessed. Results Non-alcoholic fatty liver disease was diagnosed in 55% of children identified by screening and referral. Liver disease other than NAFLD was present in 18% of those referred. Autoimmune hepatitis was the most common alternative diagnosis. Children with NAFLD had significantly (P < 0.05) higher screening ALT (98 ± 95) than children with liver disease other than NAFLD (86 ± 74). Advanced fibrosis was present in 11% of children. For the diagnosis of NAFLD, screening ALT two times the clinical ULN had a sensitivity of 57% and a specificity of 71%. Conclusions Screening of overweight and obese children in primary care for NAFLD with referral to paediatric gastroenterology has the potential to identify clinically relevant liver pathology. Consensus is needed on how to value the risk and rewards of screening and referral, to identify children with liver disease in the most appropriate manner. PMID:24117728

  12. Highly efficient transduction of primary adult CNS and PNS neurons

    PubMed Central

    Levin, Evgeny; Diekmann, Heike; Fischer, Dietmar

    2016-01-01

    Delivery and expression of recombinant genes, a key methodology for many applications in biological research, remains a challenge especially for mature neurons. Here, we report easy, highly efficient and well tolerated transduction of adult peripheral and central neuronal populations of diverse species in culture using VSV-G pseudo-typed, recombinant baculovirus (BacMam). Transduction rates of up to 80% were reliably achieved at high multiplicity of infection without apparent neuro-cytopathic effects. Neurons could be transduced either shortly after plating or after several days in culture. Co-incubation with two different baculoviruses attained near complete co-localization of fluorescent protein expression, indicating multigene delivery. Finally, evidence for functional protein expression is provided by means of cre-mediated genetic recombination and neurite outgrowth assays. Recombinant protein was already detected within hours after transduction, thereby enabling functional readouts even in relatively short-lived neuronal cultures. Altogether, these results substantiate the usefulness of baculovirus-mediated transduction of mature neurons for future research in neuroscience. PMID:27958330

  13. Plasma cathepsin D correlates with histological classifications of fatty liver disease in adults and responds to intervention

    PubMed Central

    Walenbergh, Sofie M. A.; Houben, Tom; Rensen, Sander S.; Bieghs, Veerle; Hendrikx, Tim; van Gorp, Patrick J.; Oligschlaeger, Yvonne; Jeurissen, Mike L. J.; Gijbels, Marion J. J.; Buurman, Wim A.; Vreugdenhil, Anita C. E.; Greve, Jan Willem M.; Plat, Jogchum; Hofker, Marten H.; Kalhan, Satish; Pihlajamäki, Jussi; Lindsey, Patrick; Koek, Ger H.; Shiri-Sverdlov, Ronit

    2016-01-01

    Non-alcoholic steatohepatitis (NASH) is characterized by liver lipid accumulation and inflammation. The mechanisms that trigger hepatic inflammation are poorly understood and subsequently, no specific non-invasive markers exist. We previously demonstrated a reduction in the plasma lysosomal enzyme, cathepsin D (CatD), in children with NASH compared to children without NASH. Recent studies have raised the concept that non-alcoholic fatty liver disease (NAFLD) in adults is distinct from children due to a different histological pattern in the liver. Yet, the link between plasma CatD to adult NASH was not examined. In the current manuscript, we investigated whether plasma CatD in adults correlates with NASH development and regression. Biopsies were histologically evaluated for inflammation and NAFLD in three complementary cohorts of adults (total n = 248). CatD and alanine aminotransferase (ALT) were measured in plasma. Opposite to our previous observations with childhood NASH, we observed increased levels of plasma CatD in patients with NASH compared to adults without hepatic inflammation. Furthermore, after surgical intervention, we found a reduction of plasma CatD compared to baseline. Our observations highlight a distinct pathophysiology between NASH in children and adults. The observation that plasma CatD correlated with NASH development and regression is promising for NASH diagnosis. PMID:27922112

  14. Radiation-induced liver disease in three-dimensional conformal radiation therapy for primary liver carcinoma: The risk factors and hepatic radiation tolerance

    SciTech Connect

    Liang Shixiong; Zhu Xiaodong; Xu Zhiyong

    2006-06-01

    Purpose: To identify risk factors relevant to radiation-induced liver disease (RILD) and to determine the hepatic tolerance to radiation. Methods and Materials: The data of 109 primary liver carcinomas (PLC) treated with hypofractionated three-dimensional conformal radiation therapy (3D-CRT) were analyzed. Seventeen patients were diagnosed with RILD and 13 of 17 died of it. Results: The risk factors for RILD were late T stage, large gross tumor volume, presence of portal vein thrombosis, association with Child-Pugh Grade B cirrhosis, and acute hepatic toxicity. Multivariate analyses demonstrated that the severity of hepatic cirrhosis was a unique independent predictor. For Child-Pugh Grade A patients, the hepatic radiation tolerance was as follows: (1) Mean dose to normal liver (MDTNL) of 23 Gy was tolerable. (2) For cumulative dose-volume histogram, the tolerable volume percentages would be less than: V{sub 5} of 86%, V{sub 1} of 68%, V{sub 15} of 59%, V{sub 2} of 49%, V{sub 25} of 35%, V{sub 3} of 28%, V{sub 35} of 25%, and V{sub 4} of 20%. (3) Tolerable MDTNL could be estimated by MDTNL (Gy) = -1.686 + 0.023 * normal liver volume (cm{sup 3}). Conclusion: The predominant risk factor for RILD was the severity of hepatic cirrhosis. The hepatic tolerance to radiation could be estimated by dosimetric parameters.

  15. Primary liver carcinoma and liver cirrhosis in atomic bomb survivors, Hiroshima and Nagasaki, 1961-75, with special reference to hepatitis B surface antigen

    SciTech Connect

    Asano, M.; Kato, H.; Yoshimoto, K.; Seyama, S.; Itakura, H.; Hamada, T.; Iijima, S.

    1982-12-01

    During 1961-75, 128 cases of primary liver carcinoma (PLC) in the Radiation Effects Research Foundation life-span study extended sample and 301 cases of liver cirrhosis in the pathology study sample were observed. The presence of hepatitis B surface antigen (HBsAg) was assessed in all of the cases with the use of orcein and aldehyde fuchsin stains and was confirmed by the immunofluorescence technique. The incidence of PLC was two times higher in Nagasaki than in Hiroshima, which was statistically significant, but little difference was noted in the prevalence of cirrhosis in the two cities. Findings that might possibly explain the higher PLC incidence in Nagasaki were 1) the 2.3 times higher presence in Nagasaki than in Hiroshima of HBsAg in the livers of subjects without liver disease and 2) the two times higher prevalence in Nagasaki than in Hiroshima of cirrhosis with PLC. We believe that the higher incidence of PLC in Nagasaki is attributable to hepatitis B virus infection, although other factors (e.g., immunologic competence affected by radiation) cannot be excluded. In both cities, a suggestive relationship of radiation dose to cirrhosis prevalence, but not to PCL prevalence, was noted. To clarify possible radiation effects on cirrhosis prevalence, further follow-up of the populations of these two cities is necessary.

  16. Liver Metastases of Small Intestine Neuroendocrine Tumors: Ki67 heterogeneity and WHO grade discordance with primary tumors

    PubMed Central

    Shi, Chanjuan; Gonzalez, Raul S.; Zhao, Zhiguo; Koyama, Tatsuki; Cornish, Toby C; Hande, Kenneth R; Walker, Ronald; Sandler, Martin; Berlin, Jordan; Liu, Eric H

    2015-01-01

    Objective We examined Ki67 heterogeneity within single and between synchronous liver metastases of small intestine neuroendocrine tumors. Methods There were 27 patients (10 males and 17 females) with ≥2 liver metastases. Ki67 index was used to classify the tumors into WHO grade 1, 2, or 3. Association between Ki67 heterogeneity and tumor size of liver metastases were analyzed. Correlation of tumor grade with patient survival was also evaluated. Results Primary tumors from 20 patients were graded, including 17 grade 1 and 3 grade 2. A total of 188 liver metastases were resected, including 122 (65%) grade 1, 47 (25%) grade 2, and 19 (10%) grade 3. The highest tumor grade was grade 1 in10 (37%), grade 2 in 9 (33%), and grade 3 in 8 (30%) patients. Patients with ≥1 grade 3 liver lesions were associated with a shorter progression-free survival compared to those with grade 1/2 tumors (p<0.001). A positive association was found between tumor size and Ki67 index (p=0.04) as well as between tumor size and intratumoral Ki67 heterogeneity (p<0.001). Conclusions Intratumoral and intertumoral Ki67 heterogeneity is common and is positively correlated with tumor size. The presence of ≥1 grade 3 liver lesions predicts a worse prognosis. PMID:25696798

  17. Relationship between hemoglobin levels and risk for suspected non-alcoholic fatty liver in Taiwanese adults.

    PubMed

    Bai, Chyi-Huey; Wu, Ming-Shun; Owaga, Eddy; Cheng, Shu-Yu; Pan, Wen-Harn; Chang, Jung-Su

    2014-10-31

    Body iron levels have recently been shown to be a strong predictor for non-alcoholic fatty liver disease (NAFLD). The aims of this study were to investigate the prevalence of NAFLD in a general adult population, and to investigate the relationship between body iron levels, NAFLD and the metabolic syndrome (MetS). 2186 adults participated in the third National Nutrition and Health Survey in Taiwan (NAHSIT, 2005-2008). The participants underwent anthropometry measurements and phlebotomy after an overnight fast, and those with excessive alcohol intake, iron overload of serum ferritin > 600 ng/ml, hepatitis viral infection and hepatocellular carcinoma were excluded. Suspected NAFLD was diagnosed by three alanine transaminase (ALT) cut-points: cut-point 1: serum ALT > 40 U/l; cut-point 2: ALT ≥ 25 U/l for male and ALT ≥ 17 U/l for female; and cut-point 3: ALT ≥ 35 U/l for male and ALT ≥ 26 U/l for female. The prevalence proportion of suspected NAFLD among Taiwanese adults was 6.6% (cut-point 1), 36% (cut-point 2); and 14.3% (cut-point 3). Body iron levels were significantly higher in individuals with suspected NAFLD compared with those without. Distribution of hemoglobin levels, but not serum ferritin levels, by decade of age showed strong correlation with the prevalence of suspected NAFLD in individuals with MetS. Multivariate adjusted odds ratio (OR) showed that the best predictors for suspected NAFLD with the MetS were hemoglobin [OR 1.43 (1.21-1.68); P < 0.0001] and hyperlipidemia [OR 1.52 (1.19-1.94); P = 0.0007]. In individuals without MetS, the adjusted OR of suspected NAFLD was markedly higher for hemoglobin [OR 1.25 (1.12-1.41); P < 0.0001]. In conclusion, adults with high hemoglobin levels (14.4 μg/dl for male and 13.2 μg/dl for female) are at the greatest risk for developing abnormal liver function. Hemoglobin test should be considered as a part of clinical evaluation for patients with NAFLD.

  18. Reduced Lysosomal Acid Lipase Activity in Adult Patients With Non-alcoholic Fatty Liver Disease

    PubMed Central

    Baratta, Francesco; Pastori, Daniele; Del Ben, Maria; Polimeni, Licia; Labbadia, Giancarlo; Di Santo, Serena; Piemonte, Fiorella; Tozzi, Giulia; Violi, Francesco; Angelico, Francesco

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by intra-hepatic fat accumulation and mechanisms involved in its pathogenesis are not fully explained. Lysosomal Acid Lipase (LAL) is a key enzyme in lipid metabolism. We investigated its activity in patients with fatty liver. LAL activity (nmol/spot/h) was measured in 100 adult healthy subjects (HS) and in 240 NAFLD patients. A sub-analysis on 35 patients with biopsy-proven non-alcoholic steatohepatitis (NASH) was performed. Median LAL activity was 1.15 (0.95–1.72) in HS. It was significantly reduced in NAFLD [0.78 (0.61–1.01), p < 0.001 vs. HS]. A further reduction was observed in the subgroup of NASH [0.67 (0.51–0.77), p < 0.001 vs. HS]. Patients with LAL activity below median had higher values of serum total cholesterol (p < 0.05) and LDL-c (p < 0.05), and increased serum liver enzymes (ALT, p < 0.001; AST, p < 0.01; GGT, p < 0.01). At multivariable logistic regression analysis, factors associated with LAL activity below median were ALT (OR: 1.018, 95% CI 1.004–1.032, p = 0.011) and metabolic syndrome (OR: 2.551, 95% CI 1.241–5.245, p = 0.011), whilst statin use predicted a better LAL function (OR: 0.464, 95% CI 0.248–0.866, p = 0.016). Our findings suggest a strong association between impaired LAL activity and NAFLD. A better knowledge of the role of LAL may provide new insights in NAFLD pathogenesis. PMID:26288848

  19. Reduced Lysosomal Acid Lipase Activity in Adult Patients With Non-alcoholic Fatty Liver Disease.

    PubMed

    Baratta, Francesco; Pastori, Daniele; Del Ben, Maria; Polimeni, Licia; Labbadia, Giancarlo; Di Santo, Serena; Piemonte, Fiorella; Tozzi, Giulia; Violi, Francesco; Angelico, Francesco

    2015-07-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by intra-hepatic fat accumulation and mechanisms involved in its pathogenesis are not fully explained. Lysosomal Acid Lipase (LAL) is a key enzyme in lipid metabolism. We investigated its activity in patients with fatty liver. LAL activity (nmol/spot/h) was measured in 100 adult healthy subjects (HS) and in 240 NAFLD patients. A sub-analysis on 35 patients with biopsy-proven non-alcoholic steatohepatitis (NASH) was performed. Median LAL activity was 1.15 (0.95-1.72) in HS. It was significantly reduced in NAFLD [0.78 (0.61-1.01), p < 0.001 vs. HS]. A further reduction was observed in the subgroup of NASH [0.67 (0.51-0.77), p < 0.001 vs. HS]. Patients with LAL activity below median had higher values of serum total cholesterol (p < 0.05) and LDL-c (p < 0.05), and increased serum liver enzymes (ALT, p < 0.001; AST, p < 0.01; GGT, p < 0.01). At multivariable logistic regression analysis, factors associated with LAL activity below median were ALT (OR: 1.018, 95% CI 1.004-1.032, p = 0.011) and metabolic syndrome (OR: 2.551, 95% CI 1.241-5.245, p = 0.011), whilst statin use predicted a better LAL function (OR: 0.464, 95% CI 0.248-0.866, p = 0.016). Our findings suggest a strong association between impaired LAL activity and NAFLD. A better knowledge of the role of LAL may provide new insights in NAFLD pathogenesis.

  20. Acute Liver Failure in Adults: An Evidence-Based Management Protocol for Clinicians

    PubMed Central

    Misel, Michael; Gish, Robert G.

    2012-01-01

    With the goal of providing guidance on the provision of optimal intensive care to adult patients with acute liver failure (ALF), this paper defines ALF and describes a protocol for appropriately diagnosing this relatively rare clinical entity and ascertaining its etiology, where possible. This paper also identifies the few known therapies that may be effective for specific causes of ALF and provides a comprehensive approach for anticipating, identifying, and managing complications. Finally, one of the more important aspects of care for patients with ALF is the determination of prognosis and, specifically, the need for liver transplantation. Prognostic tools are provided to help guide the clinician in this critical decision process. Management of patients with ALF is complex and challenging, even in centers where staff members have high levels of expertise and substantial experience. This evidence-based protocol may, therefore, assist in the delivery of optimal care to this critically ill patient population and may substantially increase the likelihood of positive outcomes. PMID:22675278

  1. Transformation of adult rat cardiac myocytes in primary culture.

    PubMed

    Banyasz, Tamas; Lozinskiy, Ilya; Payne, Charles E; Edelmann, Stephanie; Norton, Byron; Chen, Biyi; Chen-Izu, Ye; Izu, Leighton T; Balke, C William

    2008-03-01

    We characterized the morphological, electrical and mechanical alterations of cardiomyocytes in long-term cell culture. Morphometric parameters, sarcomere length, T-tubule density, cell capacitance, L-type calcium current (I(Ca,L)), inward rectifier potassium current (I(K1)), cytosolic calcium transients, action potential and contractile parameters of adult rat ventricular myocytes were determined on each day of 5 days in culture. We also analysed the health of the myocytes using an apoptotic/necrotic viability assay. The data show that myocytes undergo profound morphological and functional changes during culture. We observed a progressive reduction in the cell area (from 2502 +/- 70 microm(2) on day 0 to 1432 +/- 50 microm(2) on day 5), T-tubule density, systolic shortening (from 0.11 +/- 0.02 to 0.05 +/- 0.01 microm) and amplitude of calcium transients (from 1.54 +/- 0.19 to 0.67 +/- 0.19) over 5 days of culture. The negative force-frequency relationship, characteristic of rat myocardium, was maintained during the first 2 days but diminished thereafter. Cell capacitance (from 156 +/- 8 to 105 +/- 11 pF) and membrane currents were also reduced (I(Ca,L), from 3.98 +/- 0.39 to 2.12 +/- 0.37 pA pF; and I(K1), from 34.34p +/- 2.31 to 18.00 +/- 5.97 pA pF(-1)). We observed progressive depolarization of the resting membrane potential during culture (from 77.3 +/- 2.5 to 34.2 +/- 5.9 mV) and, consequently, action potential morphology was profoundly altered as well. The results of the viability assays indicate that these alterations could not be attributed to either apoptosis or necrosis but are rather an adaptation to the culture conditions over time.

  2. Primary splenic angiosarcoma with liver metastasis: A case report and literature review.

    PubMed

    Yang, Kai-Feng; Li, Yong; Wang, De-Long; Yang, Jun-Wu; Wu, Sen-Yan; Xiao, Wei-Dong

    2016-03-28

    Primary splenic angiosarcoma (PSA) is an unusual and highly malignant vascular tumour with a high rate of metastatic. Moreover, the research on prognosis of the disease is poor. The epidemiology, etiology, clinical diagnosis and treatment of the disease remain challenging, because case reports of the disease are few in number. In accordance with other malignant tumors, PSA is very aggressive, and the majority of patients in which this disease is found are at an advanced stage. Almost all patients die within 12 mo of diagnosis irrespective of treatment. We report here a woman who had complained of upper bellyache and anorexia for 10 d. Magnetic resonance imaging showed enlargement of the spleen with multiple heterogeneous masses in the lower pole of the spleen. A hand-assisted laparoscopic splenectomy was performed which allowed histopathologic diagnosis. The patient was diagnosed with PSA and liver metastasis, and succumbed to the disease 35 d after surgery. The literature was finished combined with the clinical features, diagnosis and management of PSA.

  3. [Professor Ling Changquan's experience in treating primary liver cancer: an analysis of herbal medication].

    PubMed

    Sun, Zhen; Su, Yong-hua; Yue, Xiao-qiang

    2008-12-01

    On the basis of outpatients' medical records concerning primary liver cancer (PLC), data of 552 patients (with 2020 effective prescriptions) from the Outpatient Department of Changhai Hospital treated by Professor Ling Changquan were collected. The nature, flavor and meridian distribution of the herbs used in the prescriptions were summarized by frequency method, and the features of the herbs used according to syndrome differentiation were analyzed by logistic regression. The couple herbs used were analyzed by cluster analysis. All the data were analyzed in combination with the experience of the specialist. It showed that most of the frequently used herbs were herbs for invigorating the spleen to promote appetite, removing toxic materials to inhibit tumor growth, and activating blood circulation to dissipate blood stasis. These herbs are mostly of plain or cool nature, and mainly of sweet, bitter, or acrid taste. It also showed that the most frequently used herbs for qi deficiency were Astragalus membranaceus, Atractylodes macrocephala, and Pseudostellariae; Caulis Spatholobi and Chinese jujube for blood asthenia; Fructus Corni and Ophiopogon japonicus for yin deficiency; Agastache rugosa, Semen Plantaginis and Poria for water-dampness; cape jasmine fruit and baikal skullcap root for heat excess; peach seed and Radix Paeoniae Rubra for blood stasis; Curcuma wenyujin, Akebia trifoliata and Bupleurum chinese for qi stagnation. A total of 19 pairs of couple herbs were summarized by the cluster analysis.

  4. Epidemiology of primary liver cancer in Serbia and possible connection with cyanobacterial blooms.

    PubMed

    Svirčev, Zorica; Drobac, Damjana; Tokodi, Nada; Vidović, Milka; Simeunović, Jelica; Miladinov-Mikov, Marica; Baltić, Vladimir

    2013-01-01

    Today, the occurrence of harmful cyanobacterial blooms is a common phenomenon and a potential global health problem. Cyanobacteria can produce metabolites highly toxic to humans. More than 80% of reservoirs used for water supply in Central Serbia have bloomed over the past 80 years. A 10-year epidemiological study showed a significant increase in the incidence of primary liver cancer (PLC) in the regions where water from the blooming reservoirs was used for human consumption. At the same time, no correlation was found between the incidence of PLC and other risk factors, such as cirrhosis and hepatitis viruses. Given the strong association with PLC induction and various known possible mechanisms of carcinogenic action, it is highly possible that, cyanotoxins--acting as initiator and promoter--may be the major risk factor that acts synergistically with other risk factors to cause increased incidence of PLC. However, at present, it is still not certain whether cyanotoxins alone were sufficient to induce PLC. Therefore, additional assessment of the health risks that may arise from human exposure to cyanotoxins is advisable.

  5. Primary splenic angiosarcoma with liver metastasis: A case report and literature review

    PubMed Central

    Yang, Kai-Feng; Li, Yong; Wang, De-Long; Yang, Jun-Wu; Wu, Sen-Yan; Xiao, Wei-Dong

    2016-01-01

    Primary splenic angiosarcoma (PSA) is an unusual and highly malignant vascular tumour with a high rate of metastatic. Moreover, the research on prognosis of the disease is poor. The epidemiology, etiology, clinical diagnosis and treatment of the disease remain challenging, because case reports of the disease are few in number. In accordance with other malignant tumors, PSA is very aggressive, and the majority of patients in which this disease is found are at an advanced stage. Almost all patients die within 12 mo of diagnosis irrespective of treatment. We report here a woman who had complained of upper bellyache and anorexia for 10 d. Magnetic resonance imaging showed enlargement of the spleen with multiple heterogeneous masses in the lower pole of the spleen. A hand-assisted laparoscopic splenectomy was performed which allowed histopathologic diagnosis. The patient was diagnosed with PSA and liver metastasis, and succumbed to the disease 35 d after surgery. The literature was finished combined with the clinical features, diagnosis and management of PSA. PMID:27022233

  6. New insights into molecular diagnostic pathology of primary liver cancer: Advances and challenges.

    PubMed

    Cong, Wen-Ming; Wu, Meng-Chao

    2015-11-01

    Primary liver cancer (PLC) is one of the most common malignancies worldwide with increasing incidence and accounts for the third leading cause of cancer-related mortality. Traditional morphopathology primarily emphasizes qualitative diagnosis of PLC, which is not sufficient to resolve the major concern of increasing the long-term treatment efficacy of PLC in clinical management for the modern era. Since the beginning of the 21st century, molecular pathology has played an active role in the investigation of the evaluation of the metastatic potential of PLC, detection of drug targets, prediction of recurrence risks, analysis of clonal origins, evaluation of the malignancy trend of precancerous lesions, and determination of clinical prognosis. As a result, many new progresses have been obtained, and new strategies of molecular-pathological diagnosis have been formed. Moreover, the new types of pathobiological diagnosis indicator systems for PLC have been preliminarily established. These achievements provide valuable molecular pathology-based guide for clinical formulation of individualized therapy programs for PLC. This review article briefly summarizes some relevant progresses of molecular-pathological diagnosis of PLC from the perspective of clinical translational application other than basic experimental studies.

  7. Primary cutaneous smoldering adult T-cell leukemia/ lymphoma.

    PubMed

    Gittler, Julia; Martires, Kathryn; Terushkin, Vitaly; Brinster, Nooshin; Ramsay, David

    2016-12-15

    HTLV-1 is a virus that is endemic in southwesternJapan and the Caribbean and has been implicatedin the development of ATLL. ATLL, which is anuncommon malignant condition of peripheralT-lymphocytes, is characterized by four clinicalsubtypes, which include acute, lymphomatous,chronic, and smoldering types, that are based onLDH levels, calcium levels, and extent of organinvolvement. We present a 52-year- old woman withpruritic patches with scale on the buttocks and withtender, hyperpigmented macules and papules oftwo-years duration. Histopathologic examinationwas suggestive of mycosis fungoides, laboratoryresults showed HTLV-I and II, and the patient wasdiagnosed with primary cutaneous ATLL. We reviewthe literature on HTLV-1 and ATLL and specifically theprognosis of cutaneous ATLL. The literature suggeststhat a diagnosis of ATLL should be considered amongpatients of Caribbean origin or other endemicareas with skin lesions that suggest a cutaneousT-cell lymphoma, with clinicopathologic features ofmycosis fungoides. Differentiation between ATLLand cutaneous T-cell lymphoma is imperative as theyhave different prognoses and treatment approaches.

  8. Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial.

    PubMed

    Rautiainen, Henna; Kärkkäinen, Päivi; Karvonen, A-L; Nurmi, Heimo; Pikkarainen, Pekka; Nuutinen, Hannu; Färkkilä, Martti

    2005-04-01

    Ursodeoxycholic acid (UDCA) is a safe medical therapy for primary biliary cirrhosis (PBC), but its effect on liver histology remains uncertain. Budesonide is a glucocorticoid with high receptor activity and high first-pass metabolism in liver. We evaluated the combination of budesonide and UDCA on liver histology and compared this with UDCA alone in a 3-year prospective, randomized, open multicenter study. Patients with PBC (n = 77), at stages I to III, were randomized into 2 treatment arms, A (n = 41): budesonide 6 mg/d and UDCA 15 mg/kg/d and B (n = 36): UDCA 15 mg/kg/d. Liver histology was assessed at the beginning and at the end of the study. Liver function tests and glucose and cortisol values were determined every 4 months. Paired liver biopsy specimens were available from 69 patients (A = 37 and B = 32). Stage improved 22% in group A but deteriorated 20% in group B (P = .009). Fibrosis decreased 25% in group A but increased 70% in group B (P = .0009). S-PIIINP decreased significantly in group A. Inflammation decreased in both groups, 34% in group A (P = .02), but only 10% in group B (P = NS). Serum liver enzymes decreased significantly in both treatment arms. Bilirubin values rose in group B but stayed stable in group A (A/B P = .002). A mild systemic glucocorticoid effect from budesonide was evident after 2 years. In conclusion, budesonide combined with UDCA improved liver histology, whereas the effect of UDCA alone was mainly on laboratory values. Studies with longer follow-up using a combination of budesonide and UDCA are warranted to confirm safety and effects.

  9. Relation between primary liver cancer occurrence and freshwater Cyanobacterial blooms in Serbia

    NASA Astrophysics Data System (ADS)

    Svirčev, Z.; Miladinov-Mikov, M.; Simeunović, J.; Vidović, M.; Stojanović, D.

    2009-04-01

    Since 1980 cyanobacterial blooms occurred in a large number of reservoirs, lakes and running water ecosystems (rivers and channels) in Serbia. Among 49 reservoirs examined, 32 were found in blooming condition almost every year during last 2 decades. All natural lakes and 12 river and channel localities in Vojvodina province (agricultural part) proved to be sites with cyanobacterial proliferation. The part of Central Serbia is very problematic for ground water supply. For that reason 21 reservoirs serve as drinking water suppliers. Significant and persistant cyanobacterial blooms have been recognized in 9 of them. Samples for cyanotoxin analyses were taken during and after blooms in Celije Reservoir and in drinking water in Krusevac town 2 days later. Concentratins of Microcystin-LR were 460 µg•L-1 and for Microcystin-RR 170 µg•L-1. Drinking water contained 2 and 0.6 µg•L-1, respectively. Serbia consists of 30 administrative units, in three of which studies for Primary Liver Cancer (PLC) were conducted independently: Vojvodina, where drinking-water is supplied only from deep wells where 7 regions were studied, Kosovo with a few high mountain reservoirs for water supply without cyanobacterial proliferation where 6 regions were studied, and Central Serbia, where 17 regions were studied. Central Serbia showed 7 regions with extremly high PLC incidence and 8 regions with lower PLC incidence. In the two investigated periods, the high PLC mortality of 11.6 in 1980-1995 and extremely high PLC incidence of 26 in 2000 was observed in the regions affected by heavy cyanobacterial blooms. In contrast, the regions not affected by the blooms, PLC mortality and incidence rates were substantially lower: from 1980-1995 mortality rate ammounted to 2.7 in Kosovo, 7.6 in Vojvodina, and 8.5 in the non-affected regions of Central Serbia, and in 2000 incidence rate ammounted to 4.1 (Kosovo), 6.6 (Vojvodina), and 7.5 in the non-affected regions of Central Serbia. The uneven

  10. Freshwater cyanobacterial blooms and primary liver cancer epidemiological studies in Serbia.

    PubMed

    Svircev, Zorica; Krstic, Svetislav; Miladinov-Mikov, Marica; Baltic, Vladimir; Vidovic, Milka

    2009-01-01

    A large part of Central Serbia experiences continual shortage of sufficient ground water resources. For that reason, more than 20 reservoirs serve as drinking water suppliers. Significant and persistent cyanobacterial "blooms" have been recognized in nine of them. Samples for cyanotoxin analyses were taken during and after "blooms" in Celije Reservoir and from Krusevac town-supplied tap water from that reservoir two days later. Concentration of microcystin-LR was 650 microg L(-1) in the reservoir, while the tap water contained 2.5 microg L(-1). In the two investigated periods, the high primary liver cancer (PLC) mortality of 11.6 from 1980-1990 and extremely high PLC incidence of 34.7 from 2000-2002 were observed in the regions affected by heavy cyanobacterial "blooms." In contrast, PLC mortality and incidence rates were substantially lower in the regions not affected by cyanobacterial blooms: in 1980-1990 the rate of PLC mortality amounted to 2.7 in Kosovo, 7.6 in Vojvodina, and 8.3 in the non-affected regions of Central Serbia; while in 2000-2002 PLC incidence amounted to 4.1 in Kosovo, 5.2 in Vojvodina, and 13.6 in the non- or less-affected regions of Central Serbia. Keeping in mind that the most affected PLC regions in Central Serbia (Toplicki, Niski, and Sumadijski regions) have the water supply systems based on six reservoirs found regularly in bloom during summer months and that some of the regions are also connected with two boundary "blooming" reservoirs, representing a total of eight of nine blooming reservoirs, it is easy to presume that the PLC incidence could be related to drinking water quality. The uneven geographic distribution of liver cancer in Serbia is conspicuous and hot spots could be related to drinking water supply. It is very clear that the high-risk regions for PLC occurrence correspond with drinking water reservoirs continually found with cyanobacterial blooms, and the low risk regions correspond with water supplies not affected by

  11. A Comparison of Intralesional Triamcinolone Acetonide Injection for Primary Chalazion in Children and Adults

    PubMed Central

    Lee, Jacky W. Y.; Yau, Gordon S. K.; Wong, Michelle Y. Y.; Yuen, Can Y. F.

    2014-01-01

    Purpose. To investigate outcome differences of intralesional triamcinolone acetonide (TA) injection for primary chalazia in children versus adults. Methods. A retrospective review of consecutive subjects with primary chalazion who received intralesional TA injection was conducted. A single investigator injected 0.05–0.15 mL of TA (40 mg/mL) intralesionally. Patients were stratified into the pediatric (<18 years old) and adult (≥18 years old) group. In both groups, the correlation of resolution time with chalazion size and TA dose was performed. Results. 17 children and 24 adults were enrolled, with a mean age of 7.4 ± 5.5 and 39.3 ± 16.7 years, respectively. Both groups had statistically similar baseline characteristics. There was no significant difference between the resolution time in the pediatric (18.2 ± 11.4 days) and adult (16.5 ± 11.0 days) group (P = 0.7). There were no significant complications from the TA injection. There was no significant correlation of resolution time to chalazion size (P = 0.7) nor TA dose (P = 0.3) in both groups. Conclusion. TA for the treatment of primary chalazion was equally effective in children and adults, without any significant complications, and the rate of clinical response did not appear to be dose-dependent. PMID:25386597

  12. Campylobacter fetus bacteremia with purulent pleurisy in a young adult with primary hypogammaglobulinemia.

    PubMed

    Yamagami, Keiko; Miyashita, Tomoko; Nakamura, Tomoyuki; Shirano, Michinori; Nakamura, Tadahiro; Kameda, Kazuaki; Nishijima, Masayoshi; Imanishi, Masahiro; Yang, Xi; Kanegane, Hirokazu

    2014-01-01

    A 24-year-old man presented with fever and pleural effusion predominantly containing lymphocytes. Cultures of the pleural effusion and blood revealed Campylobacter fetus, and laboratory studies showed a low serum level of immunoglobulin. The patient was diagnosed with C. fetus pleuritis, bacteremia and primary hypogammaglobulinemia, and subsequent treatment with meropenem and immunoglobulin improved his condition. Although the underlying cause of the primary hypogammaglobulinemia remains unclear, the patient's status improved under immunoglobulin replacement therapy. C. fetus pleuritis is a rare infectious disease usually observed in immunocompromised hosts. We herein describe the first report of C. fetus pleuritis in a young adult with primary hypogammaglobulinemia.

  13. Adult Antisocial Behavior and Affect Regulation among Primary Crack/Cocaine-Using Women

    ERIC Educational Resources Information Center

    Litt, Lisa Caren; Hien, Denise A.; Levin, Deborah

    2003-01-01

    The relationship between deficits in affect regulation and Adult Antisocial Behavior (ASB) in primary crack/cocaine-using women was explored in a sample of 80 inner-city women. Narrative early memories were coded for two components of affect regulation, Affect Tolerance and Affect Expression, using the Epigenetic Assessment Rating Scale (EARS;…

  14. A Meta-Analysis of Adult-Rated Child Personality and Academic Performance in Primary Education

    ERIC Educational Resources Information Center

    Poropat, Arthur E.

    2014-01-01

    Background: Personality is reliably associated with academic performance, but personality measurement in primary education can be problematic. Young children find it difficult to accurately self-rate personality, and dominant models of adult personality may be inappropriate for children. Aims: This meta-analysis was conducted to determine the…

  15. Physician Perspectives on Providing Primary Medical Care to Adults with Autism Spectrum Disorders (ASD)

    ERIC Educational Resources Information Center

    Warfield, Marji Erickson; Crossman, Morgan K.; Delahaye, Jennifer; Der Weerd, Emma; Kuhlthau, Karen A.

    2015-01-01

    We conducted in-depth case studies of 10 health care professionals who actively provide primary medical care to adults with autism spectrum disorders. The study sought to understand their experiences in providing this care, the training they had received, the training they lack and their suggestions for encouraging more physicians to provide this…

  16. Prevalence of Epilepsy in Adults with Mental Retardation and Related Disabilities in Primary Care

    ERIC Educational Resources Information Center

    McDermott, Suzanne; Moran, Robert; Platt, Tan; Wood, Hope; Isaac, Terri; Dasari, Srikanth

    2005-01-01

    Two primary care practices were used to recruit adults with and without disability. Disability groups included autism, Down syndrome, cerebral palsy, and mental retardation. The patients without disability had an epilepsy prevalence rate of 1%. The prevalence of epilepsy within the disability groups was 13% for cerebral palsy, 13.6% for Down…

  17. Laminin alpha 5, a major transcript of normal and malignant rat liver epithelial cells, is differentially expressed in developing and adult liver.

    PubMed

    Seebacher, T; Medina, J L; Bade, E G

    1997-11-25

    The laminin family of extracellular matrix glycoproteins plays a major role in cell migration and differentiation and in tumor cell invasion. As previously shown, the laminin deposited by normal and malignant rat liver epithelial cells in their extracellular matrix (ECM) and into their ECM migration tracks does not contain a typical (EHS-like) alpha 1 heavy chain. By RT-PCR screening we have now identified two alpha chains among a total of five additional laminin chains produced by these cells. Three of the newly identified chains were not previously known for the rat. Their sequences have been deposited in the EMBL nucleotide sequence data bank. The alpha 5 chain now identified is expressed at comparably high levels by both the normal and the malignant liver epithelial cells. The chain is also expressed in fetal liver together with the alpha 2 and beta 2 chains, but it is only vestigially expressed in the mature organ as shown by RT-PCR. These results suggest for alpha 5 a role in development and production of the chain by only a small subset of cells in adult liver. At the level of detection used, no changes were observed in regenerating liver after partial hepatectomy. In addition to the alpha 5 chain, the cultured cells express the beta 1 and beta 2 light chains, indicating the expression of more than one laminin isoform by the same cell line. The expression of the alpha 5 chain and of the other new non-EHS isoform chains was also analyzed in various tissues. The malignant liver epithelial cells, but not their nontumorigenic parental cells, also express, in addition to the alpha 5 chain the alpha 2 chain, which is expressed at high level by the NBT II bladder carcinoma cell line, suggesting a relationship with malignancy.

  18. Aroclor 1254 increases the genotoxicity of several carcinogens to liver primary cell cultures

    SciTech Connect

    Mendoza-Figueroa, T.; Lopez-Revilla, R.; Villa-Trevino, S.

    1985-01-01

    The genotoxicity of both direct-acting and precarcinogenic chemicals was evaluated in liver primary cell cultures (LPCC) from untreated and Aroclor 1254 (Ar) pretreated rats. Hepatocytes were isolated from partially hepatectomized rats and their DNA was labeled in vitro with (/sup 3/H) dThd; the molecular weight of single-stranded DNA was determined by alkaline sucrose sedimentation. Two parameters of DNA damage were defined: 1) the mean effective dose (ED50), i.e., the carcinogen concentration that decreased the DNA molecular weight to half the original, and 2) the DNA breaking potency (DBP), i.e., the number of breaks per DNA molecule produced by 2 h exposure to 1mM concentration of the chemical. Two hours exposure of LPCC from untreated rats to the direct-acting alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (6.8-340..mu..M) and to the precarcinogens benzo(a)pyrene (BaP) (0.05-0.33 mM) and dimethylnitrosamine (DMN) (0.45-16 mM) produced a concentration-dependent decrease in the molecular weight of DNA. Pretreatment of rats with Ar decreased significantly the sedimentation velocity of DNA and increased five, three, and two times the DBP of MNNG, BaP, and DMN, respectively. These results show that Ar-pretreatment of rats increases the genotoxicity of both direct-acting and precarcinogenic chemicals and suggest that Ar might increase the genotoxicity of chemical carcinogens perhaps by enhancing their metabolic activation, by producing direct genotoxic effects, or both. Our results also emphasize the carcinogenic risk that the environmental pollution by polychlorinated biphenyls might represent to humans.

  19. Clinical characteristics of drug-induced liver injury and primary biliary cirrhosis

    PubMed Central

    Yang, Jun; Yu, Ya-Li; Jin, Yu; Zhang, Ying; Zheng, Chang-Qing

    2016-01-01

    AIM To summarize and compare the clinical characteristics of drug-induced liver injury (DILI) and primary biliary cirrhosis (PBC). METHODS A total of 124 patients with DILI and 116 patients with PBC treated at Shengjing Hospital Affiliated to China Medical University from 2005 to 2013 were included. Demographic data (sex and age), biochemical indexes (total protein, albumin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, indirect bilirubin, alkaline phosphatase, and gamma glutamyltransferase), immunological indexes [immunoglobulin (Ig) A, IgG, IgM, antinuclear antibody, anti-smooth muscle antibody, anti-mitochondrial antibody, and anti-mitochondrial antibodies] and pathological findings were compared in PBC patients, untyped DILI patients and patients with different types of DILI (hepatocellular type, cholestatic type and mixed type). RESULTS There were significant differences in age and gender distribution between DILI patients and PBC patients. Biochemical indexes (except ALB), immunological indexes, positive rates of autoantibodies (except SMA), and number of cases of patients with different ANA titers (except the group at a titer of 1:10000) significantly differed between DILI patients and PBC patients. Biochemical indexes, immunological indexes, and positive rate of autoantibodies were not quite similar in different types of DILI. PBC was histologically characterized mainly by edematous degeneration of hepatocytes (n = 30), inflammatory cell infiltration around bile ducts (n = 29), and atypical hyperplasia of small bile ducts (n = 28). DILI manifested mainly as fatty degeneration of hepatocytes (n = 15) and spotty necrosis or loss of hepatocytes (n = 14). CONCLUSION Although DILI and PBC share some similar laboratory tests (biochemical and immunological indexes) and pathological findings, they also show some distinct characteristics, which are helpful to the differential diagnosis of the two diseases. PMID:27672278

  20. Based on surface-enhanced Raman spectroscopy analysis of serum albumin in different stages of liver disease for early screening primary liver cancer

    NASA Astrophysics Data System (ADS)

    Liao, Fadian; Ruan, Qiuyong; Lin, Juqiang; Lin, Jinyong; Zeng, Yongyi; Li, Ling; Huang, Zufang; Liu, Nenrong; Chen, Rong

    2014-09-01

    Despite the introduction of high-technology methods of detection and diagnosis, screening of primary liver cancer (PLC) remains imperfect. To diagnosis PLC earlier, Surface-enhanced Raman spectroscopy (SERS) coupled with cellulose-acetate membrane electrophoresis were introduced to separate human serum albumin and SERS spectra. Three groups (15 normal persons' samples, 17 hepatitis/cirrhosis samples, 15 cases of PLC) of serum albumin were tested. Silver colloid was used to obtain SERS spectra of human serum albumin. Principal component analysis (PCA) and linear discriminant analysis (LDA) were also employed for statistical analysis. The mean Raman spectra of three groups and the difference spectra of any two suggested that the albumin has changed in liver patients. Compared to normal groups, some Raman peaks have shifted or even disappeared in hepatitis/cirrhosis and PLCs groups. The sensitivity and specificity between PLCs and normal groups is 80% and 93.3%. Among hepatitis/cirrhosis and normal groups, the sensitivity is 88.2% and specificity is also 93.3%. Besides, the sensitivity and specificity between PLCs and hepatitis/cirrhosis groups is 86.7% and 76.5%. All the above data and results indicated that early screening of PLC is potential by SERS in different stages of liver disease before cancer occurs.

  1. Gluconeogenesis, glucose handling, and structural changes in livers of the adult offspring of rats partially deprived of protein during pregnancy and lactation.

    PubMed Central

    Burns, S P; Desai, M; Cohen, R D; Hales, C N; Iles, R A; Germain, J P; Going, T C; Bailey, R A

    1997-01-01

    Maternal protein restriction is a model of fetal programming of adult glucose intolerance. Perfused livers of 48-h- starved adult offspring of rat dams fed 8% protein diets during pregnancy and lactation produced more glucose from 6 mM lactate than did control livers from rats whose dams were fed 20% protein. In control livers, a mean of 24% of the glucose formed from lactate in the periportal region of the lobule was taken up by the most distal perivenous cells; this distal perivenous uptake was greatly diminished in maternal low protein (MLP) livers, accounting for a major fraction of the increased glucose output of MLP livers. In control livers, the distal perivenous cells contained 40% of the total glucokinase of the liver; this perivenous concentration of glucokinase was greatly reduced in MLP livers. Intralobular distribution of phosphenolpyruvate carboxykinase was unaltered, though overall increased activity could have contributed to the elevated glucose output. Hepatic lobular volume in MLP livers was twice that in control livers, indicating that MLP livers had half the normal number of lobules. Fetal programming of adult glucose metabolism may operate partly through structural alterations and changes in glucokinase expression in the immediate perivenous region. PMID:9312176

  2. Greater serum carotenoid levels associated with lower prevalence of nonalcoholic fatty liver disease in Chinese adults

    PubMed Central

    Cao, Yi; Wang, Cheng; Liu, Jun; Liu, Zhao-min; Ling, Wen-hua; Chen, Yu-ming

    2015-01-01

    Previous studies have suggested that serum carotenoids may be inversely associated with liver injury, but limited data are available from population-based studies. We examined the relationship between serum carotenoid levels and the prevalence of nonalcoholic fatty liver disease (NAFLD) in Chinese adults. A total of 2935 participants aged 40–75 years were involved in this community-based cross-sectional study. General information, lifestyle factors, serum levels of carotenoid and the presence and degree of NAFLD were determined. After adjusting for potential covariates, we observed a dose-dependent inverse association between NAFLD risk and each individual serum carotenoid and total carotenoids (all p-values < 0.001). The ORs of NAFLD for the highest (vs. lowest) quartile were 0.44 (95% CI 0.35, 0.56) for α-carotene, 0.32 (95% CI 0.25, 0.41) for β-carotene, 0.62 (95% CI 0.49, 0.79) for β-cryptoxanthin, 0.54 (95% CI 0.42, 0.68) for lycopene, 0.56 (95% CI 0.44, 0.72) for lutein + zeaxanthin and 0.41 (95% CI 0.32, 0.53) for total carotenoids. Higher levels of α-carotene, β-carotene, lutein + zeaxanthin and total carotenoids were significantly associated with a decrease in the degree of NAFLD (p-trend: < 0.001 to 0.003). Serum carotenoids are inversely associated with prevalence of NAFLD in middle aged and elderly Chinese. PMID:26256414

  3. Potential for dietary ω-3 fatty acids to prevent nonalcoholic fatty liver disease and reduce the risk of primary liver cancer.

    PubMed

    Jump, Donald B; Depner, Christopher M; Tripathy, Sasmita; Lytle, Kelli A

    2015-11-01

    Nonalcoholic fatty liver disease (NAFLD) has increased in parallel with central obesity, and its prevalence is anticipated to increase as the obesity epidemic remains unabated. NAFLD is now the most common cause of chronic liver disease in developed countries and is defined as excessive lipid accumulation in the liver, that is, hepatosteatosis. NAFLD ranges in severity from benign fatty liver to nonalcoholic steatohepatitis (NASH), and NASH is characterized by hepatic injury, inflammation, oxidative stress, and fibrosis. NASH can progress to cirrhosis, and cirrhosis is a risk factor for primary hepatocellular carcinoma (HCC). The prevention of NASH will lower the risk of cirrhosis and NASH-associated HCC. Our studies have focused on NASH prevention. We developed a model of NASH by using mice with the LDL cholesterol receptor gene ablated fed the Western diet (WD). The WD induces a NASH phenotype in these mice that is similar to that seen in humans and includes robust induction of hepatic steatosis, inflammation, oxidative stress, and fibrosis. With the use of transcriptomic, lipidomic, and metabolomic approaches, we examined the capacity of 2 dietary ω-3 (n-3) polyunsaturated fatty acids, eicosapentaenoic acid (20:5ω-3; EPA) and docosahexaenoic acid (22:6ω-3; DHA), to prevent WD-induced NASH. Dietary DHA was superior to EPA at attenuating WD-induced changes in plasma lipids and hepatic injury and at reversing WD effects on hepatic metabolism, oxidative stress, and fibrosis. The outcome of these studies suggests that DHA may be useful in preventing NASH and reducing the risk of HCC.

  4. Potential for Dietary ω-3 Fatty Acids to Prevent Nonalcoholic Fatty Liver Disease and Reduce the Risk of Primary Liver Cancer123

    PubMed Central

    Jump, Donald B; Depner, Christopher M; Tripathy, Sasmita; Lytle, Kelli A

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) has increased in parallel with central obesity, and its prevalence is anticipated to increase as the obesity epidemic remains unabated. NAFLD is now the most common cause of chronic liver disease in developed countries and is defined as excessive lipid accumulation in the liver, that is, hepatosteatosis. NAFLD ranges in severity from benign fatty liver to nonalcoholic steatohepatitis (NASH), and NASH is characterized by hepatic injury, inflammation, oxidative stress, and fibrosis. NASH can progress to cirrhosis, and cirrhosis is a risk factor for primary hepatocellular carcinoma (HCC). The prevention of NASH will lower the risk of cirrhosis and NASH-associated HCC. Our studies have focused on NASH prevention. We developed a model of NASH by using mice with the LDL cholesterol receptor gene ablated fed the Western diet (WD). The WD induces a NASH phenotype in these mice that is similar to that seen in humans and includes robust induction of hepatic steatosis, inflammation, oxidative stress, and fibrosis. With the use of transcriptomic, lipidomic, and metabolomic approaches, we examined the capacity of 2 dietary ω-3 (n–3) polyunsaturated fatty acids, eicosapentaenoic acid (20:5ω-3; EPA) and docosahexaenoic acid (22:6ω-3; DHA), to prevent WD-induced NASH. Dietary DHA was superior to EPA at attenuating WD-induced changes in plasma lipids and hepatic injury and at reversing WD effects on hepatic metabolism, oxidative stress, and fibrosis. The outcome of these studies suggests that DHA may be useful in preventing NASH and reducing the risk of HCC. PMID:26567194

  5. Gene expression profiling and differentiation assessment in primary human hepatocyte cultures, established hepatoma cell lines, and human liver tissues

    SciTech Connect

    Olsavsky, Katy M.; Page, Jeanine L.; Johnson, Mary C.; Zarbl, Helmut; Strom, Stephen C.; Omiecinski, Curtis J. . E-mail: cjo10@psu.edu

    2007-07-01

    Frequently, primary hepatocytes are used as an in vitro model for the liver in vivo. However, the culture conditions reported vary considerably, with associated variability in performance. In this study, we characterized the differentiation character of primary human hepatocytes cultured using a highly defined, serum-free two-dimensional sandwich system, one that configures hepatocytes with collagen I as the substratum together with a dilute extracellular matrix (Matrigel{sup TM}) overlay combined with a defined serum-free medium containing nanomolar levels of dexamethasone. Gap junctional communication, indicated by immunochemical detection of connexin 32 protein, was markedly enhanced in hepatocytes cultured in the Matrigel sandwich configuration. Whole genome expression profiling enabled direct comparison of liver tissues to hepatocytes and to the hepatoma-derived cell lines, HepG2 and Huh7. PANTHER database analyses were used to identify biological processes that were comparatively over-represented among probe sets expressed in the in vitro systems. The robustness of the primary hepatocyte cultures was reflected by the extent of unchanged expression character when compared directly to liver, with more than 77% of the probe sets unchanged in each of the over-represented categories, representing such genes as C/EBP{alpha}, HNF4{alpha}, CYP2D6, and ABCB1. In contrast, HepG2 and Huh7 cells were unchanged from the liver tissues for fewer than 48% and 55% of these probe sets, respectively. Further, hierarchical clustering of the hepatocytes, but not the cell lines, shifted from donor-specific to treatment-specific when the probe sets were filtered to focus on phenobarbital-inducible genes, indicative of the highly differentiated nature of the hepatocytes when cultured in a highly defined two-dimensional sandwich system.

  6. In recurrent primary biliary cirrhosis after liver transplantation, biliary epithelial cells show increased expression of mitochondrial proteins.

    PubMed

    Sasaki, Motoko; Hsu, Maylee; Yeh, Matthew M; Nakanuma, Yasuni

    2015-10-01

    In biliary epithelial lesions in primary biliary cirrhosis (PBC), mitochondrial proteins associated with deregulated autophagy are abnormally expressed. We examined whether this could be used as a diagnostic marker for end-stage PBC and recurrent PBC after liver transplantation. We examined the expression of the mitochondrial protein pyruvate dehydrogenase complex-E2 component and cytochrome c oxidase, subunit I (CCO), the autophagy-related marker microtubule-associated protein-light chain 3 (LC3), and p62/sequestosome-1 and the senescence markers p16(Ink4a) and p21(WAF1/Cip1) in small bile ducts and bile ductules in explanted livers from patients with PBC (n = 20) in comparison with liver tissue from control patients (n = 21) and post-transplant samples including recurrent PBC and cellular rejection (n = 28). Intense granular expression of mitochondrial proteins was significantly more frequent in small bile ducts in explanted livers with PBC than in control livers (p < 0.05). Post-transplant samples comprised of three groups: group A (positive for mitochondrial proteins, n = 7), group B (positive for either autophagy-related or senescence markers but negative for mitochondrial proteins, n = 7), and group C (all negative, n = 14). All but one case of group A were clinically and histologically diagnosed as recurrent PBC. In contrast, all cases of group B were diagnosed as cellular rejection. This study suggests that the expression of mitochondrial proteins in small bile ducts may be a useful diagnostic marker for end-stage PBC and recurrent PBC after liver transplantation.

  7. Urolithiasis in an Adult with Primary Obstructive Megaureter: A Case Report

    PubMed Central

    Al-Marhoon, Mohammed S.; Venkiteswaran, Khrishna P.; Shareef, Omar W.

    2013-01-01

    This is a rare case of adult primary obstructive megaureter complicated by combined uric acid-oxalate lithiasis of the ureter and renal stones. A 24-year-old male patient presented with frank hematuria on exercise of 4 years duration. The patient had an open surgery in the form of excision of stenotic segment of ureter and left ureteric re-implantation with removal of ureteric and renal stones. Congenital megaureter is a diagnosis that urologists and radiologists need to consider in the setting of isolated distal ureteral dilation, as the diagnosis of adult megaureter may require more involved surgical measures to prevent recurrence of adverse symptoms. PMID:24044065

  8. Liver cancer - hepatocellular carcinoma

    MedlinePlus

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or ...

  9. Assessment of 3-epi-25-hydroxyvitamin D levels during cholecalciferol supplementation in adults with chronic liver diseases.

    PubMed

    Stokes, Caroline S; Volmer, Dietrich A

    2016-12-01

    Recently, hepatic immaturity was cited as a possible reason for high levels of the C-3 epimer of 25-hydroxyvitamin (25(OH)D) in premature infants: however what role, if any, the liver plays in controlling epimer concentrations is unknown. This study assesses 3-epi-25-hydroxyvitamin D (3-epi-25(OH)D) levels during the course of cholecalciferol supplementation in adults with chronic liver diseases (CLD). Vitamin D metabolites were analyzed in 65 CLD patients with 25(OH)D <30 ng/mL who received 20 000 IU cholecalciferol/week for 6 months. The primary outcome assessed serum 25(OH)D and 3-epi-25(OH)D in response to supplementation. Corresponding values from 16 CLD patients with sufficient vitamin D levels receiving no supplementation were compared. The epimer was detected in all samples and at lower relative concentrations with lower vitamin D baseline status, i.e., severe vitamin D deficiency (<10 ng/mL) as compared with deficient (10-19.9 ng/mL), insufficient (20-29.9 ng/mL), or sufficient (≥30 ng/mL) vitamin D levels (2.4% vs. 4.8%, 5.2%, 5.8%, respectively; P < 0.001). Similar relative concentrations for 3-epi-25(OH)D, ranging from 4.3%-7.1% (absolute concentrations: 1.1-4.0 ng/mL; all P < 0.001), were obtained in response to cholecalciferol in all supplemented patients, regardless of inadequacy threshold. Epimer levels significantly decreased (P = 0.007) in unsupplemented patients, coinciding with decreasing serum 25(OH)D concentrations over time. No epimer differences between patients with (n = 17) or without (n = 48) cirrhosis were demonstrated. The 3-epi-25(OH)D was present in serum of all patients at comparable levels to those reported by others. Epimer levels increased linearly with increasing 25(OH)D levels after supplementation. However, no effect of cirrhosis on epimer concentrations was observed.

  10. Overall Quality of Life in Adult Biliary Atresia Survivors with or without Liver Transplantation: Results from a National Cohort.

    PubMed

    de Vries, Willemien; Lind, Robert C; Sze, Yuk-Kueng; van der Steeg, Alida F W; Sieders, Egbert; Porte, Robert Jack; Verkade, Henkjan J; Hulscher, Jan B F; Hoekstra-Weebers, Josette E H M

    2016-08-01

    Background Biliary atresia (BA) is a rare cholestatic disease of infancy. Kasai portoenterostomy and liver transplantation (LT) are the two sequential treatment options. An increasing number of patients survive into adulthood. Little is known about their health-related quality of life (HRQOL). This study aims to compare HRQOL of transplanted and nontransplanted patients in a cohort of young adult BA survivors. Patients and Methods RAND-36 and Liver Disease Index Score (LDSI) questionnaires were sent to eligible adult patients with BA. Clinical characteristics were obtained from the NeSBAR (Netherlands Study group on Biliary Atresia Registry) and the national pediatric LT database. RAND-36 domain and summary scores were compared with those of an age-matched Dutch reference group. The correlations between several clinical variables and HRQOL were analyzed. Results Mean RAND-36 domain and summary scores of transplanted (n = 15) and nontransplanted (n = 25) patients with BA (response 74%) were similar to the reference scores, with the exception of a decreased general health perception in nontransplanted patients (63 ± 21 vs. 75 ± 17; [p < 0.001], particularly in females. RAND-36 domain and summary scores were not significantly correlated to age at LT, time since LT, serum bilirubin, aspartate amino transferase or albumin levels, but were moderately to strongly correlated to LDSI total scores (r values 0.35-0.77). Conclusions Overall, young adult patients with BA have a HRQOL similar to an age-matched reference group. However, general health perception of nontransplanted patients, particularly of females, was decreased. HRQOL is correlated to liver disease symptoms but not to liver biochemistry parameters. Nontransplanted females and patients suffering from liver disease-associated symptoms may be a target for tailored supportive interventions.

  11. Smoking as a risk factor for autoimmune liver disease: what we can learn from primary biliary cirrhosis.

    PubMed

    Smyk, Daniel S; Rigopoulou, Eirini I; Muratori, Luigi; Burroughs, Andrew K; Bogdanos, Dimitrios P

    2012-01-01

    Primary biliary cirrhosis (PBC) is a cholestatic liver disease characterised by the immune-mediated destruction of biliary epithelial cells in small intrahepatic bile ducts. The disease is characterised by circulating anti-mitochondrial antibodies (AMA) as well as disease specific anti-nuclear antibodies (ANA), cholestatic liver biochemistry, and characteristic histology. The disease primarily affects middle-aged females, and its incidence is apparently increasing worldwide. Epidemiological studies have indicated several risk factors for the development of PBC, with family history of PBC, recurrent urinary tract infection, and smoking being the most widely cited. Smoking has been implicated as a risk factor in several autoimmune diseases, including the liver, by complex mechanisms involving the endocrine and immunological systems to name a few. Studies of smoking in liver disease have also shown that smoking may progress the disease towards fibrosis and subsequent cirrhosis. This review will examine the literature surrounding smoking as a risk factor for PBC, as well as a potential factor in the progression of fibrosis in PBC patients.

  12. A Rare Case of Primary Anterior Mediastinal Yolk Sac Tumor in an Elderly Adult Male

    PubMed Central

    Nakhla, Sammy G.; Sundararajan, Srinath

    2016-01-01

    Mediastinal germ cell tumors are extragonadal germ cell tumors (EGGCTs) commonly seen in children and young adults. They are more common in men. Clinically they are classified as teratomas, seminomas, and nonseminomatous germ cell tumors. Primary mediastinal yolk sac neoplasm is an extremely rare tumor. We present here a very rare case of primary yolk sac tumor of the anterior mediastinum in a 73-year-old male. Mediastinal germ cell tumors have a worse prognosis than gonadal germ cell tumors. Chemotherapy followed by adjuvant surgery improves overall response in EGGCTs. However, comorbidities can render treatment with chemotherapy and surgery challenging in elderly patients. PMID:27144043

  13. Initial manifestation of primary hyperoxaluria type I in adults-- recognition, diagnosis, and management.

    PubMed Central

    Kuiper, J J

    1996-01-01

    Primary hyperoxaluria type I may initially manifest as urolithiasis, renal insufficiency, or symptoms of systemic oxalosis. This hereditary disorder was fatal until effective therapies evolved during the past two decades. Difficulty in recognizing and diagnosing this disorder in adults is illustrated in a report of a patient eventually restored to good health by high-flux dialysis and combined renal and hepatic transplantation. I explore the molecular processes of the genetic defect and discuss clinical indicators of primary hyperoxaluria type I, manifestations of oxalosis, the pathogenesis of chronic oxalate nephropathy, and the diagnosis and management of this disease. Images Figure 2. Figure 3. Figure 4. PMID:8779202

  14. Non-invasive Investigations for the Diagnosis of Fontan-Associated Liver Disease in Pediatric and Adult Fontan Patients

    PubMed Central

    Fidai, Amyna; Dallaire, Frederic; Alvarez, Nanette; Balon, Yvonne; Clegg, Robin; Connelly, Michael; Dicke, Frank; Fruitman, Deborah; Harder, Joyce; Myers, Kimberley; Patton, David J.; Prieur, Tim; Vorhies, Erika; Myers, Robert P.; Martin, Steven R.; Greenway, Steven C.

    2017-01-01

    Fontan-associated liver disease (FALD) is a serious complication related to the chronically elevated venous pressure and low cardiac output of this abnormal circulation. However, diagnostic markers for this condition are limited. We hypothesized that specific tests for fibrosis developed for other chronic liver diseases would identify a higher prevalence of FALD than ultrasound and standard laboratory tests and that identified abnormalities would correlate with time post-Fontan. In this cross-sectional study, we assessed 19 children (average age 8.4 ± 4.3 and 5.4 ± 4.1 years post-Fontan) and 8 adults (average age 31.5 ± 8.9 and 21.1 ± 4 years post-Fontan) using standard serum laboratory investigations assessing hepatic integrity and function, the FibroTest, liver ultrasound, and transient elastography (FibroScan). In adult Fontan patients, hemoglobin, C-reactive protein, and gamma-glutamyl transpeptidase were significantly increased, and white blood cell and platelet counts were significantly decreased in comparison to the pediatric cohort. International normalized ratio was mildly elevated in both children and adults. FibroTest results were suggestive of fibrosis regardless of time post-Fontan. FibroScan measurements were significantly correlated with time post-Fontan, but the incidence of ultrasound-detected liver abnormalities was variable. No cases of hepatocellular carcinoma were identified. Abnormalities suggestive of FALD occur in both children and adults post-Fontan. Select laboratory tests, and possibly ultrasound and FibroScan in some patients, appear to have the most promise for the non-invasive detection of FALD.

  15. Bacteraemic pneumonia caused by Neisseria lactamica with reduced susceptibility to penicillin and ciprofloxacin in an adult with liver cirrhosis.

    PubMed

    Wang, Cheng-Yi; Chuang, Yu-Min; Teng, Lee-Jene; Lee, Li-Na; Yang, Pan-Chyr; Kuo, Sow-Hsong; Hsueh, Po-Ren

    2006-08-01

    This report presents a case of bacteraemic pneumonia caused by Neisseria lactamica in an adult patient with liver cirrhosis who was successfully treated with ceftriaxone. The isolate was confirmed as N. lactamica by analysis of a partial sequence of the 16S rRNA gene; it had reduced susceptibilities to penicillin (MIC 0.75 microg ml(-1)) and ciprofloxacin (MIC > or =0.5 mg l(-1)).

  16. Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q

    SciTech Connect

    Wirtz, M.K.; Samples, J.R.; Kramer, P.L.

    1997-02-01

    Glaucoma is the third-leading cause of blindness in the world, affecting >13.5 million people. Adult-on-set primary open-angle glaucoma (POAG) is the most common form of glaucoma in the United States. We present a family in which adult-onset POAG is inherited as an autosomal dominant trait. Twelve affected family members were identified from 44 at-risk individuals. The disease-causing gene was mapped to chromosome 3q21-24, with analysis of recombinant haplotypes suggesting a total inclusion region of 11.1 cM between markers D3S3637 and D3S1744. This is the first report of mapping of an adult-onset POAG gene to chromosome 3q, gene symbol GLC1C. 57 refs., 3 figs., 3 tabs.

  17. Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q.

    PubMed Central

    Wirtz, M K; Samples, J R; Kramer, P L; Rust, K; Topinka, J R; Yount, J; Koler, R D; Acott, T S

    1997-01-01

    Glaucoma is the third-leading cause of blindness in the world, affecting >13.5 million people. Adult-onset primary open-angle glaucoma (POAG) is the most common form of glaucoma in the United States. We present a family in which adult-onset POAG is inherited as an autosomal dominant trait. Twelve affected family members were identified from 44 at-risk individuals. The disease-causing gene was mapped to chromosome 3q21-24, with analysis of recombinant haplotypes suggesting a total inclusion region of 11.1 cM between markers D3S3637 and D3S1744. This is the first report of mapping of an adult-onset POAG gene to chromosome 3q, gene symbol GLC1C. PMID:9012402

  18. [Screening for attention deficit hyperactivity disorder in adult patients in primary care].

    PubMed

    Aragonès, Enric; Cañisá, Anna; Caballero, Antònia; Piñol-Moreso, Josep Lluís

    2013-05-01

    AIMS. To estimate the proportion of adult patients in primary care with a positive screening test for attention deficit hyper-activity disorder (ADHD) and to analyse their characteristics. PATIENTS AND METHODS. A cross-sectional descriptive study was performed in nine primary care clinics in the province of Tarragona. The sample consisted of 432 consecutive patients in primary care who visited for any reason, with ages ranging from 18 to 55 years. Screening for ADHD was carried out by means of the Adult ADHD Self-Report Scale (ASRS). Data about functional impact (Sheehan Disability Inventory) were obtained and a review of the patient records provided data concerning psychiatric comorbidity and the consumption of psychopharmaceuticals. RESULTS. The percentage of positive results in the screening tests was 19.9% (95% CI = 16.4-23.9%). Taking into account the sensitivity and specificity of the ASRS, the 'real' prevalence was estimated to be 12.5% (95% CI = 8.2-16.8%). None of these patients were diagnosed or treated for ADHD. Positive screening tests are associated with occupational, social and familial dysfunction, and greater perceived stress. There is also a higher level of comorbidity with affective disorders and substance abuse, as well as greater use of psychopharmaceuticals. CONCLUSIONS. Screening for ADHD in adult patients in primary care gives rise to a notably high proportion of positive screening test results, which suggests that there could be a significant prevalence of patients with ADHD. These data contrast with the absence of this diagnosis in the patient records. Further research is needed to determine the usefulness of the diagnosis of ADHD and the possible role that must be played by primary care.

  19. Bioprinted 3D Primary Liver Tissues Allow Assessment of Organ-Level Response to Clinical Drug Induced Toxicity In Vitro

    PubMed Central

    Funk, Juergen; Robbins, Justin B.; Crogan-Grundy, Candace; Presnell, Sharon C.; Singer, Thomas; Roth, Adrian B.

    2016-01-01

    Modeling clinically relevant tissue responses using cell models poses a significant challenge for drug development, in particular for drug induced liver injury (DILI). This is mainly because existing liver models lack longevity and tissue-level complexity which limits their utility in predictive toxicology. In this study, we established and characterized novel bioprinted human liver tissue mimetics comprised of patient-derived hepatocytes and non-parenchymal cells in a defined architecture. Scaffold-free assembly of different cell types in an in vivo-relevant architecture allowed for histologic analysis that revealed distinct intercellular hepatocyte junctions, CD31+ endothelial networks, and desmin positive, smooth muscle actin negative quiescent stellates. Unlike what was seen in 2D hepatocyte cultures, the tissues maintained levels of ATP, Albumin as well as expression and drug-induced enzyme activity of Cytochrome P450s over 4 weeks in culture. To assess the ability of the 3D liver cultures to model tissue-level DILI, dose responses of Trovafloxacin, a drug whose hepatotoxic potential could not be assessed by standard pre-clinical models, were compared to the structurally related non-toxic drug Levofloxacin. Trovafloxacin induced significant, dose-dependent toxicity at clinically relevant doses (≤ 4uM). Interestingly, Trovafloxacin toxicity was observed without lipopolysaccharide stimulation and in the absence of resident macrophages in contrast to earlier reports. Together, these results demonstrate that 3D bioprinted liver tissues can both effectively model DILI and distinguish between highly related compounds with differential profile. Thus, the combination of patient-derived primary cells with bioprinting technology here for the first time demonstrates superior performance in terms of mimicking human drug response in a known target organ at the tissue level. PMID:27387377

  20. Primary liver tumors in pediatric patients: proper imaging technique for diagnosis and staging.

    PubMed

    Rozell, Joseph M; Catanzano, Tara; Polansky, Stanley M; Rakita, Dmitry; Fox, Lindsay

    2014-08-01

    Liver tumors in children are rare and comprise a diverse set of both benign and malignant lesions, most of which are not clinically detected until they are large and often difficult to resect. Technological advances in diagnostic imaging have greatly influenced the surgical planning of these lesions and ultimately the clinical outcome. The intent of this article is to present an imaging algorithm for the effective and efficient workup of liver tumors in pediatric patients. This includes the appropriate timing and use of various imaging modalities, such as conventional radiographs, ultrasound, computed tomography, and magnetic resonance imaging. This article also addresses the use of sedation, intravenous contrast agents, and the benefits and limitations of specific imaging modalities. An overview of the radiologic and pathologic findings in common liver lesions in pediatric patients, as well as individual case examples demonstrating the use of the proposed workup algorithm, is provided.

  1. Prediction of radiation-induced liver disease by Lyman normal-tissue complication probability model in three-dimensional conformal radiation therapy for primary liver carcinoma

    SciTech Connect

    Xu ZhiYong; Liang Shixiong; Zhu Ji; Zhu Xiaodong; Zhao Jiandong; Lu Haijie; Yang Yunli; Chen Long; Wang Anyu; Fu Xiaolong; Jiang Guoliang . E-mail: jianggl@21cn.com

    2006-05-01

    Purpose: To describe the probability of RILD by application of the Lyman-Kutcher-Burman normal-tissue complication (NTCP) model for primary liver carcinoma (PLC) treated with hypofractionated three-dimensional conformal radiotherapy (3D-CRT). Methods and Materials: A total of 109 PLC patients treated by 3D-CRT were followed for RILD. Of these patients, 93 were in liver cirrhosis of Child-Pugh Grade A, and 16 were in Child-Pugh Grade B. The Michigan NTCP model was used to predict the probability of RILD, and then the modified Lyman NTCP model was generated for Child-Pugh A and Child-Pugh B patients by maximum-likelihood analysis. Results: Of all patients, 17 developed RILD in which 8 were of Child-Pugh Grade A, and 9 were of Child-Pugh Grade B. The prediction of RILD by the Michigan model was underestimated for PLC patients. The modified n, m, TD{sub 5} (1) were 1.1, 0.28, and 40.5 Gy and 0.7, 0.43, and 23 Gy for patients with Child-Pugh A and B, respectively, which yielded better estimations of RILD probability. The hepatic tolerable doses (TD{sub 5}) would be MDTNL of 21 Gy and 6 Gy, respectively, for Child-Pugh A and B patients. Conclusions: The Michigan model was probably not fit to predict RILD in PLC patients. A modified Lyman NTCP model for RILD was recommended.

  2. Dynamics of amino acid metabolism of primary human liver cells in 3D bioreactors

    PubMed Central

    Zeilinger, K.; Sickinger, S.; Schmidt-Heck, W.; Buentemeyer, H.; Iding, K.; Lehmann, J.; Pfaff, M.; Pless, G.; Gerlach, J.C.

    2006-01-01

    The kinetics of 18 amino acids, ammonia (NH3) and urea (UREA) in 18 liver cell bioreactor runs were analyzed and simulated by a two-compartment model consisting of a system of 42 differential equations. The model parameters, most of them representing enzymatic activities, were identified and their values discussed with respect to the different liver cell bioreactor performance levels. The nitrogen balance based model was used as a tool to quantify the variability of runs and to describe different kinetic patterns of the amino acid metabolism, in particular with respect to glutamate (GLU) and aspartate (ASP). PMID:16550345

  3. Clinical, histopathologic, and genetic features of pediatric primary myelofibrosis--an entity different from adults.

    PubMed

    DeLario, Melissa R; Sheehan, Andrea M; Ataya, Ramona; Bertuch, Alison A; Vega, Carlos; Webb, C Renee; Lopez-Terrada, Dolores; Venkateswaran, Lakshmi

    2012-05-01

    Primary myelofibrosis is a chronic myeloproliferative neoplasm characterized by cytopenias, leukoerythroblastosis, extramedullary hematopoiesis, hepatosplenomegaly and bone marrow fibrosis. Primary myelofibrosis is a rare disorder in adults; children are even less commonly affected by this entity, with the largest pediatric case series reporting on three patients. Most literature suggests spontaneous resolution of myelofibrosis without long term complications in the majority of affected children. We describe the clinical, pathologic, and molecular characteristics and outcomes of nineteen children with primary myelofibrosis treated in our center from 1984 to 2011. Most patients had cytopenia significant enough to require supportive therapy. No child developed malignant transformation and only five of the 19 children (26%) had spontaneous resolution of disease. Sequence analyses for JAK2V617F and MPLW515L mutations were performed on bone marrow samples from 17 and six patients, respectively, and the results were negative. In conclusion, analysis of this large series of pediatric patients with primary myelofibrosis demonstrates distinct clinical, hematologic, bone marrow, and molecular features from adult patients.

  4. Expression in Escherichia coli of the flavin-containing monooxygenase D (form II) from adult human liver: determination of a distinct tertiary amine substrate specificity.

    PubMed

    Lomri, N; Yang, Z; Cashman, J R

    1993-01-01

    The cDNA for a major component of the family of flavin-containing monooxygenases (FMOs) present in adult human liver (i.e., HLFMO-D) has been cloned and expressed in a prokaryotic system. Escherichia coli strain NM522 was transformed with pTrcHLFMO-D, and the HLFMO-D cDNA was expressed under the control of the Trc promoter. A variety of tertiary amine substrates [i.e., chlorpromazine and 10-[(N,N-dimethylamino)alkyl]- 2-(trifluoromethyl)phenothiazines] were efficiently oxygenated by HLFMO-D cDNA expressed in E. coli or by adult human liver microsomes. Approximate dimensions of the substrate binding channel for both adult human liver microsomal FMO and cDNA-expressed HLFMO-D were apparent from an examination of the N-oxygenation of a series of 10-[(N,N-dimethylamino)alkyl]-2-(trifluoromethyl)phenothiazines. The substrate regioselectivity studies suggest that adult human liver FMO form D possesses a distinct substrate specificity compared with form A FMO from animal hepatic sources. It is likely that the substrate specificity observed for cDNA-expressed adult human liver FMO-D may have consequences for the metabolism and distribution of tertiary amines and phosphorus- and sulfur-containing drugs in humans and may provide insight into the physiologic substrate(s) for adult human liver FMO.

  5. The distinction between juvenile and adult-onset primary open-angle glaucoma

    SciTech Connect

    Wiggs, J.L.; Haines, J.L.; Damji, K.F.

    1996-01-01

    Because of the significant differences between the juvenile and adult forms of open-angle glaucoma, especially with regard to inheritance, prevalence, severity, and age of onset, we read with interest the recent publication by Morissette et al., describing a pedigree with a phenotype that overlaps the distinctive features of juvenile-onset open-angle glaucoma (JOAG) and adult-onset primary open-angle glaucoma (usually abbreviated as POAG or COAG). These authors conclude that a gene mapped to human chromosome 1q21-q31 (GLC1A) can be responsible for both juvenile and adult forms of open-angle glaucoma. The implications of such a result could be extremely important, in light of the high prevalence of the adult form of the disease. However, while the data presented in this report suggest that variable expressivity of the GLC1A gene may lead to a broader range of onset for this form of juvenile glaucoma, these data do not identify the GLC1A gene as an important cause of POAG. To prevent misleading interpretations of this and similar studies, we wish to clarify the distinction between the juvenile and adult forms of open-angle glaucoma. 8 refs.

  6. Genus Distichopora (Cnidaria, Hydrozoa): from primary cyclosystem to adult pore organisation

    NASA Astrophysics Data System (ADS)

    Puce, S.; Pica, D.; Brun, F.; Mancini, L.; Bavestrello, G.

    2012-09-01

    This investigation provides the first detailed description of the growth stages of two Distichopora species showing the formation of a primary cyclosystem and explaining the growth process leading from primary cyclosystem to adult pore organisation. The earliest observed stage is an oval calcareous disc from which, at a later stage, a primary cyclosystem raises up. Then, the addition of new gastropores and dactylopores leads to the pore rows typical of the genus. Using X-ray computed microtomography, we are able to visualise the dense canal network that permeates the coenosteum and envelops the gastropores and the dactylopores in all the observed growth stages. In both species, the thin canals surrounding the gastropores are responsible for the formation of the new gastropores that originate between the old ones, while the thin canals placed on the external side of the dactylopore rows produce the new dactylopores.

  7. Survey of adult liver transplantation techniques (SALT): an international study of current practices in deceased donor liver transplantation

    PubMed Central

    Kluger, Michael D; Memeo, Riccardo; Laurent, Alexis; Tayar, Claude; Cherqui, Daniel

    2011-01-01

    Background There has been little focus lately on operative techniques for full graft liver transplantation, and the standard technique is unclear. Methods An internet survey addressing the key technical issues was e-mailed to programme directors. Results Responses were obtained from 93 out of 128 (73%) directors contacted. Programmes performed a median of 60 (8–240) transplants per year. Maximum mean cold time of 13 ± 3 h and maximum median steatosis of 40% (15–90%) were tolerated. The inferior vena cava was preserved by 48% of centres all the time and 43% selectively. European centres used temporary portacaval shunting (42%) four times more often than USA programmes. Venous bypass was always used when not preserving the inferior vena cava by less than 25%, and used selectively by approximately 40% of centres. Portal vein anastomosis with room for expansion (88%), graft hepatic artery to native gastroduodenal/common hepatic artery bifurcation (57%) and bile duct-to-duct (47%) were the favoured techniques. Discussion A standard international operative technique for deceased donor liver transplantation does not exist, although there is a trend towards inferior vena cava preservation. Donor selection criteria were more homogenous across programmes. As suggested by the high response rate, there likely exists interest to investigate technical variations on an international scale. PMID:21929669

  8. Strategic breakthrough in adult ABO-incompatible living donor liver transplantation: preliminary results of consecutive seven cases.

    PubMed

    Soejima, Yuji; Muto, Jyun; Matono, Rumi; Ninomiya, Mizuki; Ikeda, Tetsuo; Yoshizumi, Tomoharu; Uchiyama, Hideaki; Ikegami, Toru; Shirabe, Ken; Maehara, Yoshihiko

    2013-01-01

    ABO-incompatibility is a major obstacle to expanding exiguous donor pools in adult liver transplantation, especially in countries where grafts from deceased donors are uncommon. We present our preliminary results of ABO-incompatible (ABO-I) adult living donor liver transplantation (LDLT) using a new, simple protocol. Seven consecutive cases of ABO-I LDLT were managed by the same protocol including pre-operative administration of a single dose of rituximab (375 mg/m(2) ) followed by three to five sessions of plasma exchange before LDLT without portal infusion therapy. The triple immunosuppression protocol consisted of tacrolimus, mycophenolate mofetil and steroids, with mycophenolate mofetil starting seven d before LDLT. Splenectomy was performed for all cases. All patients are alive (100% survival) with a mean follow-up of 852 d (715-990 d). Neither antibody-mediated nor hyperacute rejection were encountered. There was only one episode of mild acute cellular rejection, for which steroid augmentation was effective. The median preformed isoagglutinin antibody titer before plasma exchange was 256, while the median antibody titer immediately before LDLT was 16. In conclusion, adult ABO-I LDLT results were excellent - comparable or even superior to those of ABO-compatible LDLT. ABO-I adult LDLT has now become a more applicable modality without the need for an appropriate donor.

  9. A Case of O1 Vibrio Cholera Bacteremia and Primary Peritonitis in a Patient With Liver Cirrhosis

    PubMed Central

    Issa, Hussain; Shorman, Mahmoud; Bseiso, Bahaa; Al-Salem, Ahmed H.

    2009-01-01

    Vibrio cholerae are Gram-negative bacteria that are differentiated into O1/O139 and non-O1/non-O139 serogroups depending on their ability to agglutinate with specific antiserum. In contrast to non-O1/non-0139 Vibrio cholerae, which are more prone to invade the bloodstream, Vibrio cholerae O1 is rarely the cause of bacteremia. We report a case of O1 Vibrio cholera bacteremia and primary peritonitis in a patient with liver cirrhosis. The literature on the subject is also reviewed. PMID:27990208

  10. Repeated dose liver micronucleus assay using adult mice with multiple genotoxicity assays concurrently performed as a combination test.

    PubMed

    Hagio, Soichiro; Furukawa, Satoshi; Abe, Masayoshi; Kuroda, Yusuke; Hayashi, Seigo; Ogawa, Izumi

    2014-06-01

    Recently, the liver micronucleus (MN) assay using young adult rats with repeated administrations has been investigated by employing a new method without partial hepatectomy or in situcollagenase perfusion as the repeated dose liver MN (RDLMN) assay by Narumi et al. (2012). In our study, in order to investigate the possibility of the RDLMN assay using young adult mice instead of rats and the feasibility of employing some genotoxicity assays along with the RDLMN assay as a combination test, two genotoxic carcinogens (N,N-diethylnitrosoamine (DEN) and cisplatin (CIS)) and a nongenotoxic carcinogen (phenobarbital sodium (PHE)) were administered to mice for 15 or 29 days. Then, the liver MN assay, peripheral blood (PB) MN assay and comet assay using the liver and kidney were concurrently performed as a combination test. DEN showed positive responses to all endpoints except MN induction in PB after 15 days of repeat administration. A cross-linking agent, CIS, showed MN induction in liver after 29 days of repeat administration, and in PB after 15 and 29 days of repeat administration, although the comet assay yielded negative responses for both organs at both sampling times. PHE yielded negative responses for all endpoints. In conclusion, it is suggested that the RDLMN assay using mice is a feasible method to be integrated into the general repeated toxicity test along with the combination assays, i.e., comet assay or PB MN assay, which would help in risk assessment for carcinogenicity by comparing the results of combination assays with each other.

  11. Pure Laparoscopic Versus Open Liver Resection for Primary Liver Carcinoma in Elderly Patients: A Single-Center, Case-Matched Study.

    PubMed

    Wang, Xi-Tao; Wang, Hong-Guang; Duan, Wei-Dong; Wu, Cong-Ying; Chen, Ming-Yi; Li, Hao; Huang, Xin; Zhang, Fu-Bo; Dong, Jia-Hong

    2015-10-01

    Pure laparoscopic liver resection (PLLR) has been reported to be as safe and effective as open liver resection (OLR) for liver lesions, and it is associated with less intraoperative blood loss, shorter hospital stay, and lower complication rate. However, studies comparing PLLR with OLR in elderly patients were limited. The aim of this study was to analyze the short-term outcome of PLLR versus OLR for primary liver carcinoma (PLC) in elderly patients.Between January 2008 and October 2014, 30 consecutive elderly patients (≥70 years) who underwent PLLR for PLC were included into analysis. Sixty patients who received OLR for PLC during the same study period were also included as a case-matched control group. Patients were well matched in terms of age, sex, comorbid illness, Child Pugh class, American Society of Anesthesiologists grade, tumor size, tumor location, and extent of hepatectomy.No significant differences were observed with regard to patient preoperative baseline status, median tumor size (Group PLLR 4.0 cm vs Group OLR 5.0 cm, P = 0.125), tumor location, extent of hepatectomy, and operation time (Group PLLR 133 minutes vs Group OLR 170 minutes, P = 0.073). Compared with OLR, the PLLR group displayed a significantly less frequent Pringle maneuver application (10.0% vs 70.0%, P < 0.001), less blood loss (100 vs 300 mL; P < 0.001), shorter hospital stay (5 vs 10 days; P < 0.001), and lower total hospitalization cost ($9147.50 vs $10,867.10, P = 0.008). The postoperative complication rates were similar between groups (Group PLLR 10.0% vs Group OLR 16.7%; P = 0.532). There was no hospital mortality in both groups.PLLR for PLC is as safe and feasible as OLR, but with less blood loss, shorter hospital stay, and lower hospitalization cost for selected elderly patients.

  12. Polychlorinated Biphenyls, Lead, and Mercury Are Associated with Liver Disease in American Adults: NHANES 2003–2004

    PubMed Central

    Cave, Matt; Appana, Savitri; Patel, Mihir; Falkner, Keith Cameron; McClain, Craig J.; Brock, Guy

    2010-01-01

    Background High-level occupational exposures to some industrial chemicals have been associated with liver diseases, including nonalcoholic fatty liver disease (NAFLD). However, the potential role of low-level environmental pollution on liver disease in the general population has not been evaluated. Objective We determined whether environmental pollutants are associated with an elevation in serum alanine aminotransferase (ALT) activity and suspected NAFLD in U.S. adults. Methods This cross-sectional cohort study evaluated adult participants without viral hepatitis, hemochromatosis, or alcoholic liver disease from the National Health and Nutrition Examination Survey (NHANES) for 2003–2004. ALT elevation was defined in men as ≥ 37 IU/L (age18–20 years) and ≥ 48 IU/L (age ≥ 21 years) and in women as ≥ 30 IU/L (age 18–20 years) and ≥ 31 IU/L (age ≥ 21 years). Adjusted odds ratios (ORs) for ALT elevation were determined across exposure quartiles for 17 pollutant subclasses comprising 111 individual pollutants present with at least a 60% detection rate. Adjustments were made for age, race/ethnicity, sex, body mass index, poverty income ratio, and insulin resistance. Individual pollutants from subclasses associated with ALT elevation were subsequently analyzed. Results The overall prevalence of ALT elevation was 10.6%. Heavy metals and polychlorinated biphenyls (PCBs) were associated with dose-dependent increased adjusted ORs for ALT elevation. Within these subclasses, increasing whole-blood levels of lead and mercury and increasing lipid-adjusted serum levels of 20 PCBs were individually associated with ALT elevation. Conclusions PCB, lead, and mercury exposures were associated with unexplained ALT elevation, a proxy marker of NAFLD, in NHANES 2003–2004 adult participants. PMID:21126940

  13. Primary mucosa-associated lymphoid tissue lymphoma of the liver: A report of two cases and review of the literature

    PubMed Central

    Obiorah, Ifeyinwa E; Johnson, Lynt; Ozdemirli, Metin

    2017-01-01

    Mucosa-associated lymphoid tissue (MALT) lymphoma of the liver is a very rare condition and thus the diagnosis may be challenging. The clinical presentation is usually variable, ranging from minimal clinical symptoms to severe end stage liver disease. In this paper, we describe the clinicopathologic findings in two cases of primary hepatic MALT lymphoma. One case is an 80-year-old female with no underlying chronic liver disease and the second case is a 30-year-old female with autoimmune hepatitis complicated by MALT lymphoma. In both specimens, there was diffuse infiltration of atypical B-lymphocytes that were positive for CD20 and CD79a, but negative for CD5, CD43 and CD10. There were occasional lymphoepithelial lesions involving the hepatocytes or bile ducts. Polymerase chain reaction analysis showed monoclonal immunoglobulin heavy chain gene rearrangement in both cases. The first case was treated with surgery but developed pulmonary recurrence a year after complete resection but went into remission following treatment with rituximab. A second recurrence occurred in the right parotid gland 7 years later, which was treated with idelalisib. The second case was effectively treated with rituximab. To our knowledge, the second case is the first reported case linked to autoimmune hepatitis. PMID:28217252

  14. Arthroscopic Treatment for Primary Septic Arthritis of the Hip in Adults

    PubMed Central

    2016-01-01

    Purpose. Primary septic arthritis is a rare differential diagnosis of acute hip pain in adults. Inspired by the success of all-arthroscopic treatment in pediatric patients, we developed a diagnostic and surgical pathway for our adult patients. Methods. Seven patients, average age 44 ± 13.7 years with acute hip pain since 4.4 ± 2.9 days in the average, were included. Septic arthritis was confirmed by joint aspiration and dissemination was excluded by MRI and standard radiographs. Surgical treatment consisted of immediate arthroscopic lavage using 4 portals for debridement, high-volume irrigation, partial synovectomy, and drainage. Results. Patients were treated in hospital for 12.4 ± 3.1 days (range 7–16 days). WBC and CRP returned to physiological levels. During the mean follow-up of 26.4 ± 19.4 months (range 13–66 months) no patient showed recurrence of infection. The 5 patients with an unimpaired hip joint prior to the infection had a mean modified Harris Hip Score of 94 ± 5.6 points (range 91–100) at final follow-up. Conclusions. Arthroscopic therapy using a minimally invasive approach with low perioperative morbidity for the treatment of primary septic arthritis of the adult hip is able to restore normal hip function in acute cases without dissemination of the infection. Level of Evidence. IV. PMID:27800188

  15. Primary solitary fibrous tumors of liver: a case report and literature review

    PubMed Central

    2013-01-01

    A 42-year-old male presented right upper abdomen pain for more than 6 days, which misdiagnose calculus of intrahepatic duct and acute cholecystitis. An approximately 1.5 cm x 1.0 cm x 1.0 cm nodule was found and resected in left lateral lobe of hepatic. Pathological examination showed spindle cell and fibroblast -like cells within the collagenous stroma. Immunohistochemically, these spindle tumor cells showed diffuse Vim and Bcl-2 positive reactivity, but S-100 protein and HMB45 were negative. The post-operative course was uneventful. Solitary fibrous tumors of the liver, although rare, should be differentiated from mesenchymal lesions of the liver. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4214341041091088. PMID:24294990

  16. Induction of fatty acid synthesis by pravastatin sodium in rat liver and primary hepatocytes.

    PubMed

    Fujioka, T; Tsujita, Y; Shimotsu, H

    1997-06-11

    We examined the effect of pravastatin sodium (pravastatin), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on fatty acid synthesis in rat liver. The repeated administration of pravastatin to rats at 250 mg/kg for 7 days led to a 2.8-fold increase in fatty acid synthesis in the liver. The diurnal change of fatty acid synthesis was not affected by the treatment. Hepatic fatty acid synthase activity was increased 3.2-fold, while acetyl-CoA carboxylase activity was not changed by the repeated administration of pravastatin. In rat hepatocytes, the incubation with 2 microg/ml pravastatin for 24 h increased fatty acid synthase activity 1.5-fold, as well as HMG-CoA reductase activity 2.8-fold. These results suggest that HMG-CoA reductase inhibitors might increase fatty acid synthesis in vivo through the induction of hepatic fatty acid synthase.

  17. Chromosome region maintenance 1 expression and its association with clinical pathological features in primary carcinoma of the liver

    PubMed Central

    XIE, QIAO-LING; LIU, YUE; ZHU, YING

    2016-01-01

    Liver cancer is the third leading cause of cancer-associated mortality worldwide. Recurrence and metastasis are the major factors affecting the prognosis; thus, investigation of the underlying molecular mechanisms of invasion and metastasis, and detection of novel drug target may improve the mortality rate of liver cancer patients. Chromosome region maintenance 1 (CRM1) recognizes specific leucine-rich nuclear export signal sequences, and its overexpression is associated with tumor-suppressor gene inactivation, proliferation, invasion and resistance to chemotherapy. The aim of the present study was to examine the association of CRM1 expression with the clinical and pathological features of primary liver cancer. In total, 152 cases diagnosed with liver cancer were included. CRM1 expression was detected in cancer tissues and adjacent normal tissues by immunohistochemical assay. No statistically significant difference was found between the CRM1 expression levels in tumor and adjacent normal tissues (P=0.106). However, CRM1 expression in adjacent normal tissues was higher compared with that in tumor tissues in the negative hepatitis B envelope antigen (HBeAg; P=0.029) and low differentiation (P=0.004) groups. In tumor tissues, CRM1 expression was significantly correlated with differentiation (P=0.045), whereas in adjacent normal tissues, CRM1 expression was significantly correlated with the tumor diameter (P=0.004). Therefore, it can be concluded that CRM1 is highly expressed in both tumor and adjacent normal tissues. Furthermore, CRM1 expression is associated with the tumor differentiation degree and diameter. Lower differentiation and larger tumor diameter resulted in higher CRM1 expression in adjacent normal tissues, and higher tendency for invasion and metastasis. In addition, the risk of invasion and metastasis remains in chronic hepatitis B patients with negative HBeAg. PMID:27347018

  18. Chromosome region maintenance 1 expression and its association with clinical pathological features in primary carcinoma of the liver.

    PubMed

    Xie, Qiao-Ling; Liu, Yue; Zhu, Ying

    2016-07-01

    Liver cancer is the third leading cause of cancer-associated mortality worldwide. Recurrence and metastasis are the major factors affecting the prognosis; thus, investigation of the underlying molecular mechanisms of invasion and metastasis, and detection of novel drug target may improve the mortality rate of liver cancer patients. Chromosome region maintenance 1 (CRM1) recognizes specific leucine-rich nuclear export signal sequences, and its overexpression is associated with tumor-suppressor gene inactivation, proliferation, invasion and resistance to chemotherapy. The aim of the present study was to examine the association of CRM1 expression with the clinical and pathological features of primary liver cancer. In total, 152 cases diagnosed with liver cancer were included. CRM1 expression was detected in cancer tissues and adjacent normal tissues by immunohistochemical assay. No statistically significant difference was found between the CRM1 expression levels in tumor and adjacent normal tissues (P=0.106). However, CRM1 expression in adjacent normal tissues was higher compared with that in tumor tissues in the negative hepatitis B envelope antigen (HBeAg; P=0.029) and low differentiation (P=0.004) groups. In tumor tissues, CRM1 expression was significantly correlated with differentiation (P=0.045), whereas in adjacent normal tissues, CRM1 expression was significantly correlated with the tumor diameter (P=0.004). Therefore, it can be concluded that CRM1 is highly expressed in both tumor and adjacent normal tissues. Furthermore, CRM1 expression is associated with the tumor differentiation degree and diameter. Lower differentiation and larger tumor diameter resulted in higher CRM1 expression in adjacent normal tissues, and higher tendency for invasion and metastasis. In addition, the risk of invasion and metastasis remains in chronic hepatitis B patients with negative HBeAg.

  19. Establishment of a primary hepatocyte culture from the small Indian mongoose (Herpestes auropunctatus) and distribution of mercury in liver tissue.

    PubMed

    Horai, Sawako; Yanagi, Kumiko; Kaname, Tadashi; Yamamoto, Masatatsu; Watanabe, Izumi; Ogura, Go; Abe, Shintaro; Tanabe, Shinsuke; Furukawa, Tatsuhiko

    2014-11-01

    The present study established a primary hepatocyte culture for the small Indian mongoose (Herpestes auropunctatus). To determine the suitable medium for growing the primary hepatic cells of this species, we compared the condition of cells cultured in three media that are frequently used for mammalian cell culture: Dulbecco's Modified Eagle's Medium, RPMI-1640, and William's E. Of these, William's E medium was best suited for culturing the hepatic cells of this species. Using periodic acid-Schiff staining and ultrastructural observations, we demonstrated the cells collected from mongoose livers were hepatocytes. To evaluate the distribution of mercury (Hg) in the liver tissue, we carried out autometallography staining. Most of the Hg compounds were found in the central region of hepatic lobules. Smooth endoplasmic reticulum, which plays a role inxenobiotic metabolism, lipid/cholesterol metabolism, and the digestion and detoxification of lipophilic substances is grown in this area. This suggested that Hg colocalized with smooth endoplasmic reticulum. The results of the present study could be useful to identify the detoxification systems of wildlife with high Hg content in the body, and to evaluate the susceptibility of wildlife to Hg toxicity.

  20. Treatment of unresectable primary and metastatic liver cancer with yttrium-90 microspheres (TheraSphere): assessment of hepatic arterial embolization.

    PubMed

    Sato, Kent; Lewandowski, Robert J; Bui, James T; Omary, Reed; Hunter, Russell D; Kulik, Laura; Mulcahy, Mary; Liu, David; Chrisman, Howard; Resnick, Scott; Nemcek, Albert A; Vogelzang, Robert; Salem, Riad

    2006-01-01

    In Canada and Europe, yttrium-90 microspheres (TheraSphere); MDS Nordion, Ottawa, Canada) are a primary treatment option for primary and secondary hepatic malignancies. We present data from 30 patients with hepatocellular carcinoma (HCC) and metastatic liver disease treated with TheraSphere from a single academic institution to evaluate the angiographically evident embolization that follows treatment. Seven interventional radiologists from one treatment center compared pretreatment and posttreatment angiograms. The reviewers were blinded to the timing of the studies. The incidence of postembolization syndrome (PES) was determined as well as objective tumor response rates by the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), and European Association for the Study of the Liver (EASL) criteria. There were 420 independent angiographic observations that were assessed using the chi-squared statistic. The pretreatment and posttreatment angiograms could not be correctly identified on average more than 43% of the time (p = 0.0004). The postprocedure arterial patency rate was 100%. The objective tumor response rates for all patients were 24%, 31%, and 72% for WHO, RECIST, and EASL criteria, respectively. All of the patients tolerated the procedure without complications and were treated on an outpatient basis, and four patients had evidence of PES. This treatment method does not result in macroscopic embolization of the hepatic arteries, thereby maintaining hepatic tissue perfusion. These data support the principle that the favorable response rates reported with TheraSphere are likely due to radiation and microscopic embolization rather than flow-related macroscopic embolization and ischemia.

  1. Incidence of Primary Mitochondrial Disease in Children Younger Than 2 Years Presenting With Acute Liver Failure

    PubMed Central

    McKiernan, Patrick; Ball, Sarah; Santra, Saikat; Foster, Katherine; Fratter, Carl; Poulton, Joanna; Craig, Kate; McFarland, Robert; Rahman, Shamima; Hargreaves, Iain; Gupte, Girish; Sharif, Khalid; Taylor, Robert W.

    2016-01-01

    ABSTRACT Background: Mitochondrial liver disease (MLD), and in particular mitochondrial DNA (mtDNA) depletion syndrome (MDS) is an important cause of acute liver failure (ALF) in infancy. Early and accurate diagnosis is important because liver transplantation (LT) is often contraindicated. It is unclear which methods are the best to diagnose MLD in the setting of ALF. Objective: The aim of the study was to determine the incidence of MLD in children younger than 2 years with ALF and the utility of routine investigations to detect MLD. Methods: Thirty-nine consecutive infants with ALF were admitted to a single unit from 2009 to 2011. All were extensively investigated using an established protocol. Genes implicated in mitochondrial DNA depletion syndrome were sequenced in all cases and tissue mtDNA copy number measured where available. Results: Five infants (17%) had genetically proven MLD: DGUOK (n = 2), POLG (n = 2), and MPV17 (1). Four of these died, whereas 1 recovered. Two had normal muscle mtDNA copy number and 3 had normal muscle respiratory chain enzymes. An additional 8 children had low hepatic mtDNA copy number but pathogenic mutations were not detected. One of these developed fatal multisystemic disease after LT, whereas 5 who survived remain well without evidence of multisystemic disease up to 6 years later. Magnetic resonance spectroscopy did not distinguish between those with and without MLD. Conclusions: Low liver mtDNA copy number may be a secondary phenomenon in ALF. Screening for mtDNA maintenance gene mutations may be the most efficient way to confirm MLD in ALF in the first 2 years of life. PMID:27482763

  2. Adult depression screening in Saudi primary care: prevalence, instrument and cost

    PubMed Central

    2014-01-01

    Background By the year 2020 depression would be the second major cause of disability adjusted life years lost, as reported by the World Health Organization. Depression is a mental illness which causes persistent low mood, a sense of despair, and has multiple risk factors. Its prevalence in primary care varies between 15.3-22%, with global prevalence up to 13% and between 17-46% in Saudi Arabia. Despite several studies that have shown benefit of early diagnosis and cost-savings of up to 80%, physicians in primary care setting continue to miss out on 30-50% of depressed patients in their practices. Methods A cross sectional study was conducted at three large primary care centers in Riyadh, Saudi Arabia aiming at estimating point prevalence of depression and screening cost among primary care adult patients, and comparing Patient Health Questionnaires PHQ-2 with PHQ-9. Adult individuals were screened using Arabic version of PHQ-2 and PHQ-9. PHQ-2 scores were correlated with PHQ-9 scores using linear regression. A limited cost-analysis and cost saving estimates of depression screening was done using the Human Capital approach. Results Patients included in the survey analysis were 477, of whom 66.2% were females, 77.4% were married, and nearly 20% were illiterate. Patients exhibiting depressive symptoms on the basis of PHQ9 were 49.9%, of which 31% were mild, 13.4% moderate, 4.4% moderate-severe and 1.0% severe cases. Depression scores were significantly associated with female gender (p-value 0.049), and higher educational level (p-value 0.002). Regression analysis showed that PHQ-2 & PHQ-9 were strongly correlated R = 0.79, and R2 = 0.62. The cost-analysis showed savings of up to 500 SAR ($133) per adult patient screened once a year. Conclusion The point prevalence of screened depression is high in primary care visitors in Saudi Arabia. Gender and higher level of education were found to be significantly associated with screened depression. Majority of cases were mild to

  3. Associations between adult attachment characteristics, medical burden, and life satisfaction among older primary care patients.

    PubMed

    Kirchmann, Helmut; Nolte, Tobias; Runkewitz, Kristin; Bayerle, Lisa; Becker, Simone; Blasczyk, Verena; Lindloh, Julia; Strauss, Bernhard

    2013-12-01

    We investigated whether attachment security, measured by the Adult Attachment Prototype Rating (AAPR), was correlated with life satisfaction, independent of sociodemographic characteristics, medical burden, and age-related coping strategies in a sample of 81 patients (69-73 years) recruited from the register of a general primary care practice. Furthermore, we examined whether patients classified as AAPR-secure reported better adjustment to medical burden in terms of higher life satisfaction than did insecure patients. Attachment security was independently related to life satisfaction. Moreover, the association between medical burden and lower life satisfaction was significantly stronger for insecure than for secure participants. Our findings indicate that interventions to improve attachment security or coping processes related to attachment could help older adults retain life satisfaction.

  4. Long-term coculture strategies for primary hepatocytes and liver sinusoidal endothelial cells.

    PubMed

    Bale, Shyam Sundhar; Golberg, Inna; Jindal, Rohit; McCarty, William J; Luitje, Martha; Hegde, Manjunath; Bhushan, Abhinav; Usta, Osman Berk; Yarmush, Martin L

    2015-04-01

    Hepatocytes and their in vitro models are essential tools for preclinical screening studies for drugs that affect the liver. Most of the current models primarily focus on hepatocytes alone and lack the contribution of non-parenchymal cells (NPCs), which are significant through both molecular and the response of the NPCs themselves. Models that incorporate NPCs alongside hepatocytes hold the power to enable more realistic recapitulation and elucidation of cell interactions and cumulative drug response. Hepatocytes and liver sinusoidal endothelial cells (LSECs) account for ∼ 80% of the liver mass where the LSECs line the walls of blood vessels, and act as a barrier between hepatocytes and blood. Culturing LSECs with hepatocytes to generate multicellular physiologically relevant in vitro liver models has been a major hurdle since LSECs lose their phenotype rapidly after isolation. To this end, we describe the application of collagen gel (1) in a sandwich and (2) as an intervening extracellular matrix layer to coculture hepatocytes with LSECs for extended periods. These coculture configurations provide environments wherein hepatocyte and LSECs, through cell-cell contacts and/or secretion factors, lead to enhanced function and stability of the cocultures. Our results show that in these configurations, hepatocytes and LSECs maintained their phenotypes when cultured together as a mixture, and showed stable secretion and metabolic activity for up to 4 weeks. Immunostaining for sinusoidal endothelial 1 (SE-1) antibody demonstrated retention of LSEC phenotype during the culture period. In addition, LSECs cultured alone maintained high viability and SE-1 expression when cultured within a collagen sandwich configuration up to 4 weeks. Albumin production of the cocultures was 10-15 times higher when LSECs were cultured as a bottom layer (with an intervening collagen layer) and as a mixture in a sandwich configuration, and native CYP 1A1/2 activity was at least 20 times higher

  5. Long-Term Coculture Strategies for Primary Hepatocytes and Liver Sinusoidal Endothelial Cells

    PubMed Central

    Bale, Shyam Sundhar; Golberg, Inna; Jindal, Rohit; McCarty, William J.; Luitje, Martha; Hegde, Manjunath; Bhushan, Abhinav; Usta, Osman Berk

    2015-01-01

    Hepatocytes and their in vitro models are essential tools for preclinical screening studies for drugs that affect the liver. Most of the current models primarily focus on hepatocytes alone and lack the contribution of non-parenchymal cells (NPCs), which are significant through both molecular and the response of the NPCs themselves. Models that incorporate NPCs alongside hepatocytes hold the power to enable more realistic recapitulation and elucidation of cell interactions and cumulative drug response. Hepatocytes and liver sinusoidal endothelial cells (LSECs) account for ∼80% of the liver mass where the LSECs line the walls of blood vessels, and act as a barrier between hepatocytes and blood. Culturing LSECs with hepatocytes to generate multicellular physiologically relevant in vitro liver models has been a major hurdle since LSECs lose their phenotype rapidly after isolation. To this end, we describe the application of collagen gel (1) in a sandwich and (2) as an intervening extracellular matrix layer to coculture hepatocytes with LSECs for extended periods. These coculture configurations provide environments wherein hepatocyte and LSECs, through cell–cell contacts and/or secretion factors, lead to enhanced function and stability of the cocultures. Our results show that in these configurations, hepatocytes and LSECs maintained their phenotypes when cultured together as a mixture, and showed stable secretion and metabolic activity for up to 4 weeks. Immunostaining for sinusoidal endothelial 1 (SE-1) antibody demonstrated retention of LSEC phenotype during the culture period. In addition, LSECs cultured alone maintained high viability and SE-1 expression when cultured within a collagen sandwich configuration up to 4 weeks. Albumin production of the cocultures was 10–15 times higher when LSECs were cultured as a bottom layer (with an intervening collagen layer) and as a mixture in a sandwich configuration, and native CYP 1A1/2 activity was at least 20 times

  6. [The hepatic differentiation of adult and fetal liver stromal cells in vitro].

    PubMed

    Kholodenko, I V; Kholodenko, R V; Manukyan, G V; Yarygin, K N

    2016-11-01

    The liver has a marked capacity for regeneration. In most cases the liver regeneration is determined by hepatocytes. The regenerative capacity of hepatocytes is significantly reduced in acute or chronic damage. In particular, repair mechanisms are not activated in patients with alcoholic cirrhosis. Organ transplantation or advanced methods of regenerative medicine can help such patients. The promising results were obtained in clinical trials involving patients with various forms of liver disease who received transplantation of autologous bone marrow stem cells. However, to improve the effectiveness of such treatment it is necessary to search for more optimal sources of progenitor cells, as well as to evaluate the possibility of using descendants of these cells differentiated in vitro. In this study we isolated stromal cells from the liver biopsies of three patients with alcoholic cirrhosis, conducted their morphological and phenotypic analysis, and evaluated the hepatic potential of these cells in vitro. The stromal cells isolated from fetal liver were used for comparison. The results of this can serve as a basis for the development of a new method for the treatment of end-stage liver disease. The stromal cells isolated from the liver biopsies for a long time proliferate in a culture and this which makes it possible to expand them to large amounts for subsequent differentiation into hepatocyte-like cells and autologous transplantation.

  7. Adult onset primary focal dystonia of the foot: an orthopaedic intervention.

    PubMed

    Logan, Loretta; Resseque, Barbara; Dontamsetti, Monica Sakshi

    2016-03-30

    A 54-year-old woman presented to a foot centre with a chief symptom of cramping in her toes, which, she believed, was of a secondary cause originating from a bunion. She was treated conservatively; however, she returned a month later as the symptoms had progressed to painful cramping of toes, toe-curling and instability while walking, due to involuntary movement of her toes. It was believed that the patient presented with a rare case of primary adult onset focal foot dystonia. This case report explains dystonia further in detail and delves into the different treatment and management options available today, including the unique orthopaedic intervention provided for this patient.

  8. Changes in the contralateral eye in uncomplicated persistent hyperplastic primary vitreous in adults.

    PubMed

    Awan, K J; Humayun, M

    1985-02-15

    In two adults (a 62-year-old man and a 71-year-old woman) uncomplicated full-blown unilateral persistent hyperplastic primary vitreous was diagnosed on the basis of characteristic clinical features and ultrasonography. In the contralateral uninvolved eyes, we found open-angle glaucoma, anomalous blood vessels along the entire circumference of the anterior chamber angle, band keratopathy, and heterochromia iridis. The axial length of one involved eye was about 0.85 mm larger than that of the uninvolved eye.

  9. Histology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis in Adults and Children.

    PubMed

    Kleiner, David E; Makhlouf, Hala R

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is the liver disease associated with obesity, diabetes, and the metabolic syndrome. Although steatosis is a key histologic feature, liver biopsies of patients with NAFLD can show a wide range of findings. Nonalcoholic steatohepatitis (NASH) is a progressive subtype of NAFLD first defined by analogy to alcoholic hepatitis. Young children may have an alternate pattern of progressive NAFLD characterized by a zone 1 distribution of steatosis, inflammation, and fibrosis. Several grading and staging systems exist, but all require adequate biopsies. Although NASH generally shows fibrosis progression over time, some patients show regression of disease.

  10. Dietary Patterns Modulate the Risk of Non-Alcoholic Fatty Liver Disease in Chinese Adults

    PubMed Central

    Yang, Chao-Qun; Shu, Long; Wang, Shuai; Wang, Jia-Jia; Zhou, Yu; Xuan, Yu-Jie; Wang, Su-Fang

    2015-01-01

    Although previous studies reported the associations between the intakes of individual foods or nutrients and the risk of non-alcoholic fatty liver disease (NAFLD), the relationship between dietary patterns and NAFLD in the Chinese population has been rarely studied to date. This study aimed to investigate the associations between dietary patterns and the risk of NAFLD in a middle-aged Chinese population. The Study subjects were 999 Chinese adults aged 45–60 years in the Anhui province who participated in the Hefei Nutrition and Health Study. Dietary intake was collected by a semi-quantitative food frequency questionnaire. NAFLD was defined as the presence of moderate-severe hepatic steatosis (by B-ultrasonic examination); the absence of excessive alcohol use (>20 g day−1 in men and 10 g day−1 in women); no use of steatogenic medications within the past six months; no exposure to hepatotoxins; and no history of bariatric surgery. Log-binomial regression analysis was used to examine the association between dietary patterns and NAFLD with adjustment of potential confounding variables. Out of 999 participants, 345 (34.5%) were classified as having NAFLD. Four major dietary patterns were identified: “Traditional Chinese”, “Animal food”, “Grains-vegetables” and “High-salt” dietary patterns. After adjusting for potential confounders, subjects in the highest quartile of the “Animal food” pattern scores had greater prevalence ratio for NAFLD (prevalence ratio (PR) = 1.354; 95% confidence interval (CI): 1.063–1.724; p < 0.05) than did those in the lowest quartile. After adjustment for body mass index (BMI), compared with the lowest quartile of the “Grains-vegetables” pattern, the highest quartile had a lower prevalence ratio for NAFLD (PR = 0.777; 95% CI: 0.618–0.977, p < 0.05). However, the “traditional Chinese” and “high-salt” dietary patterns showed no association with the risk of NAFLD. Our findings indicated that the

  11. Dietary Patterns Modulate the Risk of Non-Alcoholic Fatty Liver Disease in Chinese Adults.

    PubMed

    Yang, Chao-Qun; Shu, Long; Wang, Shuai; Wang, Jia-Jia; Zhou, Yu; Xuan, Yu-Jie; Wang, Su-Fang

    2015-06-15

    Although previous studies reported the associations between the intakes of individual foods or nutrients and the risk of non-alcoholic fatty liver disease (NAFLD), the relationship between dietary patterns and NAFLD in the Chinese population has been rarely studied to date. This study aimed to investigate the associations between dietary patterns and the risk of NAFLD in a middle-aged Chinese population. The Study subjects were 999 Chinese adults aged 45-60 years in the Anhui province who participated in the Hefei Nutrition and Health Study. Dietary intake was collected by a semi-quantitative food frequency questionnaire. NAFLD was defined as the presence of moderate-severe hepatic steatosis (by B-ultrasonic examination); the absence of excessive alcohol use (>20 g day(-1) in men and 10 g day(-1) in women); no use of steatogenic medications within the past six months; no exposure to hepatotoxins; and no history of bariatric surgery. Log-binomial regression analysis was used to examine the association between dietary patterns and NAFLD with adjustment of potential confounding variables. Out of 999 participants, 345 (34.5%) were classified as having NAFLD. Four major dietary patterns were identified: "Traditional Chinese", "Animal food", "Grains-vegetables" and "High-salt" dietary patterns. After adjusting for potential confounders, subjects in the highest quartile of the "Animal food" pattern scores had greater prevalence ratio for NAFLD (prevalence ratio (PR) = 1.354; 95% confidence interval (CI): 1.063-1.724; p < 0.05) than did those in the lowest quartile. After adjustment for body mass index (BMI), compared with the lowest quartile of the "Grains-vegetables" pattern, the highest quartile had a lower prevalence ratio for NAFLD (PR = 0.777; 95% CI: 0.618-0.977, p < 0.05). However, the "traditional Chinese" and "high-salt" dietary patterns showed no association with the risk of NAFLD. Our findings indicated that the "Animal food" dietary pattern was associated with

  12. Splenomegaly as a Primary Manifestation of Gaucher Disease in a Young Adult Woman

    PubMed Central

    Merra, Giuseppe; Lago, Antonio Dal; Ricci, Roberta; Antuzzi, Daniela; Gasbarrini, Giovanni; Gasbarrini, Antonio; Ghirlanda, Giovanni

    2008-01-01

    Gaucher disease is the most common lysosomal storage disease. It is caused by the defective activity of acid β-glucosidase, which results in the accumulation of lipid glucocerebroside in macrophages throughout the body. In this case report we describe the case of a young adult woman with splenomegaly as the primary manifestation of this pathology. This is a case of type 1 Gaucher disease because there is a lack of primary neurological involvement but we have, instead, an age-independent involvement of the visceral organs. It is very important to classify or characterize these patients in a precise manner and to make a complete diagnosis with the help of the many diagnostic resources now at our disposal, especially with genetics, radiology and new techniques of advanced microscopy, also because Gaucher disease requires a long and complex management from early life to adulthood. PMID:21897802

  13. Origin of germ cells and formation of new primary follicles in adult human ovaries

    PubMed Central

    Bukovsky, Antonin; Caudle, Michael R; Svetlikova, Marta; Upadhyaya, Nirmala B

    2004-01-01

    sophisticated adaptive mechanism created during the evolution of female reproduction. Our data indicate that the pool of primary follicles in adult human ovaries does not represent a static but a dynamic population of differentiating and regressing structures. An essential mission of such follicular turnover might be elimination of spontaneous or environmentally induced genetic alterations of oocytes in resting primary follicles. PMID:15115550

  14. Raising awareness of bronchiectasis in primary care: overview of diagnosis and management strategies in adults.

    PubMed

    Chalmers, James D; Sethi, Sanjay

    2017-12-01

    Bronchiectasis is a chronic lung disease characterised by recurrent infection, inflammation, persistent cough and sputum production. The disease is increasing in prevalence, requiring a greater awareness of the disease across primary and secondary care. Mild and moderate cases of bronchiectasis in adults can often be managed by primary care clinicians. Initial assessments and long-term treatment plans that include both pharmacological and non-pharmacological treatments, however, should be undertaken in collaboration with a secondary care team that includes physiotherapists and specialists in respiratory medicine. Bronchiectasis is often identified in patients with other lung diseases, such as chronic obstructive pulmonary disease, asthma, and in a lesser but not insignificant number of patients with other inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease. Overall goals of therapy are to prevent exacerbations, improve symptoms, improve quality of life and preserve lung function. Prompt treatment of exacerbations with antibiotic therapy is important to limit the impact of exacerbations on quality of life and lung function decline. Patient education and cooperation with health-care providers to implement treatment plans are key to successful disease management. It is important for the primary care provider to work with secondary care providers to develop an individualised treatment plan to optimise care with the goal to delay disease progression. Here, we review the diagnosis and treatment of bronchiectasis with a focus on practical considerations that will be useful to primary care.

  15. The effect of increased primary schooling on adult women's HIV status in Malawi and Uganda: Universal Primary Education as a natural experiment.

    PubMed

    Behrman, Julia Andrea

    2015-02-01

    This paper explores the causal relationship between primary schooling and adult HIV status in Malawi and Uganda, two East African countries with some of the highest HIV infection rates in the world. Using data from the 2010 Malawi Demographic Health Survey and the 2011 Uganda AIDS Indicator Survey, the paper takes advantage of a natural experiment, the implementation of Universal Primary Education policies in the mid 1990s. An instrumented regression discontinuity approach is used to model the relationship between increased primary schooling and adult women's HIV status. Results indicate that a one-year increase in schooling decreases the probability of an adult woman testing positive for HIV by 0.06 (p < 0.01) in Malawi and by 0.03 (p < 0.05) in Uganda. These results are robust to a variety of model specifications. In a series of supplementary analyses a number of potential pathways through which such effects may occur are explored. Findings indicate increased primary schooling positively affects women's literacy and spousal schooling attainment in Malawi and age of marriage and current household wealth in Uganda. However primary schooling has no effect on recent (adult) sexual behavior.

  16. Isolation and Culture of Adult Intestinal, Gastric, and Liver Organoids for Cre-recombinase-Mediated Gene Deletion.

    PubMed

    Flanagan, Dustin J; Schwab, Renate H M; Tran, Bang M; Phesse, Toby J; Vincan, Elizabeth

    2016-10-05

    The discovery of Lgr5 as a marker of adult stem cells meant that stem cell populations could be purified and studied in isolation. Importantly, when cultured under the appropriate conditions these stem cells form organoids in tissue culture that retain many features of the tissue of origin. The organoid cultures are accessible to genetic and biochemical manipulation, bridging the gap between in vivo mouse models and conventional tissue culture. Here we describe robust protocols to establish organoids from gastrointestinal tissues (stomach, intestine, liver) and Cre-recombinase mediated gene manipulation in vitro.

  17. Hypofractionated stereotactic body radiotherapy for primary and metastatic liver tumors using the novalis image-guided system: preliminary results regarding efficacy and toxicity.

    PubMed

    Iwata, Hiromitsu; Shibamoto, Yuta; Hashizume, Chisa; Mori, Yoshimasa; Kobayashi, Tatsuya; Hayashi, Naoki; Kosaki, Katsura; Ishikawa, Tetsuya; Kuzuya, Teiji; Utsunomiya, Setsuo

    2010-12-01

    www.tcrt.org The purpose of this study was to evaluate the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for primary and metastatic liver tumors using the Novalis image-guided radiotherapy system. After preliminarily treating liver tumors using the Novalis system from July 2006, we started a protocol-based study in February 2008. Eighteen patients (6 with primary hepatocellular carcinoma and 12 with metastatic liver tumor) were treated with 55 or 50 Gy, depending upon their planned dose distribution and liver function, delivered in 10 fractions over 2 weeks. Four non-coplanar and three coplanar static beams were used. Patient age ranged from 54 to 84 years (median: 72 years). The Child-Pugh classification was Grade A in 17 patients and Grade B in 1. Tumor diameter ranged from 12 to 35 mm (median: 23 mm). Toxicities were evaluated according to the Common Terminology Criteria of Adverse Events version 4.0, and radiation-induced liver disease (RILD) was defined by Lawrence's criterion. The median follow-up period was 14.5 months. For all patients, the 1-year overall survival and local control rates were 94% and 86%, respectively. A Grade 1 liver enzyme change was observed in 5 patients, but no RILD or chronic liver dysfunction was observed. SBRT using the Novalis image-guided system is safe and effective for treating primary and metastatic liver tumors. Further investigation of SBRT for liver tumors is warranted. In view of the acceptable toxicity observed with this protocol, we have moved to a new protocol to shorten the overall treatment time and escalate the dose.

  18. Associations between Nonalcoholic Fatty Liver Disease and Subclinical Atherosclerosis in Middle-Aged Adults: The Coronary Artery Risk Development in Young Adults Study

    PubMed Central

    VanWagner, Lisa B.; Ning, Hongyan; Lewis, Cora E.; Shay, Christina M.; Wilkins, John; Carr, J Jeffrey; Terry, James G.; Lloyd-Jones, Donald M.; Jacobs, David R.; Carnethon, Mercedes R.

    2014-01-01

    Objective Non-alcoholic fatty liver disease (NAFLD) is an obesity-related condition associated with cardiovascular mortality. Yet, whether or not NAFLD is independently related to atherosclerosis is unclear. In a population-based cross-sectional sample of middle-aged adults free from liver or heart disease, we tested the hypothesis that NAFLD is associated with subclinical atherosclerosis (coronary artery (CAC) and abdominal aortic calcification (AAC)) independent of obesity. Methods Participants from the Coronary Artery Risk Development in Young Adults study with CT quantification of liver fat, CAC and AAC were included (n=2,424). NAFLD was defined as liver attenuation ≤ 40 Hounsfield Units after exclusion of other causes of liver fat. CAC and AAC presence was defined as Agatston score > 0. Results Mean participant age was 50.1±3.6 years, (42.7% men, 50.0% black) and BMI was 30.6±7.2 kg/m2. The prevalence of NAFLD, CAC, and AAC was 9.6%, 27.1%, and 51.4%. NAFLD participants had increased prevalence of CAC (37.9% vs. 26.0%, p<0.001) and AAC (65.1% vs. 49.9%, p<0.001). NAFLD remained associated with CAC (OR, 1.33; 95% CI, 1.001–1.82) and AAC (OR, 1.74; 95% CI, 1.29–2.35) after adjustment for demographics and health behaviors. However, these associations were attenuated after additional adjustment for visceral adipose tissue (CAC OR, 1.05; 95% CI, 0.74–1.48, AAC OR=1.20; 95% CI, 0.86–1.67). There was no interaction by race or sex. Conclusion In contrast to prior research, these findings suggest that obesity attenuates the relationship between NAFLD and subclinical atherosclerosis. Further studies evaluating the role of NAFLD duration on atherosclerotic progression and cardiovascular events are needed. PMID:24956534

  19. Disseminated Gonococcal Infection Presenting as Bacteremia and Liver Abscesses in a Healthy Adult

    PubMed Central

    Byun, Jongkyu; Yang, John Jeongseok

    2015-01-01

    Herein, we describe a bacteremia caused by Neisseria gonorrhoeae that presented as liver abscesses. The patient had no risk factors for disseminated gonococcal infection. Periodic fever, skin rashes, and papules were present and the results of an abdominal computed tomography scan indicated the presence of small liver abscesses. The results of blood culture and 16S rRNA sequencing of the bacterial isolates confirmed the presence of N. gonorrhoeae. The patient improved with antibiotic therapy. PMID:25844265

  20. Primary and Specialty Medical Care Among Ethnically Diverse, Older Rural Adults With Type 2 Diabetes: The ELDER Diabetes Study

    ERIC Educational Resources Information Center

    Bell, Ronny A.; Quandt, Sara A.; Arcury, Thomas A.; Snively, Beverly M.; Stafford, Jeanette M.; Smith, Shannon L.; Skelly, Anne H.

    2005-01-01

    Purpose: Residents in rural communities in the United States, especially ethnic minority group members, have limited access to primary and specialty health care that is critical for diabetes management. This study examines primary and specialty medical care utilization among a rural, ethnically diverse, older adult population with diabetes.…

  1. Primary and Specialty Medical Care among Ethnically Diverse, Older Rural Adults with Type 2 Diabetes: The ELDER Diabetes Study

    ERIC Educational Resources Information Center

    Bell, Ronny A.; Quandt, Sara A.; Arcury, Thomas A.; Snively, Beverly M.; Stafford, Jeanette M.; Smith, Shannon L.; Skelly, Anne H.

    2005-01-01

    Purpose: Residents in rural communities in the United States, especially ethnic minority group members, have limited access to primary and specialty health care that is critical for diabetes management. This study examines primary and specialty medical care utilization among a rural, ethnically diverse, older adult population with diabetes.…

  2. Regulation of haematopoietic stem cell proliferation by stimulatory factors produced by murine fetal and adult liver.

    PubMed Central

    Dawood, K A; Briscoe, C V; Thomas, D B; Riches, A C

    1990-01-01

    Haematopoietic stem cells in murine fetal liver are in a proliferative state unlike those in normal bone marrow which are quiescent. A regulatory activity is produced by cells in the fetal liver which will switch quiescent normal bone marrow haematopoietic stem cells into cell cycle in vitro. This regulator from Day 15 fetal liver cells is produced by adherent cells and by cells fractionated on a Percoll gradient in the 1.064 and 1.076 g per cm3 density bands but not in the 1.123 g per cm3 band. Colony-stimulating factor cannot be detected in the supernatants containing the stem cell regulatory activity. The stimulator can be detected in supernatants produced from cell suspensions of liver cells at Day 15 and Day 17 of gestation and 24 hours and 72 hours after birth. However by 1 week after birth the production of the stimulator decreases and is undetectable 3 and 10 weeks after birth. The total numbers of haematopoietic stem cells (CFU-S) in fetal liver decrease from Day 15 of gestation and only small numbers are present 1 week after birth. Thus the decline in the production of haematopoietic stem cell proliferation stimulator correlates with the decrease in haematopoietic stem cell numbers in the liver through gestation and after birth. PMID:2323992

  3. [Severe primary liver abscess and septic pulmonary embolism due to Klebsiella pneumoniae with hypermucoviscosity phenotype].

    PubMed

    Nakamoto, Keitaro; Koide, Takashi; Nagatomo, Tomoko; Tamura, Masaki; Higaki, Manabu; Takata, Saori; Wada, Hiroo; Ishii, Haruyuki; Okazaki, Mitsuhiro; Takahashi, Shinichi; Goto, Hajime

    2011-07-01

    A 70-year-old man with diabetes mellitus seen for fever, right chest pain, and right-lung field consolidation on chest X-ray was found in thoracoabdominal computed tomography (CT) to have variable-sized nodules in both lung fields and multiple low-density hepatic areas. On physical examination, his pulse was 145 beats per minute and blood pressure 92/68mmHg, indicating a preshock state. Laboratory tests showed elevated WBC of 15,200/microL, serum-C-reactive protein (CRP) of 34.4 mg/dL, and a decreased platelet count of 16,000/microL. Suspecting liver abscesses complicated by a septic pulmonary embolism, we immediately conducted percutaneous transhepatic abscess drainage (PTAD). Liver abscess blood culture and drainage fluid grew the Klebsiella pneumoniae hypermucoviscosity phenotype, carrying the rmpA gene. Although the man had been in critical condition on admission, broad-spectrum antibiotics and PTAD treatment improved his clinical condition to where he could be discharged without problem.

  4. Higher dietary intakes of choline and betaine are associated with a lower risk of primary liver cancer: a case-control study.

    PubMed

    Zhou, Rui-Fen; Chen, Xiao-Lin; Zhou, Zhong-Guo; Zhang, Yao-Jun; Lan, Qiu-Ye; Liao, Gong-Cheng; Chen, Yu-Ming; Zhu, Hui-Lian

    2017-04-06

    The dietary intake of methyl donors is favorably associated with many diseases, but the findings regarding primary liver cancer (PLC) risk are limited. This study investigated the association between the intake of choline, betaine and methionine and PLC risk in adults. This 1:1 matched case-control study enrolled 644 hospital-based PLC patients and 644 community-based controls who were matched by sex and age, in Guangzhou, China. An interviewer-administered questionnaire and a food-frequency questionnaire were used to collect general information and dietary intake information. Conditional logistic regression showed a significantly inverse association between total choline and betaine intakes and PLC risk. The multivariable-adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) for PLC for the top (vs. bottom) tertile were 0.34 (0.24-0.49; P -trend < 0.001) for total choline and 0.67 (0.48-0.93; P -trend = 0.011) for betaine. No significant association was observed between the intake of methionine and PLC risk (P > 0.05). For individual choline compounds, higher consumptions of free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine and sphingomyelin were associated with a lower PLC risk (all P-trend < 0.05). The studied associations were not significantly modified by the folate intake (P-interactions: 0.488-0.890). Our findings suggest that higher choline and betaine intakes may be associated with a lower risk of PLC.

  5. Primary afferent plasticity following deafferentation of the trigeminal brainstem nuclei in the adult rat.

    PubMed

    De Riu, Pier Luigi; Russo, Antonella; Pellitteri, Rosalia; Stanzani, Stefania; Tringali, Giovanni; Roccazzello, Anna Maria; De Riu, Giacomo; Marongiu, Patrizia; Mameli, Ombretta

    2008-09-01

    Alpha-tyrosinated tubulin is a cytoskeletal protein that is involved in axonal growth and is considered a marker of neuronal plasticity in adult mammals. In adult rats, unilateral ablation of the left facial sensorimotor cortical areas induces degeneration of corticotrigeminal projections and marked denervation of the contralateral sensory trigeminal nuclei. Western blotting and real-time-PCR of homogenates of the contralateral trigeminal ganglion (TG) revealed consistent overexpression of growth proteins 15 days after left decortication in comparison with the ipsilateral side. Immunohistochemical analyses indicated marked overexpression of alpha-tyrosinated tubulin in the cells of the ganglion on the right side. Cytoskeletal changes were primarily observed in the small ganglionic neurons. Application of HRP-CT, WGA-HRP, and HRP to infraorbital nerves on both sides 15 days after left decortication showed a significant degree of terminal sprouting and neosynaptogenesis from right primary afferents at the level of the right caudalis and interpolaris trigeminal subnuclei. These observations suggest that the adaptive response of TG neurons to central deafferentation, leading to overcrowding and rearrangement of the trigeminal primary afferent terminals on V spinal subnuclei neurons, could represent the anatomical basis for distortion of facial modalities, perceived as allodynia and hyperalgesia, despite nerve integrity.

  6. Effect of chromium supplementation on the diabetes induced-oxidative stress in liver and brain of adult rats.

    PubMed

    Refaie, Fawzia M; Esmat, Amr Y; Mohamed, Aly F; Aboul Nour, Wael H

    2009-12-01

    This study was designed to investigate the susceptibility of liver and brain tissues, as insulinin-dependent tissues, of normal adult male rats to the oxidative challenge of subchronic supplementation with chromium picolinate (CrPic) at low (human equivalent) and high doses (2.90 and 13.20 μg Cr kg(-1) day(-1), respectively). Also, the modulative effect of CrPic administration on the enhanced oxidative stress in the liver and brain tissues of alloxan-diabetic rats was studied. Fasting serum glucose level was not modified in normal rats but significantly reduced in diabetic rats that had received CrPic supplement. A mild oxidative stress was observed in the liver and brain of CrPic-supplemented normal rats confirmed by the dose-dependent reductions in the levels of hepatic and cerebral free fatty acids, superoxide dismutase and glutathione peroxidase activities, and in contrast increased tissue malondialdehyde concentration. On the other hand, hepatic and cerebral catalase activity was reduced in the high dose group only. CrPic supplementation did not act as a peroxisome proliferator confirmed by the significant reductions in liver and brain peroxisomal palmitoyl CoA oxidase activity. The non significant alterations in liver protein/DNA and RNA/DNA ratios indicate that CrPic did not affect protein synthesis per cell, and that mild elevations in hepatic total protein and RNA concentrations might be due to block or decrease in the export rate of synthesized proteins from the liver to the plasma. In diabetic rats, elevated levels of hepatic and cerebral free fatty acids and malondialdehyde, and in contrast the overwhelmed antioxidant enzymes, were significantly modulated in the low dose group and near-normalized in the high dose group. The significant increases observed in liver total protein and RNA concentrations, as well as protein/DNA and RNA/ DNA ratios in diabetic rats supplemented with the high dose of Cr, compared to untreated diabetics, may be related to the

  7. Tissue-resident Eomes(hi) T-bet(lo) CD56(bright) NK cells with reduced proinflammatory potential are enriched in the adult human liver.

    PubMed

    Harmon, Cathal; Robinson, Mark W; Fahey, Ronan; Whelan, Sarah; Houlihan, Diarmaid D; Geoghegan, Justin; O'Farrelly, Cliona

    2016-09-01

    The adult human liver is enriched with natural killer (NK) cells, accounting for 30-50% of hepatic lymphocytes, which include tissue-resident hepatic NK-cell subpopulations, distinct from peripheral blood NK cells. In murine liver, a subset of liver-resident hepatic NK cells have altered expression of the two highly related T-box transcription factors, T-bet and eomesodermin (Eomes). Here, we investigate the heterogeneity of T-bet and Eomes expression in NK cells from healthy adult human liver with a view to identifying human liver-resident populations. Hepatic NK cells were isolated from donor liver perfusates and biopsies obtained during orthotopic liver transplantation (N = 28). Hepatic CD56(bright) NK cells were Eomes(hi) T-bet(lo) , a phenotype virtually absent from peripheral blood. These NK cells express the chemokine receptor CXCR6 (chemokine (C-X-C motif) receptor 6), a marker of tissue residency, which is absent from hepatic CD56(dim) and blood NK cells. Compared to blood populations, these hepatic CD56(bright) NK cells have increased expression of activatory receptors (NKp44, NKp46, and NKG2D). They show reduced ability to produce IFN-γ but enhanced degranulation in response to challenge with target cells. This functionally distinct population of hepatic NK cells constitutes 20-30% of the total hepatic lymphocyte repertoire and represents a tissue-resident immune cell population adapted to the tolerogenic liver microenvironment.

  8. Sex differences in liver toxicity-do female and male human primary hepatocytes react differently to toxicants in vitro?

    PubMed

    Mennecozzi, Milena; Landesmann, Brigitte; Palosaari, Taina; Harris, Georgina; Whelan, Maurice

    2015-01-01

    There is increasing amount of evidence for sex variation in drug efficiency and toxicity profiles. Women are more susceptible than men to acute liver injury from xenobiotics. In general, this is attributed to sex differences at a physiological level as well as differences in pharmacokinetics and pharmacodynamics, but neither of these can give a sufficient explanation for the diverse responses to xenobiotics. Existing data are mainly based on animal models and limited data exist on in vitro sex differences relevant to humans. To date, male and female human hepatocytes have not yet been compared in terms of their responses to hepatotoxic drugs. We investigated whether sex-specific differences in acute hepatotoxicity can be observed in vitro by comparing hepatotoxic drug effects in male and female primary human hepatocytes. Significant sex-related differences were found for certain parameters and individual drugs, showing an overall higher sensitivity of female primary hepatocytes to hepatotoxicants. Moreover, our work demonstrated that high content screening is feasible with pooled primary human hepatocytes in suspension.

  9. Association between Noninvasive Fibrosis Markers and Chronic Kidney Disease among Adults with Nonalcoholic Fatty Liver Disease

    PubMed Central

    Sesti, Giorgio; Fiorentino, Teresa Vanessa; Arturi, Franco; Perticone, Maria; Sciacqua, Angela; Perticone, Francesco

    2014-01-01

    Evidence suggests that nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are associated with an increased risk of chronic kidney disease (CKD). In this study we aimed to evaluate whether the severity of liver fibrosis estimated by NAFLD fibrosis score is associated with higher prevalence of CKD in individuals with NAFLD. To this end NAFLD fibrosis score and estimated glomerular filtration rate (eGFR) were assessed in 570 White individuals with ultrasonography-diagnosed NAFLD. As compared with subjects at low probability of liver fibrosis, individuals at high and intermediate probability showed an unfavorable cardio-metabolic risk profile having significantly higher values of waist circumference, insulin resistance, high sensitivity C-reactive protein, fibrinogen, uric acid and lower insulin-like growth factor-1 levels. Individuals at high and intermediate probability of liver fibrosis have lower eGFR after adjustment for gender, smoking, glucose tolerance status, homeostasis model assessment index of insulin resistance (HOMA-IR index), diagnosis of metabolic syndrome, statin therapy, anti-diabetes and anti-hypertensive treatments (P = 0.001). Individuals at high probability of liver fibrosis had a 5.1-fold increased risk of having CKD (OR 5.13, 95%CI 1.13–23.28; P = 0.03) as compared with individuals at low probability after adjustment for age, gender, and BMI. After adjustment for glucose tolerance status, statin therapy, and anti-hypertensive treatment in addition to gender, individuals at high probability of liver fibrosis had a 3.9-fold increased risk of CKD (OR 3.94, 95%CI 1.11–14.05; P = 0.03) as compared with individuals at low probability. In conclusion, advanced liver fibrosis, determined by noninvasive fibrosis markers, is associated with CKD independently from other known factors. PMID:24520400

  10. Health-related quality of life after liver transplantation for adult recipients.

    PubMed

    Bownik, Hillary; Saab, Sammy

    2009-11-01

    1. Pretransplantation health-related quality of life scores are affected by the etiology of liver cirrhosis, with hepatocellular and cholestatic etiologies having higher health-related quality of life scores than alcohol or viral hepatitis etiologies. 2. Posttransplantation health-related quality of life scores are not affected by the etiology of the original liver cirrhosis, but transplant recipient scores continue to remain significantly lower than those of healthy patient controls. 3. During the first 6 months after liver transplantation, the majority of physical and mental components of health-related quality of life scores improve, but these increases are not sustained in the long term. 4. At 1 year after liver transplantation, emotional and mental health-related quality of life scores begin to decrease. 5. During postoperative years 1 to 5, episodes of acute cellular rejection and patient age over 60 years decrease physical function and overall general health-related quality of life scores. 6. Beyond 5 years after orthotopic liver transplantation, age over 60, osteoporosis, and episodes of chronic rejection decrease health-related quality of life scores through decreases in the physical function and bodily pain domains. 7. Hepatitis C as an indication for liver transplantation is an independent factor in decreasing posttransplantation health-related quality of life scores. 8. Further studies are necessary that include a complete evaluation of the effects of gender, socioeconomic status, education, and ethnicity in order to better understand factors influencing post-liver transplantation health-related quality of life scores. 9. The development of a health-related quality of life assessment tool specific to transplantation could help us to more accurately assess factors (such as immunosuppression) that alter posttransplantation health-related quality of life.

  11. 13C-methacetin breath test correlates with clinical indices of liver disease severity in patients with primary biliary cirrhosis.

    PubMed

    Kochel-Jankowska, A; Hartleb, M; Jonderko, K; Kaminska, M; Kasicka-Jonderko, A

    2013-02-01

    This prospective study intended to ascertain if cytochrome P450 dependent liver function is affected in early and late histological stages of primary biliary cirrhosis (PBC). The study included 32 female PBC patients (mean age 55.4 years, range 33-70) and 16 aged-matched healthy women (mean age 52.6 years, range 38-65). In every subject a 13(C)-methacetin breath test (13(C)-MBT) was applied, and the results were related to histological Ludwig's staging system and several indices of liver disease severity comprising the MAYO-1, MAYO-2, MELD, and Child-Pugh score. The 13(C)-MBT differentiated healthy controls from the patients with Ludwig IV and Ludwig III histopathological stages of PBC. The most significant relationships (i.e. explaining >50% of the variance) were found between measurements of the momentary breath 13(C) elimination from 6 to 18 minutes as well as the 15-min or 30-min cumulative elimination and the MAYO-1 or MAYO-2 scores. The breath test poorly correlated with histopathological features of PBC, however, it accurately discriminated cirrhotic from non-cirrhotic patients (momentary breath 13(C) elimination at 40 min, AUROC 0,958). In conclusion, 13(C)-MBT correlates with clinical scoring systems, especially those specifically designed for PBC (Mayo model) and accurately recognizes the disease at the stage of cirrhosis up to 40 minutes of the test duration.

  12. Toxicity monitoring with primary cultured hepatocytes underestimates the acetaminophen-induced inflammatory responses of the mouse liver.

    PubMed

    Tachibana, Shinjiro; Shimomura, Akiko; Inadera, Hidekuni

    2011-01-01

    In vitro gene expression profiling with isolated hepatocytes has been used to assess the hepatotoxicity of certain chemicals because of animal welfare issues. However, whether an in vitro system can completely replace the in vivo system has yet to be elucidated in detail. Using a focused microarray established in our laboratory, we examined gene expression profiles in the mouse liver and primary cultured hepatocytes after treatment with different doses of acetaminophen, a widely used analgesic that frequently causes liver injury. The acute hepatotoxicity of acetaminophen was confirmed by showing the induction of an oxidative stress marker, heme oxygenase-1, elevated levels of serum transaminase, and histopathological findings. In vivo microarray and network analysis showed that acetaminophen treatment provoked alterations in relation to the inflammatory response, and that tumor necrosis factor-α plays a central role in related pathway alterations. By contrast, pathway analyses in in vitro isolated hepatocytes did not find such prominent changes in the inflammation-related networks compared with the in vivo situation. Thus, although in vitro gene expression profiles are useful for evaluating the direct toxicity of chemicals, indirect toxicities including inflammatory responses mediated by cell-cell interactions or secondary toxicity due to pathophysiological changes in the whole body may be overlooked. Our results indicate that the in vitro hepatotoxicity prediction system using isolated hepatocytes does not fully reflect the in vivo cellular response. An in vitro system may be appropriate, therefore, for high throughput screening to detect the direct hepatotoxicity of a test compound.

  13. Duodenal Neuroendocrine Carcinoma Presenting with Disseminated Liver and Bone Metastases as the Primary Manifestation: Case Report and Literature Review.

    PubMed

    Guo, Tao; Ng, Ka Kei; Chiang, Hoi Wan; Ma, Man Fei; Lin, Yi; Qian, Jia Ming

    2015-05-01

    Neuroendocrine tumors are composed by a heterogeneous group of tumors with a wide range of morphologic, functional, and behavioral characteristics. These tumors are generally slow growing and behave in an indolent fashion. However, they have the potential to spread, especially for poorly differentiated neuroendocrine carcinomas, and when they do, they can be very aggressive, with high propensity for distant metastases, and difficult to treat with current modalities. As poorly differentiated neuroendocrine carcinomas rarely occur in extrapulmonary sites, to the best of our knowledge, this is the first case report of a poorly differentiated duodenal neuroendocrine carcinoma with diffuse liver and bone metastases as the primary manifestation. Despite receiving a trial of chemotherapeutic regimen, the patient had progressive intrahepatic cholestasis and died of subacute hepatic failure.

  14. Impact of rituximab desensitization on blood-type-incompatible adult living donor liver transplantation: a Japanese multicenter study.

    PubMed

    Egawa, H; Teramukai, S; Haga, H; Tanabe, M; Mori, A; Ikegami, T; Kawagishi, N; Ohdan, H; Kasahara, M; Umeshita, K

    2014-01-01

    We evaluated the effects of rituximab prophylaxis on outcomes of ABO-blood-type-incompatible living donor liver transplantation (ABO-I LDLT) in 381 adult patients in the Japanese registry of ABO-I LDLT. Patients underwent dual or triple immunosuppression with or without B cell desensitization therapies such as plasmapheresis, splenectomy, local infusion, intravenous immunoglobulin and rituximab. Era before 2005, intensive care unit-bound status, high Model for End-Stage Liver Disease score and absence of rituximab prophylaxis were significant risk factors for overall survival and antibody-mediated rejection (AMR) in the univariate analysis. After adjustment for era effects in the multivariate analysis, only absence of rituximab prophylaxis was a significant risk factor for AMR, and there were no significant risk factors for survival. Rituximab prophylaxis significantly decreased the incidence of AMR, especially hepatic necrosis (p < 0.001). In the rituximab group, other B cell desensitization therapies had no add-on effects. Multiple or large rituximab doses significantly increased the incidence of infection, and early administration had no advantage. In conclusion, outcomes in adult ABO-I LDLT have significantly improved in the latest era coincident with the introduction of rituximab.

  15. Coping, quality of life, and hope in adults with primary antibody deficiencies

    PubMed Central

    Sigstad, Hanne Marie Høybråten; Stray-Pedersen, Asbjørg; Frøland, Stig S

    2005-01-01

    Background Living with a chronic disease, such as primary antibody deficiency, will often have consequences for quality of life. Previous quality-of-life studies in primary antibody deficiency patients have been limited to different treatment methods. We wanted to study how adults with primary antibody deficiencies manage their conditions and to identify factors that are conducive to coping, good quality of life and hope. Methods Questionnaires were sent to all patients ≥20 years of age with primary antibody deficiencies who were served by Rikshospitalet University Hospital. The questionnaires consisted of several standardized scales: Ferrans and Powers Quality of Life Index (QLI), Short Form-36 (SF-36), Jalowiec Coping Scale (JCS), Nowotny Hope Scale (NHS), and one scale we devised with questions about resources and pressures in the past. Of a total of 91, 55 patients (aged 23–76 years) answered the questionnaires. The questionnaire study were supplemented with selected interviews of ten extreme cases, five with low and five with high quality of life scores. Results Among the 55 patients, low quality of life scores were related to unemployment, infections in more than four organs, more than two additional diseases, or more than two specific occurrences of stress in the last 2–3 months. Persons with selective IgA deficiency had significantly higher QLI scores than those with other antibody deficiencies. An optimistic coping style was most frequent used, and hope values were moderately high. Based on the interviews, the patients could be divided into three groups: 1) low QLI scores, low hope values, and reduced coping, 2) low QLI scores, moderate hope values, and good coping, and 3) high QLI scores, moderate to strong hope values, and good coping. Coping was related to the patients' sense of closeness and competence. Conclusion Low quality of life scores in adults with primary antibody deficiencies were linked to unemployment and disease-related strains

  16. The effect of acupressure at third liver point on the anxiety level in patients with primary dysmenorrhea

    PubMed Central

    Kafaei-Atrian, Mahboobeh; Mirbagher-Ajorpaz, Neda; Sarvieh, Malihe; Sadat, Zohre; Asghari-Jafarabadi, Mohammad; Solhi, Mahnaz

    2016-01-01

    Background: Primary dysmenorrhea may lead to severe anxiety and pain relief during menstruation may reduce the anxiety levels. This study was aimed to determine the effect of acupressure at third liver and placebo points on the anxiety level in patients with primary dysmenorrhea. Materials and Methods: This clinical trial was conducted in parallel in the control and treatment groups for three menstrual periods at the dormitory of Kashan University of Medical Sciences between March and June 2012. Students with pain score equal to or greater than 4 were selected and divided into groups based on severity of pain using a randomized block design with the allocation ratio of 1:1. Acupressure was applied in two acupoints including third Liver point (Liv3) and placebo points. Spielberg (STAI) anxiety questionnaire was completed before and after intervention. Randomization, subjects, and data analyzer were blinded to the analysis. Chi-square tests, t-test, Mann-Whitney, paired sample t-test, and univariate analysis of variance were used for statistical analysis. P values <0.05 were considered statistically significant. Results: Mean [standard deviation (SD)] values of apparent anxiety levels before and after intervention for liv3 were 45.100 (9.769) and 38.100 (10.608), respectively. For the control group, they were 41.200 (9.795) and 38.900(10.140), respectively. Difference was significant only in the intervention group (P < 0.001). Hidden anxiety did not show a significant change before and after intervention. There was no difference between groups in apparent or hidden anxiety after intervention. Conclusions: Pressure on liv3 point reduces anxiety. As there are no previous studies on this topic, further studies with more samples are recommended. PMID:27095986

  17. Incidence of diabetes mellitus type 2 complications among Saudi adult patients at primary health care center

    PubMed Central

    Alsenany, Samira; Al Saif, Amer

    2015-01-01

    [Purpose] This study analyzed type 2 diabetes and its role in complications among adult Saudi patients. [Subjects] Patients attending four primary health care centers in Jeddah were enrolled. [Methods] A cross-sectional design study among Saudi patients attending Ministry of Health primary health care centers in Jeddah was selected for use by the Primary Health Care administration. Patients were interviewed with structured questionnaires to determine the presence of diabetes and risk factors using questions about the history of any disease. [Results] Diabetes mellitus was present in 234 subjects during the data collection period (March–June 2014). Mean patient age was 58 years; diabetes prevalence was 42% in males and 58% in females. The mean age for diabetes onset in males and females was 34 and 39 years, respectively. There was a higher incidence of obesity (75%) associated with a sedentary lifestyle (body mass index ≥25) in females (N= 96; 40%) compared with males (N= 87; 36%). In this study, >44% of individuals aged 55 or older had severe to uncontrolled diabetes with long-term complications. The age-adjusted incidence of hypertension and coronary heart disease was 38% and 24%, respectively, showing a clear incidence of diabetes associated with cardiovascular disease in Saudi Arabia. [Conclusion] This study found that a multifactorial approach to managing diabetes complication risks is needed. PMID:26180307

  18. Protein-engineered scaffolds for in vitro 3D culture of primary adult intestinal organoids.

    PubMed

    DiMarco, Rebecca L; Dewi, Ruby E; Bernal, Gabriela; Kuo, Calvin; Heilshorn, Sarah C

    2015-10-15

    Though in vitro culture of primary intestinal organoids has gained significant momentum in recent years, little has been done to investigate the impact of microenvironmental cues provided by the encapsulating matrix on the growth and development of these fragile cultures. In this work, the impact of various in vitro culture parameters on primary adult murine organoid formation and growth are analyzed with a focus on matrix properties and geometric culture configuration. The air-liquid interface culture configuration was found to result in enhanced organoid formation relative to a traditional submerged configuration. Additionally, through use of a recombinantly engineered extracellular matrix (eECM), the effects of biochemical and biomechanical cues were independently studied. Decreasing mechanical stiffness and increasing cell adhesivity were found to increase organoid yield. Tuning of eECM properties was used to obtain organoid formation efficiency values identical to those observed in naturally harvested collagen I matrices but within a stiffer construct with improved ease of physical manipulation. Increased ability to remodel the surrounding matrix through mechanical or enzymatic means was also shown to enhance organoid formation. As the engineering and tunability of recombinant matrices is essentially limitless, continued property optimization may result in further improved matrix performance and may help to identify additional microenvironmental cues that directly impact organoid formation, development, differentiation, and functional behavior. Continued culture of primary organoids in recombinant matrices could therefore prove to be largely advantageous in the field of intestinal tissue engineering for applications in regenerative medicine and in vitro tissue mimics.

  19. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats.

    PubMed

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE+ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE+HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE+HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a "two-programming" hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is "the first programming", and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as "the second programming".

  20. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    SciTech Connect

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  1. Energy balance, glucose and lipid metabolism, cardiovascular risk and liver disease burden in adult patients with type 1 Gaucher disease.

    PubMed

    Nascimbeni, Fabio; Dalla Salda, Annalisa; Carubbi, Francesca

    2016-10-20

    Gaucher disease (GD), the most prevalent lysosomal storage disease, is characterized by systemic accumulation of macrophages engorged with glycosphingolipid-laden lysosomes. Even though both lysosomes and sphingolipids play a pivotal role in metabolic homeostasis, little is known on metabolic abnormalities associated with GD. In this review, we discuss the peculiarity of energy balance and glucose and lipid metabolism in adult type 1 GD patients. Moreover, we evaluate the potential relationship between these metabolic derangements, cardiovascular risk and chronic liver disease. The limited data available show that adult type 1 GD is characterized by a hypermetabolic state, peripheral insulin resistance and hypolipidemia with markedly reduced HDL-cholesterol levels, partially reverted by enzyme replacement therapy (ERT) or substrate reduction therapy (SRT). Although this unfavorable metabolic profile has not been associated with increased incidence of type 2 diabetes and premature atherosclerosis, a natural history study has shown that cardio-cerebrovascular events and malignancy are the leading causes of death in treated type 1 GD patients. Hepatomegaly is frequently observed in GD and ERT/SRT are highly effective in reducing liver volume. Nevertheless, patients with GD may be at increased risk of long-term liver complications including cirrhosis and hepatocellular carcinoma. The role that ERT/SRT and/or lifestyle habits may have on such metabolic features of GD patients, and subsequently on long-term prognosis, deserves further investigations. To gain more insights into the peculiarity of GD metabolism may serve both surveillance and treatment purposes by helping to identify new markers of disease severity and define an updated natural history of GD.

  2. Familial occurrence of autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis in a mother and her daughter.

    PubMed

    Omori, Kaoru; Yoshida, Kanako; Yokota, Masaki; Daa, Tsutomu; Kan, Masahiro

    2016-10-01

    We encountered two patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family. A 68-year-old woman presented at our hospital from a previous medical institution because of the diagnosis of primary biliary cholangitis. Her 49-year-old daughter was admitted with liver dysfunction 4 years later. When compared, these two related patients were found to have overlapping features of primary biliary cholangitis and autoimmune hepatitis. Their human leukocyte antigen haplotype was DRB1*04:05/DRB1*15:02. The clinical and biochemical findings of these two patients immediately improved following treatment with a combination of prednisolone and ursodeoxycholic acid, in accordance with the Japanese guidelines. It is extremely important to identify such pathological conditions as quickly as possible, particularly with the appearance of severe liver dysfunction due to liver cirrhosis, as observed in our case. The Japanese guidelines are considered to be a realistic and useful clinical policy for the swift and efficient treatment of patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis. We suggest that our two patients presented with a genetic predisposition to autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family.

  3. Histopathological effects of sub-chronic lamivudine-artesunate co-administration on the liver of diseased adult Wistar rats

    PubMed Central

    Olurishe, Temidayo Olutoyin; Kwanashie, Helen Ochuko; Anuka, Joseph; Muktar, Haruna; Bisalla, Mohammed

    2011-01-01

    Background: Lamivudine and artesunate are sometimes co administered in HIV-malaria co morbidity. Both drugs are used concurrently in presumptive malaria treatment and simultaneous HIV post exposure prophylaxis. Aim: The aim of this study was to investigate the effect of lamivudine-artesunate co administration on the histology of the liver of diseased adult Wistar rats. Materials and Methods: Five groups of rats of both sexes were used for the study and placed on feed and water ad libitum. Disease state consisted of immunosuppression with cyclophosphamide, and infection with Plasmodium berghei. Group 1 animals served as vehicle control, while group 2 were the diseased controls. Group 3 animals received 20 mg/kg lamivudine for three weeks, while group 4 similarly received 20 mg/kg Lamivudine but also received 10 mg/kg artesunate from day 12. Animals in group 5 received 10 mg/kg artesunate from day 12. All drugs were administered intraperitoneally. The animals were treated for twenty-one days, at the end of which they were sacrificed and their livers fixed in 10% formalin for histological studies. Result: Results from the study show the presence of regions of focal necrosis and perivascular cuffing with animals that received artesunate. Hemosiderosis was a common feature in all the parasitized groups, while fatty degeneration was observed in the group that received artesunate alone. Conclusion: Concurrent lamivudine-artesunate administration resulted in some histopathological changes in the liver. This study suggests there may be considerable histological changes with repeated occurrence of malaria and immunosuppression that may warrant intermittent lamivudine-artesunate administration, and may require evaluation as well as monitoring of liver function during such therapeutic interventions. PMID:22540106

  4. Standardized surgical techniques for adult living donor liver transplantation using a modified right lobe graft: a video presentation from bench to reperfusion.

    PubMed

    Hwang, Shin; Ha, Tae-Yong; Ahn, Chul-Soo; Moon, Deok-Bog; Kim, Ki-Hun; Song, Gi-Won; Jung, Dong-Hwan; Park, Gil-Chun; Lee, Sung-Gyu

    2016-08-01

    After having experienced more than 2,000 cases of adult living donor liver transplantation (LDLT), we established the concepts of right liver graft standardization. Right liver graft standardization intends to provide hemodynamics-based and regeneration-compliant reconstruction of vascular inflow and outflow. Right liver graft standardization consists of the following components: Right hepatic vein reconstruction includes a combination of caudal-side deep incision and patch venoplasty of the graft right hepatic vein to remove the acute angle between the graft right hepatic vein and the inferior vena cava; middle hepatic vein reconstruction includes interposition of a uniform-shaped conduit with large-sized homologous or prosthetic grafts; if the inferior right hepatic vein is present, its reconstruction includes funneling and unification venoplasty for multiple short hepatic veins; if donor portal vein anomaly is present, its reconstruction includes conjoined unification venoplasty for two or more portal vein orifices. This video clip that shows the surgical technique from bench to reperfusion was a case presentation of adult LDLT using a modified right liver graft from the patient's son. Our intention behind proposing the concept of right liver graft standardization is that it can be universally applicable and may guarantee nearly the same outcomes regardless of the surgeon's experience. We believe that this reconstruction model would be primarily applied to a majority of adult LDLT cases.

  5. Langerhans cell histiocytosis misdiagnosed as liver cancer and pituitary tumor in an adult: A case report and brief review of the literature

    PubMed Central

    MA, JING; JIANG, YONGFANG; CHEN, XIANGYU; GONG, GUOZHONG

    2014-01-01

    Langerhans cell histiocytosis (LCH) is a rare proliferative disorder in which pathological Langerhans cells accumulate in a variety of organs. LCH usually affects the bone, skin and lymph nodes of children; however, LCH occasionally affects vital organs, including the liver, spleen and pituitary gland. The present study reports a case of an adult LCH patient with marked liver damage, splenomegaly and pituitary damage treated using a new therapeutic strategy. This case was misdiagnosed as liver cancer and pituitary tumor on the basis of abdominal ultrasound, abdominal magnetic resonance imaging (MRI) and head MRI. The final diagnosis was established by identifying the proliferation of cluster of differentiation 1a-positive LCs in liver tissues. A new regimen of combined 12-week therapy of prednisolone/desmopressin/vincristine and 10 months of maintenance therapy of prednisolone/vinblastine/6-mercaptopurine improved symptoms, liver function and blood cell tests. PMID:24765185

  6. Epigenomic annotation of noncoding mutations identifies mutated pathways in primary liver cancer

    PubMed Central

    Lowdon, Rebecca F.

    2017-01-01

    Evidence that noncoding mutation can result in cancer driver events is mounting. However, it is more difficult to assign molecular biological consequences to noncoding mutations than to coding mutations, and a typical cancer genome contains many more noncoding mutations than protein-coding mutations. Accordingly, parsing functional noncoding mutation signal from noise remains an important challenge. Here we use an empirical approach to identify putatively functional noncoding somatic single nucleotide variants (SNVs) from liver cancer genomes. Annotation of candidate variants by publicly available epigenome datasets finds that 40.5% of SNVs fall in regulatory elements. When assigned to specific regulatory elements, we find that the distribution of regulatory element mutation mirrors that of nonsynonymous coding mutation, where few regulatory elements are recurrently mutated in a patient population but many are singly mutated. We find potential gain-of-binding site events among candidate SNVs, suggesting a mechanism of action for these variants. When aggregating noncoding somatic mutation in promoters, we find that genes in the ERBB signaling and MAPK signaling pathways are significantly enriched for promoter mutations. Altogether, our results suggest that functional somatic SNVs in cancer are sporadic, but occasionally occur in regulatory elements and may affect phenotype by creating binding sites for transcriptional regulators. Accordingly, we propose that noncoding mutation should be formally accounted for when determining gene- and pathway-mutation burden in cancer. PMID:28333948

  7. Targeted therapy of multiple liver metastases after resected solitary gastric metastasis and primary pulmonary adenocarcinoma

    PubMed Central

    Ding, Ling-yu; Liu, Ke-jun; Jiang, Zhe-long; Wu, Hai-ying; Wu, Shi-xiu

    2016-01-01

    Gastric metastases from lung adenocarcinoma are rare and usually asymptomatic. A 61-year-old woman was referred to our department because of a right lower pulmonary mass found on a chest X-ray film in August 2012. Right lower lobectomy was performed for pulmonary adenocarcinoma. Four months later, she developed epigastric discomfort. A fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT) scan showed a malignancy at the cardias of the stomach. A biopsy diagnosed poorly differentiated carcinoma and a gastric carcinoma was suspected. She underwent a subtotal gastrectomy and part of esophagectomy. The histologic diagnosis was metastasis from the pulmonary adenocarcinoma. She visited us again for her increasing level of carcinoembryonic antigen (CEA) after two months. FDG-PET/CT showed multiple malignant lesions in her liver, considering metastases from pulmonary origin. As she harbored activating epidermal growth factor receptor (EGFR) mutation, she received erlotinib from April, 2013. She survives 4 years after the lung resection and is still on erotinib treatment with complete response. Although gastric metastasis from lung cancer is considered a late stage of the disease, a radical resection might provide survival in solitary metastasis. Moreover, systemic therapy was emphasized after local treatment in some late stage cases. PMID:27829227

  8. Impact of Patient Portal Secure Messages and Electronic Visits on Adult Primary Care Office Visits

    PubMed Central

    Crane, Sarah J.; Chaudhry, Rajeev; Ebbert, Jon O.; Ytterberg, Karen; Tulledge-Scheitel, Sidna M.; Stroebel, Robert J.

    2014-01-01

    Abstract Introduction: Secure messages and electronic visits (“e-visits”) through patient portals provide patients with alternatives to face-to-face appointments, telephone contact, letters, and e-mails. Limited information exists on how portal messaging impacts face-to-face visits in primary care. Materials and Methods: We conducted a retrospective cohort study of 2,357 primary care patients who used electronic messaging (both secure messages and e-visits) on a patient portal. Face-to-face appointment frequencies (visits/year) of each patient were calculated before and after the first message in a matched-pairs analysis. We analyzed visit frequencies with and without adjustments for a first message surge in visits, and we examined subgroups of high message utilizers and long-term users. Results: Primary care patients who sent at least one message (secure message or e-visit) had a mean of 2.43 (standard deviation [SD] 2.3) annual face-to-face visits before the first message and 2.47 (SD 2.8) after, a nonsignificant difference (p=0.45). After adjustment for a first message surge in visits, no significant visit frequency differences were observed (mean, 2.35 annual visits per patient both before and after first message; p=0.93). Subgroup analysis also showed no significant change in visit frequency for patients with higher message utilization or for those who had used the messaging feature longer. Conclusions: No significant change in face-to-face visit frequency was observed following implementation of portal messaging. Secure messaging and e-visits through a patient portal may not result in a change of adult primary care face-to-face visits. PMID:24350803

  9. Retinoid Homeostatic Gene Expression in Liver, Lung and Kidney: Ontogeny and Response to Vitamin A-Retinoic Acid (VARA) Supplementation from Birth to Adult Age

    PubMed Central

    Owusu, Sarah A.; Ross, A. Catharine

    2016-01-01

    Vitamin A (VA, retinol) metabolism is homeostatically controlled, but little is known of its regulation in the postnatal period. Here, we determined the postnatal trajectory of VA storage and metabolism in major compartments of VA metabolism–plasma, liver, lung, and kidney from postnatal (P) day 1 to adulthood. We also investigated the response to supplementation with VARA, a combination of VA and 10% all-trans-retinoic acid that previously was shown to synergistically increase retinol uptake and storage in lung. Nursling pups of dams fed a VA-marginal diet received an oral dose of oil (placebo) or VARA on each of four neonatal days: P1, P4, P7, and P10; and again as adults. Tissues were collected 6 h after the final dosing on P1, P4, P10, and at adult age. Gene transcripts for Lrat and Rbp4 in liver and Raldh-1 and Raldh-3 in lung, did not differ in the neonatal period but were higher, P<0.05, in adults, while Cyp26B1, Stra6, megalin, and Raldh-2 in lung did not differ from perinatal to adult ages. VARA supplementation increased total retinol in plasma, liver and lung, with a dose-by-dose accumulation in neonatal liver and lung, while transcripts for Lrat in liver, megalin in kidney, Cyp26A1/B1 in liver and lung, respectively, and Stra6 in lung, were all increased, suggesting pathways of VA uptake, storage and RA oxidation were each augmented after VARA. VARA decreased hepatic expression of Rbp4, responsible for VA trafficking from liver to plasma, and, in lung, of Raldh-1 and Raldh-2, which function in RA production. Our results define retinoid homeostatic gene expression from neonatal and adult age and show that while supplementation with VARA acutely alters retinol content and retinoid homeostatic gene expression in neonatal and adult lung, liver and kidney, VARA supplementation of neonates increased adult-age VA content only in the liver. PMID:26731668

  10. Elevated Liver Function Enzymes Are Related to the Development of Prediabetes and Type 2 Diabetes in Younger Adults

    PubMed Central

    Nguyen, Quoc Manh; Srinivasan, Sathanur R.; Xu, Ji-Hua; Chen, Wei; Hassig, Susan; Rice, Janet; Berenson, Gerald S.

    2011-01-01

    OBJECTIVE Elevations in alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT), surrogate markers of liver dysfunction and nonalcoholic fatty liver, are considered as part of metabolic syndrome and related type 2 diabetes. However, information is limited regarding the long-term predictability of ALT and GGT in the development of prediabetes and type 2 diabetes. RESEARCH DESIGN AND METHODS In this retrospective cohort study, normoglycemic (n = 874), prediabetic (n = 101), and diabetic (n = 80) adults aged 26–50 years (average age 41.3 years) were followed over an average period of 16 years since their young adulthood (aged 18–38 years, average age 25.1 years), with measurements of cardiometabolic risk factor variables including ALT and GGT. RESULTS The follow-up prevalence rate of adult diabetes status by quartiles of baseline ALT and GGT levels showed an adverse trend for both prediabetes (P < 0.05) and diabetes (P < 0.01). In a longitudinal multivariate logistic regression analysis that included anthropometric, hemodynamic, and metabolic variables, as well as alcohol consumption and smoking, individuals with elevated baseline ALT and GGT levels (per 1-SD increment) were 1.16 and 1.20 times, respectively, more likely to develop diabetes (P = 0.05 for ALT and P < 0.01 for GGT); no such associations were noted for prediabetes. Regarding the predictive value of ALT and GGT, the area under the receiver operating curve analysis yielded C values ranging from 0.70 to 0.82, with values significantly higher for diabetes compared with prediabetes. CONCLUSIONS These findings in younger adults suggest potential clinical utility of including ALT and GGT as biomarkers in diabetes risk assessment formulations. PMID:21953798

  11. In-hospital Mobility Variations across Primary Diagnoses among Older Adults

    PubMed Central

    Valiani, Vincenzo; Gao, Shiyao; Chen, Zhiguo; Swami, Sunil; Harle, Christopher A.; Lipori, Gigi; Sourdet, Sandrine; Wu, Samuel; Nayfield, Susan G.; Sabbá, Carlo; Pahor, Marco; Manini, Todd M.

    2016-01-01

    Objectives To examine the relationship between primary diagnoses and mobility impairment and recovery among hospitalized older adults. Design Prospective cohort study. Setting UF Health Shands Hospital, an 852-bed level I trauma center located in Gainesville, Florida. Participants 18,551 older adults (≥65 years) with 29,148 hospitalizations between 1/2009 and 4/2014. Measurements Incident and discharge mobility impairment and recovery were assessed using the Braden activity subscale score that was recorded by the nursing staff at every shift change–approximately three times per day. Primary diagnosis ICD-9 codes were used as predictors and re-categorized by using the Agency for Health Care Research and Quality Clinical Classification Software. Results Out of the 15,498 hospital records where the patient was initially observed to “walk frequently”, 3,186 (20.6%) developed incident mobility impairment (chair-fast or bedfast). Primary diagnoses with a surgical or invasive procedure were the most prevalent (77.2 %) among the hospital observations with incident mobility impairment; otherwise primary diagnoses without surgery were much more associated with discharge mobility impairment (59%). The highest incidence of mobility impairment occurred in patients with heart valve disorders and aortic and peripheral/visceral artery aneurysms (6.24 and 6.05 events per 30 person-days, respectively); septicemia showed the highest incidence rate for mobility limitation at discharge (0.94 events per 30 person-days). Mobility impairment was observed in 13,650 (46.8% of total) records at admission and 5,930 (43.44%) were observed to recover to a state of walking occasionally or frequently. Osteoarthritis and cancer of gastrointestinal organs/peritoneum had the highest incidence rate for mobility recovery (7.68 and 5.63 events per 30 person-days respectively). Conclusions Approximately 1 out of 5 patients who were mobile at admission became significantly impaired during

  12. Thyroid gland metastasis arising from primary liver cholangiocarcinoma: The first case report involving surgical operation

    PubMed Central

    Park, Min Ho; Cho, Jin Seong; Lee, Ji Shin; Kim, Hee Kyung; Yoon, Jung Han

    2011-01-01

    Introduction A primary cancer causing thyroid metastasis is extremely rare. In western countries, the most common primary tumors causing thyroid metastases include kidney, lung, breast, and gastrointestinal cancers. In contrast, breast is the most common primary site, followed by kidney, colon, and lung cancers in Korea. To the best of our knowledge, surgically confirmed thyroid metastasis from cholangiocarcinoma has not been reported. Herein, we report the first case of thyroid metastasis secondary to cholangiocarcinoma on which surgery was performed. Presentation of case A 55-year-old man was diagnosed with hepatic malignancy in December 2008. He subsequently received 2 cycles of transarterial chemoembolization and 4 cycles of radio-frequency ablation between 2008 and 2010. At follow-up in January 2011, brain metastasis was identified in the right parietal area secondary to cholangiocarcinoma. In April 2011, the patient was found to have palpable masses on the left thyroid and lateral neck. The patient subsequently underwent total thyroidectomy followed by left radical neck dissection. Intraoperatively, an ill-defined mass measuring 6.0 cm was found infiltrating the subcutaneous tissue into the prevertebral fascia. Microscopic and immunohistochemical findings confirmed that the thyroid masses and lymph nodes were metastatic cholangiocarcinoma. Discussion Positive immunohistochemical staining for cytokeratin 7, cytokeratin 19, and AFP and negative results for TG, TTF-1, and cytokeratin 20 can be definitely helpful in arriving at a correct diagnosis. Conclusion To the best of our knowledge, this is the first case report on surgically resected thyroid and lateral neck metastases secondary to cholangiocarcinoma. PMID:22288052

  13. Assessing the Quality of a Nonrandomized Pragmatic Trial for Primary Prevention of Falls among Older Adults

    PubMed Central

    Albert, Steven M.; Edelstein, Offer; King, Jennifer; Flatt, Jason; Lin, Chyongchiou J.; Boudreau, Robert; Newman, Anne B.

    2014-01-01

    Background Current approaches to falls prevention mostly rely on secondary and tertiary prevention and target individuals at high risk of falls. An alternative is primary prevention, in which all seniors are screened, referred as appropriate, and educated regarding falls risk. Little information is available on research designs that allow investigation of this approach in the setting of aging services delivery, where randomization may not be possible. Methods Healthy Steps for Older Adults, a statewide program of the Pennsylvania (PA) Department of Aging, involves a combination of education about falls and screening for balance problems, with referral to personal physicians and home safety assessments. We developed a nonrandomized statewide trial, Falls Free PA, to assess its effectiveness in reducing falls incidence over 12 months. We recruited 814 seniors who completed the program (503 first time participants, 311 people repeating the program) and 1020 who did not participate in the program, from the same sites. We assessed the quality of this nonrandomized design by examining recruitment, follow-up across study groups, and comparability at baseline. Results Of older adults approached in senior centers, 90.5% (n=2219) signed informed consent, and 1834 (82.4%) completed baseline assessments and were eligible for follow-up. Attrition in the three groups over 12 months was low and non-differential (<10% for withdrawal and <2% for other loss to follow-up). Median follow-up, which involved standardized monthly assessment of falls, was 10 months in all study groups. At baseline the groups did not differ in measures of health or falls risk factors. Conclusions Comparable status at baseline, recruitment from common sites, and similar experience with retention suggest that the nonrandomized design will be effective for assessment of this approach to primary prevention of falls. PMID:24488533

  14. Activity, Inhibition, and Induction of Cytochrome P450 2J2 in Adult Human Primary Cardiomyocytes

    PubMed Central

    Evangelista, Eric A.; Kaspera, Rüdiger; Mokadam, Nahush A.; Jones, J. P.

    2013-01-01

    Cytochrome P450 2J2 plays a significant role in the epoxidation of arachidonic acid to signaling molecules important in cardiovascular events. CYP2J2 also contributes to drug metabolism and is responsible for the intestinal clearance of ebastine. However, the interaction between arachidonic acid metabolism and drug metabolism in cardiac tissue, the main expression site of CYP2J2, has not been examined. Here we investigate an adult-derived human primary cardiac cell line as a suitable model to study metabolic drug interactions (inhibition and induction) of CYP2J2 in cardiac tissue. The primary human cardiomyocyte cell line demonstrated similar mRNA-expression profiles of P450 enzymes to adult human ventricular tissue. CYP2J2 was the dominant isozyme with minor contributions from CYP2D6 and CYP2E1. Both terfenadine and astemizole oxidation were observed in this cell line, whereas midazolam was not metabolized suggesting lack of CYP3A activity. Compared with recombinant CYP2J2, terfenadine was hydroxylated in cardiomyocytes at a similar Km value of 1.5 μM. The Vmax of terfenadine hydroxylation in recombinant enzyme was found to be 29.4 pmol/pmol P450 per minute and in the cells 6.0 pmol/pmol P450 per minute. CYP2J2 activity in the cell line was inhibited by danazol, astemizole, and ketoconazole in submicromolar range, but also by xenobiotics known to cause cardiac adverse effects. Of the 14 compounds tested for CYP2J2 induction, only rosiglitazone increased mRNA expression, by 1.8-fold. This cell model can be a useful in vitro model to investigate the role of CYP2J2-mediated drug metabolism, arachidonic acid metabolism, and their association to drug induced cardiotoxicity. PMID:24021950

  15. Occupational and environmental risk factors of adult primary brain cancers: a systematic review.

    PubMed

    Gomes, J; Al Zayadi, A; Guzman, A

    2011-04-01

    The incidence of brain neoplasm has been progressively increasing in recent years in the industrialized countries. One of the reasons for this increased incidence could be better access to health care and improved diagnosis in the industrialized countries. It also appears that Caucasians have a higher incidence than blacks or Hispanics or Asians. A number of risk factors have been identified and described including the genetic, ethnic and age-based factors. Certain occupational and environmental factors are also believed to influence the risk of primary adult brain tumors. Potential occupational and environmental factors include exposure to diagnostic and therapeutic radiations, electromagnetic radiation from cellular phones and other wireless devices, infectious agents, air pollution and residence near landfills and high-voltage power lines and jobs as firefighters, farmers, physician, chemists and jobs in industries such as petrochemical, power generation, synthetic rubber manufacturing, agricultural chemicals manufacturing. The purpose of this systematic review is to examine occupational and environmental risk factors of brain neoplasm. A range of occupational and environmental exposures are evaluated for significance of their relationship with adult primary brain tumors. On the basis of this review we suggest a concurrent evaluation of multiple risk factors both within and beyond occupational and environmental domains. The concurrent approach needs to consider better exposure assessment techniques, lifetime occupational exposures, genotypic and phenotypic characteristics and lifestyle and dietary habits. This approach needs to be interdisciplinary with contributions from neurologists, oncologists, epidemiologists and molecular biologists. Conclusive evidence that has eluded multitude of studies with single focus and single exposure needs to multifaceted and multidisciplinary.

  16. Compound heterozygote mutations in SPG7 in a family with adult-onset primary lateral sclerosis

    PubMed Central

    Yang, Yi; Lynch, David R.; Lukas, Thomas; Ahmeti, Kreshnik; Sleiman, Patrick M.A.; Ryan, Eanna; Schadt, Kimberly A.; Newman, Jordan H.; Deng, Han-Xiang; Siddique, Nailah

    2016-01-01

    Objective: To identify the genetic defect for adult-onset primary lateral sclerosis (PLS) in a family with 5 patients. Methods: Whole-exome sequencing was performed to identify the shared genetic variants in 3 affected members in a PLS family with 5 affected individuals. Sanger sequencing was used for validation of the variants and for cosegregation analysis. Mitochondrial activity for both patients and unaffected siblings was measured using a SeaHorse metabolic analyzer. Results: Whole-exome sequencing and subsequent cosegregation analysis demonstrated that compound heterozygous missense variants L695P and I743T in SPG7 were the only mutations cosegregating with the disease in an autosomal recessive fashion in this family. The parents and siblings are genetically heterozygous and clinically unaffected. Functional studies suggested that the PLS-associated SPG7 mutants affect mitochondrial function when glucose is reduced. Conclusions: Compound heterozygote mutations in SPG7 are associated with adult-onset PLS, extending the spectrum of SPG7-linked neurologic diseases. Patients with the PLS phenotype should have genetic testing for paraplegin, especially when the condition is familial. PMID:27123479

  17. A quality-of-life measure for adults with primary ciliary dyskinesia: QOL–PCD

    PubMed Central

    Behan, Laura; Dunn Galvin, Audrey; Alpern, Adrianne; Morris, Anjana M.; Carroll, Mary P.; Knowles, Michael R.; Leigh, Margaret W.; Quittner, Alexandra L.

    2015-01-01

    Primary ciliary dyskinesia (PCD) is characterised by chronic suppurative lung disease, rhino-sinusitis, hearing impairment and sub-fertility. We have developed the first multidimensional measure to assess health-related quality of life (HRQoL) in adults with PCD (QOL–PCD). Following a literature review and expert panel meeting, open-ended interviews with patients investigated the impact of PCD on HRQoL in the UK and North America (n=21). Transcripts were content analysed to derive saturation matrices. Items were rated for relevance by patients (n=49). Saturation matrices, relevance scores, literature review, evaluation of existing measures, and expert opinion contributed to development of a preliminary questionnaire. The questionnaire was refined following cognitive interviews (n=18). Open-ended interviews identified a spectrum of issues unique to adults with PCD. Saturation matrices confirmed comprehensive coverage of content. QOL–PCD includes 48 items covering the following seven domains: Physical Functioning, Emotional Functioning, Treatment Burden, Respiratory and Sinus Symptoms, Ears and Hearing, Social Functioning, and Vitality and Health Perceptions. Cognitive testing confirmed that content was comprehensive and the items were well-understood by respondents. Content validity and cognitive testing supported the items and structure. QOL–PCD has been translated into other languages and is awaiting psychometric testing. PMID:25976687

  18. Voluntary physical exercise promotes ocular dominance plasticity in adult mouse primary visual cortex.

    PubMed

    Kalogeraki, Evgenia; Greifzu, Franziska; Haack, Franziska; Löwel, Siegrid

    2014-11-12

    Ocular dominance (OD) plasticity in the mouse primary visual cortex (V1) declines during aging and is absent beyond postnatal day (P) 110 when mice are raised in standard cages (SCs; Lehmann and Löwel, 2008). In contrast, raising mice in an enriched environment (EE) preserved a juvenile-like OD plasticity into late adulthood (Greifzu et al., 2014). EE raising provides the mice with more social interactions, voluntary physical exercise, and cognitive stimulation compared with SC, raising the question whether all components are needed or whether one of them is already sufficient to prolong plasticity. To test whether voluntary physical exercise alone already prolongs the sensitive phase for OD plasticity, we raised mice from 7 d before birth to adulthood in slightly larger than normal SCs with or without a running wheel (RW). When the mice were older than P135, we visualized V1 activity before and after monocular deprivation (MD) using intrinsic signal optical imaging. Adult RW-raised mice continued to show an OD shift toward the open eye after 7 d of MD, while age-matched SC mice without a RW did not show OD plasticity. Notably, running just during the 7 d MD period restored OD plasticity in adult SC-raised mice. In addition, the OD shift of the RW mice was mediated by a decrease of deprived-eye responses in V1, a signature of "juvenile-like" plasticity. We conclude that voluntary physical exercise alone is sufficient to promote plasticity in adult mouse V1.

  19. Metabolic conversion of 12-O-tetradecanoylphorbol-13-acetate in adult and newborn mouse skin and mouse liver microsomes.

    PubMed

    Berry, D L; Bracken, W M; Fischer, S M; Viaje, A; Slaga, T J

    1978-08-01

    Tritiated 12-O-tetradecanoylphorbol-13-acetate (TPA) was applied to adult mouse skin; at specified time intervals the mice were killed, and the labeled phorbol was extracted and subjected to separation and quantitation by high-pressure liquid chromatography. After 24 hr, TPA comprised greater than 96% of the recovered label from the skin, and its apparent half-life was 17.8 hr. Pretreatment of adult skin with TPA for 4 weeks before treatment with labeled TPA resulted in an increase in the clearance rate of TPA from the skin. Skin from newborn mice was capable of converting TPA into monoesters and phorbol, but the clearance rate in the adult was about 12 times more rapid than it was in the newborn. Epidermal homogenates converted TPA into 12-O-tetradecanoylphorbol, phorbol-13-acetate, and phorbol. Hepatic homogenates were able to convert TPA to monoesters and phorbol at rates 14 to 15 times faster than were epidermal homogenates. Attempts to isolate any previously undescribed metabolites of TPA by use of liver homogenates were unsuccessful, and mixed-function oxidation did not contribute to the metabolism of TPA. From inhibitor studies it was judged that esterases were implicated in the conversion of TPA to monoesters and phorbol. The results support the hypothesis that the tumor-promoting activity of TPA is directly related to its concentration in a specific tissue and that conversion of TPA to an active metabolite probably does not occur.

  20. Parents in transition: Experiences of parents of young people with a liver transplant transferring to adult services.

    PubMed

    Wright, J; Elwell, L; McDonagh, J E; Kelly, D A; Wray, J

    2017-02-01

    Predictors of successful transition from pediatric to adult services include ability to self-manage and engage with healthcare services. Parents have a key role in healthcare management throughout childhood and adolescence including encouraging development of self-management skills in their children. Transition to adult services can be challenging for parents and young people, yet parents' views regarding transition remain largely unexplored. Nine parents of pediatric liver transplant recipients (15.2-25.1 yr) participated in semistructured interviews. Interviews were analyzed using IPA. Analysis revealed three key themes: "emotional impact of transplantation," "protection vs. independence," and "ending relationships and changing roles." Parents expressed the dichotomous nature of the desire to promote independence in their child while still maintaining control and protection, and discussed how changing roles and relationships were difficult to navigate. Parents are important facilitators of young people's development of self-management skills for successful transfer to adult services. Parents should be supported to move from a "managerial" to a "supervisory" role during transition to help young people engage independently with the healthcare team. Findings support the development of interventions for parents to emphasize their role in transition and guide the transfer of self-management skills from parent to young person.

  1. Most Uninsured Adults Could Schedule Primary Care Appointments Before The ACA, But Average Price Was $160.

    PubMed

    Saloner, Brendan; Polsky, Daniel; Kenney, Genevieve M; Hempstead, Katherine; Rhodes, Karin V

    2015-05-01

    Provisions of the Affordable Care Act (ACA) allow millions more Americans to obtain health insurance. However, a sizable number of people remain uninsured because they live in states that have not expanded Medicaid coverage or because they feel that Marketplace coverage is not affordable. Using data from a ten-state telephone survey in which callers posed as patients, we examined prices for primary care visits offered by physician offices to new uninsured patients in 2012-13, prior to ACA insurance expansions. Patients were quoted a mean price of $160. Significantly lower prices for the uninsured were offered by family practice offices compared to general internists, in offices participating in Medicaid managed care plans, and in federally qualified health centers. Prices were also lower for offices in ZIP codes with higher poverty rates. Only 18 percent of uninsured callers were told that they could bring less than the full amount to the visit and arrange to pay the rest later. ACA insurance expansions could greatly decrease out-of-pocket spending for low-income adults seeking primary care. However, benefits of health reform are likely to be greater in states expanding Medicaid eligibility.

  2. Cholestatic liver diseases from child to adult: the diversity of MDR3 disease.

    PubMed

    Kubitz, R; Bode, J; Erhardt, A; Graf, D; Kircheis, G; Müller-Stöver, I; Reinehr, R; Reuter, S; Richter, J; Sagir, A; Schmitt, M; Donner, M

    2011-06-01

    The phospholipidfloppase MDR3 (gene symbol: ABCB4) is expressed in the canalicular membrane of hepatocytes and mediates the biliary excretion of phosphatidylcholine, which is required for the formation of mixed micelles in bile. Several mutations of ABCB4 have been identified, which cause cholestatic liver diseases of varying severity including progressive familial intrahepatic cholestasis type 3 (PFIC-3), intrahepatic cholestasis of pregnancy (ICP) and the low phospholipid associated cholelithiasis syndrome (LPAC). Here, we report on four new (S1076N; L 23Hfs16X; c.286 + 1G > A; Q 1181E) and one known (S27G) MDR3 mutations in eight patients of three families. The patients presented with a wide spectrum of liver diseases. The clinical presentation and decisive laboratory findings or the association to a trend-setting family history led to the identification of the genetic background in these patients. Even the same mutation may be associated with varying disease progression.

  3. Serum prolactin in patients with liver disease in comparison with healthy adults: A preliminary cross-sectional study

    PubMed Central

    Jha, Sumit Kant; Kannan, Sridharan

    2016-01-01

    Introduction: Studies from the west have shown raised prolactin levels in patients with liver disease. Considering the lacunae on Indian context, we conducted the present study with an objective to assess the prolactin levels in patients with cirrhosis and viral hepatitis with or without features of encephalopathy. The data presented here are the results of the preliminary analysis. Materials and Methods: The present study was a prospective, cohort study among patients diagnosed as either viral hepatitis or cirrhosis liver. A cohort of normal healthy adults was selected based on history and laboratory investigations (complete blood count, liver and renal function tests). Serum prolactin was measured for all the study participants, and Kruskal–Wallis H-test with post-hoc Dunn's test was used to analyze the significance of the differences in the levels between various groups. Tests of diagnostic accuracy were used to assess the prediction capability of serum prolactin with a cut-off level of 50 ng/ml. Results: A total of 70 patients (10 - normal healthy; 25 - acute viral hepatitis; 35 - cirrhosis liver) were recruited in the present study with the median (range) age in years of 56 (34–68) and male: female ratio of 2:1. A statistically significant (P < 0.05) increase in the serum prolactin was observed in patients with cirrhosis with or without encephalopathy. But, among the patients with viral hepatitis, a significant elevation was observed only in patients with encephalopathy. Additionally, a statistically significant association was observed between serum prolactin levels with serum bilirubin (ρ =0.67, P = 0.04) and aspartate aminotransferase (ρ =0.72, P = 0.05). A cut-off value of 50 ng/ml of serum prolactin was found to predict the mortality. A total of 4/12 (33.3%) with prolactin value of <50 ng/ml died while 11/23 (47.8%) died with values >50 ng/ml (P < 0.05). Similarly, in patients with viral hepatitis with encephalopathy features, 1/4 (25%) with

  4. Inhibitor and temperature effect on catalase in the liver of adult diploid and haploid Rana rugosa.

    PubMed

    Kashiwagi, A; Kashiwagi, K; Takase, M; Hanada, H; Yamashita, M; Naitoh, T; Nakamura, M

    1998-01-01

    The authors succeeded in raising a single mature haploid Rana rugosa female to the age of 2 years from an egg artificially fertilized with ultraviolet-irradiated sperm. In order to discover why this particular haploid individual should survive so long, hydrogen peroxide detoxifying catalase in the liver of this individual and age-matched diploids was examined and compared for total activity, temperature stability, and chemical inhibition. Total activity was found to be significantly higher in the haploid frog than in the diploids, suggesting that this particular haploid had a unique system for hydrogen peroxide detoxification which protected the liver against cell death, preventing hepatic failure, and leading to a prolonged survival. Liver catalase from the haploid proved to be more labile to aminotriazole and urea, losing 60-70% of its original activity after 30 min treatment, whereas diploid catalase lost only 40% under the same conditions. Haploid and diploid catalase responded similarly to heat, however. It seems likely that inhibitor-binding sites differ considerably between the catalase of normal diploids and the catalase of this particular haploid, while overall structure is generally similar.

  5. Dual impact of chronic liver disease and amaebiasis on immunopathogenesis of primary osteoarthritis in Egyptians.

    PubMed

    El-Dardiry, Samia A; Shafik, Sherine R; Wagih, Ayman; Amir, El-Amir M; El-Yamany, Sahar; Selim, Sahar; Amr, Yaser; Hawas, Samir El-Sayed

    2007-08-01

    Sixty cases with primary knee OA were equally categorized into six groups with EHI (Gs 1, 2, 3) or without (Gs 4, 5, 6). GI included cases with HCV, GII cases with RHS & HCV and GIII cases with a history of non-active schistosomiasis whereas Gs 4, 5 & 6 included cases without EHI. Clinical examination with inclusion criteria of pathological manifestations w\\as associated with biochemical evaluation of adhesion molecules (E-selectin, P-selectin, intracellular adhesion molecule-3 "ICAM-3") in plasma and synovial fluid. Synovial fluid indices (IgG, IgA, IgM, & C3) were evaluated as well as indices of inflammation and oxidative stress (Beta 2 microglobulin, Haptaglobulin, fibronectin, total thiol, superoxide dismutase, thiobarbituric acid reactive substance & hyaluronan) in synovial fluid and indices activating fibrogenesis in serum and plasma (procollagen III, plasma prolidase, Interleukin-1 beta, Interleukin-6 & TNF alpha). The results showed a positive relationship between indices activating vascular damage, fibrogenesis and immuno-inflammatory response with higher change magnitude in EHI cases particularly with combined HCV & RHS. This implement the dual role of hepatic insult and intestinal amoebiasis on immune mediated mechanisms activating inflammatory response in OA cases reflecting common signaling pathways associated with pathogenesis of multifaceted origin.

  6. Transcriptional profiling suggests that Nevirapine and Ritonavir cause drug induced liver injury through distinct mechanisms in primary human hepatocytes.

    PubMed

    Terelius, Ylva; Figler, Robert A; Marukian, Svetlana; Collado, Maria S; Lawson, Mark J; Mackey, Aaron J; Manka, David; Qualls, Charles W; Blackman, Brett R; Wamhoff, Brian R; Dash, Ajit

    2016-08-05

    Drug induced liver injury (DILI), a major cause of pre- and post-approval failure, is challenging to predict pre-clinically due to varied underlying direct and indirect mechanisms. Nevirapine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) and Ritonavir, a protease inhibitor, are antiviral drugs that cause clinical DILI with different phenotypes via different mechanisms. Assessing DILI in vitro in hepatocyte cultures typically requires drug exposures significantly higher than clinical plasma Cmax concentrations, making clinical interpretations of mechanistic pathway changes challenging. We previously described a system that uses liver-derived hemodynamic blood flow and transport parameters to restore primary human hepatocyte biology, and drug responses at concentrations relevant to in vivo or clinical exposure levels. Using this system, primary hepatocytes from 5 human donors were exposed to concentrations approximating clinical therapeutic and supra-therapeutic levels of Nevirapine (11.3 and 175.0 μM) and Ritonavir (3.5 and 62.4 μM) for 48 h. Whole genome transcriptomics was performed by RNAseq along with functional assays for metabolic activity and function. We observed effects at both doses, but a greater number of genes were differentially expressed with higher probability at the toxic concentrations. At the toxic doses, both drugs showed direct cholestatic potential with Nevirapine increasing bile synthesis and Ritonavir inhibiting bile acid transport. Clear differences in antigen presentation were noted, with marked activation of MHC Class I by Nevirapine and suppression by Ritonavir. This suggests CD8+ T cell involvement for Nevirapine and possibly NK Killer cells for Ritonavir. Both compounds induced several drug metabolizing genes (including CYP2B6, CYP3A4 and UGT1A1), mediated by CAR activation in Nevirapine and PXR in Ritonavir. Unlike Ritonavir, Nevirapine did not increase fatty acid synthesis or activate the respiratory electron chain

  7. Long-term impact of liver transplantation on respiratory function and nutritional status in children and adults with cystic fibrosis.

    PubMed

    Dowman, J K; Watson, D; Loganathan, S; Gunson, B K; Hodson, J; Mirza, D F; Clarke, J; Lloyd, C; Honeybourne, D; Whitehouse, J L; Nash, E F; Kelly, D; van Mourik, I; Newsome, P N

    2012-04-01

    Early liver transplant (LT) has been advocated for patients with cystic fibrosis liver disease (CFLD) and evidence of deterioration in nutritional state and respiratory function to prevent further decline. However, the impact of single LT on long-term respiratory function and nutritional status has not been adequately addressed. We performed a retrospective analysis of the outcomes of 40 (21 adult/19 pediatric) patients with CFLD transplanted between 1987 and 2009 with median follow-up of 47.8 months (range 4-180). One and five-year actuarial survival rates were 85%/64% for adult and 90%/85% for pediatric LT cohorts, respectively. Lung function remained stable until 4 years (FEV(1) % predicted; pretransplant 48.4% vs. 45.9%, 4 years posttransplant) but declined by 5 years (42.4%). Up to 4 years posttransplant mean annual decline in FEV(1) % was lower (0.74%; p = 0.04) compared with the predicted 3% annual decline in CF patients with comorbidity including diabetes. Number of courses of intravenous antibiotics was reduced following LT, from 3.9/year pretransplant to 1.1/year, 5 years posttransplant. Body mass index was preserved posttransplant; 18.0 kg/m(2) (range 15-24.3) pretransplant versus 19.6 kg/m(2) (range 16.4-22.7) 5 years posttransplant. In conclusion, LT is an effective treatment for selected patients with cirrhosis due to CFLD, stabilizing aspects of long-term lung function and preserving nutritional status.

  8. Biliary complications secondary to late hepatic artery thrombosis in adult liver transplant patients.

    PubMed

    Margarit, C; Hidalgo, E; Lázaro, J L; Murio, E; Charco, R; Balsells, J

    1998-01-01

    Biliary complications (BC) are the usual presentation of late hepatic artery thrombosis (HAT) of the liver graft. Our aim was to study the clinical features and outcome of BC secondary to HAT compared to BC which occurred in liver transplant (LT) patients with patent vessels. We present a retrospective study of 224 LTs performed in 204 patients between 1988 and 1996. The mean recipient x s age was 51 years. A choledochocholedochostomy without T-tube was used as biliary reconstruction in most cases (67%); in 12%, a choledochojejunostomy was performed. An iliac conduit was necessary in 15% of cases and back-table arterial reconstruction was performed in 10% of cases of anatomic variants in graft arteries. Different donor, recipient and intraoperative variables, as well as treatment and outcome. were studied in the two groups of patients presenting BC with or without HAT. BC occurred in 38 cases (17%) whereas HAT was diagnosed in 11 cases (4.9%). Therefore, 23% of BC encountered after LT were secondary to HAT. Nine cases of late HAT manifested as BC, septicaemia (88%) and hepatic bilomas (8 cases). Percutaneous or surgical drainage of hepatic bilomas was performed in all cases, followed by retransplantation in six cases (66%). BC secondary to HAT appeared later than the rest of BC. Donor age was the only significant predisposing factor found in our study. Graft survival is significantly reduced as most patients needed retransplantation. In conclusion, BC secondary to HAT presented later in livers from older donors in the form of biliary sepsis and hepatic biloma. Retransplantation was ultimately required in most cases and graft survival was significantly diminished.

  9. Liver peroxisomal alanine:glyoxylate aminotransferase and the effects of mutations associated with Primary Hyperoxaluria Type I: An overview.

    PubMed

    Oppici, Elisa; Montioli, Riccardo; Cellini, Barbara

    2015-09-01

    Liver peroxisomal alanine:glyoxylate aminotransferase (AGT) (EC 2.6.1.44) catalyses the conversion of l-alanine and glyoxylate to pyruvate and glycine, a reaction that allows glyoxylate detoxification. Inherited mutations on the AGXT gene encoding AGT lead to Primary Hyperoxaluria Type I (PH1), a rare disorder characterized by the deposition of calcium oxalate crystals primarily in the urinary tract. Here we describe the results obtained on the biochemical features of AGT as well as on the molecular and cellular effects of polymorphic and pathogenic mutations. A complex scenario on the molecular pathogenesis of PH1 emerges in which the co-inheritance of polymorphic changes and the condition of homozygosis or compound heterozygosis are two important factors that determine the enzymatic phenotype of PH1 patients. All the reported data represent relevant steps toward the understanding of genotype/phenotype correlations, the prediction of the response of the patients to the available therapies, and the development of new therapeutic approaches. This article is part of a Special Issue entitled: Cofactor-dependent proteins: evolution, chemical diversity and bio-applications.

  10. Adult T-cell leukemia/lymphoma: a case report of primary cutaneous tumoral type

    PubMed Central

    Lyra-da-Silva, Julia Ocampo; de Mello Gonzaga, Yung Bruno; de Melo Espíndola, Otávio; de Andrada-Serpa, Maria José; Dib, Cassio; Jeunon, Thiago

    2012-01-01

    Background: Adult T-cell leukemia/lymphoma (ATLL) is a distinctive peripheral T- lymphocytic malignancy associated with human T-cell lymphotropic virus type 1 (HTLV-1). It may closely resemble other skin lymphomas, particularly mycosis fungoides (MF). Case report: A 38-year-old woman presented some ellipsoid scaling patches lasting 18 months and developed a large tumoral lesion in the abdomen, which were previously diagnosed as MF. Although histopathologic and immunohistochemistry findings were in consonance with this diagnosis, the fast progression of the disease raised the suspicion that it could represent another type of T-cell lymphoma. The work-up revealed a positive anti-HTLV-1 serology and molecular studies confirmed the monoclonal integration of HTLV-1 provirus into neoplastic cells of the skin, but not into circulating lymphocytes. Extensive investigations were unable to demonstrate any systemic involvement. The final diagnosis was of primary cutaneous type of ATLL. The patient was submitted to a chemotherapy regimen with cyclophosphamide, doxorubicin, vincristine and prednisone, later to conjugated dexamethasone and surgical cytoreduction and then to a second line treatment with gemcitabine, resulting in partial response. A bone marrow heterologous transplantation was performed, but failed to achieve a sustained remission. Discussion: ATLL is a rare lymphoid malignancy in non-endemic HTLV-1 areas, the diagnosis of which could be missed if not highly suspected. In addition to the four subtypes of Shimoyama classification (acute, lymphomatous, chronic and smoldering), a fifth one denominated primary cutaneous and characterized by presence of lesions only in the skin had been proposed and is herein exemplified. PMID:23785591

  11. Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy.

    PubMed

    Redei, E E; Andrus, B M; Kwasny, M J; Seok, J; Cai, X; Ho, J; Mohr, D C

    2014-09-16

    An objective, laboratory-based diagnostic tool could increase the diagnostic accuracy of major depressive disorders (MDDs), identify factors that characterize patients and promote individualized therapy. The goal of this study was to assess a blood-based biomarker panel, which showed promise in adolescents with MDD, in adult primary care patients with MDD and age-, gender- and race-matched nondepressed (ND) controls. Patients with MDD received cognitive behavioral therapy (CBT) and clinical assessment using self-reported depression with the Patient Health Questionnaire-9 (PHQ-9). The measures, including blood RNA collection, were obtained before and after 18 weeks of CBT. Blood transcript levels of nine markers of ADCY3, DGKA, FAM46A, IGSF4A/CADM1, KIAA1539, MARCKS, PSME1, RAPH1 and TLR7, differed significantly between participants with MDD (N=32) and ND controls (N=32) at baseline (q< 0.05). Abundance of the DGKA, KIAA1539 and RAPH1 transcripts remained significantly different between subjects with MDD and ND controls even after post-CBT remission (defined as PHQ-9 <5). The ROC area under the curve for these transcripts demonstrated high discriminative ability between MDD and ND participants, regardless of their current clinical status. Before CBT, significant co-expression network of specific transcripts existed in MDD subjects who subsequently remitted in response to CBT, but not in those who remained depressed. Thus, blood levels of different transcript panels may identify the depressed from the nondepressed among primary care patients, during a depressive episode or in remission, or follow and predict response to CBT in depressed individuals.

  12. Insulin Resistance in Adult Primary Care Patients With a Surrogate Index, Guadalajara, Mexico, 2012

    PubMed Central

    Espinel-Bermúdez, María Claudia; Robles-Cervantes, José Antonio; del Sagrario Villarreal-Hernández, Liliana; Villaseñor-Romero, Juan Pablo; Hernández-González, Sandra Ofelia; González-Ortiz, Manuel; Martínez-Abundis, Esperanza; Pérez-Rubio, Karina Griselda

    2015-01-01

    Introduction Insulin resistance (IR) is a key molecular disorder related with diabetes mellitus, obesity, and cardiovascular disease. The objective of this study was to determine IR in adult primary care patients using the triglyceride/glucose (TyG) index [(Ln TG (mg/dL) × FG (mg/dL))/2]. Methods We conducted a cross-sectional secondary analysis and identified IR subjects according to the TyG index. Results There were 1500 patients included. Significant differences were found between the IR group versus the insulin-sensitive group, respectively: age (in years), 46.4 ± 9.34 versus 40.24 ± 11.27 (P < 0.001); fasting glucose (mg/dL), 99.87 ± 11.95 versus 84.62 ± 6.59 (P < 0.001); total cholesterol (mg/dL), 203.21 ± 37.38 versus 173.91 ± 33.99 (P < 0.001); triglycerides (mg/dL), 226.40 ± 96.66 versus 111.27 ± 23.44 (P < 0.001); uric acid (mg/dL), 6.09 ± 1.59 versus 4.77 ± 1.40 (P < 0.001); and TyG index, 4.96 ± 0.21 versus 4.48 ± 0.13 (P < 0.001). The cutoff of the TyG index for IR was 4.68 or greater. Conclusions The TyG index allows for early diagnosis of IR in primary health care. PMID:25503090

  13. A comparison of whole genome gene expression profiles of HepaRG cells and HepG2 cells to primary human hepatocytes and human liver tissues.

    PubMed

    Hart, Steven N; Li, Ye; Nakamoto, Kaori; Subileau, Eva-anne; Steen, David; Zhong, Xiao-bo

    2010-06-01

    HepaRG cells, derived from a female hepatocarcinoma patient, are capable of differentiating into biliary epithelial cells and hepatocytes. More importantly, differentiated HepaRG cells are able to maintain activities of many xenobiotic-metabolizing enzymes, and expression of the metabolizing enzyme genes can be induced by xenobiotics. The ability of these cells to express and induce xenobiotic-metabolizing enzymes is in stark contrast to the frequently used HepG2 cells. The previous studies have mainly focused on a set of selected genes; therefore, it is of significant interest to know the extent of similarity of gene expression at whole genome levels in HepaRG cells and HepG2 cells compared with primary human hepatocytes and human liver tissues. To accomplish this objective, we used Affymetrix (Santa Clara, CA) U133 Plus 2.0 arrays to characterize the whole genome gene expression profiles in triplicate biological samples from HepG2 cells, HepaRG cells (undifferentiated and differentiated cells), freshly isolated primary human hepatocytes, and frozen liver tissues. After using similarity matrix, principal components, and hierarchical clustering methods, we found that HepaRG cells globally transcribe genes at levels more similar to human primary hepatocytes and human liver tissues than HepG2 cells. In particular, many genes encoding drug-processing proteins are transcribed at a more similar level in HepaRG cells than in HepG2 cells compared with primary human hepatocytes and liver samples. The transcriptomic similarity of HepaRG with primary human hepatocytes is encouraging for use of HepaRG cells in the study of xenobiotic metabolism, hepatotoxicology, and hepatocyte differentiation.

  14. Sleep time and pattern of adult individuals in primary care in an Asian urbanized community

    PubMed Central

    Tan, Ngiap Chuan; Tan, Mui Suan; Hwang, Siew Wai; Teo, Chia Chia; Lee, Zhi Kang Niccol; Soh, Jing Yao Jonathan; Koh, Yi Ling Eileen; How, Choon How

    2016-01-01

    Abstract Sleep norms vary between individuals, being affected by personal, communal, and socioeconomic factors. Individuals with sleep time which deviate from the population norm are at risks of adverse mental, cardiovascular, and metabolic health. Sleep-related issues are common agenda for consultation in primary care. This study aimed to determine the sleep time, pattern, and behavior of multiethnic Asian individuals who attended public primary care clinics in an urban metropolitan city-state. Standardized questionnaires were assistant-administered to adult Asian individuals who visited 2 local public primary care clinics in north-eastern and southern regions of Singapore. The questionnaire included questions on demographic characteristics, self-reported sleep time, patterns, and behavior and those originated from the American National Sleep Foundation Sleep Diary. The data were collated, audited, rectified, and anonymized before being analyzed by the biostatistician. Individuals with 7 h sleep time or longer were deemed getting adequate sleep. Chi-squared or Fisher exact test was used to test the association between the demographic and behavioral variables and sleep time. Next, regression analysis was performed to identify key factors associated with their sleep time. A total of 350 individuals were recruited, with higher proportion of those of Chinese ethnicity reporting adequate sleep. Almost half (48.1%) of those who slept <7 h on weekdays tended to sleep ≥7 h on weekends. More individuals who reported no difficulty falling asleep, had regular sleep hours and awakening time, tended to sleep adequately. Those who slept with children, studied, read leisurely, used computer or laptops in their bedrooms, drank caffeinated beverages or smoked had inadequate sleep. Those who perceived sufficient sleep and considered 8 h as adequate sleep time had weekday and weekend sleep adequacy. Sleep time varied according to ethnicity, employment status, personal

  15. Mental ability performance among adults with type 2 diabetes in primary care.

    PubMed

    Mount, David L; Lambert, Michael C

    2009-06-01

    Aim and method The present university-based outpatient clinic, cross-sectional study assessed cognitive performance in a sample of 137 adults, with the primary objective of determining differences in cognitive performance as a function of gender and hypertension status in a type 2 diabetes cohort.Results Approximately 64% of the sample was 65 years old and younger, and 50 subjects had > 13 years of education. Global mental ability scores were relatively similar by age grouping, and higher-ordered cognitive functioning and reading literacy were strongly correlated, r (98) = 0.62, P < 0.01. Approximately 30% of the sample posted global mental ability scores in the slow learner range on tasks measuring attention, immediate memory and verbal reasoning. Males achieved higher cognitive functioning scores compared to females on multiple mental ability tasks. The presence of hypertension was associated with significantly worse cognitive performance compared to those subjects without hypertension, t = 2.11, P = 0.03. Approximately 57% of the hypertension group was classified as mild cognitive impaired.Conclusion While approximately half of the general population can be expected to demonstrate an average range of performance on cognitive ability measures, such an expectation could be inappropriately generalised to persons diagnosed with type 2 diabetes, even among those who were high school educated.

  16. Mental ability performance among adults with type 2 diabetes in primary care

    PubMed Central

    2009-01-01

    Aim and method The present university-based outpatient clinic, cross-sectional study assessed cognitive performance in a sample of 137 adults, with the primary objective of determining differences in cognitive performance as a function of gender and hypertension status in a type 2 diabetes cohort. Results Approximately 64% of the sample was 65 years old and younger, and 50 subjects had > 13 years of education. Global mental ability scores were relatively similar by age grouping, and higher-ordered cognitive functioning and reading literacy were strongly correlated, r (98) = 0.62, P < 0.01. Approximately 30% of the sample posted global mental ability scores in the slow learner range on tasks measuring attention, immediate memory and verbal reasoning. Males achieved higher cognitive functioning scores compared to females on multiple mental ability tasks. The presence of hypertension was associated with significantly worse cognitive performance compared to those subjects without hypertension, t = 2.11, P = 0.03. Approximately 57% of the hypertension group was classified as mild cognitive impaired. Conclusion While approximately half of the general population can be expected to demonstrate an average range of performance on cognitive ability measures, such an expectation could be inappropriately generalised to persons diagnosed with type 2 diabetes, even among those who were high school educated. PMID:22477898

  17. Misdiagnosis of primary pleomorphic rhabdomyosarcoma of the right thigh in a young adult: A case report

    PubMed Central

    Yu, Xiaolong; Yang, Yong; Zhang, Bin; Liu, Hucheng; Guo, Runsheng; Dai, Min

    2016-01-01

    Pleomorphic rhabdomyosarcoma (PRMS) is a rare type of soft tissue tumor accounting for <2% of all adult sarcomas. The present study describes a case of a 28-year-old male patient with primary PRMS of the right thigh. The patient was initially diagnosed with a schwannoma and underwent conservative therapy at a local hospital. At the 6-month follow-up, the patient reported a marked increase in the size of the mass. Finally, the patient underwent fine-needle aspiration and total tumor resection. The tumor measured 11×9×5 cm3 in size and was located in the vastus intermedius muscle. According to histological and immunohistochemical findings, a diagnosis of PRMS was confirmed by an expert pathology consultant. Postoperative follow-up at 3 months revealed no evidence of recurrent disease or residual side effects from therapy. However, it is imperative that such cases are closely monitored following surgery, in order to evaluate the long-term efficacy of the procedure, since misdiagnosis may increase the risk of recurrence and metastasis. The present case is noteworthy due to the misdiagnosis of PRMS, the large size of the mass and the young age of the patient. PMID:27588141

  18. Secondary malignant neoplasms following radiotherapy for primary cancer in children and young adults.

    PubMed

    Harbron, Richard W; Feltbower, Richard G; Glaser, Adam; Lilley, John; Pearce, Mark S

    2014-04-01

    A study was conducted to investigate secondary malignant neoplasm (SMN) occurrence following radiotherapy (RT) for cancer in children and young adults, to examine the spatial distribution of SMNs in relation to the irradiated field, and to evaluate a possible role of bystander effects in SMN distribution. Forty-two SMNs were identified among 7257 subjects diagnosed with cancer while living in Yorkshire, UK. Thirty-two of these occurred in patients receiving RT. Distances between SMN locations and RT field edge were estimated along with dose at SMN site. Expected radiation-induced SMN frequency in remote tissues receiving less than 0.1 Gy was predicted using risk estimates based on atomic bombing data. After a median follow-up period of 7.58 years, patients treated with RT were at a nearly five-fold increased risk of developing a subsequent primary neoplasm than the general population in the 0-29 years age range. The most common type of secondary malignancy associated with RT was of the central nervous system (28%), followed by sarcoma (25%) and leukemia (19%). Considering only solid SMNs developing 5 years or more from treatment, the spatial distribution showed a strong pattern of proximity to the irradiated field, with 68% occurring in-field or within 8 cm of the field edge. The SMN frequency in distant tissues receiving doses of less than 0.1 Gy was low but compatible with local absorbed dose.

  19. [Primary immune thrombocytopenia in adults in Mexico: national characteristics and the relation to international literature].

    PubMed

    Meillón-García, Luis Antonio; García-Chávez, Jaime; Gómez-Almaguer, David; Gutiérrez-Espíndola, Guillermo R; Martínez-Murillo, Carlos

    2014-01-01

    In order to identify the clinical approach of a sample of Mexican hematologists for primary immune thrombocytopenia (ITP) in adults in Mexico, we applied an electronic survey via the internet to identify common practices for the diagnosis and treatment of ITP and draw a comparison between the information from these hematologists with international guidelines or the international literature. The results were analyzed using measures of central tendency. The sample was 21 medical hematologists, predominantly from Mexico City (average age: 51.4 years). A total of 66.7% of the surveyed physicians use international guidelines to make therapeutic decisions, and 43% defined ITP including the numerical concept (< 100 x 10(9)/l). We found some differences between requested clinical exams and tests indicated by the guidelines. In first-line treatment (except emergency), 91% of the participants start with prednisone and 24% use dexamethasone. Danazol is used in persistent ITP by most (41%) of the specialists. In second-line treatment, 67% would indicate splenectomy. Some differences were found between clinical practice of the hematologists in Mexico versus guidelines recommendations.

  20. Primary hyperoxaluria in an adult presenting with end-stage renal failure together with hypercalcemia and hypothyroidism.

    PubMed

    Karadag, Serhat; Gursu, Meltem; Aydin, Zeki; Uzun, Sami; Dogan, Oner; Ozturk, Savas; Kazancioglu, Rumeyza

    2011-10-01

    Primary hyperoxaluria (PH) is a rare genetic disorder characterized by overproduction of oxalate due to specific enzyme deficiencies in glyoxylate metabolism. The primary clinical presentation is in the form of recurrent urolithiasis, progressive nephrocalcinosis, end-stage renal disease, and systemic oxalosis. Herein, we present a case of PH who was diagnosed at 47 years of age after 6 years on hemodialysis. He presented with fatigue, anorexia, weight loss, and was found to have cachexia, diffuse edema, hepatomegaly, ascites, hypercalcemia, hyperphosphatemia, hypoalbuminemia, low parathyroid hormone levels, lytic and resorptive areas in the vertebrae, diffusely increased echogenity of the liver, multiple renal stones, and bilateral nephrocalcinosis. Bone marrow biopsy showed calcium oxalate crystals and crystal granulomas. The liver biopsy could not be performed. The absence of an identifiable reason for secondary forms, the severity of the clinical presentation, and pathological findings led to the diagnosis of PH2. He died while waiting for a potential liver and kidney donor. The presented case is consistent with the literature as he had renal stone disease in the third decade and end-stage renal disease in the fifth decade. Hypercalcemia was thought to be due to osteoclast-stimulating activity of macrophages constituting the granuloma. Erythropoietin-resistant anemia and hypothyroidism were thought to be due to accumulation of oxalate in the bone marrow and thyroid gland, respectively. It is very important to keep in mind the possibility of PH when faced with a patient with nephrocalcinosis and oxalate stone disease.

  1. A Nation-Wide Epidemiological Study of Newly Diagnosed Primary Spine Tumor in the Adult Korean Population, 2009–2011

    PubMed Central

    Sohn, Seil; Kim, Jinhee; Chung, Chun Kee; Lee, Na Rae; Sohn, Moon Jun; Kim, Sung Hwan

    2017-01-01

    Objective This 2009–2011 nation-wide study of adult Koreans was aimed to provide characteristics, medical utilization states, and survival rates for newly diagnosed patients with primary nonmalignant and malignant spine tumors. Methods Data for patients with primary spine tumors were selected from the Korean Health Insurance Review and Assessment Service database. The data included their age, sex, health insurance type, co-morbidities, medical cost, and hospital stay duration. Hospital stay duration and medical costs per person occurring in one calendar year were used. In addition, survival rates of patients with primary malignant spine tumors were evaluated. Results The incidence rate of a primary spine tumor increased with age, and the year of diagnosis (p≤0.0001). Average annual medical costs ranged from 1627 USD (pelvis & sacrum & coccyx tumors) to 6601 USD (spinal cord tumor) for primary nonmalignant spine tumor and from 12137 USD (spinal meningomas) to 20825 USD (pelvis & sacrum & coccyx tumors) for a primary malignant spine tumor. Overall survival rates for those with a primary malignant spine tumor were 87.0%, 75.3%, and 70.6% at 3, 12, and 24 months, respectively. The Cox regression model results showed that male sex, medicare insurance were significantly positive factors affecting survival after a diagnosis of primary malignant spine tumor. Conclusion Our study provides a detailed view of the characteristics, medical utilization states, and survival rates of patients newly diagnosed with primary spine tumors in Korea. PMID:28264240

  2. Presence of HBsAg and anti-HBs in patients with primary liver cancer or hepatic metastases.

    PubMed

    Nastac, E; Stoian, M; Iosipenco, M; Iordache, C

    1985-01-01

    The presence of HBsAg was detected in the serum of 1 out of 13 patients with chronic hepatitis, in 2 out of the 7 patients with liver metastases, but in none of the 10 patients with hepatocellular carcinoma (HCC) investigated. HBsAg could be visualized by orcein staining in the liver cells of 66.6% of the HCC patients, in 50% of the patients with liver metastases and in 40% of the patients with liver cirrhosis. The prevalence of anti-HBs was low both in HCC patients and in the control groups. The possible significance of these findings is discussed.

  3. Functional liver tissue engineering by an adult mouse liver-derived neuro-glia antigen 2-expressing stem/progenitor population.

    PubMed

    Zhang, Hongyu; Siegel, Christopher T; Li, Jing; Lai, Jiejuan; Shuai, Ling; Lai, Xiangdong; Zhang, Yujun; Jiang, Yan; Bie, Ping; Bai, Lianhua

    2016-09-17

    Deaths due to end-stage liver diseases (ESLD) are increasingly registered annually in the world. Liver transplantation is the ultimate treatment for ESLD to date, which has been hampered by a critical shortage of organs. The potential of decellularized liver scaffolds (DLS) derived from solid organs as a three dimensional (3D) platform has been evolved as a promising approach in liver tissue engineering for translating functional liver organ replacements, but questions still exist regarding the optimal cell population for seeding in DLS and the preparation of the DLS themselves. The aim of our study was to utilize a sodium dodecyl sulfate (SDS) decellularization procedure in combination with a low concentration of trypsin (0.005%)-EDTA (0.002%) process to manufacture DLS from whole mouse livers and recellularized with hepatic stem/progenitors for use in liver tissue engineering and injured liver treatment. Results showed that the DLS generated with all the necessary microstructure and the extracellular components to support seeded hepatic stem/progenitor cell attachment, functional hepatic cell differentiation. Hepatic differentiation from stem/progenitor cells loaded by DLS was more efficient than that of the stem/progenitor cells in the 2D cell culture model. In summary, the method of DLS loaded by hepatic stem/progenitor cells provided by this study was effective in maintaining DLS extracellular matrix (ECM) to introduce seeded stem/progenitor cell differentiation, hepatic-like tissue formation and functional hepatic protein production in vitro that promoted functional recovery and survival in a mouse model of dimethylnitrosamine (DEN)-induced liver cirrhosis after auxiliary heterotopic liver transplantation.

  4. Relationship between grip strength and newly diagnosed nonalcoholic fatty liver disease in a large-scale adult population

    PubMed Central

    Meng, Ge; Wu, Hongmei; Fang, Liyun; Li, Chunlei; Yu, Fei; Zhang, Qing; Liu, Li; Du, Huanmin; Shi, Hongbin; Xia, Yang; Guo, Xiaoyan; Liu, Xing; Bao, Xue; Su, Qian; Gu, Yeqing; Yang, Huijun; Bin Yu; Wu, Yuntang; Sun, Zhong; Niu, Kaijun

    2016-01-01

    Enhanced muscle strength is often related to improved insulin sensitivity and secretion, control of lipid metabolism, and increased secretion of myokines. These factors have emerged as important mechanisms involved in the development and progression of nonalcoholic fatty liver disease (NAFLD), implying that muscle strength may be a useful predictor for NAFLD. We aimed to assess the relationship between grip strength (GS) and NAFLD in a large-scale adult population. GS was assessed using an electronic hand-grip dynamometer, and NAFLD was diagnosed by the liver ultrasonography. Multiple logistic regression analysis was used to assess the relationship between the quartiles of GS per body weight and the prevalence of NAFLD. After adjusting for potentially confounding factors, the odds ratios (95% confidence interval) for overall NAFLD, NAFLD with normal alanine aminotransferase levels, and NAFLD with elevated alanine aminotransferase levels across the quartiles of GS were 1.00 (reference), 0.89 (0.78, 1.01), 0.77 (0.67, 0.89), and 0.67 (0.57, 0.79); 1.00 (reference), 0.91 (0.80, 1.04), 0.79 (0.68, 0.92), and 0.72 (0.61, 0.85); 1.00 (reference), 0.77 (0.61, 0.98), 0.67 (0.51, 0.86), and 0.53 (0.40, 0.71) (all P for trend < 0.01), respectively. This is the first study shows that increased GS is independently associated with lower prevalence of NAFLD. PMID:27616599

  5. Impact of e-cigarette refill liquid with or without nicotine on liver function in adult rats.

    PubMed

    El Golli, Narges; Jrad-Lamine, Aicha; Neffati, Hajira; Rahali, Dalila; Dallagi, Yosra; Dkhili, Houssem; Ba, Nathalie; El May, Michele V; El Fazaa, Saloua

    2016-07-01

    This study was conducted to evaluate the effects of e-cigarette refill liquid administration alone or with nicotine on the antioxidant defense status, functional and histopathological changes in adult rat liver tissue. For this purpose, 32 rats were treated for 28 days as follows: control group was injected intra-peritoneally with physiological saline; e-cigarette 0% treated group received an intra-peritoneal injection of e-liquid without nicotine diluted in physiological saline, e-cigarette-treated group received an intra-peritoneal injection of e-liquid containing 0.5 mg of nicotine/kg of body weight/day diluted in physiological saline and nicotine-treated group received an intra-peritoneal injection of 0.5 mg of nicotine/kg of body weight/day diluted in physiological saline. In e-liquid without nicotine-exposed group, activities of the liver biomarkers aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase increase. Interestingly, oxidative stress indicators showed decreased total protein content, associated with a reduction in the antioxidant enzymes activities superoxide dismutase, catalase and glutathione-S-transferase, and an elevation in malondialdehyde content, highlighting the promotion of lipid peroxidation and oxidative stress. Histological studies identified inflammatory cells infiltration and cell death. Thus, e-liquid seems to promote oxidative tissue injuries, which in turn lead to the observed histopathological finding. In comparison, nicotine alone induced less oxidative stress and less histopathological disorders, whereas e-liquid with nicotine gave rise to more histopathological injuries. Thereby, e-liquid, per se, is able to induce hepatotoxicity and supplementation with nicotine worsens this state.

  6. Adults with ADHD: use and misuse of stimulant medication as reported by patients and their primary care physicians.

    PubMed

    Lensing, Michael B; Zeiner, Pål; Sandvik, Leiv; Opjordsmoen, Stein

    2013-12-01

    This study investigated the agreement on treatment for attention-deficit/hyperactivity disorder (ADHD) between adults with ADHD and the primary care physicians responsible for their treatment. Adults with ADHD and the primary care physicians responsible for their ADHD treatment completed a survey. The κ-statistic assessed physician-patient agreement on ADHD treatment variables. The eligible sample consisted of 274 patients with confirmed current or previous psychopharmacological treatment for ADHD and the physicians responsible for their treatment. We received 159 questionnaires (58.0 %) with sufficient information from both sources. There were no significant differences between participants and nonparticipants (N = 115) on ADHD sample characteristics. Participants' mean age was 37.6 years, and 75 (47.2 %) were females. There was high agreement for current pharmacological treatment for ADHD, current and last ADHD drug prescription, treatment for substance use, and misuse of stimulant medication. Agreement for nonpharmacological treatment for ADHD and treatment termination because of the side effects was low. A minority of participants from both sources reported misuse of stimulant medication. There was a moderate correlation between the physicians' clinical judgment and patients' self-report on current functioning. The study showed that primary care physicians and their patients agreed on the pharmacological but not the nonpharmacological, treatments given. They also agreed on patients' current functioning. Physicians and patients reported low levels of misuse of stimulant medication. The results show that pharmacological treatment for adults with ADHD can be safely undertaken by primary care physicians.

  7. A Novel Predictor of Posttransplant Portal Hypertension in Adult-To-Adult Living Donor Liver Transplantation: Increased Estimated Spleen/Graft Volume Ratio

    PubMed Central

    Gyoten, Kazuyuki; Mizuno, Shugo; Kato, Hiroyuki; Murata, Yasuhiro; Tanemura, Akihiro; Azumi, Yoshinori; Kuriyama, Naohisa; Kishiwada, Masashi; Usui, Masanobu; Sakurai, Hiroyuki; Isaji, Shuji

    2016-01-01

    Background In adult living donor liver transplantation (ALDLT), graft-to-recipient weight ratio of less than 0.8 is incomplete for predicting portal hypertension (>20 mm Hg) after reperfusion. We aimed to identify preoperative factors contributing to portal venous pressure (PVP) after reperfusion and to predict portal hypertension, focusing on spleen volume-to-graft volume ratio (SVGVR). Methods In 73 recipients with ALDLT between 2002 and 2013, first we analyzed survival according to PVP of 20 mm Hg as the threshold, evaluating the efficacy of splenectomy. Second, we evaluated various preoperative factors contributing to portal hypertension after reperfusion. Results All of the recipients with PVP greater than 20 mm Hg (n = 19) underwent PVP modulation by splenectomy, and their overall survival was favorable compared with 54 recipients who did not need splenectomy (PVP ≤ 20 mm Hg). Graft-to-recipient weight ratio had no correlation with PVP. Multivariate analysis revealed that estimated graft and spleen volume were significant factors contributing to PVP after reperfusion (P < 0.0001 and P < 0.0001, respectively). Furthermore, estimated SVGVR showed a significant negative correlation to PVP after reperfusion (R = 0.652), and the best cutoff value for portal hypertension was 0.95. Conclusions In ALDLT, preoperative assessment of SVGVR is a good predictor of portal hypertension after reperfusion can be used to indicate the need for splenectomy before reperfusion. PMID:27472097

  8. The Association between Dietary Vitamin A and Carotenes and the Risk of Primary Liver Cancer: A Case–Control Study

    PubMed Central

    Lan, Qiu-Ye; Zhang, Yao-Jun; Liao, Gong-Cheng; Zhou, Rui-Fen; Zhou, Zhong-Guo; Chen, Yu-Ming; Zhu, Hui-Lian

    2016-01-01

    Dietary intake of vitamin A (VA) and carotenes has shown beneficial effects for decreasing the risk of some types of cancer, but findings on the risk of primary liver cancer (PLC) are inconsistent. This case–control study explored the associations between the dietary intake of VA and carotenes and the risk of PLC. We recruited 644 incident PLC patients (diagnosed within one month of each other) and 644 age- and gender-matched controls in Guangzhou, China. A food frequency questionnaire was used to assess habitual dietary intake. Logistic regression analyses found that higher intakes of VA and carotenes were independently associated with decreased PLC risk (all P-trend < 0.001). The multivariable-adjusted ORs (95% CI) of PLC for the highest (vs. lowest) quartile were 0.34 (0.24–0.48) for vitamin A and 0.35 (0.25–0.49) for carotenes. The associations were not significantly modified by smoking, alcohol, or tea drinking (P-interactions: 0.062–0.912). Dose–response analysis showed a U-shaped VA–PLC relationship, with sharply decreased risks at the intakes of about 1000 μg retinol equivalent (RE)/day, and then slowly went down toward the flat-bottomed risks with the lowest risk at 2300 μg RE/day. Our findings suggest that greater intake of retinol, carotenes, and total VA may decrease PLC risk among the Chinese population at an intake of 1000 μg RE/day or greater from food sources. PMID:27727160

  9. Long-term results of combined liver-kidney transplantation for primary hyperoxaluria type 1: the French experience.

    PubMed

    Compagnon, Philippe; Metzler, Philippe; Samuel, Didier; Camus, Christophe; Niaudet, Patrick; Durrbach, Antoine; Lang, Philippe; Azoulay, Daniel; Duvoux, Christophe; Bayle, Francois; Rivalan, Joseph; Merville, Pierre; Pascal, Gerard; Thervet, Eric; Bensman, Albert; Rostaing, Lionel; Deschenes, Georges; Morcet, Jeff; Feray, Cyrille; Boudjema, Karim

    2014-12-01

    Primary hyperoxaluria type 1 (PH1) is a hepatic metabolic defect leading to end-stage renal failure. The posttransplant recurrence of kidney disease can suggest a need for combined liver-kidney transplantation (LKT). However, the risk of LKT is theoretically far higher than the risk of kidney-alone transplantation (KAT). An unselected consecutive series of 54 patients with PH1 was analyzed according to the type of transplantation initially performed between May 1979 and June 2010 at 10 French centers. The duration of dialysis, extrarenal lesions, age, and follow-up were similar between the groups. Postoperative morbidity and mortality did not differ between the groups, and 10-year patient survival rates were similar for the LKT (n = 33) and KAT groups (n = 21; 78% versus 70%). Kidney graft survival at 10 years was better after LKT (87% versus 13%, P < .001) . Four patients (12.1%) lost their first kidney graft in the LKT group, whereas 19 (90%) did in the KAT group (P < .001). The recurrence of oxalosis occurred in 11 renal grafts (52%) in the KAT group but in none in the LKT group (P < .001). End-stage renal failure resulting from rejection was also higher in the KAT group (19% versus 9%, P < 0.0001). A second kidney transplant was performed for 15 patients (71%) in the KAT group versus 4 patients (12%) in the LKT group (P < 0.001). In conclusion, LKT for PH1 provides better kidney graft survival, less rejection, and similar long-term patient survival and is not associated with an increased short-term mortality risk. LKT must be the first-line treatment for PH1 patients with end-stage renal disease.

  10. Cobalt induces oxidative stress in isolated liver mitochondria responsible for permeability transition and intrinsic apoptosis in hepatocyte primary cultures.

    PubMed

    Battaglia, Valentina; Compagnone, Alessandra; Bandino, Andrea; Bragadin, Marcantonio; Rossi, Carlo Alberto; Zanetti, Filippo; Colombatto, Sebastiano; Grillo, Maria Angelica; Toninello, Antonio

    2009-03-01

    It is well established that cobalt mediates the occurrence of oxidative stress which contributes to cell toxicity and death. However, the mechanisms of these effects are not fully understood. This investigation aimed at establishing if cobalt acts as an inducer of mitochondrial-mediated apoptosis and at clarifying the mechanism of this process. Cobalt, in the ionized species Co(2+), is able to induce the phenomenon of mitochondrial permeability transition (MPT) in rat liver mitochondria (RLM) with the opening of the transition pore. In fact, Co(2+) induces mitochondrial swelling, which is prevented by cyclosporin A and other typical MPT inhibitors such as Ca(2+) transport inhibitors and bongkrekic acid, as well as anti-oxidant agents. In parallel with mitochondrial swelling, Co(2+) also induces the collapse of electrical membrane potential. However in this case, cyclosporine A and the other MPT inhibitors (except ruthenium red and EGTA) only partially prevent DeltaPsi drop, suggesting that Co(2+) also has a proton leakage effect on the inner mitochondrial membrane. MPT induction is due to oxidative stress, as a result of generation by Co(2+) of the highly damaging hydroxyl radical, with the oxidation of sulfhydryl groups, glutathione and pyridine nucleotides. Co(2+) also induces the release of the pro-apoptotic factors, cytochrome c and AIF. Incubation of rat hepatocyte primary cultures with Co(2+) results in apoptosis induction with caspase activation and increased level of expression of HIF-1alpha. All these observations allow us to state that, in the presence of calcium, Co(2+) is an inducer of apoptosis triggered by mitochondrial oxidative stress.

  11. Validation of limited sampling strategy for the estimation of mycophenolic acid exposure in Chinese adult liver transplant recipients.

    PubMed

    Hao, Chen; Erzheng, Chen; Anwei, Mao; Zhicheng, Yu; Baiyong, Shen; Xiaxing, Deng; Weixia, Zhang; Chenghong, Peng; Hongwei, Li

    2007-12-01

    Mycophenolate mofetil (MMF) is indicated as immunosuppressive therapy in liver transplantation. The abbreviated models for the estimation of mycophenolic acid (MPA) area under the concentration-time curve (AUC) have been established by limited sampling strategies (LSSs) in adult liver transplant recipients. In the current study, the performance of the abbreviated models to predict MPA exposure was validated in an independent group of patients. A total of 30 MPA pharmacokinetic profiles from 30 liver transplant recipients receiving MMF in combination with tacrolimus were used to compare 8 models' performance with a full 10 time-point MPA-AUC. Linear regression analysis and Bland-Altman analysis were used to compare the estimated MPA-AUC0-12h from each model against the measured MPA-AUC0-12h. A wide range of agreement was shown when estimated MPA-AUC0-12h was compared with measured MPA-AUC0-12h, and the range of coefficient of determination (r2) was from 0.479 to 0.936. The model based on MPA pharmacokinetic parameters C1h, C2h, C6h, and C8h had the best ability to predict measured MPA-AUC0-12h, with the best coefficient of determination (r2=0.936), the excellent prediction bias (2.18%), the best prediction precision (5.11%), and the best prediction variation (2SD=+/-7.88 mg.h/L). However, the model based on MPA pharmacokinetic sampling time points C1h, C2h, and C4h was more suitable when concerned with clinical convenience, which had shorter sampling interval, an excellent coefficient of determination (r2=0.795), an excellent prediction bias (3.48%), an acceptable prediction precision (14.37%), and a good prediction variation (2SD=+/-13.23 mg.h/L). Measured MPA-AUC0-12h could be best predicted by using MPA pharmacokinetic parameters C1h, C2h, C6h, and C8h. The model based on MPA pharmacokinetic parameters C1h, C2h, and C4h was more feasible in clinical application.

  12. Identifying adults at risk of COPD who need confirmatory spirometry in primary care

    PubMed Central

    Hill, Kylie; Hodder, Richard; Blouin, Maria; Heels-Ansdell, Diane; Guyatt, Gordon; Goldstein, Roger

    2011-01-01

    Abstract Objective To examine the usefulness of a symptom-based case-finding questionnaire (CFQ) and the Medical Research Council (MRC) dyspnea scale in identifying which individuals with known risk factors for chronic obstructive pulmonary disease (COPD) require targeted spirometry in primary care. Design Cross-sectional study. Setting Three community primary care practices in Ontario. Participants Men and women 40 years of age and older with a smoking history of 20 pack-years or more. Main outcome measures We administered a CFQ for the presence of cough, sputum, wheeze, dyspnea, and recurrent respiratory infections (possible range of scores from 0 to 5) and applied the MRC dyspnea scale to assess the severity of COPD (possible range of scores from 1 to 5). Spirometric measures of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were collected, with COPD defined as a postbronchodilator FEV1/FVC of less than 0.7 and FEV1 of less than 80% of the predicted value. Using spirometric data to confirm the diagnosis of COPD, likelihood ratios, pretest and posttest probabilities, and area under a receiver operating characteristic curve were calculated for the total CFQ and MRC scores. Results Scores for the CFQ and MRC dyspnea scale were available for 996 and 829 participants, respectively. The likelihood ratios for a total CFQ score of 3 or higher and an MRC dyspnea score of 4 or 5 were 1.82 (95% confidence interval [CI] 1.48 to 2.22) and 4.22 (95% CI 2.08 to 8.56), respectively. The likelihood ratios for a total CFQ score of 2 or less and an MRC dyspnea score of 1 were 0.75 (95% CI 0.66 to 0.85) and 0.50 (95% CI 0.39 to 0.65), respectively. Area under the receiver operating characteristic curve was 0.62 (95% CI 0.58 to 0.67; P < .001) for the total CFQ scores and 0.64 (95% CI 0.60 to 068; P < .001) for the MRC dyspnea scores. Conclusion In adults with known risk factors, the likelihood of having moderate to severe COPD is increased in those who

  13. Economic burden to primary informal caregivers of hospitalized older adults in Mexico: a cohort study

    PubMed Central

    2013-01-01

    Background The burden of out of pocket spending for the Mexican population is high compared to other countries. Even patients insured by social security institutions have to face the cost of health goods, services or nonmedical expenses related to their illness. Primary caregivers, in addition, experience losses in productivity by taking up responsibilities in care giving activities. This situation represents a mayor economic burden in an acute care setting for elderly population. There is evidence that specialized geriatric services could represent lower overall costs in these circumstances and could help reduce these burdens. The aim of this study was to investigate economic burden differences in caregivers of elderly patients comparing two acute care services (Geriatric and Internal Medicine). Specifically, economic costs associated with hospitalization of older adults in these two settings by evaluating health care related out of pocket expenditures (OOPE), non-medical OOPE and indirect costs. Methods A comparative analysis of direct and indirect costs in hospitalised elderly patients (60-year or older) and their primary informal caregivers in two health care settings, using a prospective cohort was performed. Economic burden was measured by out of pocket expenses and indirect costs (productivity lost) due to care giving activities. The analysis included a two-part model, the first one allowing the estimation of the probability of observing any health care related and non-medical OOPE; and the second one, the positive observations or expenditures. Results A total of 210 subjects were followed during their hospital stay. Of the total number of subjects 95% reported at least one non-medical OOPE, being daily transportation the most common expense. Regarding medical OOPE, medicines were the most common expense, and the mean numbers of days without income were 4.12 days. Both OOPE and indirect costs were significantly different between type of services, with less

  14. PNPLA3 I148M Variant Influences Circulating Retinol in Adults with Nonalcoholic Fatty Liver Disease or Obesity12

    PubMed Central

    Mondul, Alison; Mancina, Rosellina M; Merlo, Andrea; Dongiovanni, Paola; Rametta, Raffaela; Montalcini, Tiziana; Valenti, Luca; Albanes, Demetrius; Romeo, Stefano

    2015-01-01

    Background: Retinol is a lipid-soluble essential nutrient that is stored as retinyl esters in lipid droplets of hepatic stellate cells. Patatin-like phospholipase domain-containing 3 (PNPLA3), through its retinyl-palmitate lipase activity, releases retinol from lipid droplets in hepatic stellate cells in vitro and ex vivo. We have shown that the genetic variant I148M (rs738409) reduces the PNPLA3 retinyl-palmitate lipase activity. Objective: The aim of the present genetic association study was to test whether overweight/obese carriers of the PNPLA3 148M mutant allele had lower circulating concentrations of retinol than individuals who are homozygous for the 148I allele. Methods: PNPLA3 I148M (rs738409) was genotyped by Taqman assay in 76 overweight/obese individuals [BMI (kg/m2) ≥25; mean ± SD age: 59.7 ± 11.4 y; male gender: 70%] with a histologic diagnosis of nonalcoholic fatty liver disease (NAFLD; namely the Milan NAFLD cohort) and in 413 obese men (BMI ≥30; mean ± SD age: 57.1 ± 4.9 y) from the α-Tocopherol, β-Carotene Cancer Prevention (ATBC) Study. Serum concentrations of retinol and α-tocopherol were measured by HPLC in both cohorts. β-Carotene concentrations in the ATBC study were measured by using HPLC. Results: The PNPLA3 148M mutant allele was associated with lower fasting circulating concentrations of retinol (β = −0.289, P = 0.03) in adults with NAFLD (Milan NAFLD cohort). The PNPLA3 148M mutant allele was also associated with lower fasting circulating concentrations of retinol in adults with a BMI ≥30 (ATBC study; β = −0.043, P = 0.04). Conclusion: We showed for the first time, to our knowledge, that carriers of the PNPLA3 148M allele with either fatty liver plus obesity or obesity alone have lower fasting circulating retinol concentrations. PMID:26136587

  15. Exploring knowledge, attitudes, and practices toward older adults with hypertension in primary care

    PubMed Central

    Chotisiri, Luckwirun; Yamarat, Khemika; Taneepanichskul, Surasak

    2016-01-01

    Purpose High blood pressure increases the risk of cardiovascular and kidney diseases. The purpose of this study was to explore a baseline of hypertension knowledge, attitudes, and practices among older adults with hypertension at a sub-district Health Promoting Hospital in the Pathum Thani province of Thailand. Patients and methods A cross-sectional study was conducted at the outpatient clinic of the sub-district Health Promoting Hospital, one of the primary care sectors, between January and March 2015, and a total of 144 cases were recruited. All clinical parameters were collected and a structured questionnaire was used. Data were analyzed by means of descriptive statistics and chi-square tests. Results Most of the participants (74.3%) were females, and their mean age was 66.1 years. Two-thirds (66.7%) were married, unemployed/retired (67.4%), and had completed elementary education (79.2%). The screenings showed that their mean blood pressure was 136.4 (±14.4)/79.2 (±10.1) mmHg, the group’s mean body mass index was 24.9 kg/m2 (± 3.6 kg/m2), and their mean waist circumference was 88.6 cm (±7.1 cm) for males and 85.7 cm (±6.8 cm) for females. In addition, their mean score of hypertension knowledge was high, and most of the participants had a neutral attitude toward hypertension; their practices in terms of dietary and exercise habits for controlling blood pressure were low in nature. Conclusion This study indicated that increasing patients’ practices would be useful for promoting their healthy behaviors to achieve blood pressure control. PMID:27822057

  16. Primary mature cystıc teratoma mimickıng an adrenal mass in an adult male patient.

    PubMed

    Okulu, Emrah; Ener, Kemal; Aldemir, Mustafa; Isik, Evren; Irkkan, Cigdem; Kayigil, Onder

    2014-02-01

    Teratomas are bizarre neoplasms derived from embryonic tissues that are typically found only in the gonadal and sacrococcygeal regions of adults. Primary retroperitoneal teratomas are rare and present challenging management options. We report a case of a unilateral primary retroperitoneal mature cystic teratoma mimicking an adrenal mass in a 54-year-old male patient. Complete resection of the adrenal mass was performed by the flank approach by using the 11th rib resection. Because of the risk of malignancy, follow-up radiographic studies were performed to ensure the oncologic efficacy of resection. The patient has been free of recurrence for longer than 12 months.

  17. Acute myeloid leukemia of a primary hepatic carcinoma patient after liver transplantation: a case report and literature review

    PubMed Central

    Wu, Wen-Jun; Dong, Meng-Meng; Chen, Yun; He, Jing-Song; Huang, He; Cai, Zhen

    2015-01-01

    Living donor liver transplantation (LDLT) is an important means to treat end-stage liver disease. Although effective immunosuppressant medication greatly assists the survival of patients, it is likely to promote infections and cancer. Acute leukemia (AL) is a rare complication after LDLT and up to now only 1 case of post-transplantation AL has occurred in our liver transplantation center after more than 1,600 LDLT interventions since 1993. In the present report, we describe a rare case of subsequent acute myeloid leukemia (AML), 27 months after LDLT and review the literature of this infrequent complication. PMID:26722593

  18. Adult Opisthorchis felineus major protein fractions deduced from transcripts: comparison with liver flukes Opisthorchis viverrini and Clonorchis sinensis.

    PubMed

    Pomaznoy, Mikhail; Tatkov, Sergey; Katokhin, Alexey; Afonnikov, Dmitry; Babenko, Vladimir; Furman, Dagmara; Brusentsov, Ilya; Belavin, Pavel; Najakshin, Alexandr; Guselnikov, Sergey; Vasiliev, Gennady; Sivkov, Anton; Prokhortchouk, Egor; Skryabin, Konstantin; Mordvinov, Viatcheslav

    2013-10-01

    The epidemiologically important liver flukes Opisthorchis felineus, Opisthorchis viverrini, and Clonorchis sinensis are of interest to health professionals, epidemiologists, pharmacologists, and molecular biologists. Recently the transcriptomes of the latter two species were intensively investigated. However our knowledge on molecular biology of O. felineus is scarce. We report the first results of the O. felineus transcriptome analysis. We isolated and annotated a total of 2560 expressed sequence tag (EST) sequences from adult O. felineus (deposited within the database of expressed sequence tags (dbEST), under accession numbers GenBank: JK624271-JK626790, JK006511-JK006547, JK649790-JK649792). Clustering and analysis resulted in the detection of 267 contigs. Of the protein sequences deduced from these, 82% had homologs in the NCBI (nr) protein database and 63% contained conserved domains, allowing the functions to be interpreted using the Gene Ontology terms. Comprehensive analysis of Opisthorchiidae- and Trematoda-specific substitutions within amino acid sequences deduced for the proteins myoglobin, vitelline precursor protein, cathepsin F, and 28kDa glutathione transferase was carried out. The gene set of the 32 ribosomal proteins for the three Opisthorchiidae species with the addition of available Schistosoma and Fasciola orthologs was created and is provided in the supplementary. The orthologous gene set created was used for inferring phylogeny within the Trematoda with special attention to interrelations within the Opisthorchiidae. The phylogenetic analysis revealed a closer relationship between C. sinensis and O. viverrini and some divergence of O. felineus from either O. viverrini or C. sinensis.

  19. Research in the Integration of Behavioral Health for Adolescents and Young Adults in Primary Care Settings: A Systematic Review.

    PubMed

    Richardson, Laura P; McCarty, Carolyn A; Radovic, Ana; Suleiman, Ahna Ballonoff

    2017-03-01

    Despite the recognition that behavioral and medical health conditions are frequently intertwined, the existing health care system divides management for these issues into separate settings. This separation results in increased barriers to receipt of care and contributes to problems of underdetection, inappropriate diagnosis, and lack of treatment engagement. Adolescents and young adults with mental health conditions have some of the lowest rates of treatment for their conditions of all age groups. Integration of behavioral health into primary care settings has the potential to address these barriers and improve outcomes for adolescents and young adults. In this paper, we review the current research literature for behavioral health integration in the adolescent and young adult population and make recommendations for needed research to move the field forward.

  20. Analysis of DNA strand breaks induced in rodent liver in vivo, hepatocytes in primary culture, and a human cell line by chlorinated acetic acids and chlorinated acetaldehydes

    SciTech Connect

    Chang, L.W.; Daniel, F.B. ); DeAngelo, A.B. )

    1992-01-01

    An alkaline unwinding assay was used to quantitate the induction of DNA strand breaks (DNA SB) in the livers of rats and mice treated in vivo, in rodent hepatocytes in primary culture, and in CCRF-CEM cells, a human lymphoblastic leukemia cell line, following treatment with tri-(TCA), di-(CA), and mono-(MCA) chloroacetic acid and their corresponding aldehydes, tri-(chloralhydrate, CH), di(DCAA) and mono-(CAA) chloroacetaldehyde. None of the chloracetic acids induced DNA SB in the livers of rats at 4 hr following a single administration of 1-10 mmole/kg. TCA (10 mmole/kg) and DCA (5 and 10 mmole/kg) did produce a small amount of strand breakage in mice (7% at 4hr) but not at 1 hr. N-nitrosodiethylamine (DENA), an established alkylating agent and a rodent hepatocarcinogen, produced DNA SB in the livers of both species. TCA, DCA, and MCA also failed to induce DNA strand breaks in splenocytes and epithelial cells derived from the stomach and duodenum of mice treated in vivo. None of the three chloroacetaldehydes induced DNA SB in either mouse or rat liver. These studies provide further evidence that the chloroacetic acids lack genotoxic activity not only in rodent liver, a tissue in that they induce tumors, but in a variety of other rodent tissues and cultured cell types. Two of the chloroacetaldehydes, DCAA and CAA, are direct acting DNA damaging agents in CCRF-CEM cells, but not in liver or splenocytes in vivo or in cultured hepatocytes. CH showed no activity in any system investigated. 58 refs., 6 figs., 2 tabs.

  1. Successful treatment of parenteral nutrition-associated liver disease in an adult by use of a fish oil-based lipid source.

    PubMed

    Venecourt-Jackson, Esra; Hill, Simon J; Walmsley, Russell S

    2013-01-01

    Liver disease occurs in 15% to 40% of adults on long-term parenteral nutrition, with steatosis being more common than cholestasis in the adult population. This problem has been well reported in the pediatric population, but we describe the case of a man who became profoundly jaundiced after being on parenteral nutrition for 3 y and responded rapidly to a change in lipid source from soybean and olive oil-based emulsion (ClinOleic) to a fish oil-based lipid emulsion (Omegaven).

  2. The lack of protective effects of tea supplementation on liver and jejunal epithelium in adult rats exposed to cadmium and lead.

    PubMed

    Tomaszewska, Ewa; Winiarska-Mieczan, Anna; Dobrowolski, Piotr

    2015-11-01

    Adult rats at the age of 12 weeks were divided into the control group and groups supplemented with green (GT), black (BT), red (RT), or white (WT) tea extracts. The diet (except that for the control) was mixed with 7 mg Cd/kg and 50 mg Pb/kg. The experiment lasted 12 weeks. Basal haematology and plasma biochemical parameters as well as the histomorphometrical parameters of jejunal epithelium and liver were determined. The lowest body mass was found in the RT and WT groups. Some functional (increased plasma ALT and AST, and the de Ritis coefficient) and structural changes in the liver (slight fatty degenerative changes, an increase in the intercellular space) were evident irrespective of the type of tea in the Cd and Pb poisoned rats. This toxic effect was visible especially in rats drinking black or red tea. However, the rats had no elevated LDH and ALT activities. The highest content of Cd and Pb in the liver and blood plasma was found in rats drinking red tea. Based on the results obtained, it is clear that long-term exposure of adult rats with a mature intestinal barrier to Cd and Pb contamination, under higher exposure conditions than the current estimates of weekly exposure of the general population to Cd and Pb through diet, causes a toxic effect, especially in the liver, and can change the structure of intestinal mucosa, irrespective of tea administration.

  3. Dose of Phenobarbital and Age of Treatment at Early Life are Two Key Factors for the Persistent Induction of Cytochrome P450 Enzymes in Adult Mouse Liver

    PubMed Central

    Tien, Yun-Chen; Liu, Ke; Pope, Chad; Wang, Pengcheng; Ma, Xiaochao

    2015-01-01

    Drug treatment of neonates and infants and its long-term consequences on drug responses have emerged in recent years as a major challenge for health care professionals. In the current study, we use phenobarbital as a model drug and mouse as an in vivo model to demonstrate that the dose of phenobarbital and age of treatment are two key factors for the persistent induction of gene expression and consequential increases of enzyme activities of Cyp2b, Cyp2c, and Cyp3a in adult livers. We show that phenobarbital treatment at early life of day 5 after birth with a low dose (<100 mg/kg) does not change expression and enzyme activities of Cyp2b, Cyp2c, and Cyp3a in adult mouse liver, whereas phenobarbital treatment with a high dose (>200 mg/kg) significantly increases expression and enzyme activities of these P450s in adult liver. We also demonstrate that phenobarbital treatment before day 10 after birth, but not at later ages, significantly increases mRNAs, proteins, and enzyme activities of the tested P450s. Such persistent induction of P450 gene expression and enzyme activities in adult livers by phenobarbital treatment only occurs within a sensitive age window early in life. The persistent induction in gene expression and enzyme activities is higher in female mice than in male mice for Cyp2b10 but not for Cyp2c29 and Cyp3a11. These results will stimulate studies to evaluate the long-term impacts of drug treatment with different doses at neonatal and infant ages on drug metabolism, therapeutic efficacy, and drug-induced toxicity throughout the rest of life. PMID:26400395

  4. Metabolic profiling of fatty liver in young and middle‐aged adults: Cross‐sectional and prospective analyses of the Young Finns Study

    PubMed Central

    Würtz, Peter; Suomela, Emmi; Lehtovirta, Miia; Kangas, Antti J.; Jula, Antti; Mikkilä, Vera; Viikari, Jorma S.A.; Juonala, Markus; Rönnemaa, Tapani; Hutri‐Kähönen, Nina; Kähönen, Mika; Lehtimäki, Terho; Soininen, Pasi; Ala‐Korpela, Mika; Raitakari, Olli T.

    2016-01-01

    Nonalcoholic fatty liver is associated with obesity‐related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease. We performed comprehensive metabolic profiling to assess how circulating metabolites, such as lipoprotein lipids, fatty acids, amino acids, and glycolysis‐related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty‐eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population‐based Young Finns Study from serum collected in 2001 (n = 1,575), 2007 (n = 1,509), and 2011 (n = 2,002). Fatty liver was diagnosed by ultrasound in 2011 when participants were aged 34‐49 years (19% prevalence). Cross‐sectional associations as well as 4‐year and 10‐year risks for fatty liver were assessed by logistic regression. Metabolites across multiple pathways were strongly associated with the presence of fatty liver (P < 0.0007 for 60 measures in age‐adjusted and sex‐adjusted cross‐sectional analyses). The strongest direct associations were observed for extremely large very‐low‐density lipoprotein triglycerides (odds ratio [OR] = 4.86 per 1 standard deviation, 95% confidence interval 3.48‐6.78), other very‐low‐density lipoprotein measures, and branched‐chain amino acids (e.g., leucine OR = 2.94, 2.51‐3.44). Strong inverse associations were observed for high‐density lipoprotein measures, e.g., high‐density lipoprotein size (OR = 0.36, 0.30‐0.42) and several fatty acids including omega‐6 (OR = 0.37, 0.32‐0.42). The metabolic associations were attenuated but remained significant after adjusting for waist, physical activity, alcohol consumption, and smoking (P < 0.0007). Similar aberrations in the metabolic profile were observed already 10 years before fatty liver diagnosis. Conclusion: Circulating lipids, fatty acids, and amino acids reflect fatty liver independently of routine metabolic risk

  5. Adult Visual Experience Promotes Recovery of Primary Visual Cortex from Long-Term Monocular Deprivation

    ERIC Educational Resources Information Center

    Fischer, Quentin S.; Aleem, Salman; Zhou, Hongyi; Pham, Tony A.

    2007-01-01

    Prolonged visual deprivation from early childhood to maturity is believed to cause permanent visual impairment. However, there have been case reports of substantial improvement of binocular vision in human adults following lifelong visual impairment or deprivation. These observations, together with recent findings of adult ocular dominance…

  6. An Update of the Mayo Clinic Cohort of Patients With Adult Primary Central Nervous System Vasculitis

    PubMed Central

    Salvarani, Carlo; Brown, Robert D.; Christianson, Teresa; Miller, Dylan V.; Giannini, Caterina; Huston, John; Hunder, Gene G.

    2015-01-01

    Abstract Primary central nervous system vasculitis (PCNSV) is an uncommon condition in which lesions are limited to vessels of the brain and spinal cord. Because the clinical manifestations are not specific, the diagnosis is often difficult, and permanent disability and death are frequent outcomes. This study is based on a cohort of 163 consecutive patients with PCNSV who were examined at the Mayo Clinic over a 29-year period from 1983 to 2011. The aim of the study was to define the characteristics of these patients, which represents the largest series in adults reported to date. A total of 105 patients were diagnosed by angiographic findings and 58 by biopsy results. The patients diagnosed by biopsy more frequently had at presentation cognitive dysfunction, greater cerebrospinal fluid total protein concentrations, less frequent cerebral infarcts, and more frequent leptomeningeal gadolinium-enhanced lesions on magnetic resonance imaging (MRI), along with less mortality and disability at last follow-up. The patients diagnosed by angiograms more frequently had at presentation hemiparesis or a persistent neurologic deficit or stroke, more frequent infarcts on MRI and an increased mortality. These differences were mainly related to the different size of the vessels involved in the 2 groups. Although most patients responded to therapy with glucocorticoids alone or in conjunction with cyclophosphamide and tended to improve during the follow-up period, an overall increased mortality rate was observed. Relapses occurred in one-quarter of the patients and were less frequent in patients treated with prednisone and cyclophosphamide compared with those treated with prednisone alone. The mortality rate and degree of disability at last follow-up were greater in those with increasing age, cerebral infarctions on MRI, angiographic large vessel involvement, and diagnosis made by angiography alone, but were lower in those with gadolinium-enhanced lesions on MRI and in those with

  7. Anti-Neurotrophic Effects from Autoantibodies in Adult Diabetes Having Primary Open Angle Glaucoma or Dementia

    PubMed Central

    Zimering, Mark B.; Moritz, Thomas E.; Donnelly, Robert J.

    2013-01-01

    Aim: To test for anti-endothelial and anti-neurotrophic effects from autoantibodies in subsets of diabetes having open-angle glaucoma, dementia, or control subjects. Methods: Protein-A eluates from plasma of 20 diabetic subjects having glaucoma or suspects and 34 age-matched controls were tested for effects on neurite outgrowth in rat pheochromocytoma PC12 cells or endothelial cell survival. The mechanism of the diabetic glaucoma autoantibodies’ neurite-inhibitory effect was investigated in co-incubations with the selective Rho kinase inhibitor Y27632 or the sulfated proteoglycan synthesis inhibitor sodium chlorate. Stored protein-A eluates from certain diabetic glaucoma or dementia subjects which contained long-lasting, highly stable cell inhibitory substances were characterized using mass spectrometry and amino acid sequencing. Results: Diabetic primary open angle glaucoma (POAG) or suspects (n = 20) or diabetic dementia (n = 3) autoantibodies caused significantly greater mean inhibition of neurite outgrowth in PC12 cells (p < 0.0001) compared to autoantibodies in control diabetic (n = 24) or non-diabetic (n = 10) subjects without glaucoma (p < 0.01). Neurite inhibition by the diabetic glaucoma autoantibodies was completely abolished by 10 μM concentrations of Y27632 (n = 4). It was substantially reduced by 30 mM concentrations of sodium chlorate (n = 4). Peak, long-lasting activity survived storage ×5 years at 0–4°C and was associated with a restricted subtype of Ig kappa light chain. Diabetic glaucoma or dementia autoantibodies (n = 5) caused contraction and process retraction in quiescent cerebral cortical astrocytes effects which were blocked by 5 μM concentrations of Y27632. Conclusion: These data suggest that autoantibodies in subsets of adult diabetes having POAG (glaucoma suspects) and/or dementia inhibit neurite outgrowth and promote a reactive astrocyte morphology by a mechanism which may involve

  8. Autoimmune liver disease panel

    MedlinePlus

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider ...

  9. Efficacy of the Omega-3 Index in predicting non-alcoholic fatty liver disease in overweight and obese adults: a pilot study.

    PubMed

    Parker, Helen M; O'Connor, Helen T; Keating, Shelley E; Cohn, Jeffrey S; Garg, Manohar L; Caterson, Ian D; George, Jacob; Johnson, Nathan A

    2015-09-14

    Non-alcoholic fatty liver disease (NAFLD) is an independent predictor of CVD in otherwise healthy individuals. Low n-3 PUFA intake has been associated with the presence of NAFLD; however, the relationship between a biomarker of n-3 status - the Omega-3 Index - and liver fat is yet to be elucidated. A total of eighty overweight adults (fifty-six men) completed the anthropometric and biochemical measurements, including the Omega-3 Index, and underwent proton magnetic resonance spectroscopy assessment of liver fat. Bivariate correlations and multiple regression analyses were performed with reference to prediction of liver fat percentage. The mean Omega-3 Index was high in both NAFLD (intrahepatic lipid concentration≥5·5 %) and non-NAFLD groups. The Omega-3 Index, BMI, waist circumference, glucose, insulin, TAG, high-sensitive C-reactive protein (hsCRP) and alanine aminotransferase (ALT) were positively correlated, and HDL and erythrocyte n-6:n-3 ratio negatively correlated with liver fat concentration. Regression analysis found that simple anthropometric and demographic variables (waist, age) accounted for 31 % of the variance in liver fat and the addition of traditional cardiometabolic blood markers (TAG, HDL, hsCRP and ALT) increased the predictive power to 43 %. The addition of the novel erythrocyte fatty acid variable (Omega-3 Index) to the model only accounted for a further 3 % of the variance (P=0·049). In conclusion, the Omega-3 Index was associated with liver fat concentration but did not improve the overall capacity of demographic, anthropometric and blood markers to predict NAFLD.

  10. Liver metastases

    MedlinePlus

    Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic; Colorectal cancer - liver metastases; Colon cancer - liver metastases; Esophageal cancer - liver metastases; Lung cancer - liver metastases; Melanoma - liver metastases

  11. Molecular and immunocytochemical characterization of primary neuronal cultures from adult rat brain: Differential expression of neuronal and glial protein markers.

    PubMed

    Ray, Balmiki; Bailey, Jason A; Sarkar, Sumit; Lahiri, Debomoy K

    2009-11-15

    Neurobiological studies using primary neuronal cultures commonly employ fetal-derived neurons, but much less often adult brain-derived neurons. Our goal is to perform morphological and molecular characterization of primary neuronal cultures from adult rat brain, including the relative expression of neuronal and glial cell markers at different time points. We tested the hypothesis that long-term neuronal viability is compatible with glial proliferation in adult neuron culture. We examined neuron culture from adult rat brain, which was maintained at steady state up to 24 days, and characterized them on the basis of cellular, molecular and biochemical properties at different time points of the culture. We identified neuronal and glial cells by both immunocytochemical and western immunoblotting techniques using NSE and Tau as neuronal markers and GFAP as glial protein marker, which revealed the presence of predominantly neuronal cells in the initial phase of the culture and a rise in glial cells from day 12 onwards. Notably, neuronal cells were preserved in the culture along with the glial cells even at day 24. Transfection of the cultured cells with a GFP expression vector and plasmids containing a luciferase reporter gene under the control of two different gene promoters demonstrated DNA transfectability. Taken together, these results suggest a differential expression of neuronal and glial cells at different time points and long-term neuronal viability in the presence of glial proliferation. Such adult neurons serve as a suitable system for the application of neurodegeneration models and for drug target discovery in various brain disorders including Alzheimer's disease.

  12. LIVER INJURY, LIVER PROTECTION, AND SULFUR METABOLISM

    PubMed Central

    Miller, L. L.; Whipple, G. H.

    1942-01-01

    Protein-depleted dogs are very susceptible to injurious agents—in particular, chloroform. Methionine given shortly before chloroform anesthesia will give complete protection against chloroform. Methionine (or cysteine plus choline) given 3 or 4 hours after chloroform anesthesia will give significant protection against the liver injury of chloroform anesthesia. Methionine given more than 4 hours after chloroform anesthesia gives no protection against liver injury. Choline alone given before chloroform gives no protection against liver injury. The protein-depleted dogs have livers which are deficient in both nitrogen and sulfur, but sulfur is depleted more than is the nitrogen. The N/S ratio therefore rises. Methionine or cystine feeding promptly makes up this liver sulfur deficit. Viable liver cells are necessary for this uptake of sulfur. Livers of fetuses in utero or of newborn pups tolerate a chloroform anesthesia which will cause fatal liver injury in adults. The nitrogen and sulfur values of these fetus or pup livers are within the high normal values for adults. Blood-forming cells are present in the fetus or pup livers during this period. When these blood islands are eliminated during the 3rd or 4th week of life, the liver then becomes normally susceptible to chloroform liver injury. Methionine or methionine-rich protein digests (e.g. casein) or various proteins by mouth or by vein should prove useful to protect the liver against certain types of injury and to aid in organ repair. PMID:19871248

  13. Primary Human Hepatocytes Repopulate Livers of Mice After In Vitro Culturing and Lentiviral-Mediated Gene Transfer

    PubMed Central

    Bierwolf, Jeanette; Volz, Tassilo; Lütgehetmann, Marc; Allweiss, Lena; Riecken, Kristoffer; Warlich, Michael; Fehse, Boris; Kalff, Joerg C.; Dandri, Maura

    2016-01-01

    Cell-based therapies represent a promising alternative to orthotopic liver transplantation. However, therapeutic effects are limited by low cell engraftment rates. We recently introduced a technique creating human hepatocyte spheroids for potential therapeutic application. The aim of this study was to evaluate whether these spheroids are suitable for engraftment in diseased liver tissues. Intrasplenic spheroid transplantation into immunodeficient uPA/SCID/beige mice was performed. Hepatocyte transduction ability prior to transplantation was tested by lentiviral labeling using red-green-blue (RGB) marking. Eight weeks after transplantation, animals were sacrificed and livers were analyzed by immunohistochemistry and immunofluorescence. To investigate human hepatocyte-specific gene expression profiles in mice, quantitative real-time-PCR was applied. Human albumin and alpha-1-antitrypsin concentrations in mouse serum were quantified to assess the levels of human chimerism. Precultured human hepatocytes reestablished their physiological liver tissue architecture and function upon transplantation in mice. Positive immunohistochemical labeling of the proliferating cell nuclear antigen revealed that human hepatocytes retained their in vivo proliferation capacity. Expression profiles of human genes analyzed in chimeric mouse livers resembled levels determined in native human tissue. Extensive vascularization of human cell clusters was detected by demonstration of von Willebrand factor activity. To model gene therapy approaches, lentiviral transduction was performed ex vivo and fluorescent microscopic imaging revealed maintenance of RGB marking in vivo. Altogether, this is the first report demonstrating that cultured and retroviral transduced human hepatocyte spheroids are able to engraft and maintain their regenerative potential in vivo. PMID:27068494

  14. S100 protein positive dendritic cells in primary biliary cirrhosis and other chronic inflammatory liver diseases. Relevance to pathogenesis?

    PubMed Central

    Demetris, A. J.; Sever, C.; Kakizoe, S.; Oguma, S.; Starzl, T. E.; Jaffe, R.

    1989-01-01

    A study to determine the location of dendritic cells, in chronic inflammatory liver disease was performed. S100 protein positivity and dendritic cytoplasmic morphology were used to identify dendritic cells. S100 protein positive dendritic cells (S100 + DC) were found inside the basement membrane between biliary epithelial cells of septal bile ducts of livers affected by early stage PBC, but were not present at later stages. S100 + DC also were seen in areas of piecemeal necrosis in chronic active hepatitis of various etiologies. In contrast, intra-epithelial S100 + DC were not found with any consistency in sclerosing cholangitis, secondary biliary cirrhosis, extrahepatic biliary atresia, or chronic liver allograft rejection, all of which are characterized by inflammatory bile duct damage. The possible relevance of DC in the pathogenesis of PBC is discussed. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2705505

  15. Prolonged rest period enables the detection of micronucleated hepatocytes in the liver of young adult rats after a single dose of diethylnitrosamine or mitomycin C.

    PubMed

    Shimada, Keisuke; Yamamoto, Mika; Takashima, Miyuki; Seki, Jiro; Miyamae, Yoichi; Wakata, Akihiro

    2015-09-01

    A repeated-dose micronucleus assay utilizing young adult rat hepatocytes was recently developed to evaluate the genotoxicity. In this assay, accumulation of micronucleated hepatocytes (MNHEPs) induced by repeated dosing of genotoxic chemicals is considered to be a key factor in the detection of micronuclei induction. Then, we hypothesized that the period following chemical exposure enable the detection of MNHEP induction in young adult rats, namely that MNHEPs can be generated from chromosomally damaged cells and accumulate following initiation of chemical exposure until sampling. We therefore measured MNHEP induction at 2 or 4 weeks after a single oral administration of 12.5, 50, or 100mg/kg of diethylnitrosamine (DEN) or an intraperitoneal administration of 0.5, 1.0, or 2.0mg/kg of mitomycin C (MMC) to young adult rats. Results showed a statistically significant, dose-dependent increase in the numbers of MNHEPs in DEN- or MMC-treated rats, indicating that prolonged rest period following a single dose of a genotoxic chemical enables the detection of MNHEP induction in the liver of young adult rats. From these results, a single oral administration of 50mg/kg of DEN with a 2- or 4- week rest period can be used as a positive control in repeated-dose liver micronucleus assays. This procedure is superior in terms of labor saving and animal welfare to repeated dosing of DEN.

  16. Intrauterine metabolic programming alteration increased susceptibility to non-alcoholic adult fatty liver disease in prenatal caffeine-exposed rat offspring.

    PubMed

    Wang, Linlong; Shen, Lang; Ping, Jie; Zhang, Li; Liu, Zhongfen; Wu, Yong; Liu, Yansong; Huang, Hegui; Chen, Liaobin; Wang, Hui

    2014-01-30

    An increase in susceptibility to metabolic syndromes (MetS) in rat offspring that experienced prenatal caffeine exposure (PCE) has been previously demonstrated. The present study aimed to clarify this increased susceptibility and elucidate the mechanism of foetal origin that causes or contributes to adult non-alcoholic fatty liver disease (NAFLD) as a result of PCE. Based on the results from both foetal and adult studies of rats that experienced PCE (120 mg/kgd), the foetal weight and serum triglyceride levels decreased significantly and hepatocellular ultrastructure was altered. Foetal livers exhibited inhibited insulin-like growth factor-1 (IGF-1), enhanced lipogenesis and reduced lipid output. In adult female offspring of PCE+lab chow, lipid synthesis, oxidation and output were enhanced, whereas lipogenesis was inhibited in their male conterparters. Furthermore, in adult offspring of PCE+ high-fat diet, catch-up growth appeared obvious with enhanced hepatic IGF-1, especially in females. Both males and females showed increased lipid synthesis and reduced output, which were accompanied by elevated serum triglyceride. Severe NAFLD appeared with higher Kleiner scores. Gluconeogenesis was continuously enhanced in females. Therefore, increased susceptibility to diet-induced NAFLD in PCE offspring was confirmed, and it appears to be mediated by intrauterine glucose and alterations in lipid metabolic programming. This altered programming enhanced foetal hepatic lipogenesis and reduced lipid output in utero, which continued into the postnatal phase and reappeared in adulthood with the introduction of a high-fat diet, thereby aggravating hepatic lipid accumulation and causing NAFLD.

  17. Primary liver injury and delayed resolution of liver stiffness after alcohol detoxification in heavy drinkers with the PNPLA3 variant I148M

    PubMed Central

    Rausch, Vanessa; Peccerella, Teresa; Lackner, Carolin; Yagmur, Eray; Seitz, Helmut-Karl; Longerich, Thomas; Mueller, Sebastian

    2016-01-01

    AIM To investigate the influence of PNPLA3 genotype in heavy drinkers on serum markers and liver stiffness (LS) during alcohol withdrawal and its association with histology. METHODS Caucasian heavy drinkers (n = 521) with a mean alcohol consumption of 192.1 g/d (median alcohol consumption: 169.0 g/d; 95%CI: 179.0-203.3) were enrolled at the Salem Medical Center, University of Heidelberg. LS was measured by transient elastography (Fibroscan, Echosens SA, Paris, France). LS and serum markers were prospectively studied in these patients with all stages of alcoholic liver disease (steatosis, steatohepatitis, fibrosis) prior and after alcohol detoxification with a mean observation interval of 6.2 ± 3.2 d. A liver biopsy with histological analysis including the Kleiner score was obtained in 80 patients. RESULTS The PNPLA3 rs738409 genotype distribution for CC, CG and GG was 39.2%, 52.6% and 8.2%. GG genotype primarily correlated with histological steatohepatitis (r = 0.404, P < 0.005), ballooning (r = 0.319, P < 0.005) and less with steatosis (r = 0.264, P < 0.05). Mean LS was lowest in CC carriers (13.1 kPa) as compared to CG and GG carriers (17.6 and 17.2 kPa). Notably, LS primarily correlated with fibrosis stage (r = 0.828, P < 0.005), ballooning (r = 0.516, P < 0.005), steatohepatitis (r = 0.319, P < 0.005) but not with steatosis. After alcohol withdrawal, LS did not change in CC carriers, significantly decreased in CG-carriers from 17.6 to 12.7 kPa but to a lesser extent in GG carriers from 17.6 to 14.5 kPa. This was due to prolonged resolution of inflammation with significantly elevated aspartate transaminase levels after alcohol withdrawal in GG carriers. Non-invasive fibrosis assessment by LS in all patients showed a significantly higher F0 rate as compared to the biopsy cohort (47% vs 6%) with 3.8% more CC carriers while 3.7% less were seen in the F4 cirrhosis group. Thus, about 20% of patients with alcoholic liver cirrhosis would be attributable to PNPLA3 G

  18. Evaluation of liver function impairment and lipid peroxidation induced by lantana camara leaf powder administration in adult rat serum and liver.

    PubMed

    Saini, N; Singh, J; Sehgal, R; Ojha, S

    2007-05-30

    Lantana camara is a common weed and certain medicinal properties have been attributed to this plant, but most varieties of this plant are reported to be highly toxic to animals. The plant is a native of America but a few varieties are indigenous to tropical Asia and Africa. The present investigation was done to study the hepatotoxic and lipid peroxidative effects of this noxious weed on female Wistar rats. Eighty four percent (84%) increase was observed in the activity of AST in group B and 120% increase was noted in group C in serum. In, liver tissue this increase was 66% and 258%. In the case of ALT, 165% increase was observed in group B and 219% increase was observed in group C in serum. In, liver there was 46% increase in group B and 216% increase in group C in the ALT activity. Similarly, 30% and 50% increase in group B and 120% and 300% increase in group C in the activity of ALP was observed with respect to control group. The overall protein concentration was increased in serum and decreased in liver tissue. Lipid peroxidation in liver tissue was inhibited by 22% in group B and 55% in group C. Thus Lantana camara is a toxic plant which produces severe hepatotoxicity in rats, but it also prevented lipid peroxidation that may suggest that Lantana camara may be acting as antioxidant but, exactly which of its component is responsible for this activity is not known and needs future investigations.

  19. Hepatoprotective Activity of Water Extracts from Chaga Medicinal Mushroom, Inonotus obliquus (Higher Basidiomycetes) Against Tert-Butyl Hydroperoxide-Induced Oxidative Liver Injury in Primary Cultured Rat Hepatocytes.

    PubMed

    Hong, Ki Bae; Noh, Dong Ouk; Park, Yooheon; Suh, Hyung Joo

    2015-01-01

    We examined the hepatoprotective activity of Inonotus obliquus water extract (IO-W) against tert-butyl hydroperoxide (t-BHP)-induced oxidative liver injury in the primary cultured rat hepatocyte. The 50% radical scavenging concentrations (SC50s) of IO-W for radical-scavenging activity against 2,2'-azino-bis-(3-ethylbenzothi- azoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) were 5.19 mg/mL and 0.39 mg/mL, respectively. IO-W pretreatment to the primary cultured hepatocytes significantly (p<0.05) protected the cells from t-BHP-induced cytotoxic injury even at a low concentration of IO-W (10 µg/mL). The cellular leakage of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH), as well as malondialdehyde (MDA) formation caused by t-BHP were significantly (p<0.05) suppressed by IO-W pretreatment (>100 µg/ mL). In conclusion, this study demonstrates that IO-W exhibited hepatoprotective activity against t-BHP-induced oxidative liver injury in the primary cultured hepatocyte probably via its abilities of quenching free radicals, inhibiting the leakage of ALT, AST, and LDH, and decreasing MDA formation.

  20. Comorbidity and its impact in adult patients with attention-deficit/hyperactivity disorder: a primary care perspective.

    PubMed

    Babcock, Thomas; Ornstein, Craig S

    2009-05-01

    The objective of this manuscript was to review the literature relevant to the primary care practitioner concerning comorbidity and its impact on diagnosis and treatment efficacy in adults with attention-deficit/hyperactivity disorder (ADHD). A MEDLINE literature review was performed using the keywords: attention-deficit/hyperactivity disorder; psychiatric comorbidity; bipolar disorder; major depressive disorder; oppositional defiant disorder; conduct disorder; and substance use disorder. The authors assessed and summarized literature identified as relevant to primary care practitioners. Results demonstrated high rates of psychiatric comorbidity in patients with ADHD. These comorbid disorders, coupled with the differing characteristics of ADHD symptoms in adults versus children, may complicate accurate diagnosis and treatment of ADHD. Controlled clinical trials indicate that the presence of comorbidity does not substantially alter the safety and efficacy of ADHD pharmacotherapy and that treatment of ADHD can sometimes improve symptoms of the comorbid disorder. Although rates of psychiatric comorbidity are high in adults with ADHD, available data suggest that the benefits of pharmacotherapy for ADHD are not compromised by the presence of psychiatric comorbidity.

  1. Sleep paralysis and trauma, psychiatric symptoms and disorders in an adult African American population attending primary medical care.

    PubMed

    Mellman, Thomas A; Aigbogun, Notalelomwan; Graves, Ruth Elaine; Lawson, William B; Alim, Tanya N

    2008-01-01

    The occurrence of sleep paralysis (SP) absent narcolepsy appears to not be uncommon in African Americans and probably other non-European groups. Prior research has linked SP to trauma and psychiatric disorders and suggested a specific relationship to panic disorder in African Americans. The objective of our study was to evaluate relationships of SP with trauma, concurrent psychiatric symptoms and lifetime psychiatric diagnoses in an adult African American population recruited from primary care. Cross sectional study with surveys and diagnostic interviews; Patients attending primary care clinics filled out a survey that determined the 6 month prevalence and associated features of SP, a panic disorder screen, the self-rated Hamilton Depression Scale, and an inventory of trauma exposure. A subset of trauma-exposed participants (N = 142) received comprehensive diagnostic interviews that incorporated the Structured Clinical Interview for DSM-IV and the Clinician Assessed PTSD Scale. Four hundred and forty-one adults participated (mean age-40.0 SD = 13.3, 68% female, 95% African American). Fourteen percent endorsed recent SP. In approximately 1/3 of those with SP, episodes also featured panic symptoms. SP was strongly associated with trauma history, and concurrent anxiety and mood symptoms. SP was not associated with specific psychiatric disorders other than lifetime (but not current) alcohol or substance use disorders. Our findings suggest that SP is not uncommon in adult African Americans and is associated with trauma and concurrent distress but not with a specific psychiatric diagnosis.

  2. Serum uric acid is independently and linearly associated with risk of nonalcoholic fatty liver disease in obese Chinese adults

    PubMed Central

    Liu, Chang-Qin; He, Chun-Mei; Chen, Ning; Wang, Dongmei; Shi, Xiulin; Liu, Yongwen; Zeng, Xin; Yan, Bing; Liu, Suhuan; Yang, Shuyu; Li, Xiaoying; Li, Xuejun; Li, Zhibin

    2016-01-01

    The present study aimed to explore the independent association and potential pathways between serum uric acid (SUA) and nonalcoholic fatty liver disease (NAFLD). 1365 community-living obese Chinese adults who received hepatic ultrasonography scanning were included. The prevalence rates of NAFLD were 71.5% for men and 53.8% for women. Compared with controls, NAFLD subjects showed significantly increased SUA levels (333.3 ± 84.9 v.s. 383.4 ± 93.7 μmol/L) and prevalence rate of hyperuricemia (HUA) (25.7% v.s. 47.3%, p < 0.001). After adjustment for insulin resistance (IR), components of metabolic syndrome (MetS) and other potential confounders, elevated SUA is independently associated with increased risk of NAFLD, with the adjusted OR of 1.528–2.031 (p < 0.001). By using multivariable fractional polynomial (MFP) modeling, the best FP transformation model shows that SUA was independently and linearly associated with risk of NAFLD. The one-pathway model by using structural equation modeling (SEM) about the relationships among SUA, IR, components of metabolic syndrome and NAFLD fits well (χ2 = 57.367, p < 0.001; CFI = 0.998; TLI = 0.992; and RMSEA = 0.048) and shows SUA might increase the risk of NAFLD directly besides of the indirect effects through increasing fasting insulin, blood pressure, triglyceride and decreasing HDL-C levels. Our results imply that elevated SUA may play an important role in NAFLD pathogenesis. PMID:27924915

  3. FDG-PET/CT Imaging Predicts Histopathologic Treatment Responses after Neoadjuvant Therapy in Adult Primary Bone Sarcomas

    DOE PAGES

    Benz, Matthias R.; Czernin, Johannes; Tap, William D.; ...

    2010-01-01

    Purpose . Tmore » he aim of this study was to prospectively evaluate whether FDG-PET allows an accurate assessment of histopathologic response to neoadjuvant treatment in adult patients with primary bone sarcomas. Methods . Twelve consecutive patients with resectable, primary high grade bone sarcomas were enrolled prospectively. FDG-PET/CT imaging was performed prior to the initiation and after completion of neoadjuvant treatment. Imaging findings were correlated with histopathologic response. Results . Histopathologic responders showed significantly more pronounced decreases in tumor FDG-SUVmax from baseline to late follow up than non-responders ( 64 ± 19 % versus 29 ± 30 %, resp.; P = .03 ). Using a 60% decrease in tumor FDG-uptake as a threshold for metabolic response correctly classified 3 of 4 histopathologic responders and 7 of 8 histopathologic non-responders as metabolic responders and non-responders, respectively (sensitivity, 75%; specificity, 88%). Conclusion . These results suggest that changes in FDG-SUVmax at the end of neoadjuvant treatment can identify histopathologic responders and non-responders in adult primary bone sarcoma patients.« less

  4. Study origin of germ cells and formation of new primary follicles in adult human and rat ovaries.

    PubMed

    Bukovsky, Antonin; Gupta, Satish K; Virant-Klun, Irma; Upadhyaya, Nirmala B; Copas, Pleas; Van Meter, Stuart E; Svetlikova, Marta; Ayala, Maria E; Dominguez, Roberto

    2008-01-01

    The central thesis regarding the human ovaries is that, although primordial germ cells in embryonal ovaries are of extraovarian origin, those generated during the fetal period and in postnatal life are derived from the ovarian surface epithelium (OSE) bipotent cells. With the assistance of immune system-related cells, secondary germ cells and primitive granulosa cells originate from OSE stem cells in the fetal and adult human gonads. Fetal primary follicles are formed during the second trimester of intrauterine life, prior to the end of immune adaptation, possibly to be recognized as self-structures and renewed later. With the onset of menarche, a periodical oocyte and follicular renewal emerges to replace aging primary follicles and ensure that fresh eggs for healthy babies are always available during the prime reproductive period. The periodical follicular renewal ceases between 35 and 40 yr of age, and the remaining primary follicles are utilized during the premenopausal period until exhausted. However, the persisting oocytes accumulate genetic alterations and may become unsuitable for ovulation and fertilization. The human OSE stem cells preserve the character of embryonic stem cells, and they may produce distinct cell types, including new eggs in vitro, particularly when derived from patients with premature ovarian failure or aging and postmenopausal ovaries. Our observations also indicate that there are substantial differences in follicular renewal between adult human and rat ovaries. As part of this chapter, we present in detail protocols utilized to analyze oogenesis in humans and to study interspecies differences when compared to the ovaries of rat females.

  5. The RFC1 80G>A, among Common One-Carbon Polymorphisms, Relates to Survival Rate According to DNA Global Methylation in Primary Liver Cancers

    PubMed Central

    Moruzzi, Sara; Udali, Silvia; Ruzzenente, Andrea; Guglielmi, Alfredo; Guarini, Patrizia; Martinelli, Nicola; Conci, Simone; Mazzi, Filippo; Pattini, Patrizia; Tammen, Stephanie A.; Olivieri, Oliviero; Pizzolo, Francesca; Choi, Sang-Woon

    2016-01-01

    Polymorphisms within one-carbon metabolism genes have been largely studied in relation to cancer risk for the function of this pathway in nucleotide synthesis and DNA methylation. Aims of this study were to explore the possible link among several common functional gene polymorphisms within one-carbon metabolism and survival rate in primary liver cancers, i.e., hepatocellular carcinoma and cholangiocarcinoma, and to assess the additional effect of global DNA methylation on survival rate and mortality risk. Forty-seven primary liver cancer patients were genotyped for ten polymorphisms: DHFR 19bp ins/del, TS 2rpt-3rpt, MTHFD1 1958G>A, MTHFR 677C>T, MTR 2756A>G, MTRR 66A>G, RFC1 80G>A, SHMT1 1420C>T, BHMT 716 A>G, TC II 776C>G. Methylation was determined in peripheral blood mononuclear cells (PBMCs) DNA as methylcytosine (mCyt) content using LC/MS/MS. Among the polymorphisms analysed, the RFC1 80G>A (rs1051266) influenced the survival rate in primary liver cancers. The RFC1 80AA was associated to a significantly reduced survival rate (22.2%) as compared to both GG and GA genotypes (61.5% and 76% respectively, p = 0.005). When the cancer patients were stratified according to the mCyt median value as high (>5.34%) or low (≤5.34%), the concomitant presence of AA genotype and low mCyt level led to a significantly worse survival rate as compared to the G allele carriership (p<0.0001) with a higher Hazard Ratio (HR = 6.62, p = 0.001). The subjects carrying the AA genotype in association with high mCyt did not show a significant difference in survival rate as compared with the G allele carriers (p = 0.919). The RFC1 80G>A polymorphism influenced the survival rate, and the presence of RFC1 80AA genotype with low global methylation in PBMCs DNA was associated with poorer prognosis and higher mortality risk, therefore highlighting novel molecular signatures potentially helpful to define prognostic markers for primary liver cancers. PMID:27936032

  6. A review of primary care interventions to improve health outcomes in adult survivors of adverse childhood experiences.

    PubMed

    Korotana, Laurel M; Dobson, Keith S; Pusch, Dennis; Josephson, Trevor

    2016-06-01

    Research has consistently demonstrated a link between the experience of adverse childhood experiences (ACEs) and adult health conditions, including mental and physical health problems. While a focus on the prevention or mitigation of adversity in childhood is an important direction of many programs, many individuals do not access support services until adulthood, when health problems may be fairly engrained. It is not clear which interventions have the strongest evidence base to support the many adults who present to services with a history of ACEs. The current review examines the evidence base for psychosocial interventions for adults with a history of ACEs. The review focuses on interventions that may be provided in primary care, as that is the setting where most patients will first present and are most likely to receive treatment. A systematic review of the literature was completed using PsycInfo and PubMed databases, with 99 studies identified that met inclusion and exclusion criteria. These studies evaluated a range of interventions with varying levels of supportive evidence. Overall, cognitive-behavioral therapies (CBT) have the most evidence for improving health problems - in particular, improving mental health and reducing health-risk behaviors - in adults with a history of ACEs. Expressive writing and mindfulness-based therapies also show promise, whereas other treatments have less supportive evidence. Limitations of the current literature base are discussed and research directions for the field are provided.

  7. Frequency-change in DPOAE evoked by 1 s/octave sweeping primaries in newborns and adults.

    PubMed

    AlMakadma, Hammam A; Henin, Simon; Prieve, Beth A; Dyab, Walid M; Long, Glenis R

    2015-10-01

    Distortion product otoacoustic emissions (DPOAE) in newborns and adults were evoked by sweeping primaries up and down in frequency at 1 s/octave. Sweeping up and down in frequency resulted in changes in the amplitude vs. frequency functions of the composite DPOAE and its two major components. In addition, DPOAE component phases differed slightly between the up- and down-swept conditions. The changes in amplitude vs. frequency functions were quantified using a covariate correlation technique, yielding single-valued estimates of the magnitude of the frequency changes. Separate analyses were performed for the entire DPOAE frequency range and split into low and high frequency ranges. There were consistent changes in newborn and adult composite DPOAEs and reflection components, but not generator components. Adults had significant frequency changes in the composite DPOAE for all frequency ranges and in the reflection component for the entire frequency range. Newborns had significant frequency change in the reflection component for all frequency ranges. Differences in frequency change between adults and newborns may stem from developmental changes in cochlear processing. Alignment of the component phase differences between the up- and down-swept conditions resulted in elimination of frequency-change in reconstructed composite DPOAEs.

  8. The effect of pharmacist-led interventions in optimising prescribing in older adults in primary care: A systematic review

    PubMed Central

    Riordan, David O; Walsh, Kieran A; Galvin, Rose; Sinnott, Carol; Kearney, Patricia M; Byrne, Stephen

    2016-01-01

    Objective: To evaluate studies of pharmacist-led interventions on potentially inappropriate prescribing among community-dwelling older adults receiving primary care to identify the components of a successful intervention. Data sources: An electronic search of the literature was conducted using the following databases from inception to December 2015: PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, MEDLINE (through Ovid), Trip, Centre for Reviews and Dissemination databases, Cochrane Database of Systematic Reviews, ISI Web of Science, ScienceDirect, ClinicalTrials.gov, metaRegister of Controlled Trials, ProQuest Dissertations & Theses Database (Theses in Great Britain, Ireland and North America). Review methods: Studies were included if they were randomised controlled trials or quasi-randomised studies involving a pharmacist-led intervention compared to usual/routine care which aimed to reduce potentially inappropriate prescribing in older adults in primary care. Methodological quality of the included studies was independently assessed. Results: A comprehensive literature search was conducted which identified 2193 studies following removal of duplicates. Five studies met the inclusion criteria. Four studies involved a pharmacist conducting a medication review and providing feedback to patients or their family physician. One randomised controlled trial evaluated the effect of a computerised tool that alerted pharmacists when elderly patients were newly prescribed potentially inappropriate medications. Four studies were associated with an improvement in prescribing appropriateness. Conclusion: Overall, this review demonstrates that pharmacist-led interventions may improve prescribing appropriateness in community-dwelling older adults. However, the quality of evidence is low. The role of a pharmacist working as part of a multidisciplinary primary care team requires further investigation to optimise prescribing in this group of patients. PMID

  9. Effects of dietary phenochlor DP5 on microsomal enzymes, liver, and blood lipids in adult male and female rats after subchronic and perinatal exposures

    SciTech Connect

    Poul, J.M.

    1987-08-01

    PCBs have numerous toxic effects on laboratory animals, namely hepatotoxicity, immunotoxicity, reproductive and hormonal effects, mutagenic and carcinogenic potency (Safe 1984). They have been recognized as potent inducers of many microsomal drug metabolizing enzymes in several species. Moreover, treatment of rats with PCBs gave rise to altered lipid metabolism with accumulation of lipids in the liver. In most of these studies male rats have been used. However, sex differences in the effects of xenobiotics on microsomal drug metabolizing enzymes have been shown particularly with PCBs and little was known about differences in the effects of PCBs on lipid metabolism. This study was designed to investigate the effects of a subchronic treatment with Phenochlor DP5 on some microsomal drug metabolizing enzyme activities and on liver and blood lipids of male and female rats. The long-term effects of DP5 administration during pre and postnatal period on adult microsomal enzyme activities and liver and blood lipids of both sexes have also been studied. A possible xenobiotic imprinting of the hepatic monooxygenase system during neonatal period has been shown recently, and it has been recognized that some functional defects which often manifest themselves in adult period may be induced prenatally or before weaning.

  10. Differential effects of long-term exposure to Aroclor 1254 on lipid secretion by primary cultures of adult rat hepatocytes

    SciTech Connect

    Mendoza-Figueroa, T.; Hernandez, A.; Lopez, L.

    1992-06-01

    PCBs produce hepatic triglyceride (TG) accumulation (fatty liver) in experimental animals and humans exposed accidentally and occupationally. It has been suggested that this effect could be due to a block in TG secretion. On the other hand, increased levels of plasmatic TG and cholesterol have been described in rats after dietary exposure to Aroclor 1254 (Aro) and other PCBs; hypertriglyceridemia and hypertension have been also described in humans exposed for long periods to low concentrations of PCBs. Since the study of hepatic lipid metabolism and its alteration by toxic chemicals is complicated in the whole animal, short term cultures of adult rat hepatocytes have been used. We have described a system for the long term culture of adult rat hepatocytes which for several weeks maintain differentiated functions, like fatty acid and TG synthesis and their export to the culture medium. In this paper we used this culture system to study the effect of long-term exposure to micromolar concentrations of Aro on the secretion of lipids by cultured hepatocytes. 27 refs., 4 figs., 1 tab.

  11. The Role of National Adult Education Centre in Curriculum Development in Somalia in Selected Government Primary Adult Schools of Mogadisho. African Studies in Curriculum Development and Evaluation, No. 109.

    ERIC Educational Resources Information Center

    Bahar, Ismail F. S.

    A study of curriculum development in Somalia focused on the role of the National Adult Education Centre (NAEC) and involvement of teachers and inspectors. The sample consisted of 80 Mogadisho primary adult school teachers. Information sources were related literature, teacher questionnaires, and unstructured interviews with school inspectors,…

  12. Model for end-stage liver disease exceptions committee activity in Argentina: does it provide justice and equity among adult patients waiting for a liver transplant?

    PubMed Central

    McCormack, Lucas; Gadano, Adrián; Lendoire, Javrer; Quiñonez, Emilio; Imventarza, Oscar; Andriani, Oscar; Toselli, Lorenzo; Gil, Octavio; Gondolesi, Gabriel; Bisigniano, Liliana; de Santibañes, Eduardo

    2010-01-01

    Background In 2005, the model of end-stage liver disease (MELD)-based allocation system was adopted to assess potential liver transplant (LT) recipients in Argentina. The aim of the present study was to revise the activity of the MELD Exception Experts Committee. Methods Between 2005 and 2009, 1623 patients were listed for LT. Regulation provides extra-MELD points for amyloidosis, hepatopulmonary syndrome (HPS) and T2 hepatocellular carcinoma (T2 HCC). Centres could also request priority for other situations. Using a prospective database, we identified patients in whom priority points were requested. Pathology reports of explanted livers were analysed for patients with T2 HCC. Results From 234 out of 1623 (14.4%) requests, the overall approval rate was 60.2% including: 2 amyloidosis, 6 HPS, 111 T2 HCC and 22 non-regulated situations. Of the 111 patients with T2 HCC, 6 died (5.4%), 8 had tumour progression (7.2%), 94 were transplanted (84.2%) and 3 are still waiting. An explants correlation showed that presumed diagnosis of T2HCC was incorrect in 20/94 (22%) and was correct in only 41/94 (43%) cases being T1 HCC in 9 and T3 HCC in 23. Conclusions MELD exceptions are frequently requested in Argentina. Unfortunately, most receiving priority points for T2 HCC benefited by medical error or imaging limitations. An intense review process is urgently needed to maintain equity and justice in the allocation system. PMID:20887320

  13. Evaluation of in vivo genotoxicity by thioacetamide in a 28-day repeated-dose liver micronucleus assay using male young adult rats.

    PubMed

    Sui, Hajime; Matsumoto, Hirotaka; Wako, Yumi; Kawasako, Kazufumi

    2015-03-01

    The repeated-dose liver micronucleus (RDLMN) assay has the potential to detect liver carcinogens and can be integrated into general toxicological studies. In this study, thioacetamide (TAA) was tested in 14- and 28-day RDLMN assays to assess the performance of the assay. The test substance, TAA, was administered orally to 6-week-old male Crl:CD (SD) rats once daily for 14 or 28 days at a dosage of 5, 10 or 20mg/kg/day. Hepatocytes were collected approximately 24h after the last TAA administration, and the incidence of micronuclei was assessed. In this study, bone marrow micronucleus assays were also conducted in the same animals. The 14- and 28-day RDLMN assays indicated that none of the TAA dosages significantly increased the proportion of micronucleated hepatocytes. Bone marrow micronucleus assays with TAA also provided negative results. It is known that TAA is a liver carcinogen in mice and rats. In the previous genotoxic studies, the Ames test and the chromosomal aberration test using CHL/IU cells have yielded negative results [1-4]. The liver micronucleus assay using young adult rats singly dosed with TAA (75 and 150mg/kg) also produced negative results [5]. TAA gave positive results only in the mouse bone marrow micronucleus assays [6,7].

  14. Microscopy, culture, and sensitive management of uncomplicated urinary tract infections in adults in the primary care setting.

    PubMed

    Sivathasan, Niroshan; Rakowski, Krzysztof R

    2011-06-01

    The high prevalence of urinary tract infections (UTIs) places a significant burden on healthcare systems. Clinicians may over-manage the issue, and there is great variability in practice, with economic- and resource- implications. Up to 40% of patients with a suspected UTI do not have an infection. Using PubMed (Medline) to shortlist relevant papers in English from the last 30 years, and further sub-selection to include only uncomplicated UTIs in adults in primary care, we reviewed the literature pertaining to uncomplicated UTIs, and how it should be managed efficiently in the primary care setting. In general practice, there is no advantage to routinely request microscopy and culture of urine samples in the presence of an appropriate history and urinalysis reagent-strip testing. If antibiotics are required, then a 3-day course shall suffice. Larger epidemiological studies focusing on more susceptible sub-populations may provide better guidance for discriminatory factors to produce an algorithm for treatment.

  15. Liver transplant

    MedlinePlus

    Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

  16. Preparation and Culture of Myogenic Precursor Cells/Primary Myoblasts from Skeletal Muscle of Adult and Aged Humans.

    PubMed

    Soriano-Arroquia, Ana; Clegg, Peter D; Molloy, Andrew P; Goljanek-Whysall, Katarzyna

    2017-02-16

    Skeletal muscle homeostasis depends on muscle growth (hypertrophy), atrophy and regeneration. During ageing and in several diseases, muscle wasting occurs. Loss of muscle mass and function is associated with muscle fiber type atrophy, fiber type switching, defective muscle regeneration associated with dysfunction of satellite cells, muscle stem cells, and other pathophysiological processes. These changes are associated with changes in intracellular as well as local and systemic niches. In addition to most commonly used rodent models of muscle ageing, there is a need to study muscle homeostasis and wasting using human models, which due to ethical implications, consist predominantly of in vitro cultures. Despite the wide use of human Myogenic Progenitor Cells (MPCs) and primary myoblasts in myogenesis, there is limited data on using human primary myoblast and myotube cultures to study molecular mechanisms regulating different aspects of age-associated muscle wasting, aiding in the validation of mechanisms of ageing proposed in rodent muscle. The use of human MPCs, primary myoblasts and myotubes isolated from adult and aged people, provides a physiologically relevant model of molecular mechanisms of processes associated with muscle growth, atrophy and regeneration. Here we describe in detail a robust, inexpensive, reproducible and efficient protocol for the isolation and maintenance of human MPCs and their progeny - myoblasts and myotubes from human muscle samples using enzymatic digestion. Furthermore, we have determined the passage number at which primary myoblasts from adult and aged people undergo senescence in an in vitro culture. Finally, we show the ability to transfect these myoblasts and the ability to characterize their proliferative and differentiation capacity and propose their suitability for performing functional studies of molecular mechanisms of myogenesis and muscle wasting in vitro.

  17. Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations.

    PubMed

    Slike, Bonnie M; Creegan, Matthew; Marovich, Mary; Ngauy, Viseth

    2017-01-01

    Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity) may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb) responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT) of 250 to baseline (<20) after 10-20 years post vaccination. This contrasted with a comparator group of adults, ages 35-49, who were vaccinated with Dryvax® as children. In the childhood vaccinees, titers persisted for >30 years with a GMT of 210 (range 112-3234). This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.

  18. Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations

    PubMed Central

    Slike, Bonnie M.; Creegan, Matthew

    2017-01-01

    Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity) may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb) responses to vaccinia waned after 5–10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT) of 250 to baseline (<20) after 10–20 years post vaccination. This contrasted with a comparator group of adults, ages 35–49, who were vaccinated with Dryvax® as children. In the childhood vaccinees, titers persisted for >30 years with a GMT of 210 (range 112–3234). This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program. PMID:28046039

  19. Environmental Ligands of the Aryl Hydrocarbon Receptor and Their Effects in Models of Adult Liver Progenitor Cells

    PubMed Central

    Vondráček, Jan; Machala, Miroslav

    2016-01-01

    The toxicity of environmental and dietary ligands of the aryl hydrocarbon receptor (AhR) in mature liver parenchymal cells is well appreciated, while considerably less attention has been paid to their impact on cell populations exhibiting phenotypic features of liver progenitor cells. Here, we discuss the results suggesting that the consequences of the AhR activation in the cellular models derived from bipotent liver progenitors could markedly differ from those in hepatocytes. In contact-inhibited liver progenitor cells, the AhR agonists induce a range of effects potentially linked with tumor promotion. They can stimulate cell cycle progression/proliferation and deregulate cell-to-cell communication, which is associated with downregulation of proteins forming gap junctions, adherens junctions, and desmosomes (such as connexin 43, E-cadherin, β-catenin, and plakoglobin), as well as with reduced cell adhesion and inhibition of intercellular communication. At the same time, toxic AhR ligands may affect the activity of the signaling pathways contributing to regulation of liver progenitor cell activation and/or differentiation, such as downregulation of Wnt/β-catenin and TGF-β signaling, or upregulation of transcriptional targets of YAP/TAZ, the effectors of Hippo signaling pathway. These data illustrate the need to better understand the potential role of liver progenitors in the AhR-mediated liver carcinogenesis and tumor promotion. PMID:27274734

  20. The Impact of Checking the Health of Adults with Intellectual Disabilities on Primary Care Consultation Rates, Health Promotion and Contact with Specialists

    ERIC Educational Resources Information Center

    Felce, David; Baxter, Helen; Lowe, Kathy; Dunstan, Frank; Houston, Helen; Jones, Glyn; Grey, Jill; Felce, Janet; Kerr, Michael

    2008-01-01

    Background: Studies have found that health checking in primary care led to the identification of previously unrecognized morbidity among adults with intellectual disabilities. The aim here was to evaluate whether health checking stimulated increased consultation with the general practitioner or another member of the primary care team, increased…

  1. Treatment of Unresectable Primary and Metastatic Liver Cancer with Yttrium-90 Microspheres (TheraSphere (registered) ): Assessment of Hepatic Arterial Embolization

    SciTech Connect

    Sato, Kent; Lewandowski, Robert J.; Bui, James T.; Omary, Reed; Hunter, Russell D.; Kulik, Laura; Mulcahy, Mary; Liu, David; Chrisman, Howard; Resnick, Scott; Nemcek, Albert A.; Vogelzang, Robert; Salem, Riad

    2006-08-15

    In Canada and Europe, yttrium-90 microspheres (TheraSphere); MDS Nordion, Ottawa, Canada) are a primary treatment option for primary and secondary hepatic malignancies. We present data from 30 patients with hepatocellular carcinoma (HCC) and metastatic liver disease treated with TheraSphere from a single academic institution to evaluate the angiographically evident embolization that follows treatment. Seven interventional radiologists from one treatment center compared pretreatment and posttreatment angiograms. The reviewers were blinded to the timing of the studies. The incidence of postembolization syndrome (PES) was determined as well as objective tumor response rates by the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), and European Association for the Study of the Liver (EASL) criteria. There were 420 independent angiographic observations that were assessed using the chi-squared statistic. The pretreatment and posttreatment angiograms could not be correctly identified on average more than 43% of the time (p = 0.0004). The postprocedure arterial patency rate was 100%. The objective tumor response rates for all patients were 24%, 31%, and 72% for WHO, RECIST, and EASL criteria, respectively. All of the patients tolerated the procedure without complications and were treated on an outpatient basis, and four patients had evidence of PES. This treatment method does not result in macroscopic embolization of the hepatic arteries, thereby maintaining hepatic tissue perfusion. These data support the principle that the favorable response rates reported with TheraSphere are likely due to radiation and microscopic embolization rather than flow-related macroscopic embolization and ischemia.

  2. Is Antibiotic Prophylaxis for Percutaneous Radiofrequency Ablation (RFA) of Primary Liver Tumors Necessary? Results From a Single-Center Experience

    SciTech Connect

    Bhatia, Shivank S.; Echenique, Ana Froud, Tatiana Suthar, Rekha Lawson, Ivy Dalal, Ravi; Yrizarry, Jose Narayanan, Govindarajan

    2015-08-15

    PurposeThe purpose of this study was to evaluate need for antibiotic prophylaxis for radiofrequency ablation (RFA) of liver tumors in patients with no significant co-existing risk factors for infection.Materials and MethodsFrom January 2004 to September 2013, 83 patients underwent 123 percutaneous RFA procedures for total of 152 hepatocellular carcinoma (HCC) lesions. None of the patients had pre-existing biliary enteric anastomosis (BEA) or any biliary tract abnormality predisposing to ascending biliary infection or uncontrolled diabetes mellitus. No pre- or post-procedure antibiotic prophylaxis was provided for 121 procedures. Data for potential risk factors were reviewed retrospectively and analyzed for the frequency of infectious complications, including abscess formation.ResultsOne patient (1/121 (0.8 %) RFA sessions) developed a large segment 5 liver abscess/infected biloma communicating with the gallbladder 7 weeks after the procedure, successfully treated over 10 weeks with IV and PO antibiotic therapy and percutaneous catheter drainage. This patient did not receive any antibiotics prior to RFA. During the procedure, there was inadvertent placement of RFA probe tines into the gallbladder. No other infectious complications were documented.ConclusionThese data suggest that the routine use of prophylactic antibiotics for liver RFA is not necessary in majority of the patients undergoing liver ablation for HCC and could be limited to patients with high-risk factors such as the presence of BEA or other biliary abnormalities, uncontrolled diabetes mellitus, and large centrally located tumors in close proximity to central bile ducts. Larger randomized studies are needed to confirm this hypothesis.

  3. Adult Primary Spinal Epidural Extraosseous Ewing's Sarcoma: A Case Report and Review of the Literature

    PubMed Central

    Thomas, Cheddhi; Modrek, Aram S.; Bayin, N. Sumru; Snuderl, Matija; Schiff, Peter B.

    2016-01-01

    Background. Extraosseous Ewing's sarcoma in the spinal epidural space is a rare malignancy, especially in adults. Case Presentation. A 40-year-old male presented with back pain and urinary hesitancy. MRI revealed a thoracic extradural mass with no osseous involvement. He underwent surgery for gross total resection of the mass, which was diagnosed as Ewing's sarcoma. He was subsequently treated with chemoradiotherapy. He remains disease-free 1 year after surgery. Review of the literature indicated only 45 previously reported cases of spinal epidural extraosseous Ewing's sarcoma in adults. Conclusions. Extraosseous Ewing's sarcoma in the spinal epidural space is a rare clinical entity that should be included in the differential for spinal epidural masses. Its treatment is multidisciplinary but frequently requires surgical intervention due to compressive neurologic symptoms. Gross total resection appears to correlate with improved outcomes. PMID:27610254

  4. Comparison of primary repair and patch plasty procedure on the P wave in adult atrial septal defect closure

    PubMed Central

    Ucak, Alper; Temizkan, Veysel; Ugur, Murat; Selcuk, Arif; Yilmaz, Ahmet Turan; Yedekci, Ahmet Erturk; Uz, Omer

    2016-01-01

    Summary Introduction: In this study we compared the effects of two different surgical procedures for closure of adult atrial septal defect (ASD) on postoperative P-wave changes. Methods: Patients who underwent cardiac surgery for secundum type ASD closure were evaluated retrospectively. Seventy-two patients with primary repair of ASD and 29 patients with pericardial patch plasty repair were compared according to Pmax, Pmin and P-wave dispersions (Pd). Results: In each group, the increases in postoperative maximum P-wave duration (Pmax) and minimum P-wave duration (Pmin) were statistically significant. There was no statistically significant difference between post- and pre-operative Pd values. In the comparison between group 1 and group 2 in terms of postoperative P-wave changes (Pmax, Pmin, Pd) there was no statistically significant difference. Conclusion: Comparing patch plasty and primary repair for the surgical closure of ASD in the early to mid-postoperative period, no difference was found and both surgical procedures can be performed in adult ASDs. PMID:27149297

  5. Comparative effects of contraction and angiotensin II on growth of adult feline cardiocytes in primary culture

    NASA Technical Reports Server (NTRS)

    Wada, H.; Zile, M. R.; Ivester, C. T.; Cooper, G. 4th; McDermott, P. J.

    1996-01-01

    The purposes of this study were 1) to determine whether angiotensin II causes growth of adult feline cardiocytes in long-term culture, 2) to compare the growth effects of angiotensin II with those resulting from electrically stimulated contraction, and 3) to determine whether the anabolic effects of contraction are exerted via the angiotensin type 1 receptor. Adult feline cardiocytes were cultured on laminin-coated trays in a serum-free medium. Cardiocytes were either electrically stimulated to contract (1 Hz, 5-ms pulse duration, alternating polarity) or were nonstimulated and quiescent. Quiescent cells were studied as controls and after treatment with angiotensin II (10(-8) M), losartan (10(-6) M; an angiotensin type 1-receptor antagonist), or angiotensin II plus losartan. Contracting cells were studied in the presence and absence of angiotensin II or losartan. In quiescent cardiocytes, angiotensin II treatment on day 7 significantly increased protein synthesis rates by 22% and protein content per cell by 17%. The effects of angiotensin II were completely blocked by losartan. Electrically stimulated contraction on days 4 and 7 in culture significantly increased protein synthesis rate by 18 and 38% and protein content per cell by 19 and 46%, respectively. Angiotensin II treatment did not further increase protein synthesis rate or protein content in contracting cardiocytes. Furthermore, losartan did not block the anabolic effects of contraction on protein synthesis rates or protein content. In conclusion, angiotensin II can exert a modest anabolic effect on adult feline cardiocytes in culture. In contracting feline cardiocytes, angiotensin II has no effect on growth. Growth caused by electrically stimulated contraction occurs more rapidly and is greater in magnitude than that caused by angiotensin II. Growth of contracting adult feline cardiocytes is not dependent on activation of the angiotensin receptor.

  6. Overlap syndromes among autoimmune liver diseases.

    PubMed

    Rust, Christian; Beuers, Ulrich

    2008-06-07

    The three major immune disorders of the liver are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Variant forms of these diseases are generally called overlap syndromes, although there has been no standardised definition. Patients with overlap syndromes present with both hepatitic and cholestatic serum liver tests and have histological features of AIH and PBC or PSC. The AIH-PBC overlap syndrome is the most common form, affecting almost 10% of adults with AIH or PBC. Single cases of AIH and autoimmune cholangitis (AMA-negative PBC) overlap syndrome have also been reported. The AIH-PSC overlap syndrome is predominantly found in children, adolescents and young adults with AIH or PSC. Interestingly, transitions from one autoimmune to another have also been reported in a minority of patients, especially transitions from PBC to AIH-PBC overlap syndrome. Overlap syndromes show a progressive course towards liver cirrhosis and liver failure without treatment. Therapy for overlap syndromes is empiric, since controlled trials are not available in these rare disorders. Anticholestatic therapy with ursodeoxycholic acid is usually combined with immunosuppressive therapy with corticosteroids and/or azathioprine in both AIH-PBC and AIH-PSC overlap syndromes. In end-stage disease, liver transplantation is the treatment of choice.

  7. A liver abscess deprived a healthy adult of eyesight: endogenous endophthalmitis associated with a pyogenic liver abscess caused by serotype K1 Klebsiella pneumonia.

    PubMed

    Maruno, Takahisa; Ooiwa, Yoko; Takahashi, Ken; Kodama, Yuzo; Takakura, Shunji; Ichiyama, Satoshi; Chiba, Tsutomu

    2013-01-01

    Klebsiella pneumonia usually causes urinary tract infections, pneumonia, and other infectious diseases in hospitalized and immunocompromised patients. Among the types of Klebsiella pneumonia, serotype K1 is known to be a highly virulent pathogen. We herein report the case of a healthy 63-year-old man with a pyogenic liver abscess and bilateral endogenous endophthalmitis caused by serotype K1 Klebsiella pneumonia. Although the patient received percutaneous abscess drainage and antibiotic therapy, he lost his eyesight. To improve the poor prognoses of ocular complications, providing both an earlier diagnosis and treatment is critical.

  8. Low Plasma Zinc Is Associated with Higher Mitochondrial Oxidative Stress and Faster Liver Fibrosis Development in the Miami Adult Studies in HIV Cohort.

    PubMed

    Martinez, Sabrina S; Campa, Adriana; Li, Yinghui; Fleetwood, Christina; Stewart, Tiffanie; Ramamoorthy, Venkataraghavan; Baum, Marianna K

    2017-04-01

    Background: Oxidative stress and reduced antioxidants may be a trigger for liver fibrogenesis. Reducing oxidative stress through higher antioxidant concentration may be a potential antifibrotic target.Objective: We aimed to investigate longitudinally whether plasma zinc, an antioxidant, is related to mitochondrial oxidative stress and the progression of liver fibrosis in the Miami Adult Studies in HIV (MASH) cohort.Methods: A prospective observational cohort study was conducted in 487 predominantly African American HIV-monoinfected and HIV/hepatitis C virus (HCV)-coinfected adults with a mean ± SD age of 47.08 ± 7.67 y from the MASH cohort and followed for a median of 34 mo. Blood was collected for plasma zinc and measures were used to calculate the fibrosis-4 (FIB-4) score (aspartate amino transferase, alanine aminotransferase, and platelets). Plasma zinc deficiency was defined as <0.75 mg/L. Total DNA was extracted from peripheral blood mononuclear cells and mitochondrial DNA (mtDNA) 8-hydroxyguanosine (8-oxo-dG) was determined. Adjusted mixed models were used to assess the relations between zinc, stage of liver disease, and oxidative stress over time and compared between HIV and HIV/HCV groups.Results: Zinc concentrations (β: -0.368, SE = 0.172; P = 0.033) and deficiency were associated with lower FIB-4 scores over time (β: 0.381, SE = 0.118; P = 0.001). Compared with those who were not zinc deficient, zinc-deficient participants had an increased risk of having more-progressed liver disease (OR: 1.91; 95% CI: 1.15, 3.16; P = 0.012). Higher mtDNA 8-oxo-dG was associated with zinc deficiency (β: 0.049, SE = 0.024; P = 0.044) and higher FIB-4 scores over time (β: 0.597, SE = 0.168, P < 0.001).Conclusions: Lower plasma zinc concentrations were associated with liver fibrosis progression and mitochondrial oxidative stress in the HIV and HIV/HCV groups. Zinc may play a role in the impact of liver disease outcomes.

  9. Care of Older Adults: Role of Primary Care Physicians in the Treatment of Cataracts and Macular Degeneration.

    PubMed

    Marra, Kyle V; Wagley, Sushant; Kuperwaser, Mark C; Campo, Rafael; Arroyo, Jorge G

    2016-02-01

    This article aims to facilitate optimal management of cataracts and age-related macular degeneration (AMD) by providing information on indications, risk factors, referral guidelines, and treatments and to describe techniques to maximize quality of life (QOL) for people with irreversible vision loss. A review of PubMed and other online databases was performed for peer-reviewed English-language articles from 1980 through August 2012 on visual impairment in elderly adults. Search terms included vision loss, visual impairment, blind, low vision, QOL combined with age-related, elderly, and aging. Articles were selected that discussed vision loss in elderly adults, effects of vision impairment on QOL, and care strategies to manage vision loss in older adults. The ability of primary care physicians (PCPs) to identify early signs of cataracts and AMD in individuals at risk of vision loss is critical to early diagnosis and management of these common age-related eye diseases. PCPs can help preserve vision by issuing aptly timed referrals and encouraging behavioral modifications that reduce risk factors. With knowledge of referral guidelines for soliciting low-vision rehabilitation services, visual aids, and community support resources, PCPs can considerably increase the QOL of individuals with uncorrectable vision loss. By offering appropriately timed referrals, promoting behavioral modifications, and allocating low-vision care resources, PCPs may play a critical role in preserving visual health and enhancing the QOL for the elderly population.

  10. A Systematic Review of Depression Treatments in Primary Care for Latino Adults

    ERIC Educational Resources Information Center

    Cabassa, Leopoldo J.; Hansen, Marissa C.

    2007-01-01

    Objective: A systematic literature review of randomized clinical trials (RCTs) assessing depression treatments in primary care for Latinos is conducted. The authors rate the methodological quality of studies, examine cultural and linguistic adaptations, summarize clinical outcomes and cost-effectiveness findings, and draw conclusions for improving…

  11. Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection

    PubMed Central

    Bowlus, Christopher L

    2016-01-01

    Primary biliary cholangitis (PBC), previously known as primary biliary “cirrhosis”, is a rare autoimmune liver disease characterized by the hallmark autoantibodies to mitochondrial antigens and immune-mediated destruction of small bile duct epithelial cells leading to cholestasis and cirrhosis. Surprisingly, while immune modulators have not been effective in the treatment of PBC, supplementation with the hydrophilic bile acid (BA) ursodeoxycholic acid (UDCA) has been demonstrated to slow the disease progression. However, a significant minority of PBC patients do not have a complete response to UDCA and remain at risk of continued disease progression. Although the mechanisms of action are not well understood, UDCA provided proof of concept for BA therapy in PBC. Obeticholic acid (OCA), a novel derivative of the human BA chenodeoxycholic acid, is a potent agonist of the nuclear hormone receptor farnesoid X receptor, which regulates BA synthesis and transport. A series of clinical trials of OCA in PBC, primarily in combination with UDCA, have established that OCA leads to significant reductions in serum alkaline phosphatase that are predicted to lead to improved clinical outcomes, while dose-dependent pruritus has been the most common adverse effect. On the basis of these studies, OCA was given conditional approval by the US Food and Drug Administration with plans to establish the long-term clinical efficacy of OCA in patients with advanced PBC. PMID:27621676

  12. Dramatic reduction of liver cancer incidence in young adults: 28 year follow-up of etiological interventions in an endemic area of China

    PubMed Central

    Sun, Zongtang

    2013-01-01

    Qidong City, China, has had high liver cancer incidence from endemic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin. Based on etiologic studies, we began interventions in 1980 to reduce dietary aflatoxin and initiate neonatal HBV vaccination. We studied trends in liver cancer incidence rates in the 1.1 million inhabitants of Qidong and examined trends in aflatoxin exposure, staple food consumption, HBV infection markers and annual income. Aflatoxin exposure declined greatly in association with economic reform, increased earnings and educational programs to shift staple food consumption in the total population from moldy corn to fresh rice. A controlled neonatal HBV vaccination trial began in 1983 and ended in November, 1990, when vaccination was expanded to all newborns. Liver cancer incidence fell dramatically in young adults. Compared with 1980–83, the age-specific liver cancer incidence rates in 2005–08 significantly decreased 14-fold at ages 20–24, 9-fold at ages 25–29, 4-fold at ages 30–34, 1.5-fold at ages 35–39, 1.2-fold at ages 40–44 and 1.4-fold at ages 45–49, but increased at older ages. The 14-fold reduction at ages 20–24 might reflect the combined effects of reduced aflatoxin exposure and partial neonatal HBV vaccination. Decrease incidence in age groups >25 years could mainly be attributable to rapid aflatoxin reduction. Compared with 1980–83, liver cancer incidence in 1990–93 significantly decreased 3.4-fold at ages 20–24, and 1.9-fold at ages 25–29 when the first vaccinees were <11 years old. PMID:23322152

  13. A complete treatment of adult living donor liver transplantation: a review of surgical technique and current challenges to expand indication of patients.

    PubMed

    Lee, S-G

    2015-01-01

    The growing disparity between the number of liver transplant candidates and the supply of deceased donor organs has motivated the development of living donor liver transplantation (LDLT). Over the last two decades, the operation has been markedly improved by innovations rendering modern results comparable with those of deceased donor liver transplantation (DDLT). However, there remains room for further innovation, particularly in adult living donor liver transplantation (ALDLT). Unlike whole-size DDLT and pediatric LDLT, size-mismatching between ALDLT graft and recipient body weight and changing dynamics of posttransplant allograft regeneration have remained major challenges. A better understanding of the complex surgical anatomy and physiologic differences of ALDLT helps avoid small-for-size graft syndrome, graft congestion from outflow obstruction and graft hypoperfusion from portal flow steal. ALDLT for high-urgency patients (Model for End-Stage Liver Disease score >30) can achieve results comparable to DDLT in high volume centers. Size limitations of partial grafts and donor safety issues can be overcome with dual grafts and modified right-lobe grafts that preserve the donor's middle hepatic vein trunk. Extended application of LDLT for unresectable hepatocellular carcinoma above Milan criteria is an optional strategy at the cost of slightly compromised survival. ABO-blood group incompatibility obstacles have been broken down by introducing a paired donor exchange program and refined peri-operative management of ABO-incompatible ALDLT. This review focuses on recent innovations of surgical techniques, safe donor selection, current strategies to expand ALDLT with broadened patient selection criteria and important aspects of teamwork required for success.

  14. Real-life management of primary immune thrombocytopenia (ITP) in adult patients and adherence to practice guidelines.

    PubMed

    Lozano, María Luisa; Revilla, N; Gonzalez-Lopez, T J; Novelli, S; González-Porras, J R; Sánchez-Gonzalez, B; Bermejo, N; Pérez, S; Lucas, F J; Álvarez, M T; Arilla, M J; Perera, M; do Nascimento, J; Campos, R M; Casado, L F; Vicente, V

    2016-06-01

    Very few data exist on the management of adult patients diagnosed with primary immune thrombocytopenia (ITP). The objectives of this study were to describe the diagnostic and treatment patterns for ITP and to compare the findings to recent ITP guidelines. We retrospectively analyzed the medical records of adult ITP patients diagnosed with primary ITP between January 2011 and June 2012 and examined whether management strategies were consistent or not with eight recent guideline-recommended practices. Overall, median age at the diagnosis of the disease (n = 101) was 58 years and median platelet count 12 × 10(9)/L with 75.2 % of patients having symptoms of ITP. The study perceived two major shortcomings in the diagnostic approach: (1) failure to perform peripheral blood film examination in 22.8 % of patients, a test that is mandatory by all guidelines, and (2) ordinary bone marrow assessment in more than half of the patients at diagnosis (50.5 %), a test not routinely recommended by guidelines. Low appropriateness in therapeutic management of patients included (1) unjustified use of intravenous immunoglobulin in the absence of bleeding in 54.8 % of patients and (2) splenectomy not being deferred until 6-12 months from diagnosis (median 161 days). Data also reflect a trend towards the early use of thrombopoietin receptor agonists in the treatment of patients who are refractory to any first-line therapy. We have recognized important areas of inapropriateness in the diagnostic and therapeutic management of adult ITP patients. Compliance with established guidelines should be encouraged in order to improve patient outcomes.

  15. Effect of culture conditions on microRNA expression in primary adult control and COPD lung fibroblasts in vitro.

    PubMed

    Ikari, Jun; Smith, Lynette M; Nelson, Amy J; Iwasawa, Shunichiro; Gunji, Yoko; Farid, Maha; Wang, Xingqi; Basma, Hesham; Feghali-Bostwick, Carol; Liu, Xiangde; DeMeo, Dawn L; Rennard, Stephen I

    2015-04-01

    In vitro cell cultures, including lung fibroblasts, have been used to identify microRNAs (miRNAs) associated with chronic obstructive pulmonary disease (COPD) pathogenesis. However, culture conditions may affect miRNA expression. We examined whether miRNA expression in primary adult lung fibroblasts varies with cell density or passage in vitro and whether culture conditions confound the identification of altered miRNA expression in COPD lung fibroblasts. Primary adult control and COPD lung fibroblasts were cultured until passage 3 or 8, after which cells were further cultured for 3 or 7 d (low vs. high density). Then, cells at low density were cultured with serum-free media, and those at high density were cultured with serum-free media in the absence or presence of interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) for 24 h. RNA was extracted to perform miRNA microarray from which 1.25-fold differential expression and 10% false discovery rate were applied to identify "invariant" and "variant" miRNA for the various culture conditions. Of the 2226 miRNAs evaluated, 39.0% for cell density, 40.7% for cell passage, and 29.4% for both conditions were identified as "invariant" miRNAs. Furthermore, 38.1% of the evaluated miRNAs were "invariant" for cell passage with IL-1β and TNF-α. Differentially expressed miRNAs between control and COPD lung fibroblasts were identified with and without IL-1β and TNF-α, and of these, 32 out of the 34 top-ranked miRNAs exceeded the differences due to culture conditions. Thus, culture conditions may affect miRNA expression of adult human lung fibroblasts. Nevertheless, in vitro cultures can be used to assess differential miRNA expression in COPD lung fibroblasts.

  16. Corticosteroid Risk Function of Severe Infection in Primary Immune Thrombocytopenia Adults. A Nationwide Nested Case-Control Study.

    PubMed

    Moulis, Guillaume; Palmaro, Aurore; Sailler, Laurent; Lapeyre-Mestre, Maryse

    2015-01-01

    Corticosteroid (CS)-related infection risk in immune thrombocytopenia (ITP) is unknown. The aim of this study was to assess the adjusted CS risk function of severe infection in persistent or chronic primary ITP adults. We designed a nested case-control study in the FAITH cohort. This cohort is built through the French national health insurance database named SNIIRAM and includes all treated incident persistent or chronic primary ITP adults in France (ENCePP n°4574). Patients who entered the FAITH cohort between 2009 and 2012 were eligible (n = 1805). Cases were patients with infection as primary diagnosis code during hospitalization. Index date was the date of first hospitalization for infection. A 2:1 matching was performed on age and entry date in the cohort. Various CS exposure time-windows were defined: current user, exposure during the 1/3/6 months preceding index date and from the entry date. CS doses were converted in prednisone equivalent (PEQ). The cumulative CS doses were averaged in each time-window to obtain daily PEQ dosages. Each CS exposure definition was assessed using multivariate conditional regression models. During the study period, 161 cases (9 opportunistic) occurred. The model with the best goodness of fit was CS exposure during the month before the index date (OR: 2.48, 95% CI: 1.61-3.83). The dose-effect relation showed that the risk existed from averaged daily doses ≥5 mg PEQ (vs. <5 mg: 2.09, 95% CI: 1.17-3.71). The risk of infection was mainly supported by current or recent exposure to CS, even with low doses.

  17. Neonatal neuroblastoma with adrenal primary and metastasis to the liver: A case report and a review of literature

    PubMed Central

    Omoseebi, Oladipo; Odubanjo, Mosebolatan Olatokunboh; Akinde, Olakanmi Ralph; Ikeri, Nzechukwu Z.; Ademuyiwa, Adesoji O.; Adeyomoye, Adekunle A. O.

    2016-01-01

    We report the case of a 23-day-old neonate with neuroblastoma (NBL) in the right adrenal gland and widespread metastases to the liver. This raises the possibility of foetal NBL, which was missed during periodic ultrasonography done during the mother's pregnancy. We hope that this report would increase the awareness of physicians about foetal, congenital and neonatal NBL; and of sonographers about space-occupying lesions in the foetus. The clinicopathologic features and the management of neonatal NBL are discussed. PMID:28051057

  18. Sorafenib Tosylate With or Without Doxorubicin Hydrochloride in Treating Patients With Locally Advanced or Metastatic Liver Cancer

    ClinicalTrials.gov

    2016-12-30

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma; BCLC Stage D Adult Hepatocellular Carcinoma; Localized Non-Resectable Adult Liver Carcinoma; Recurrent Adult Liver Carcinoma

  19. 'SIMPLES': a structured primary care approach to adults with difficult asthma.

    PubMed

    Ryan, Dermot; Murphy, Anna; Ställberg, Björn; Baxter, Noel; Heaney, Liam G

    2013-09-01

    The substantial majority of patients with asthma can expect minimal breakthrough symptoms on standard doses of inhaled corticosteroids with or without additional add-on therapies. SIMPLES is a structured primary care approach to the review of a person with uncontrolled asthma which encompasses patient education monitoring, lifestyle and pharmacological management and addressing support needs which will achieve control in most patients. The small group of patients presenting with persistent asthma symptoms despite being prescribed high levels of treatment are often referred to as having 'difficult asthma'. Some will have difficult, 'therapy resistant' asthma, some will have psychosocial problems which make it difficult for them to achieve asthma control and some may prove to have an alternative diagnosis driving their symptoms. A few patients will benefit from referral to a 'difficult asthma' clinic. The SIMPLES approach, aligned with close co-operation between primary and specialist care, can identify this patient group, avoid inappropriate escalation of treatment, and streamline clinical assessment and management.

  20. Predictors of treatment satisfaction among older adults with anxiety in a primary care psychology program.

    PubMed

    Hundt, Natalie E; Armento, Maria E A; Porter, Bennett; Cully, Jeffrey A; Kunik, Mark E; Stanley, Melinda

    2013-04-01

    Increasing numbers of patients are treated in integrated primary care mental health programs. The current study examined predictors of satisfaction with treatment in patients from a randomized clinical trial of late-life generalized anxiety disorder (GAD) in primary care. Higher treatment satisfaction was associated with receiving CBT rather than enhanced usual care. Treatment credibility, treatment expectancies, social support, and improvements in depression and anxiety symptoms predicted higher treatment satisfaction in the total sample. In the CBT group, only credibility and adherence with treatment predicted satisfaction. This suggests that older patients receiving CBT who believe more strongly in the treatment rationale and follow the therapist's recommendations more closely are likely to report satisfaction at the end of treatment. In addition, this study found that adherence mediated the relationship between treatment credibility and treatment satisfaction. In other words, patients' perceptions that the treatment made sense for them led to greater treatment adherence which then increased their satisfaction with treatment.

  1. Office-Based Case Finding for Chronic Obstructive Pulmonary Disease in Older Adults in Primary Care

    PubMed Central

    Lee, Linda

    2016-01-01

    Background. Chronic Obstructive Pulmonary Disease (COPD) is underdiagnosed in primary care. Aim. To explore the utility of proactive identification of COPD in patients 75 years of age and older in a Canadian primary care setting. Methods. Canadian Thoracic Society (CTS) screening questions were administered to patients with a smoking history of 20 pack-years or more; those with a positive screen were referred for postbronchodilator spirometry. Results. A total of 107 patients (21%), of 499 screened, had a 20-pack-year smoking history; 105 patients completed the CTS screening. Forty-four (42%) patients were positive on one or more questions on the screening; significantly more patients with a previous diagnosis of COPD (64%) were positive on the CTS compared to those without a previous diagnosis of COPD (30%). Of those who were not previously diagnosed with COPD (N = 11), four (36%) were newly diagnosed with COPD. Conclusion. A systematic two-stage method of screening for COPD, using CTS screening questions followed by spirometric confirmation, is feasible in the context of a busy primary care setting. More research is needed to assess the value of restricting screening to patients with a smoking history of 20 pack-years and on the sensitivity and specificity of these measures. PMID:27445513

  2. Primary Care Opportunities to Prevent Unintentional Home Injuries: A Focus on Children and Older Adults

    PubMed Central

    McDonald, Eileen M.; Mack, Karin; Shields, Wendy C.; Lee, Robin P.; Gielen, Andrea C.

    2016-01-01

    Unintentional injuries are a persistent public health problem in the United States. A new health care landscape has the potential to create a clinical environment that fosters greater involvement by health care providers in injury prevention. The aim of this article is to provide evidence supporting the need for engagement by primary care providers in unintentional home injury prevention along with examples of how this could be accomplished. We know a great deal about what population groups are at risk for certain types of injuries. We also know that many injuries can be prevented through policies, programs, and resources that ensure safe environments and promote safe behaviors. For example, the Centers for Disease Control and Prevention’s STEADI (Stopping Elderly Accidents, Deaths, and Injuries) initiative comprises clinical decision support tools and educational materials for health care providers. Two effective interventions that have demonstrated a reduction in falls among children are the redesign of baby walkers (engineering) and the mandated use of window guards (enforcement). Primary care clinicians can play a key role in promoting their patient’s safety. Taken collectively, a focused attention on preventing unintentional home injuries by primary care providers can contribute to the reduction of injuries and result in optimal health for all. PMID:27141210

  3. Gastrointestinal and liver disease in Adult Life After Childhood Cancer in Scandinavia: A population-based cohort study.

    PubMed

    Asdahl, Peter Haubjerg; Winther, Jeanette Falck; Bonnesen, Trine Gade; De Fine Licht, Sofie; Gudmundsdottir, Thorgerdur; Holmqvist, Anna Sällfors; Malila, Nea; Tryggvadottir, Laufey; Wesenberg, Finn; Dahlerup, Jens Frederik; Olsen, Jørgen Helge; Hasle, Henrik

    2016-10-01

    Survival after childhood cancer diagnosis has remarkably improved, but emerging evidence suggests that cancer-directed therapy may have adverse gastrointestinal late effects. We aimed to comprehensively assess the frequency of gastrointestinal and liver late effects among childhood cancer survivors and compare this frequency with the general population. Our population-based cohort study included all 1-year survivors of childhood and adolescent cancer in Denmark, Finland, Iceland, Norway and Sweden diagnosed from the 1940s and 1950s. Our outcomes of interest were hospitalization rates for gastrointestinal and liver diseases, which were ascertained from national patient registries. We calculated standardized hospitalization rate ratios (RRs) and absolute excess rates comparing hospitalizations of any gastrointestinal or liver disease and for specific disease entities between survivors and the general population. The study included 31,132 survivors and 207,041 comparison subjects. The median follow-up in the hospital registries were 10 years (range: 0-42) with 23% of the survivors being followed at least to the age of 40 years. Overall, survivors had a 60% relative excess of gastrointestinal or liver diseases [RR: 1.6, 95% confidence interval (CI): 1.6-1.7], which corresponds to an absolute excess of 360 (95% CI: 330-390) hospitalizations per 100,000 person-years. Survivors of hepatic tumors, neuroblastoma and leukemia had the highest excess of gastrointestinal and liver diseases. In addition, we observed a relative excess of several specific diseases such as esophageal stricture (RR: 13; 95% CI: 9.2-20) and liver cirrhosis (RR: 2.9; 95% CI: 2.0-4.1). Our findings provide useful information about the breadth and magnitude of late complications among childhood cancer survivors and can be used for generating hypotheses about potential exposures related to these gastrointestinal and liver late effects.

  4. Violence victimization after HIV infection in a US probability sample of adult patients in primary care.

    PubMed Central

    Zierler, S; Cunningham, W E; Andersen, R; Shapiro, M F; Nakazono, T; Morton, S; Crystal, S; Stein, M; Turner, B; St Clair, P; Bozzette, S A

    2000-01-01

    OBJECTIVES: This study estimated the proportion of HIV-infected adults who have been assaulted by a partner or someone important to them since their HIV diagnosis and the extent to which they reported HIV-seropositive status as a cause of the violence. METHODS: Study participants were from a nationally representative probability sample of 2864 HIV-infected adults who were receiving medical care and were enrolled in the HIV Costs and Service Utilization Study. All interviews (91% in person, 9% by telephone) were conducted with computer-assisted personal interviewing instruments. Interviews began in January 1996 and ended 15 months later. RESULTS: Overall, 20.5% of the women, 11.5% of the men who reported having sex with men, and 7.5% of the heterosexual men reported physical harm since diagnosis, of whom nearly half reported HIV-seropositive status as a cause of violent episodes. CONCLUSIONS: HIV-related care is an appropriate setting for routine assessment of violence. Programs to cross-train staff in antiviolence agencies and HIV care facilities need to be developed for men and women with HIV infection. PMID:10667181

  5. Impairment of liver synthetic function and the production of plasma proteins in primary breast cancer patients on doxorubicincyclophosphamide (AC) protocol.

    PubMed

    Saleem, Zikria; Ahmad, Mobasher; Hashmi, Furqan Khurshid; Saeed, Hamid; Aziz, Muhammad Tahir

    2016-09-01

    Doxorubicin and Cyclophosphamide (AC protocol) combination is usually considered as a first line therapy in newly diagnosed breast cancer patients. Thus, a retrospective observational study was conducted to monitor the effect of AC protocol on liver synthetic functions and production of plasma proteins in breast cancer patients, reporting to specialized cancer care hospital of Lahore, Pakistan. A total of 75 patients (n=75) on AC protocol with breast cancer were observed in this study. The patient data including age, gender, body surface area, dosage, disease status and laboratory biochemical values were recorded by reviewing historical treatment records. Pre-treatment values were taken as baseline values for albumin, globulin, blood urea nitrogen (BUN), albumin/globulin (A/G) ratio and total proteins. The baseline values were compared after each cycle of by applying ANOVA using statistical tool SPSS® version 21. The plasma levels of blood urea nitrogen (BUN), total protein and globulin dropped significantly (p<0.05) in patients of all age groups. However, the albumin levels were not significantly changed (p>0.05). The A/G ratio level increased (p<0.05) as a result of reduction in globulin levels. Significant changes in plasma protein levels were observed in the elderly patients (50 to 65 years) than patients between 20 to 50 years of age. AC protocol impairs liver synthetic functions as observed by decreased blood urea nitrogen (BUN) and plasma protein levels.

  6. A Kazal-type serine proteinase inhibitor from chicken liver (clTI-1): purification, primary structure, and inhibitory properties.

    PubMed

    Kubiak, Agnieszka; Jakimowicz, Piotr; Polanowski, Antoni

    2009-08-01

    Low-molecular-mass trypsin inhibitor (clTI-1; chicken liver Trypsin Inhibitor-1) was purified from chicken liver by extraction with perchloric acid, ammonium sulfate precipitation, a combination of ethanol-acetone fractionation followed by gel filtration, ion-exchange chromatography and RP-HPLC on a C18 column. The inhibitor occurs in two isoforms with molecular masses of 5938.56 and 6026.29 Da (determined by MALDI TOFF mass spectrometry). The complete amino acid sequences of both isoforms were determined (UniProtKB/Swiss-Prot P85000; ISK1L_CHICK). The inhibitor shows a high homology to Kazal-type family inhibitors, especially to trypsin/acrosin inhibitors and pancreatic secretory trypsin inhibitors. clTI-1 inhibits both bovine and porcine trypsin (K(a)=1.1 x 10(9) M(-1) and 2.5 x 10(9) M(-1), respectively). Significant differences were shown in the inhibition of the anionic and cationic forms of chicken trypsin (K(a)=4.5 x 10(8) M(-1) and 1.2 x 10(10) M(-1)). Weak interaction with human plasmin (K(a)=1.2 x 10(7) M(-1)) was also revealed.

  7. Liver Transplant

    MedlinePlus

    ... Home > Your Liver > Liver Disease Information > Liver Transplant Liver Transplant Explore this section to learn more about ... resource. www.paulcox.com.au Why is the liver important? The liver is the second largest organ ...

  8. Liver Biopsy

    MedlinePlus

    ... Series Urinary Tract Imaging Urodynamic Testing Virtual Colonoscopy Liver Biopsy What is a liver biopsy? A liver biopsy is a procedure that ... remove the liver tissue sample. What is the liver and what does it do? The liver is ...

  9. Influence of levamisole and Freund's adjuvant on mouse immunisation with antigens of adults of the liver fluke Fasciola hepatica Linnaeus, 1758.

    PubMed

    Gutierrez-Sanchez, Maria de Los Angeles; Luna-Herrera, Julieta; Trejo-Castro, Lauro; Montenegro-Cristino, Natividad; Almanza-Gonzalez, Alfredo; Escobar-Gutierrez, Alejandro; de la Rosa-Arana, Jorge Luis

    2015-08-28

    We have studied the influence of both levamisole (AL) and Freund's adjuvant (AF) on the immunisation of mice with the secretory antigens of adults of the liver fluke Fasciola hepatica Linnaeus, 1758. Total IgG antibodies were detected in all groups where the F. hepatica antigen was administered, been levels of IgG1 increased respect to IgG2a antibodies. During immunisation, IL-4 and IFN-γ were only detected in AL and AF groups, but after infection, IL-4 boosted in all groups. IFN-γ increased two fold in AF and AL groups compared to the saline solution (AS) group. Worm recovering was of 32-35% in groups administered without antigen whereas in AS, AL and AF groups recovering was of 25%, 12% and 8%, respectively. Macroscopical lesions in the liver were scarce in AL and AF groups. Our data suggest that immunisation of mice with antigens of F. hepatica enhances the immune response avoiding both liver damage and worm establishment after challenge infection. The murine model of fasciolosis has appeared to be useful to elucidate the mechanism by which the parasite modulates immune responses toward a Th2 type but also the development of Th1 type-inducing vaccines.

  10. Adult-onset nemaline myopathy in a dog presenting with persistent atrial standstill and primary hypothyroidism.

    PubMed

    Nakamura, R K; Russell, N J; Shelton, G D

    2012-06-01

    A nine-year-old neutered female mixed breed dog presented for evaluation following a five-day history of lethargy, inappetence, weakness, abdominal distension and generalised muscle atrophy. Persistent vatrial standstill with a junctional rhythm was identified on electrocardiogram. Echocardiogram identified moderate dilation of all cardiac chambers and mild thickening of the mitral and tricuspid valves. Serology was negative for Neospora caninum and Toxoplasma gondii. Permanent pacemaker implantation was performed in addition to endomyocardial and skeletal muscle biopsies. Cryosections from the biceps femoris muscle showed numerous nemaline rod bodies while endomyocardial biopsies were possibly consistent with end-stage myocarditis. Rod bodies have rarely been reported in the veterinary literature. To the authors' knowledge, this is the first report of adult-onset nemaline rod myopathy and hypothyroidism with concurrent cardiac disease in a dog.

  11. Lipid-mediated transfection of normal adult human hepatocytes in primary culture.

    PubMed

    Ourlin, J C; Vilarem, M J; Daujat, M; Harricane, M C; Domergue, J; Joyeux, H; Baulieux, J; Maurel, P

    1997-04-05

    The aim of this work was to develop a procedure for the lipid-mediated transfection of DNA into normal adult human hepatocytes in culture. Cells were plated in a serum-free culture medium at various cell densities, on plastic or collagen-coated dishes, both in the absence and in the presence of epidermal growth factor (EGF). The cells were incubated for various periods of time with mixtures of DNA-lipofectin or DNA-3 beta[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-chol) liposomes, and the efficiency of transfection was assessed by measuring the activity of reporter genes, beta-galactosidase or chloramphenicol acetyl-transferase (CAT). For comparison, similar experiments were carried out with human cell lines including HepG2, Caco-2, and WRL68. The efficiency of transfection (in percentage of cells) was not significantly different after transfection with lipofectin or DC-chol and comprised between 0.04 and 1.7% (extreme values) for different cultures. The efficiency of transfection decreased as the age or density of the culture increased and increased in cultures treated with EGF. Direct measurement of the rate of DNA synthesis suggested that the efficiency of transfection was related to the number of cells entering the S phase. Under the same conditions, the efficiency of transfection was one to two orders of magnitude greater in the three cell lines. A plasmid harboring 660 bp of the 5'-flanking region of CYP1A1 (containing two xenobiotic enhancer elements) fused upstream of the promoter of thymidine kinase and the CAT reporter gene was constructed. When this plasmid was transfected in human hepatocytes, CAT activity was induced as expected. We conclude that normal adult human hepatocytes can be transfected with exogenous DNA and that the transfected construct is regulated in the manner expected from in vivo studies.

  12. Primary and rescue immune tolerance induction in children and adults: a multicentre international study with a VWF-containing plasma-derived FVIII concentrate.

    PubMed

    Oldenburg, J; Jiménez-Yuste, V; Peiró-Jordán, R; Aledort, L M; Santagostino, E

    2014-01-01

    Most studies on immune tolerance induction (ITI) therapy in haemophilia A patients are focused on primary ITI in children. Here we report on the ITI outcome in a large retrospective cohort, including adults and patients with rescue ITI, treated with a pdFVIII/VWF concentrate. Retrospective data from haemophilic patients (FVIII< 2%) with inhibitors from 22 centres in Spain, Italy and Germany, who underwent primary or rescue ITI with pdFVIII/VWF concentrate, were collected. Complete success (CS), partial success (PS) and failure were defined based on the criteria of the consensus recommendations of the 2006 International ITI Workshop. A total of 41 cases of primary ITI (32 children and 9 adults) and 19 cases of rescue ITI (17 children and 2 adults) were evaluated. Success (CS+PS) rate of 87% was achieved in primary ITI and 74% in the higher risk profile of rescue ITI. Eight of nine (85%) patients with poorest prognosis (three or more of the known risk factors of poor response to ITI) achieved success (CS+PS). CS of 100% was observed in eight primary ITI patients with titre at start of ITI ≤2.5 BU and inhibitor peak ≤25 BU. The favourable response rates in primary and rescue ITI in children and in adult patients, even in the presence of poor prognostic factors, should be encouraged for broadening the indication of immune tolerance therapy in haemophilia A patients with inhibitors.

  13. Elevated circulating CD14(low)CD16(+) monocyte subset in primary biliary cirrhosis correlates with liver injury and promotes Th1 polarization.

    PubMed

    Peng, Anping; Ke, Peifeng; Zhao, Rong; Lu, Xinyi; Zhang, Cheng; Huang, Xianzhang; Tian, Guangjun; Huang, Jun; Wang, Jinli; Invernizzi, Pietro; Chen, Qubo; Zhuang, Junhua

    2016-11-01

    Primary biliary cirrhosis (PBC) is a progressive autoimmune liver disease in which monocytes/macrophages infiltration and skewed T helper type (Th) 1 and Th17 cell responses participate in the development of the disease. Human peripheral blood monocytes are heterogeneous and can be divided into classical CD14(high)CD16(-), intermediate CD14(high)CD16(+), and nonclassical CD14(low)CD16(+) monocyte subsets. Compared to classical monocytes, CD16(+) monocytes are generally termed pro-inflammatory monocytes and play an important pathogenic role in autoimmune diseases. However, little is known about the immunophenotype and immunopathogenic role of peripheral blood CD16(+) monocytes in PBC. Thus, we investigated the phenotype and function of these circulating monocyte subsets from PBC patients. The frequencies of circulating CD14(high)CD16(+) and CD14(low)CD16(+) subpopulation were increased in disease compared with healthy controls. Among them, CD14(low)CD16(+) monocyte subset positively correlated with disease progress, liver damage indicators and serum C-reactive protein, respectively. Furthermore, the frequencies of Th1 and Th17 cells were upregulated and CD14(low)CD16(+) monocyte subset was also positively associated with Th1 cell frequency in PBC. Using a vitro coculture model, we further found that CD14(low)CD16(+) monocytes promoted Th1 cell polarization compared to classical monocytes. Interleukin-12 (IL-12) and direct contact of patient CD4(+)T cell and CD14(low)CD16(+) monocytes, were responsible for CD14(low)CD16(+) monocytes promotion of Th1 cells polarization in PBC. Our study demonstrated that the enhanced CD14(low)CD16(+) monocyte subset participated in fostering liver damage and inflammatory responses, and promoted Th1 cells skewing in PBC.

  14. Lack of protective effect of D-003, a mixture of high-molecular-weight primary acids from sugar cane wax, on liver damage induced by galactosamine in rats.

    PubMed

    Noa, Miriam; Mendoza, Sarahí; Mas, Rosa; Mendoza, Nilda

    2005-01-01

    D-003 is a mixture of very-high-molecular-weight aliphatic primary acids purified from sugar cane wax, wherein octacosanoic acid is the most abundant. Experimental and clinical studies have shown that D-003 lowers cholesterol and prevents plasma lipoprotein peroxidation (LP). D-003 has protected against the histological changes characteristic of CCl4- and paracetamol-induced hepatic injury in rats, in which LP plays a pivotal role for explaining the resulting hepatotoxicity. Galactosamine induces hepatotoxicity associated with depressed RNA and protein synthesis, not with LP. The aim of this study was to evaluate whether D-003 could prevent hepatoxicity induced by mechanisms others than increased LP. We investigated the effects on galactosamine hepatotoxicity in rats distributed into five groups: a negative control group, a positive control group, and three groups treated with galactosamine and D-003 (5, 25, and 100 mg/kg). To induce liver damage, galactosamine (800 mg/kg) was injected intraperitoneally 30 minutes after dosing with vehicle or D-003. Twenty-four hours later, rats were sacrificed, and livers were immediately removed for histopathological studies. Livers from