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Sample records for hepatomegaly

  1. Severe ARDS may cause right heart failure with extreme hepatomegaly but without hepatic failure.

    PubMed

    Søreide, E; Harboe, S; Søndenaa, K

    2002-08-01

    A young trauma patient developed severe adult respiratory distress syndrome (ARDS), right heart failure, hepatic congestion and an extreme hepatomegaly but no hepatic failure. The patient needed 100% oxygen during ventilatory support for 80 days and was weaned from the ventilator after more than 100 days. The hepatomegaly gradually disappeared. Four months after the injury, the anatomical shape of the lungs, heart and liver were normalized. This case illustrates that severe ARDS may cause right heart failure and extreme hepatomegaly due to venous congestion in the liver and spleen, but without hepatic failure.

  2. Congestive Hepatomegaly

    MedlinePlus

    ... or out of the liver? Gallstones Gluten intolerance Heart failure High blood pressure Am I Correct? More Videos News HealthDay Better Efforts Could Help Rid the U.S. of Hepatitis B, C: Report TUESDAY, March 28, 2017 (HealthDay News) -- Improved prevention, screening and treatment could ...

  3. New approaches to the quantitation of hypertrophy and hyperplasia in hepatomegaly.

    PubMed

    Carthew, P; Edwards, R E; Nolan, B M

    1998-12-28

    A histological method utilizing the optical dissector principle has been developed for determining the contribution of hypertrophy and hyperplasia to the hepatomegaly induced by the peroxisome proliferator gemfibrozil. The optical dissector is a technique derived from the 'new stereology' and has been used to estimate the number of hepatocyte nuclear profiles, that are present in a reference volume of tissue. The overall changes due to hypertrophy and hyperplasia in the rat liver after gemfibrozil treatment, did not reach significance, although the zonal hypertrophy change did. This indicated that although there was a 20% increase in liver weight with treatment, the hepatomegaly was caused by a combination of hypertrophy and hyperplasia, neither of which, on its own, was significantly different from the control values. The distinction of hyperplasia from hypertrophy, using a purely histological method, will be useful in assessing whether treatment related sustained hyperplasia is occurring in the liver.

  4. [Hepatomegaly due to glycogen storage disease and type 1 diabetes mellitus].

    PubMed

    Flotats Bastardas, M; Miserachs Barba, M; Ricart Cumeras, A; Clemente León, M; Gussinyer Canadell, M; Yeste Fernández, D; Albisu Aparicio, María A; Carrascosa Lezcano, A

    2007-08-01

    Patients with type 1 diabetes and poor metabolic control can develop hepatomegaly due to intrahepatic glycogen deposition. If these patients also have elevated liver enzymes, dyslipidemia, cushingoid features and delayed growth or sexual maturation, Mauriac syndrome can be diagnosed. This disorder is common and reversible with optimization of insulin therapy. We report three adolescents with type 1 diabetes and a long-standing history of poor glycemic control, who developed hepatomegaly, elevated liver enzymes and dyslipidemia with preserved liver function. One of these patients also had delayed growth and another had hypogonadotropic hypogonadism. Liver ultrasound showed changes suggestive of glycogenosis. In all three patients, optimization of insulin therapy achieved good glycemic control and reversed the manifestations within 2 weeks. The etiology of Mauriac syndrome is controversial since both prolonged hyperglycemia and hyperinsulinization produce glycogen accumulation in the liver. Hypercortisolism (due to ketosis or hypoglycemia) contributes to glycogen storage and also causes growth and sexual maturation delay.

  5. Assessment Hepatomegaly and liver Enzymes in 100 Patients with beta Thalassemia Major in Mashhad, Iran

    PubMed Central

    Hashemizadeh, H; Noori, R; kolagari, SH

    2012-01-01

    Background Frequent blood transfusion in patients with beta thalassemia major can lead to iron overload especially in liver. Chronic iron overload could cause cirrhosis of the liver. Transfusion- transmitted hepatitis B and C also could develop cirrhosis in individuals. Materials and Methods The present cross- sectional descriptive study is to assess hepatomegaly and liver enzymes in 100 patients with beta thalassemia major, ages between 2-18 years old. The study was carried out retrospectively. One hundred medical records have chosen from 400 samples of thalassemia major patients, who are under a regular care of the department of sarvar clinic. Results Out of these patients, 55% were male and 45% female. The mean age of thalassemia patients was 10.8± 4.4 years. The mean and S. D of hemoglobin, ferritin, deferoxamine dosage was 8.5 ± 1.5g/dl , 2183 ± 1528 ng , 30 ± 11.16 mg/kg, respectively. Forty six percent of them had hepatomegaly. The mean and S. D of AST and ALT were 95± 70 IU/L and 70 ±35U/L respectively. Splenectomy was performed on 44% of patient. Conclusion Hepatomegaly is one of the most common findings in the thalassemic patient that induced with hemosiderosis and hepatitis. PMID:24575259

  6. The quantitative distinction of hyperplasia from hypertrophy in hepatomegaly induced in the rat liver by phenobarbital.

    PubMed

    Carthew, P; Edwards, R E; Nolan, B M

    1998-07-01

    A histological method utilizing the optical dissector principle has been developed for determining the absolute numbers of rat hepatocytes in the liver after treatment with phenobarbital (PB). The optical dissector is a technique derived from the "new stereology" used to measure the number of features, in this case hepatocyte nuclear profiles, that are present in a reference volume of tissue. The method has been applied to distinguish between the hepatomegaly that commonly occurs in rodents after treatment with chemicals, due to an increase in the number of cells caused by cell division (hyperplasia), rather than the size of cells (hypertrophy). In the case of PB treatment, the hepatomegaly was found to be partly due to hypertrophy and partly to hyperplasia after 2 weeks of treatment. While the increase in the absolute number of hepatocytes was not significant after 2 weeks, after 12 weeks of treatment with PB the number of hepatocytes was significantly increased, compared to the controls at that time point. PCNA labeling index measurements of liver hepatocytes confirmed that there was a significant increase in the growth fraction of hepatocytes during PB treatment. The induction of hyperplasia can be associated with an increased risk of eventual liver tumor formation, and the distinction of hyperplasia from hypertrophy, using a purely histological method, for the determination of increases in absolute hepatocyte cell numbers, will be useful in assessing whether treatment-related sustained hyperplasia is occurring in the liver, although this methodology could be applied to any organ.

  7. Ibuprofen hepatic encephalopathy, hepatomegaly, gastric lesion and gastric pentadecapeptide BPC 157 in rats.

    PubMed

    Ilic, Spomenko; Drmic, Domagoj; Zarkovic, Kamelija; Kolenc, Danijela; Brcic, Luka; Radic, Bozo; Djuzel, Viktor; Blagaic, Alenka Boban; Romic, Zeljko; Dzidic, Senka; Kalogjera, Livije; Seiwerth, Sven; Sikiric, Predrag

    2011-09-30

    Chronic ibuprofen (0.4 g/kg intraperitoneally, once daily for 4 weeks) evidenced a series of pathologies, not previously reported in ibuprofen-dosed rats, namely hepatic encephalopathy, gastric lesions, hepatomegaly, increased AST and ALT serum values with prolonged sedation/unconsciousness, and weight loss. In particular, ibuprofen toxicity was brain edema, particularly in the cerebellum, with the white matter being more affected than in gray matter. In addition, damaged and red neurons, in the absence of anti-inflammatory reaction was observed, particularly in the cerebral cortex and cerebellar nuclei, but was also present although to a lesser extent in the hippocampus, dentate nucleus and Purkinje cells. An anti-ulcer peptide shown to have no toxicity, the stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, 10 μg, 10 ng/kg) inhibited the pathology seen with ibuprofen (i) when given intraperitoneally, immediately after ibuprofen daily or (ii) when given in drinking water (0.16 μg, 0.16 ng/ml). Counteracted were all adverse effects, such as hepatic encephalopathy, the gastric lesions, hepatomegaly, increased liver serum values. In addition, BPC 157 treated rats showed no behavioral disturbances and maintained normal weight gain. Thus, apart from efficacy in inflammatory bowel disease and various wound treatments, BPC 157 was also effective when given after ibuprofen.

  8. Peliosis hepatis presenting with massive hepatomegaly in a patient with idiopathic thrombocytopenic purpura.

    PubMed

    Kim, Sun Bean; Kim, Do Kyung; Byun, Sun Jeong; Park, Ji Hye; Choi, Jin Young; Park, Young Nyun; Kim, Do Young

    2015-12-01

    Peliosis hepatis is a rare condition that can cause hepatic hemorrhage, rupture, and ultimately liver failure. Several authors have reported that peliosis hepatis develops in association with chronic wasting disease or prolonged use of anabolic steroids or oral contraceptives. In this report we describe a case in which discontinuation of steroid therapy improved the condition of a patient with peliosis hepatis. Our patient was a 64-year-old woman with a history of long-term steroid treatment for idiopathic thrombocytopenic purpura . Her symptoms included abdominal pain and weight loss; the only finding of a physical examination was hepatomegaly. We performed computed tomography (CT) and magnetic resonance imaging (MRI) of the liver and a liver biopsy. Based on these findings plus clinical observations, she was diagnosed with peliosis hepatis and her steroid treatment was terminated. The patient recovered completely 3 months after steroid discontinuation, and remained stable over the following 6 months.

  9. [Hereditary fructose intolerance (HFI) as cause of isolated gamma GT rise in a 5-year old boy with hepatomegaly].

    PubMed

    Wössmann, W; Wiemann, J; Körber, F; Gortner, L

    2000-01-01

    The diagnosis of HFI is easily missed during childhood. It should be suspected in children presenting with hepatomegaly and an isolated increase in GGT. A carefully taken nutritional history forms the basis of the diagnosis of HFI which can be confirmed by molecular analysis with a sensitivity of > 95%. I.v. fructose tolerance tests and liver biopsies often can be omitted.

  10. The Use of Beta-Adrenergic Blockade in Preventing Trauma-Induced Hepatomegaly

    PubMed Central

    Barrow, Robert E.; Wolfe, Robert R.; Dasu, Mohan R.; Barrow, Laura N.; Herndon, David N.

    2006-01-01

    Objective: The objective of this study was to test the hypothesis that hepatomegaly in burned children can be attenuated or reversed by blocking lipolysis and reducing free fatty acids delivered to the liver. Summary Background Data: Accelerated lipolysis in severely burned children has been shown to play an important role in the accumulation of hepatic TGs. Severely burned children who survive 10 days or more after injury commonly have enlarged livers often twice or more normal size for their sex, age, and weight. Methods: Ninety-eight children, 2 to 18 years of age, with burns covering more than 40% of their body surface and who received either propranolol (β-adrenergic blockade) or placebo were studied. Liver weights were measured by ultrasonic scanning. Body composition changes were identified by dual-image x-ray absorptiometry and validated by whole-body potassium-40 scintillation counting. Discarded abdominal cutaneous adipose tissue was collected before and after propranolol or placebo for microarray analysis. Results: In 80% of severely burned children studied not receiving propranolol, liver sizes increased by 100% or more while 86% of burned children receiving propranolol showed a decrease or no change in liver size over the same period of time after injury. Gene expression patterns of adipose tissue after propranolol treatment showed that all of the identified genes related to lipid metabolism were down-regulated. Conclusions: Data reported here support the hypothesis that β-adrenergic blockade can reduce delivery of fatty acids to the liver and hepatic congestion commonly found in severely burned children by inhibiting lipolysis and reducing hepatic blood flow. PMID:16371745

  11. Development of an updated PBPK model for trichloroethylene and metabolites in mice, and its application to discern the role of oxidative metabolism in TCE-induced hepatomegaly

    SciTech Connect

    Evans, M.V. Chiu, W.A.; Okino, M.S.; Caldwell, J.C.

    2009-05-01

    Trichloroethylene (TCE) is a lipophilic solvent rapidly absorbed and metabolized via oxidation and conjugation to a variety of metabolites that cause toxicity to several internal targets. Increases in liver weight (hepatomegaly) have been reported to occur quickly in rodents after TCE exposure, with liver tumor induction reported in mice after long-term exposure. An integrated dataset for gavage and inhalation TCE exposure and oral data for exposure to two of its oxidative metabolites (TCA and DCA) was used, in combination with an updated and more accurate physiologically-based pharmacokinetic (PBPK) model, to examine the question as to whether the presence of TCA in the liver is responsible for TCE-induced hepatomegaly in mice. The updated PBPK model was used to help discern the quantitative contribution of metabolites to this effect. The update of the model was based on a detailed evaluation of predictions from previously published models and additional preliminary analyses based on gas uptake inhalation data in mice. The parameters of the updated model were calibrated using Bayesian methods with an expanded pharmacokinetic database consisting of oral, inhalation, and iv studies of TCE administration as well as studies of TCE metabolites in mice. The dose-response relationships for hepatomegaly derived from the multi-study database showed that the proportionality of dose to response for TCE- and DCA-induced hepatomegaly is not observed for administered doses of TCA in the studied range. The updated PBPK model was used to make a quantitative comparison of internal dose of metabolized and administered TCA. While the internal dose of TCA predicted by modeling of TCE exposure (i.e., mg TCA/kg-d) showed a linear relationship with hepatomegaly, the slope of the relationship was much greater than that for directly administered TCA. Thus, the degree of hepatomegaly induced per unit of TCA produced through TCE oxidation is greater than that expected per unit of TCA

  12. Four cases of type 1 diabetes mellitus showing sharp serum transaminase increases and hepatomegaly due to glycogenic hepatopathy.

    PubMed

    Ikarashi, Yuichi; Kogiso, Tomomi; Hashimoto, Etsuko; Yamamoto, Kuniko; Kodama, Kazuhisa; Taniai, Makiko; Torii, Nobuyuki; Takaike, Hiroko; Uchigata, Yasuko; Tokushige, Katsutoshi

    2017-03-01

    Poorly controlled diabetes mellitus (DM) patients sometimes show serum transaminase elevations due to steatohepatitis. However, we experienced four cases with type 1 DM with sharp elevations in serum transaminases that could not be explained by steatohepatitis alone and showed bright liver. They were diagnosed with glycogenic hepatopathy (GH) clinicopathologically. The four patients had a median age of 22.5 years (range, 19-29 years) and 12.5 (4-15)-year histories of type 1 DM and showed marked increases in serum transaminases (aspartate aminotransferase, 698 U/L [469-2763 U/L]; alanine transaminase, 255 U/L [216-956 U/L]). Diabetes mellitus control was poor and hemoglobin A1c was 12.7% (11-16.5%). Three cases had a past history of diabetic ketoacidosis. Hepatomegaly and hyperdense liver were seen on computed tomography scans. Magnetic resonance imaging showed low intensity in T2-weighted images. The pathological findings revealed pale and swollen hepatocytes and glycogenated nuclei. The architecture of the liver was preserved, and steatosis and fibrosis were mild. The cytoplasm of hepatocytes stained densely positive with periodic acid-Schiff, and the positive staining disappeared after diastase digestion, suggesting glycogen deposition. No other cause of hepatitis was evident, and the diagnosis was GH. Elevated transaminases improved within 1 month with good glycemic control. Transaminase elevations were observed several times in three cases with poor glycemic control. Glycogenic hepatopathy is rare, but extremely high serum elevations of transaminases are important to identify clinically. Despite showing a good clinical course in general, GH sometimes recurs and requires strict glycemic control. Clinicians should be aware of and recognize GH when dealing with uncontrolled DM patients.

  13. Repeated inhalation exposure to octamethylcyclotetrasiloxane produces hepatomegaly, transient hepatic hyperplasia, and sustained hypertrophy in female Fischer 344 rats in a manner similar to phenobarbital.

    PubMed

    McKim, J M; Kolesar, G B; Jean, P A; Meeker, L S; Wilga, P C; Schoonhoven, R; Swenberg, J A; Goodman, J I; Gallavan, R H; Meeks, R G

    2001-04-15

    Octamethylcyclotetrasiloxane (D4) has been described as a phenobarbital-like inducer of hepatic enzymes. Phenobarbital (PB) and phenobarbital-like chemicals induce transient hepatic and thyroid hyperplasia and sustained hypertrophy in rats and mice. The extent to which these processes are involved with D4-induced hepatomegaly is not known. The present study has evaluated the effects of repeated inhalation exposure to D4 vapors on hepatic and thyroid cell proliferation and hypertrophy with respect to time and exposure concentration. Female Fischer 344 rats were exposed via whole body inhalation to 0 ppm D4, 700 ppm D4 vapors (6 h/day; 5 days/week), or 0.05% PB in drinking water over a 4-week period. Incorporation of 5'-bromo-2-deoxyuridine (BrdU) and the abundance of proliferating cell nuclear antigen were used as indicators of cell proliferation. Designated animals from each treatment group were euthanized on study days 6, 13, and 27. The effect of D4 exposure concentration on hepatic cell proliferation was evaluated at 0, 7, 30, 70, 150, 300, or 700 ppm. Liver-to-body weight ratios in animals exposed to 700 ppm D4 were increased 18, 20, and 22% over controls while PB-treated animals showed increases of 33, 27, and 27% over controls on days 6, 13, and 27 respectively. Hepatic incorporation of BrdU following exposure to D4 was highest on day 6 (labeling index = 15-22%) and was at or below control values by day 27. This pattern of transient hyperplasia was observed in all hepatic lobes examined and was similar to the pattern observed following treatment with PB.

  14. Over-dose insulin and stable gastric pentadecapeptide BPC 157. Attenuated gastric ulcers, seizures, brain lesions, hepatomegaly, fatty liver, breakdown of liver glycogen, profound hypoglycemia and calcification in rats.

    PubMed

    Ilic, S; Brcic, I; Mester, M; Filipovic, M; Sever, M; Klicek, R; Barisic, I; Radic, B; Zoricic, Z; Bilic, V; Berkopic, L; Brcic, L; Kolenc, D; Romic, Z; Pazanin, L; Seiwerth, S; Sikiric, P

    2009-12-01

    We focused on over-dose insulin (250 IU/kg i.p.) induced gastric ulcers and then on other disturbances that were concomitantly induced in rats, seizures (eventually fatal), severely damaged neurons in cerebral cortex and hippocampus, hepatomegaly, fatty liver, increased AST, ALT and amylase serum values, breakdown of liver glycogen with profound hypoglycemia and calcification development. Calcium deposits were present in the blood vessel walls, hepatocytes surrounding blood vessels and sometimes even in parenchyma of the liver mainly as linear and only occasionally as granular accumulation. As an antidote after insulin, we applied the stable gastric pentadecapeptide BPC 157 (10 microg/kg) given (i) intraperitoneally or (ii) intragastrically immediately after insulin. Controls received simultaneously an equivolume of saline (5 ml/kg). Those rats that survived till the 180 minutes after over-dose application were further assessed. Interestingly, pentadecapeptide BPC 157, as an antiulcer peptide, may besides stomach ulcer consistently counteract all insulin disturbances and fatal outcome. BPC 157 rats showed no fatal outcome, they were mostly without hypoglycemic seizures with apparently higher blood glucose levels (glycogen was still present in hepatocytes), less liver pathology (i.e., normal liver weight, less fatty liver), decreased ALT, AST and amylase serum values, markedly less damaged neurons in brain and they only occasionally had small gastric lesions. BPC 157 rats exhibited mostly only dot-like calcium presentation. In conclusion, the success of BPC 157 therapy may indicate a likely role of BPC 157 in insulin controlling and BPC 157 may influence one or more causative process(es) after excessive insulin application.

  15. Two-dimensional electrophoresis of liver proteins: characterization of a drug-induced hepatomegaly in rats.

    PubMed

    Newsholme, S J; Maleeff, B F; Steiner, S; Anderson, N L; Schwartz, L W

    2000-06-01

    Two-dimensional electrophoresis (2-DE) of liver proteins was applied to further characterize an unusual drug-induced increase in hepatocellular rough endoplasmic reticulum (RER) in Sprague-Dawley rats given a substituted pyrimidine derivative. Absolute liver weights of drug-treated rats (9.9 +/- 0.4 g) increased above vehicle-treated controls (7.2 +/- 0.2 g) by 37%. Light microscopy revealed diffuse granular basophilia of the hepatocellular cytoplasm, uncharacteristic of hepatocytes and suggested cells rich in ribosomes, which was confirmed by electron microscopy. Immunostaining for cell proliferation, viz., 5-bromo-2'-deoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA), indicated marked hepatocellular proliferative activity. 2-DE of solubilized liver using an ISO-DALT gel system indicated significant (p<0.001) quantitative changes in at least 17 liver proteins (12 increased, 5 decreased) compared to controls. The protein with the largest increase was homologous to acute-phase reactant, contrapsin-like protein inhibitor-6. Other markedly upregulated proteins were methionine adenosyltransferase, a catalyst in methionine/ATP metabolism and mitochondrial HMG-CoA synthase, involved in cholesterol synthesis. The complementary strategies of 2-DE coupled either with database spot mapping or protein isolation and amino acid sequencing successfully identified a subset of proteins from xenobiotic-damaged rodent livers, the expression of which differed from controls. However, the current bioinformatics platform for rodent hepatic proteins and limited knowledge of specific protein functionality restricted application of this proteomics profile to further define a mechanistic basis for this unusual hepatotoxicity.

  16. Hypophosphatemic Rickets: Presenting Features of Fanconi—Bickel Syndrome

    PubMed Central

    Roy, Mahua; Bose, K.; Paul, D. K.; Anand, Puja

    2011-01-01

    Fanconi-Bickel Syndrome (FBS) is a rare variety of glycogen storage disease (GSD). Characterized by massive hepatomegaly due to glycogen accumulation, severe hypophosphatemic rickets, and marked growth retardation due to proximal renal tubular dysfunction. We report a young boy presented as hypophosphatemic rickets with hepatomegaly and subsequently diagnosed as FBS. PMID:22937383

  17. Genetics Home Reference: glycogen storage disease type III

    MedlinePlus

    ... people with GSDIIIa have a weakened heart muscle (cardiomyopathy), but affected individuals usually do not experience heart ... Hepatomegaly Health Topic: Carbohydrate Metabolism Disorders Health Topic: Cardiomyopathy Health Topic: Cirrhosis Health Topic: Liver Diseases Health ...

  18. 20 CFR Appendix to Subpart D of... - Unknown Title

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... right-sided congestive failure as evidenced by peripheral edema and liver enlargement, with: (A) Right... hepatomegaly or peripheral or pulmonary edema, with: (A) Cardio-thoracic ratio of 55 percent or greater,...

  19. 20 CFR Appendix to Subpart D of... - Unknown Title

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... right-sided congestive failure as evidenced by peripheral edema and liver enlargement, with: (A) Right... hepatomegaly or peripheral or pulmonary edema, with: (A) Cardio-thoracic ratio of 55 percent or greater,...

  20. Genetics Home Reference: D-bifunctional protein deficiency

    MedlinePlus

    ... unusually large space between the bones of the skull (fontanel). An enlarged liver (hepatomegaly) occurs in about ... Accessibility FOIA Viewers & Players U.S. Department of Health & Human Services National Institutes of Health National Library of ...

  1. Wilson disease

    MedlinePlus

    ... muscle control, muscle tremors, loss of thinking and IQ, loss of memory, and confusion (delirium or dementia) Liver or spleen disorders (including hepatomegaly and splenomegaly ) Lab tests may include: Complete blood count ( CBC ) Serum ceruloplasmin ...

  2. COMPARISON OF BIOMARKERS IN WORKERS EXPOSED TO 2,4,6-TRINITROTOLUENE

    EPA Science Inventory

    2,4,6-Trinitrotoluene (TNT) is an important occupational and environmental pollutant. In TNT-exposed humans, the notable toxic manifestations have included aplastic anemia, toxic hepatitis, cataracts, hepatomegaly, and liver cancer. Therefore, we developed methods to biomonitor w...

  3. Genetics Home Reference: carnitine-acylcarnitine translocase deficiency

    MedlinePlus

    ... People with CACT deficiency also usually have excess ammonia in the blood (hyperammonemia), an enlarged liver (hepatomegaly), ... Information & Resources MedlinePlus (3 links) Health Topic: Lipid Metabolism Disorders Health Topic: Mitochondrial Diseases Health Topic: Newborn ...

  4. Genetics Home Reference: dihydrolipoamide dehydrogenase deficiency

    MedlinePlus

    ... cardiomyopathy). Other features of this condition include excess ammonia in the blood (hyperammonemia), a buildup of molecules ... Hepatomegaly Encyclopedia: Lactic Acidosis Health Topic: Amino Acid Metabolism Disorders Health Topic: Genetic Brain Disorders Genetic and ...

  5. Abdominal mass

    MedlinePlus

    ... lumpy mass in the right upper quadrant. Liver enlargement (hepatomegaly) can cause a firm, irregular mass below ... the kidney (usually only affects one kidney). Spleen enlargement (splenomegaly) can sometimes be felt in the left- ...

  6. Haemangioma-thrombocytopenia syndrome--a case report.

    PubMed

    Liam, C K; Nuruddin, R

    1989-09-01

    A 29 year old Chinese female who presented with spontaneous purpura, was found to have gross hepatomegaly and thrombocytopenia. The thrombocytopenia responded to steroid therapy but relapsed when the dose of steroid was tapered down. Subsequent investigations revealed that the hepatomegaly was due to a large haemangioma of her liver. For symptomatic hepatic haemangioma, surgical excision is the treatment of choice; this was refused by the patient.

  7. 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

  8. Glycogenic hepatopathy, an underdiagnosed cause of relapsing hepatitis in uncontrolled type 1 diabetes mellitus

    PubMed Central

    Sarkhy, Ahmed A. Al; Zaidi, Zafar A.; Babiker, Amir M.

    2017-01-01

    Glycogenic hepatopathy is a rare condition that causes significant hepatomegaly and elevated liver enzyme levels in uncontrolled type 1 diabetic patients. It develops due to excessive accumulation of glycogen in the hepatocytes. It is typically reversible with good glycemic control and rarely progresses to mild fibrosis, but not cirrhosis. PMID:28042636

  9. GADD45ß, an anti-tumor gene, inhibits avian leukosis virus subgroup J replication in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian leukosis virus subgroup J (ALV-J) is a retrovirus that induces neoplasia, hepatomegaly, immunosuppression and poor performance in chickens. The tumorigenic and pathogenic mechanisms of ALV-J remain a hot topic. To explore anti-tumor genes that confer genetic resistance to ALV-J infection in ch...

  10. Feline porphyria associated with anemia, severe hepatic disease, and renal calculi

    PubMed Central

    Schnier, Jonathan J.; Hanna, Paul

    2010-01-01

    A 13-year-old, neutered male domestic cat presented with signs of weight loss, anemia, and hepatomegaly. Pathognomonic signs of porphyria were identified. Charcoal-like renal calculi and severe liver changes were observed, neither of which has been previously reported in association with feline porphyria. PMID:21197209

  11. Stent Angioplasty of Closed Mesocaval Shunt in a Patient with Budd-Chiari Syndrome

    SciTech Connect

    Sancak, Tanzer; Karagulle, Ayse Tuba; Bilgic, Sadik; Sanlidilek, Umman; Yerdel, Mehmet Ali

    2002-08-15

    Budd-Chiari syndrome (BCS) is an uncommon disorder caused by hepatic venous outflow obstruction. It is characterized by ascites, hepatomegaly and abdominal pain. Percutaneous intervention shave recently been used for the treatment of BCS. We present a case of BCS with a closed mesocaval shunt which was reopened with a self-expandable metallic stent.

  12. The Effects of Scavenging on Waste Methoxyflurane Concentrations in Veterinary Operating Room Air

    DTIC Science & Technology

    1981-01-01

    an increased percentage of fetal anomalies 1 have occurred following exposure of chick eggs to methoxyflurane (28). High subanesthetic concentrations...of methoxyflurane have also caused fetal growth retardation in rats (25). Hepatomegaly and histologic changes of the liver have been demonstrated in

  13. Genetics Home Reference: Pompe disease

    MedlinePlus

    ... muscle tone (hypotonia), an enlarged liver (hepatomegaly), and heart defects. Affected infants may also fail to gain weight and grow at the expected rate (failure to thrive) and have breathing problems. If untreated, this form ... leads to death from heart failure in the first year of life. The ...

  14. Fanconi-Bickel syndrome--two cases report.

    PubMed

    Sotelo, Norberto; García, Ramiro; Tostado, René; Dhanakotti, Nagasharmila

    2008-01-01

    A one year eight month old male child and his nine month old female sibling were presented with Growth retardation, abdominal distension, doll-like faces, hepatomegaly, phosphaturia, proximal renal tubular dysfunction. The elder sibling also presented with glucosuria, hyperglycemia, hypoinsulinemia. The younger one later presented with galactosemia. Biopsy of liver on these two patients revealed the accumulation of glycogen in hepatocytes.

  15. A rare cause of right upper quadrant pain in a 17-year-old female.

    PubMed

    Nwankwo, Nwabundo; Barbaryan, Aram; Ali, Alaa M; Mirrakhimov, Aibek E

    2013-01-01

    A 17-year-old Hispanic female presented to our hospital with complaints of right upper quadrant abdominal pain, vomiting, and fever. Physical exam was positive for hepatomegaly. Abdominal computed tomography showed multiple hypoechoic liver masses. Liver biopsy was done, which was diagnostic for hepatic epithelioid hemangioendothelioma.

  16. Feline porphyria associated with anemia, severe hepatic disease, and renal calculi.

    PubMed

    Schnier, Jonathan J; Hanna, Paul

    2010-10-01

    A 13-year-old, neutered male domestic cat presented with signs of weight loss, anemia, and hepatomegaly. Pathognomonic signs of porphyria were identified. Charcoal-like renal calculi and severe liver changes were observed, neither of which has been previously reported in association with feline porphyria.

  17. CYP1A2 IS NOT REQUIRED FOR 2, 3, 7, 8-TETRACHLORODIBENZO-P-DIOXIN-INDUCED IMMUNOSUPPRESSION

    EPA Science Inventory

    ABSTRACT
    One of the most sensitive and reproducible immunotoxic endpoints of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) exposure is suppression of the antibody response to sheep red blood cells (SRBCs) in mice. Immunosuppression occurs in concert with hepatomegaly and associ...

  18. Unusual presentation of tuberculosis in an elderly male: a case report.

    PubMed

    Kandel, Ramesh; Bhattarai, Bhawana; Maharjan, Santosh

    2015-01-01

    Tuberculous liver abscess is an extremely rare condition, even in tuberculosis endemic countries. A 68-year-old male presented with 2 months of fever, significant weight loss, and hepatomegaly. Ultrasonography revealed a right hepatic lobe abscess. Guided aspiration of the fluid showed tubercular bacilli. He had no evidence of active Tuberculosis elsewhere.

  19. Unusual presentation of tuberculosis in an elderly male: a case report

    PubMed Central

    Kandel, Ramesh; Bhattarai, Bhawana; Maharjan, Santosh

    2015-01-01

    Key Clinical Message Tuberculous liver abscess is an extremely rare condition, even in tuberculosis endemic countries. A 68-year-old male presented with 2 months of fever, significant weight loss, and hepatomegaly. Ultrasonography revealed a right hepatic lobe abscess. Guided aspiration of the fluid showed tubercular bacilli. He had no evidence of active Tuberculosis elsewhere. PMID:25678973

  20. Aggressive therapy improves cirrhosis in glycogen storage disease type IX.

    PubMed

    Tsilianidis, Laurie A; Fiske, Laurie M; Siegel, Sara; Lumpkin, Chris; Hoyt, Kate; Wasserstein, Melissa; Weinstein, David A

    2013-06-01

    Glycogen storage disease type IX (GSD IX) is described as a benign condition that often does not require treatment. Most patients with the disease are thought to outgrow the childhood manifestations, which include hepatomegaly, poor growth, and ketosis with or without hypoglycemia. Long term complications including fibrosis and cirrhosis have seldom been reported in the most common subtype, GSD IXα. We present two cases of children with GSD IXα who had fibrosis at the time of diagnosis in addition to the commonly reported disease manifestations. Structured therapy with frequent doses of uncooked cornstarch and protein supplementation was initiated, and both children responded with improved growth velocity, increased energy, decreased hepatomegaly and improved well-being. Additionally, radiographic features of fibrosis improved. We propose that GSD IXα is not a benign condition. Even in patients with a less severe presentation, consideration of a structured treatment regimen to improve quality of life appears warranted.

  1. Technetium-99m-labeled red blood cells in the evaluation of hemangiomas of the liver in infants and children

    SciTech Connect

    Miller, J.H.

    1987-09-01

    The vascular origin lesions of the liver (capillary hemangioma/infantile hemangioendothelioma) that present in infancy or early childhood often have a typical clinical picture of hepatomegaly and congestive heart failure. These lesions rarely present as asymptomatic hepatomegaly, simulating a primary hepatic malignancy. These lesions may also simulate a primary or secondary hepatic malignancy on cross-sectional imaging or angiography. Scintigraphic evaluations with technetium-99m-labeled red blood cells offers an accurate method of identification of these lesions, and allows differentiation from other common primary or secondary hepatic masses in infancy or childhood. This scintigraphic method may also be used to follow these patients after medical, radiation, or embolization therapy. Experience with seven patients with these tumors is reported and compared with eight children with other primary or secondary liver tumors also evaluated by this method.

  2. A case of leptospirosis simulating colon cancer with liver metastases

    PubMed Central

    Granito, Alessandro; Ballardini, Giorgio; Fusconi, Marco; Volta, Umberto; Muratori, Paolo; Sambri, Vittorio; Battista, Giuseppe; Bianchi, Francesco B.

    2004-01-01

    We report a case of a 61-year-old man who presented with fatigue, abdominal pain and hepatomegaly. Computed tomography (CT) of the abdomen showed hepatomegaly and multiple hepatic lesions highly suggestive of metastatic diseases. Due to the endoscopic finding of colon ulcer, colon cancer with liver metastases was suspected. Biochemically a slight increase of transaminases, alkaline phosphatase and gammaglutamyl transpeptidase were present; α - fetoprotein, carcinoembryogenic antigen and carbohydrate 19-9 antigen serum levels were normal. Laboratory and instrumental investigations, including colon and liver biopsies revealed no signs of malignancy. In the light of spontaneous improvement of symptoms and CT findings, his personal history was revaluated revealing direct contact with pigs and their tissues. Diagnosis of leptospirosis was considered and confirmed by detection of an elevated titer of antibodies to leptospira. After two mo, biochemical data, CT and colonoscopy were totally normal. PMID:15285043

  3. [POEMS syndrome: role and value of interleukin-6].

    PubMed

    Andrès, E; Courouau, F; Kaltenbach, G; Maloisel, F; Imler, M

    1996-01-01

    POEMS syndrome is a systemic disorder with peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. The association of POEMS syndrome with lympho-proliferative disorder is very commun. The pathogenesis remains poorly understood but implication of cytokines (interleukins 1 and 6) is suspected. We report a case of a classic POEMS syndrome (with polyneuropathy, hepatomegaly, diabetes melitus, hyperpigmentation, monoclonal IgG lambda, anasarca and solitary plasmocytoma), associated with high serum levels of interleukin 6.

  4. Hepatobiliary Ultrasonographic Abnormalities in Adult Patients with Sickle Cell Anaemia in Steady State in Ile-Ife, Nigeria

    PubMed Central

    Oguntoye, Oluwatosin O.; Ndububa, Dennis A.; Yusuf, Musah; Bolarinwa, Rahman A.; Ayoola, Oluwagbemiga O.

    2017-01-01

    Summary Background Sickle cell anaemia (SCA) is associated with structural manifestations in the hepatobiliary axis. This study aimed to investigate the hepatobiliary ultrasonographic abnormalities in adult patients with sickle cell anaemia in steady state attending the Haematology clinic of a federal tertiary health institution in Ile-Ife, Nigeria. Material/Methods Basic demographic data as well as right upper abdominal quadrant ultrasonography of 50 consecutive sickle cell anaemia patients were compared with those of 50 age- and sex-matched subjects with HbAA as controls. Results Each of the study groups (patients and controls) comprised of 21 (42%) males and 29 (58%) females. The age range of the patients was 18–45 years with a mean (±SD) of 27.6±7.607 years, while that of the controls was 21–43 years with a mean (±SD) of 28.0±5.079 years (p=0.746). Amongst the patients, 32 (64%) had hepatomegaly, 15 (30%) cholelithiasis and 3 (6%) biliary sludge. Fourteen (28%) of the patients had normal hepatobiliary ultrasound findings. In the control group, one (2%) person had cholelithiasis, one (2%) biliary sludge, one (2%) fatty liver and none hepatomegaly. Forty-seven (94%) of the controls had normal hepatobiliary ultrasound findings. There was a statistically significant difference in the prevalence of hepatomegaly and cholelithiasis between the patients and controls (p value <0.001 for both comparisons). Conclusions In this study, hepatomegaly, cholelithiasis and biliary sludge were the most common hepatobiliary ultrasound findings in patients with sickle cell anaemia. Ultrasonography is a useful tool for assessing hepatobiliary abnormalities in patients with sickle cell anaemia. PMID:28105246

  5. Acute disseminated toxoplasmosis in a juvenile cheetah (Acinonyx jubatus).

    PubMed

    Lloyd, Christopher; Stidworthy, Mark F

    2007-09-01

    A juvenile cheetah (Acinonyx jubatus) died with rapidly progressive pyrexia, tachypnea, abdominal effusion, and hepatomegaly. Postmortem examination revealed lesions consistent with acute disseminated infection with Toxoplasma gondii. The presence of this organism was confirmed in multiple organs by immunohistochemistry and polymerase chain reaction. To the best of our knowledge, we propose this to be the first reported case of primary acute disseminated toxoplasmosis in a cheetah.

  6. The left-sided pancreas

    SciTech Connect

    Dunn, G.D.; Gibson, R.N.

    1986-06-01

    Ultrasonography (US) performed in nine patients (two with pancreatic carcinoma, one with hepatomegaly), six with no relevant abdominal disease) showed the pancreas to lie wholly to the left of the aorta. This not uncommon location may give rise to difficulty in demonstrating the pancreas on real-time US scans. The superior mesenteric vessels and splenic vein remain useful land-marks for locating the head of the pancreas in this position.

  7. Keratosis follicularis spinulosa decalvans. An infant with failure to thrive, deafness, and recurrent infections.

    PubMed

    Britton, H; Lustig, J; Thompson, B J; Meyer, S; Esterly, N B

    1978-05-01

    A 10-month-old male infant had keratosis follicularis spinulosa decalvans, an X-linked dominant disorder. His cutaneous abnormalities consisted of generalized hyperkeratosis, spiny follicular papular lesions, universal alopecia, and hypoplastic nails. Ocular changes characteristic of the disease were also present. Unusual findings included deafness, failure to thrive, predisposition to bacterial infections without demonstrable immune defect, and transient hepatomegaly with abnormal liver function studies.

  8. Comparison of the efficacy of cardamom (Elettaria cardamomum) with pioglitazone on dexamethasone-induced hepatic steatosis, dyslipidemia, and hyperglycemia in albino rats.

    PubMed

    Nitasha Bhat, G M; Nayak, Nagendra; Vinodraj, K; Chandralekha, N; Mathai, Paul; Cherian, J

    2015-01-01

    To evaluate the efficacy of cardamom with pioglitazone on dexamethasone-induced hepatic steatosis, dyslipidemia, and hyperglycemia in albino rats. There were four groups of 6 rats each. First group received dexamethasone alone in a dose of 8 mg/kg intraperitoneally for 6 days to induce metabolic changes and considered as dexamethasone control. Second group received cardamom suspension 1 g/kg/10 mL of 2% gum acacia orally 6 days before dexamethasone and 6 days during dexamethasone administration. Third group received pioglitazone 45 mg/kg orally 6 days before dexamethasone and 6 days during dexamethasone administration. Fourth group did not receive any medication and was considered as normal control. Fasting blood sugar, lipid profile, blood sugar 2 h after glucose load, liver weight, liver volume were recorded, and histopathological analysis was done. The effects of cardamom were compared with that of pioglitazone. Dexamethasone caused hepatomegaly, dyslipidemia and hyperglycemia. Both pioglitazone and cardamom significantly reduced hepatomegaly, dyslipidemia, and hyperglycemia (P < 0.01). Reduction of blood sugar levels after glucose load was significant with pioglitazone in comparison to cardamom (P < 0.01). Cardamom has comparable efficacy to pioglitazone in preventing dexamethasone-induced hepatomegaly, dyslipidemia, and fasting hyperglycemia.

  9. IGF-II induced by hepatitis B virus X protein regulates EMT via SUMO mediated loss of E-cadherin in mice

    PubMed Central

    Ha, Hye-Lin; Kwon, Taeho; Bak, In Seon; Erikson, Raymond L.; Kim, Bo Yeon; Yu, Dae-Yeul

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer mortality. Prognosis of this disease largely depends on its stage. An Enlarged liver, due to dysplasia, may be a critical point in the multi-step progression to HCC. The mechanism underlying hepatomegaly in human and mouse models are poorly understood. We previously reported we observed enlarged liver in hepatitis B virus X protein (HBx) expressing mice (HBx mice). Here we identify the critical role of HBx induced IGF-II in hepatomegaly in mice and abnormal cell growth in human hepatoma cells. We found that HBx induced IGF-II is essential to induce epithelial-mesenchymal transition (EMT) through loss of E-cadherin. In mouse liver, loss of E-cadherin was mediated by post-translational regulation, at least in part, by protease and SUMOylation not by transcriptional regulation. In contrast, in hepatoma cell line (HepG2 cells) Akt signal pathway controls the mRNA expression level of EMT-related transcription factors, especially Twist, in addition to post- translational modification through SUMOylation. Thus, IGF-II-mediated loss of E-cadherin is central in developing hepatomegaly in mice and abnormal cell growth in the hepatoma cell line. HBx induced IGF-II represents a potential biomarker, which is also a therapeutic target in HCC. PMID:27486970

  10. A genetic screen in zebrafish identifies the mutants vps18, nf2 and foie gras as models of liver disease.

    PubMed

    Sadler, Kirsten C; Amsterdam, Adam; Soroka, Carol; Boyer, James; Hopkins, Nancy

    2005-08-01

    Hepatomegaly is a sign of many liver disorders. To identify zebrafish mutants to serve as models for hepatic pathologies, we screened for hepatomegaly at day 5 of embryogenesis in 297 zebrafish lines bearing mutations in genes that are essential for embryonic development. Seven mutants were identified, and three have phenotypes resembling different liver diseases. Mutation of the class C vacuolar protein sorting gene vps18 results in hepatomegaly associated with large, vesicle-filled hepatocytes, which we attribute to the failure of endosomal-lysosomal trafficking. Additionally, these mutants develop defects in the bile canaliculi and have marked biliary paucity, suggesting that vps18 also functions to traffic vesicles to the hepatocyte apical membrane and may play a role in the development of the intrahepatic biliary tree. Similar findings have been reported for individuals with arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome, which is due to mutation of another class C vps gene. A second mutant, resulting from disruption of the tumor suppressor gene nf2, develops extrahepatic choledochal cysts in the common bile duct, suggesting that this gene regulates division of biliary cells during development and that nf2 may play a role in the hyperplastic tendencies observed in biliary cells in individuals with choledochal cysts. The third mutant is in the novel gene foie gras, which develops large, lipid-filled hepatocytes, resembling those in individuals with fatty liver disease. These mutants illustrate the utility of zebrafish as a model for studying liver development and disease, and provide valuable tools for investigating the molecular pathogenesis of congenital biliary disorders and fatty liver disease.

  11. Hypertransaminasemia and fatal lung disease: a case report

    PubMed Central

    2013-01-01

    Glycogenosis type II (Pompe disease) is a rare autosomal recessive genetic disorder caused by mutations in the gene encoding the lysosomal enzyme acid α-glucosidase. The classic form is characterized by severe cardiac involvement, generalized hypotonia and exitus early in life. Presenting symptoms and signs of the disease may be neglected or underestimated, thus delaying the diagnosis. Respiratory manifestations mainly occur because of respiratory muscle weakness. However, additional mechanisms can favor the development of pulmonary complications that result in fatal respiratory failure. We herein describe a case of an infant with glycogenosis type II presenting with hepatomegaly and hypertransaminasemia, who rapidly developed fatal lung disease. PMID:23391190

  12. Lambda light chain myeloma presenting as nodular hepatic lesion: a clinical rarity.

    PubMed

    Pal, Santanu; Chattopadhyay, Bitoti; Chatterjee, Atri; Bhattacharya, Biswamit

    2014-01-01

    We report a case of a 63-year-old lady presenting with pain in the right hypochondrium, jaundice, anorexia, and firm tender hepatomegaly with remarkably high serum alkaline phosphatase. Abdominal ultrasonography revealed a hypoechoic solid space-occupying lesion in right lobe of liver which was cytologically diagnosed as hepatic plasmacytoma. Serum and urine immunofixation electrophoresis, serum free light chain ratio, and bone marrow examination further confirmed the presence of lambda light chain multiple myeloma in the background. The patient achieved complete remission after four cycles of induction therapy with thalidomide and dexamethasone protocol and consolidated with further four cycles of the same regimen.

  13. Fasciolopsiasis in a five year old girl.

    PubMed

    Naher, B S; Shahid, A T; Khan, K A; Nargis, S; Hoque, M M

    2013-04-01

    A 5 year old girl hailing from Keraniganj, presented with the complaints of fever, periumbilical pain and vomiting. In vomitus, Fasciolopsis buski worm in adult form was identified by naked eye examination. In stool, ova of Fasciolopsis buski were also observed under microscope. Clinically she was pale and had hepatomegaly. Microcytic hypochromic anaemia with normal liver function test was found on lab investigation. She was diagnosed as a case of Fasciolopsiasis and treated with Praziquantel and on follow up visit she was found to be free of symptom.

  14. [Hemophagocytic syndrome associated to hepatitis].

    PubMed

    Sandoval-Ramírez, Eunice; Camacho-Meza, Ignacio; Eduardo-Solís, Nery; Plascencia-Tabares, Oswaldo; Navarro-Olivos, Efraín; Ortiz-Aldana, Francisco Ignacio

    2016-01-01

    Hemophagocytic syndrome is characterized by increased proliferation and activation of antigen presenting cells (histiocytes) in bone marrow and other organs of the reticuloendothelial system as well as CD8+ T cells that threatens life of patients. The predominant clinical manifestations such as fever, cytopenia, hepatitis, coagulopathy, neurological symptoms and multiple organ failure are related to systemic inflammation. We report the case of an infant who started with jaundice, abdominal pain, vomiting and malaise, at admission, hepatomegaly, splenomegaly and biochemically with features suggestive of hepatocellular inflammation and progressive cholestasis with poor outcome, it was added persistent fever, seizures, anemia, thrombocytopenia, leukopenia, elevated ferritin and hypertriglyceridemia integrating hemophagocytic syndrome with fatal outcome despite immunosuppressive therapy.

  15. [Neonatal dengue in Peru: a case report].

    PubMed

    Silva Delgado, Hermann; Ruiz Ríos, Juan Carlo; Vela Barbarán, Erick Leray; Rengifo Del Aguila, Deicy; García M, María; Rodríguez Benavides, Luis; Mendoza-Ticona, Alberto

    2011-03-01

    We present the case of a full-term female newborn, whose mother died seven days postpartum from multi-organ failure due to severe dengue confirmed by NS1 antigen detection and positive IgM. The newborn did not have any complication, but at the fourth day of life she developed fever, jaundice, signs of plasma leakage, thrombocytopenia, hepatomegaly, ascitis, and others signs of systemic inflammation response syndrome. She fully recovered with supportive treatment. The RT-PCR test of a peripheral blood sample revealed a positive result for the dengue virus serotype 2, confirming the first case of neonatal dengue reported in Peru.

  16. Autoimmune Lymphoproliferative Syndrome (ALPS) in a Boy with Massive Lymphadenopathy.

    PubMed

    Kianifar, Hamid Reza; Khalesi, Maryam; Farid, Reza; Badiee, Zahra; Rastin, Maryam; Ahanchian, Hamid

    2010-09-01

    Autoimmune lymphoproliferative syndrome (ALPS) is an uncommon nonmalignant lymphoproliferative disease which is characterized by chronic, persistent or recurrent lymphadenopathy, splenomegaly, hepatomegaly, immune cytopenia , hypergammaglobinemia and increased risk of lymphoma. We report a 2-year old boy with hepatosplenomegaly as first presentation. Petechial and purpuric rashes with massive cervical lymphadenopathies developed 10 months later.In laboratory tests anemia, thrombocytopenia and hypergammaglobinemia were observed. According to flocytometry increased double negative T cells and by apoptosis assay decrease apoptosis of lymphocytes accompanied clinical manifestations, thus diagnosis of ALPS was established. In conclusion; in all patients with massive lymphadenopathy and hepatosplenomegay; especially with cytopenia; ALPS should be considered.

  17. [Multiple myeloma (IgG-kappa) infiltrating central nervous system, lymph nodes, liver, and kidneys, and with elevation of IgE].

    PubMed

    Toyota, Shigeo; Nakamura, Norihiko; Dan, Kazuo

    2004-05-01

    A 63-year-old man was admitted because of general malaise, fever, headache, generalized lymphadenopathy and hepatomegaly in July 2002. He was diagnosed as having multiple myeloma (MM) (IgG-kappa type) with atypical plasma cells in the bone marrow, lymph nodes and cerebrospinal fluid. Systemic and intrathecal chemotherapy were effective. Because of an increase of polyclonal IgE, electrophoretic patterns revealed an M-peak which was not as sharp as that in IgG myeloma. IgE production is not impaired by the pathologic process in MM patients.

  18. Leber's congenital amaurosis associated with hyperthreoninemia.

    PubMed

    Hayasaka, S; Hara, S; Mizuno, K; Narisawa, K; Tada, K

    1986-04-15

    Two siblings had Leber's congenital amaurosis. The girl (Patient 1) showed blindness shortly after birth, absent pupillary light reflex, and multiple round, white spots in both fundi. Her serum threonine level was increased (2.0 to 5.3 mg/dl; normal, 0.78 to 1.82 mg/dl). She died of massive pericardial effusion four months after birth. Her brother (Patient 2) was nearly blind shortly after birth. He had a poor pupillary light reflex and a nearly extinguished electroretinographic response. He also had hyperthreoninemia, hyperthreoninuria, hepatomegaly, and mental and physical retardation. We suspect a close relationship between hyperthreoninemia and Leber's congenital amaurosis in these siblings.

  19. Hyperimmunoglobulinemia D and periodic fever syndrome; treatment with etanercept and follow-up.

    PubMed

    Topaloğlu, Rezan; Ayaz, Nuray Aktay; Waterham, Hans R; Yüce, Aysel; Gumruk, Fatma; Sanal, Ozden

    2008-10-01

    The hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) is an autoinflammatory syndrome. It is caused by the mutations of the mevalonate kinase gene. There is no consensus for specific therapy of HIDS, but there are some case reports and studies in regards to its treatment with drugs like colchicine, steroids, nonsteroid anti-inflammatory drugs, simvastatin, anakinra, thalidomide, and etanercept. We are reporting a case evaluated for the complaints of abdominal pain and febrile episodes with massive hepatomegaly, not common finding on physical examination, its treatment with etanercept, and long-term follow-up.

  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. Spotted black snake (Pseudechis guttatus) envenomation in a maned wolf (Chrysocyon brachyurus).

    PubMed

    Portas, Timothy J; Montali, Richard J

    2007-09-01

    Envenomation by a spotted black snake (Pseudechis guttatus), following multiple bites on the buccal mucosa of a captive maned wolf (Chrysocyon brachyurus), caused the animal's collapse, hemolysis, rhabdomyolysis, local tissue necrosis, hepatic and renal failure, and subsequent death. The wolf died despite intensive supportive care including antivenom administration, fluid support, and a blood transfusion. Gross necropsy findings included myocardial and intestinal hemorrhage, pulmonary congestion, hepatomegaly, and splenomegaly. Microscopic examination of formalin-fixed tissues demonstrated pulmonary and abdominal visceral hemorrhage, acute nephrosis with casts, multifocal hepatic necrosis, and splenic congestion.

  2. The first case of leptospirosis in the Zadar area.

    PubMed

    Dzelalija, B; Ruzić, E; Kasun, D

    2000-01-01

    In September 1999, a 56-year-old butcher was admitted to the General Hospital in Zadar because of fever, headache, severe pain in the calf muscles and thighs, conjunctivitis, rash, hepatomegaly and jaundice. The initial diagnosis was septic shock, and the patient was admitted to the internal medicine ward. Microscopic agglutination test showed a fourfold rise of antibodies to Leptospira sejroe in the three serum samples. These serologic findings and laboratory findings of leukocytosis, thrombocytopenia, increased serum aminotransferases, blood urea nitrogen and creatinine, proteinuria and leukocyturia indicated that Leptospira sejroe was the etiologic agent of the disease in the patient presented.

  3. Progeria with post-streptococcal glomerulonephritis: a rare case report with differential diagnosis.

    PubMed

    Sebastian, Alphy A; Ahsan, Auswaf K

    2013-02-01

    Hutchinson-Gilford progeria syndrome is a rare autosomal dominant disorder associated with skin fragility. It is characterized by craniofacial disproportion, delayed dentition, micrognathia, and plucked bird appearance. The genetic defect is mainly de nova mutation in the lamin A gene. This report describes a 16-year-old patient with classical features of progeria along with post-streptococcal glomerulonephritis. The symptoms of hepatomegaly were also present in the patient. The differential diagnoses of this lesion are also discussed in detail in this literature.

  4. Computed tomography of the spleen and liver in sickle cell disease

    SciTech Connect

    Magid, D.; Fishman, E.K.; Siegelman, S.S.

    1984-08-01

    The spleen was assessed in 10 patients with sickle cell disease studied with computed tomography (CT) for abdominal pain and/or unexplained fever. Patients with homozygous sickle cell anemia were found to have small, densely calcified spleens with occasional low-density infarcts. Five of six had hepatomegaly, and there was one case each of hepatic abscess, infarcts, and hemochromatosis. All patients with heterozygous sickle cell disease were found to have splenomegaly, with a variety of findings including acute hemorrhage, acute and chronic infarcts, rupture, and possible sequestration. It was concluded that CT is useful for evaluating the status of the spleen and liver in symptomatic patients with sickle cell disease.

  5. [Melioidosis: report of the first case in a northern state of México].

    PubMed

    Boroel-Cervantes, Carlos; Ibarra-Valdez, Mónica; Miranda-Pacheco, Sandra; Sánchez-Camarena, Elías; Wolburgth-Franco, Tamara; Ortìz-González, Andrés; Domínguez-Ríos, José Luis

    2017-01-01

    The melioidosis, is an infection caused by Burkhordelia pseudomallei that comprises heterogeneous clinical syndromes with acute or chronic evolution. The objective of this article is to report a case with unusual presentation and outside the known epidemiological context. We present the case of a 48-year-old man who came to our hospital with fever and a history of an abscess in the right subscapular region, physical examination showed hepatomegaly, splenomegaly, fever, without pulmonary symptoms. Within study it reveal multiple abscesses in liver and spleen, requiring surgical exploration and antibiotics (meropenem/vancomycin). Blood cultures reveal Burkhordelia pseudomallei adding trimethoprim/sulfamethoxazole with resolution of symptoms.

  6. Laparoscopic grasper for intramedullary biopsy: a technique to improve tissue sampling.

    PubMed

    Xia, Zhan; Takano, Angela Maria; Sittampalam, Kesavan; Howe, Tet Sen

    2014-08-01

    Fluorodeoxyglucose (FDG) hepatic superscan refers to the diffuse intense uptake of 18F-FDG in the liver on positron emission tomography (PET), with reduced physiological activity in the brain and heart. The common causes include lymphoma and metastasis. In this case report, we describe the imaging features of tuberculosis as a rare cause of FDG hepatic superscan. PET imaging may be the only clue to a diagnosis of hepatic tuberculosis, as other imaging modalities may demonstrate only nonspecific hepatomegaly. It is important to consider this entity in the differential diagnosis of patients presenting with FDG hepatic superscan and proceed with liver biopsy for a definitive diagnosis.

  7. A Rare Case of Persistent Lactic Acidosis in the ICU: Glycogenic Hepatopathy and Mauriac Syndrome

    PubMed Central

    Alvarez, George F.

    2016-01-01

    Mauriac syndrome is a rare disorder that can present with the single feature of glycogenic hepatopathy in children and adults with poorly controlled diabetes mellitus. An often underrecognized finding of glycogenic hepatopathy is lactic acidosis and hyperlactatemia. Primary treatment of glycogenic hepatopathy is improved long-term blood glucose control. Resolution of symptoms and hepatomegaly will occur with improvement in hemoglobin A1C. We present here a case of a young adult female presenting to the intensive care unit with Mauriac syndrome. This case demonstrates exacerbation of lactic acidosis in a patient with glycogenic hepatopathy treated for diabetic ketoacidosis with high dose insulin and dextrose. PMID:27699071

  8. [Ulcerative colitis and amyloidosis. Presentation of a case and review of the literature].

    PubMed

    Triviño, A; Sánchez Lombraña, J L; Linares, A; Pérez, R; Herrero Zapatero, A; Rodrigo, L

    1992-08-01

    A case of ulcerative colitis associated with secondary amyloidosis in a 62-year-old man who died from septic shock and pneumonia complicating head injury is reported. Amyloid deposition was incidentally found at autopsy. Proteinuria and hepatomegaly discovered a few days before his death were the only signs of amyloidosis. The postmortem examination showed chronic ulcerative colitis (remitting form) with pseudo-polyps and amyloid deposition in the liver, spleen, pancreas, rectum, adrenals and kidneys. Although secondary amyloidosis complicating with Crohn's disease has been frequently reported, amyloidosis associated with ulcerative colitis has been exceptionally described and only 10 cases have been collected from the literature.

  9. [Chronic Budd-Chiari syndrome can cause liver cirrhosis].

    PubMed

    Karlsen, Stine; Nielsen, Dennis Tønner; Grønbæk, Henning

    2012-06-11

    Budd-Chiari syndrome (BCS) is a rare disease defined by congestive hepatopathy with obstruction of the hepatic venous outflow tract. Classical symptoms and signs include ascites, hepatomegaly, abdominal pain and various degrees of liver dysfunction. BCS is predominantly caused by thrombosis, malformations and venous compression. We present a case, in which BCS was the cause of liver cirrhosis complicated with refractory ascites and which can be misinterpreted as hepatocellular carcinoma nodules. The diagnosis was confirmed during the transjugular intrahepatic portosystemic shunt procedure with successful vascular stenting resolving the ascites formation.

  10. Mauriac syndrome: growth failure and type 1 diabetes mellitus.

    PubMed

    Kim, Mimi S; Quintos, J B

    2008-08-01

    Growth failure in Type 1 Diabetes Mellitus (T1DM) can occur for several reasons. Mauriac syndrome is a rare cause of severe growth failure in T1DM. There may be different forms and etiologies involved in Mauriac syndrome. However, there are common features noted in these patients. We have compiled a review of cases reported in English in the last 30 years. With adequate insulin treatment there is reversal of growth failure and hepatomegaly if present. However, overly aggressive insulin delivery could result in rapid deterioration of diabetic retinopathy and nephropathy. Close monitoring of growth and pubertal maturation in children with T1DM is essential.

  11. Integrated imaging of hepatic tumors in childhood. Part II. Benign lesions (congenital, reparative, and inflammatory)

    SciTech Connect

    Miller, J.H.; Greenspan, B.S.

    1985-01-01

    The authors have encountered benign liver masses as frequently as malignant lesions in children with hepatomegaly. Lesions studied included abscesses, cavernous hemangioma/hemangioendothelioma, adenoma of glycogen storage disease, choledochal cysts, focal nodular hyperplasia, cystic hepatoblastoma, and hamartoma. An intergrated imaging protocol involving ultrasound, computed tomography, and scintigraphy proved to be more helpful than any one modality in establishing the benign or malignant nature of a hepatic neoplasm and the type of tumor, which is of particular importance when surgical exploration and/or biopsy is contraindicated.

  12. Capillary bedside blood glucose measurement in neonates: missing a diagnosis of galactosemia.

    PubMed

    Özbek, Mehmet Nuri; Öcal, Murat; Tanrıverdi, Sibel; Baysal, Birsen; Deniz, Ahmet; Öncel, Kahraman; Demirbilek, Hüseyin

    2015-03-01

    A number of factors may lead to inaccuracy in measurement of capillary blood glucose with a glucometer. Measurement of other carbohydrate molecules such as galactose and fructose along with glucose can potentially be a cause of error. We report a newborn patient who was referred to our hospital with conjugated bilirubinemia, hepatomegaly and high capillary blood glucose levels measured with a glucometer. Simultaneous biochemical measurements revealed normal blood glucose levels. Further investigation led to a diagnosis of classical galactosemia. Capillary blood glucose level measured with glucometer also dropped to normal values following cessation of breastfeeding and initiation of feeding with a lactose-free formula.

  13. Galactosemia presenting as recurrent sepsis.

    PubMed

    Rathi, Narendra; Rathi, Akanksha

    2011-12-01

    Galactosemia is a treatable metabolic disorder caused by the deficiency of enzyme galactose-1-phosphate uridyl transferase (GALT) and inherited as an autosomal recessive trait. A case of neonate manifesting with recurrent Escherichia coli sepsis is presented here which turned out to be a classic galactosemia. No other common presenting features were observed in this infant except cataract on slit lamp examination. To the best of our knowledge, there is no case of galactosemia reported in literature which presented with recurrent neonatal sepsis without hepatomegaly, hyperbilirubinemia, bleeding disorder, vomiting, diarrhea, failure to thrive, hypoglycemia, coagulopathy, hemolysis or renal tubular acidosis.

  14. Farber's disease type IV presenting with cholestasis and neonatal liver failure: report of two cases.

    PubMed

    Willis, Asha; Vanhuse, Cherie; Newton, Kimberly P; Wasserstein, Melissa; Morotti, Raffaella A

    2008-01-01

    We report 2 siblings diagnosed with Farber's disease type IV. Type IV is a subtype of Farber's disease that presents in the neonatal period and usually initially lacks the triad of symptoms, including painful and deformed joints, subcutaneous nodules, and hoarse cry, classically seen in the other subtypes. While it is well known that all neonates with type IV present with hepatomegaly, a previously unrecognized presentation is that of cholestatic jaundice and rapidly evolving liver failure. We describe 2 siblings who presented with jaundice in the neonatal period and discuss the clinical data and variation in pathologic findings that should be considered for the diagnosis.

  15. [Congenital tumor-like histiocytosis of the liver with cholestasis in a newborn infant].

    PubMed

    Cermáková, M; Stejskal, J

    1983-05-01

    A female newborn weighing 2650 g had hepatomegaly and deepening obstructive jaundice. She died of hepatic failure three weeks later. There were grayish white periportal histiocytic nodules of 1-2 mm in diameter. Histiocytes contained a small amount of neutral lipids and PAS-positive material. Single elements had multiple nuclei arranged in circles like in Touton cells. Bile duct and ductules were among them. The picture resembled the C variant of Niemann-Pick's disease but basic histochemical tests on fixed tissue excluded this possibility. The pathogenesis of unique disease remained obscure.

  16. Disseminated Coccidioidomycosis with Clinically Evident Splenomegaly in an Immunocompetent Host, First Case Reported in the literature

    PubMed Central

    Bird, Garrett R.; Libke, Robert D.; Billelo, John F.; Parks, Nancy A.; Pollard, John S.

    2009-01-01

    Coccidioidomycosis is a dimorphic fungus endemic to the southwestern United States, Central and South America. We report a case of a previously healthy person who presented with respiratory failure and disseminated Coccidioidomycosis who eventually had a fatal outcome. Coccidioidomycosis, or “Valley Fever” has been called the “great imitator” (1) as it can have a wide variety of clinical presentations. This case is unique as it represents the first described case of an immunocompetent host with rapidly progressing, disseminated coccidioidomycosis with clinically apparent splenomegaly and hepatomegaly. PMID:21264046

  17. Ruptured chordae tendineae of the posterior leaflet of the tricuspid valve as a cause of tricuspid regurgitation following blunt chest trauma.

    PubMed

    dos Santos, J; de Marchi, C H; Bestetti, R B; Corbucci, H A; Pavarino, P R

    2001-01-01

    A 12-year-old boy suffered a blunt chest trauma. Some hours later, a pulsatile bilateral jugular venous distension, a holosystolic murmur heard at the low parasternal border and hepatomegaly were observed. On echocardiography, ruptured chordae tendineae of the posterior leaflet of the tricuspid valve, as well as tricuspid regurgitation were detected. He remained asymptomatic during hospital stay and was discharged home in good condition. Thus, isolated ruptured chordae tendineae of the posterior leaflet of the tricuspid valve is another cause of tricuspid regurgitation following blunt chest trauma.

  18. Differentiating biliary atresia from other causes of cholestatic jaundice.

    PubMed

    Robie, Daniel K; Overfelt, Sarah R; Xie, Li

    2014-09-01

    Diagnosis of biliary atresia (BA) in infants presenting with cholestatic jaundice (CJ) requires exploratory surgery with cholangiography. However, the lack of a standardized approach to preoperative evaluation of infants with CJ can lead to a high number of negative surgical explorations. We reviewed our experience with CJ and BA to determine preoperative variables that might reliably identify BA. Infants explored for possible BA over a 5-year period were retrospectively reviewed. Preoperative clinical indices and liver biopsy results were reviewed. Statistical analysis was conducted by Student's t test and Fisher's exact test (P < 0.05). Twenty patients were identified, 10 with BA and 10 without (50% negative exploration rate). Nuclear cholescintigraphy (HIDA) excretion into the gastrointestinal tract was absent in all BA and in 8 of 10 without BA. Hepatomegaly was more common in the BA group (OR = 9.3, P = 0.07). BA had higher mean (± standard error) serum gamma-glutamyl transpeptidase levels (542 ± 130 vs 139 ± 25.8 U/L in non-BA, P = 0.03). There were insignificant differences in sex, type of feeding, TPN exposure and sepsis between the two groups. Although our small sample size limits conclusions, we suggest screening infants with CJ by measuring GGT levels, absence of hepatomegaly, presence of cholic stools and/or excretion on HIDA scan to undergo pecutaneous liver biopsy given the lower likelihood of BA necessary.

  19. Role of laparoscopy in ureteropelvic junction obstruction with concomitant pathology: a case series study

    PubMed Central

    El-Fayoumi, Abdel-Rahman; Gakis, Georgios; Amend, Bastian; Khairul-Asri, Mohd Ghani; Stenzl, Arnulf; Schwentner, Christian

    2015-01-01

    Introduction Laparoscopic pyeloplasty is considered a standard treatment for ureteropelvic junction obstruction (UPJO). However, the presence of another pathology makes it a more challenging operation and guides the surgeon towards open conversion. In this study, we present our experience in difficult pyeloplasty cases managed by laparoscopy. Material and methods Six patients (4 females and 2 males) with an average age of 44 and a range of 27 to 60 years old, were diagnosed for UPJO. Three were on the left side and 3 on the right side. In addition to UPJO, 2 patients had renal stones, one patient had both renal ptosis and an umbilical hernia, 3 patients had a para-pelvic cyst, hepatomegaly and malrotated kidney, respectively. All patients had a preoperative ultrasound, CT or IVU, and a renal isotope scan. Laparoscopic pyeloplasty was performed according to the dismembered Anderson-Hynes technique with auxiliary maneuver, according to the pathology. Results All patients were treated successfully for UPJO and the concomitant pathologies, except hepatomegaly and malrotation. Mean operative time was 125 minutes and estimated blood loss was <50 ml. Conclusions Laparoscopic pyeloplasty can be performed in difficult situations provided that the surgeon has enough experience with laparoscopy. PMID:26855804

  20. Interventional therapeutic techniques in Budd-Chiari syndrome

    SciTech Connect

    Bilbao, Jose Ignacio; Pueyo, Jesus Ciro; Longo, Jesus Maria; Arias, Mercedes; Herrero, Jose Ignacio; Benito, Alberto; Barettino, Maria Dolores; Perotti, Juan Pablo; Pardo, Fernando

    1997-03-15

    Purpose. To analyze the results obtained with percutaneous therapeutic procedures in patients with Budd-Chiari syndrome (BCHS). Methods. Between August 1991 and April 1993, seven patients with BCHS were treated in our hospital. Three presented with a congenital web; in another three cases the hepatic veins and/or the inferior vena cava (IVC) were compromised after major hepatic surgery; one patient presented with a severe stenosis of the intrahepatic IVC due to hepatomegaly. Results. One of the patients with congenital web has required several new dilatations due to restenosis; one patient required a transjugular intrahepatic portosystemic shunt procedure while awaiting a liver transplantation. The two postsurgical patients with stenosed hepatic veins did not require any new procedure after the placement of metallic endoprostheses. However, the patient with liver transplantation presented IVC restenosis after balloon angioplasty that required the deployment of metallic endoprostheses. In the patient with hepatomegaly a self-expandable prosthesis was placed in the intrahepatic portion of the IVC before (4 months) a liver transplantation. Conclusion. Interventional therapeutic techniques offer a wide variety of possibilities for the treatment of patients with BCHS. For IVC stenoses, the results obtained with balloon angioplasty are at least as good as those obtained with surgery.

  1. Anti-diabetic effect of amorphastilbol through PPARα/γ dual activation in db/db mice

    SciTech Connect

    Lee, Woojung; Ham, Jungyeob; Kwon, Hak Cheol; Kim, Yong Kee; Kim, Su-Nam

    2013-03-01

    Highlights: ► Amorphastilbol stimulates the transcriptional activities of both PPARα and PPARγ. ► Amorphastilbol improves glucose and lipid impairment in db/db mice. ► There are no side effects, such as hepatomegaly, in amorphastilbol-treated mice. ► Amorphastilbol can be used as a potential therapeutic agent against T2DM. - Abstract: Peroxisome proliferator-activated receptors (PPARs) have been considered as desirable targets for metabolic syndrome treatments, even though their specific agonists have several side effects, including body weight gain, edema, and tissue failure. The effects of amorphastilbol (APH) on glucose- and lipid metabolism were investigated with in vitro 3T3-L1 adipocyte systems and in vivo db/db mice model. APH selectively stimulates the transcriptional activities of both PPARα and PPARγ, which are able to enhance fatty acid oxidation and glucose utilization. Furthermore, APH improves glucose and lipid impairment in db/db mice. More importantly, there are no significant side effects, such as weight gain or hepatomegaly, in APH-treated animals, implying that APH do not adversely affect liver or lipid metabolism. All our data suggest that APH can be used as potential therapeutic agents against type 2 diabetes and related metabolic disorders, including obesity, by enhancing glucose and lipid metabolism.

  2. The Association of Metabolic Syndrome, Insulin Resistance and Non-alcoholic Fatty Liver Disease in Overweight/Obese Children

    PubMed Central

    El-Koofy, Nehal M.; Anwar, Ghada M.; El-Raziky, Mona S.; El-Hennawy, Ahmad M.; El-Mougy, Fatma M.; El-Karaksy, Hanaa M.; Hassanin, Fetouh M.; Helmy, Heba M.

    2012-01-01

    Background/Aim: To study the prevalence of metabolic syndrome (MS), insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) in overweight/obese children with clinical hepatomegaly and/or raised alanine aminotransferase (ALT). Patients and Methods: Thirty-three overweight and obese children, aged 2-13 years, presenting with hepatomegaly and/or raised ALT, were studied for the prevalence of MS, IR and NAFLD. Laboratory analysis included fasting blood glucose, serum insulin, serum triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and liver biochemical profile, in addition to liver ultrasound and liver biopsy. Results: Twenty patients (60.6%) were labeled with MS. IR was present in 16 (48.4%). Fifteen (44%) patients had biopsy-proven NAFLD. Patients with MS were more likely to have NAFLD by biopsy (P=0.001). Children with NAFLD had significantly higher body mass index, waist circumference, ALT, total cholesterol, LDL-c, TG, fasting insulin, and lower HDL-c compared to patients with normal liver histology (P< 0.05) and fitted more with the criteria of MS (80% vs. 44%). IR was significantly more common among NAFLD patients (73% vs. 28%). Conclusion: There is a close association between obesity, MS, IR and NAFLD. Obese children with clinical or biochemical hepatic abnormalities are prone to suffer from MS, IR and NAFLD. PMID:22249092

  3. Autoimmune lymphoproliferative syndrome with neonatal onset.

    PubMed

    Naveed, Muhammad; Khamis Butt, Umar Bin; Mannan, Jovaria

    2014-05-01

    We describe 2 cases of autoimmune lymphoproliferative syndrome (ALPS), which is a rare disorder of auto-immunity, chronic persistent or recurrent lymphadenopathy, splenomegaly, hepatomegaly and hyper gamma globulinemia (1gG, 1gA). Both cases presented in neonatal period which is a rare age of presentation in this disease. A 20 days old female neonate presented with respiratory symptoms which rapidly progressed needing ventilatory support. There was hepatomegaly and no auscultatory findings in the chest. Serial CBCs (complete blood counts) showed persistent leucocytosis with predominant lymphocytosis. Her chest X-ray showed left sided consolidation which responded poorly to antibiotics. Her prompt clinical response to steroids raised the suspicion of autoimmunity and the diagnosis was established after a negative bone marrow examination for leukemia and a positive result for ALPS on flow cytometry. The second case presented with anemia, thrombocytopenia starting in neonatal period followed by persistent lymphadenopathy, hepatosplenomegaly and recurrent infections which responded poorly to antibiotics. Diagnosis was delayed due to low index of suspicion, and finally achieved with multiple radiological studies, histopathology and flow cytometry.

  4. RNA-sequencing analysis reveals the hepatotoxic mechanism of perfluoroalkyl alternatives, HFPO2 and HFPO4, following exposure in mice.

    PubMed

    Wang, Jianshe; Wang, Xiaoyang; Sheng, Nan; Zhou, Xiujuan; Cui, Ruina; Zhang, Hongxia; Dai, Jiayin

    2017-04-01

    The toxicological impact of traditional perfluoroalkyl chemicals has led to the elimination and restriction of these substances. However, many novel perfluoroalkyl alternatives remain unregulated and little is known about their potential effects on environmental and human health. Daily administration of two alternative perfluoroalkyl substances, HFPO2 and HFPO4 (1 mg kg(-1) body weight), for 28 days resulted in hepatomegaly and hepatic histopathological injury in mice, particularly in the HFPO4 group. We generated and compared high-throughput RNA-sequencing data from hepatic tissues in control and treatment group mice to clarify the mechanism of HFPO2 and HFPO4 hepatotoxicity. We identified 146 (101 upregulated, 45 downregulated) and 1295 (716 upregulated, 579 downregulated) hepatic transcripts that exhibited statistically significant changes (fold change ≥2 or ≤0.5, false discovery rate < 0.05) after HFPO2 and HFPO4 treatment, respectively. Among them, 111 (82 upregulated, 29 downregulated) transcripts were changed in both groups, and lipid metabolism associated genes were dominant. Thus, similar to their popular predecessors, HFPO2 and HFPO4 exposure exerted hepatic effects, including hepatomegaly and injury, and altered lipid metabolism gene levels in the liver, though HFPO4 exerted greater hepatotoxicity than HFPO2. The unregulated use of these emerging perfluoroalkyl alternatives may affect environmental and human health, and their biological effects need further exploration. Copyright © 2016 John Wiley & Sons, Ltd.

  5. A comparative study of hepatitis caused by scrub typhus and viral hepatitis A in South Korea.

    PubMed

    Lee, Jun; Kim, Dong-Min; Yun, Na Ra; Byeon, Yu Mi; Kim, Young Dae; Park, Chan Guk; Kim, Man Woo; Han, Mi Ah

    2011-11-01

    We compared clinical features and laboratory findings of 104 patients with hepatitis A and 197 patients with scrub typhus. Nausea, vomiting, abdominal pain, hepatomegaly, and jaundice were common in patient with hepatitis A, and fever and headache were significantly more common in patients with scrub typhus. At presentation, an alanine aminotransferase (ALT) level ≥ 500 U/L was observed in 1% of scrub typhus patients and in 87.5% of hepatitis A patients (P < 0.001). A bilirubin level ≥ 1.3 mg/dL was observed in 16.8% of scrub typhus patients and 90.4% of hepatitis A patients. The ALT:lactate dehydrogenase ratio was ≤ 5 in 97.4% of the patients with scrub typhus and > 5 in 95.2% of those with hepatitis A (P < 0.001). Fever, headache, rash, and eschar are findings that indicate scrub typhus. An ALT level ≥ 500 U/L (adjusted odds ratio = 0.011) a bilirubin level ≥ 1.3 (adjusted odds ratio = 0.024), an ALT:lactate dehydrogenase ratio > 5, and hepatomegaly are indications of viral hepatitis A.

  6. Venous outflow obstruction and portopulmonary hypertension after orthotopic liver transplantation

    PubMed Central

    Aguirre-Avalos, Guadalupe; Covarrubias-Velasco, Marco Antonio; Rojas-Sánchez, Antonio Gerardo

    2013-01-01

    Patient: Female, 54 Final Diagnosis: Suprahepatic inferior vena cava anastomosis stricture Symptoms: Ascites • fatigue • lower limb edema • hepatomegaly Medication: — Clinical Procedure: — Specialty: Transplantology • Critical Care Medicine Objective: Unusual clinical course Background: Suprahepatic inferior vena cava anastomosis stricture is an unusual vascular complication after orthotopic liver transplantation with the “piggyback” technique. Clinical manifestations are dependent upon the severity of the stenosis. Portopulmonary hypertension after orthotopic liver transplantation is a complication that carries high mortality due to cardiopulmonary dysfunction. The pathogenesis of pulmonary vascular disorders after orthotopic liver transplantation remains uncertain. Case Report: We report a case of acute right heart pressure overload after surgical correction of the suprahepatic inferior vena cava anastomotic stricture in a 54-year-old woman who had preexisting pulmonary arterial hypertension associated with portal hypertension after orthotopic liver transplantation. Twenty months posttransplantation, she developed fatigue and progressive ascites. On admission, the patient had hepatomegaly, ascites, and lower limb edema. Symptoms in the patient developed gradually over time. Conclusions: Recurrent portal hypertension by vascular complications is a cause of pulmonary arterial hypertension after orthotopic liver transplantation. Clinical manifestations of suprahepatic inferior vena cava anastomotic stenosis are dependent upon their severity. Sildenafil is an effective drug for treatment of pulmonary arterial hyper-tension after portal hypertension by vascular complications. PMID:24046802

  7. [Two siblings of Leber's congenital amaurosis with an increase in very long chain fatty acid in blood: relationship between peroxisomal disorders and Leber's congenital amaurosis].

    PubMed

    Haginoya, K; Aikawa, J; Noro, T; Watanabe, M; Iinuma, K; Narisawa, K; Tada, K

    1989-07-01

    We reported two siblings of Leber's congenital amaurosis associated with increased level of very long chain fatty acid (VLCFA) in blood. Case 1, a 3 1/2-year-old boy had congenital blindness, severe psychomotor retardation, hepatomegaly, profound hypotonia, loss of deep tendon reflexes, muscular atrophy and weakness, and non-convulsive status epilepticus characterized by a sudden respiratory failure, and also showed a flat electroretinogram, non-pigmentary retinal degeneration, severe atrophy of the brain stem and cerebellum, hepatic fibrosis, decreased motor and sensory conduction velocities and atlanto-axial instability. Sural nerve biopsy revealed severely decreased number of total myelinated fibers without remarkable demyelination or remyelination. Case 2, an elder sister of case 1, with pigmentary retinal degeneration, hepatomegaly and pericarditis had died at 3 months. Autopsy revealed hypomyelination and heterotopy of the cerebral white matter, hepatic fibrosis, renal microcysts and normal adrenal cytoarchitecture. In case 1, the level of VLCFA was increased twofold and sevenfold of controls in serum and in red cell membrane, respectively. Phytanic or trihydroxycholestanoic acid was not detected in the serum and bile. Normal shaped peroxisomes were definitely recognized in biopsied liver by means of electronmicroscopic histochemistry. From the above findings, these patients was thought to be a new variant of peroxisomal disorders relating to degradation of VLCFA, other than Zellweger syndrome, infantile Refsum disease and infantile adrenoleukodystrophy. It was concluded that peroxisomal functions should be studied in cases of Leber's congenital amaurosis.

  8. Anti-fasciola IgG isotypes among patients with fascioliasis before and after treatment.

    PubMed

    Hassan, M M; Mostafa, N E; Ramadan, M; Nassar, A; Hassounah, O; Omar, O

    2000-08-01

    Stool examination using modified Kato thick smear method was performed to detect Fasciola eggs and other parasites. Abdominal pain was the major presenting symptom (83.3%) followed by pallor (71.6%) and fever (16.7%). Anaemia and hepatomegaly were recorded in 70% of patients compared to 25% with splenomegaly. Abdominal ultrasonography revealed hepatomegaly and common bile duct dilatation in 70% of patients. Moreover, 6 cases showed Olympic game rings which is diagnostic. All of patients had positive IgG4 levels, 58 cases were found positive for specific total IgG and IgG1, whereas, only 36 cases had positive IgG2 levels (60%). All negative control group showed no cross reactions. On the other hand, ELISA detecting IgG4 showed the highest specificity (95%), followed by IgG2 (85%) and the least specific test was obtained with detection of IgG (70%) and IgG1 (65%). One week after treatment, 90% of patients were completely cured. One and 3 months after treatment, the cure rate was 83.3%. In completely cured patients, none of anti-Fasciola isotypes was significantly changed.

  9. A novel homozygous no-stop mutation in G6PC gene from a Chinese patient with glycogen storage disease type Ia.

    PubMed

    Gu, Lei-Lei; Li, Xin-Hua; Han, Yue; Zhang, Dong-Hua; Gong, Qi-Ming; Zhang, Xin-Xin

    2014-02-25

    Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive genetic disorder resulting in hypoglycemia, hepatomegaly and growth retardation. It is caused by mutations in the G6PC gene encoding Glucose-6-phosphatase. To date, over 80 mutations have been identified in the G6PC gene. Here we reported a novel mutation found in a Chinese patient with abnormal transaminases, hypoglycemia, hepatomegaly and short stature. Direct sequencing of the coding region and splicing-sites in the G6PC gene revealed a novel no-stop mutation, p.*358Yext*43, leading to a 43 amino-acid extension of G6Pase. The expression level of mutant G6Pase transcripts was only 7.8% relative to wild-type transcripts. This mutation was not found in 120 chromosomes from 60 unrelated healthy control subjects using direct sequencing, and was further confirmed by digestion with Rsa I restriction endonuclease. In conclusion, we revealed a novel no-stop mutation in this study which expands the spectrum of mutations in the G6PC gene. The molecular genetic analysis was indispensable to the diagnosis of GSD-Ia for the patient.

  10. A Post-Developmental Genetic Screen for Zebrafish Models of Inherited Liver Disease

    PubMed Central

    Kim, Seok-Hyung; Wu, Shu-Yu; Baek, Jeong-In; Choi, Soo Young; Su, Yanhui; Flynn, Charles R.; Gamse, Joshua T.; Ess, Kevin C.; Hardiman, Gary; Lipschutz, Joshua H.; Abumrad, Naji N.; Rockey, Don C.

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease such as simple steatosis, nonalcoholic steatohepatitis (NASH), cirrhosis and fibrosis. However, the molecular pathogenesis and genetic variations causing NAFLD are poorly understood. The high prevalence and incidence of NAFLD suggests that genetic variations on a large number of genes might be involved in NAFLD. To identify genetic variants causing inherited liver disease, we used zebrafish as a model system for a large-scale mutant screen, and adopted a whole genome sequencing approach for rapid identification of mutated genes found in our screen. Here, we report on a forward genetic screen of ENU mutagenized zebrafish. From 250 F2 lines of ENU mutagenized zebrafish during post-developmental stages (5 to 8 days post fertilization), we identified 19 unique mutant zebrafish lines displaying visual evidence of hepatomegaly and/or steatosis with no developmental defects. Histological analysis of mutants revealed several specific phenotypes, including common steatosis, micro/macrovesicular steatosis, hepatomegaly, ballooning, and acute hepatocellular necrosis. This work has identified multiple post-developmental mutants and establishes zebrafish as a novel animal model for post-developmental inherited liver disease. PMID:25950913

  11. Hepatic tuberculosis in absence of disseminated abdominal tuberculosis.

    PubMed

    Desai, Chirag S; Josh, Anand G; Abraham, Philip; Desai, Devendra C; Deshpande, Ramesh B; Bhaduri, Anita; Shah, Sudeep R

    2006-01-01

    Liver involvement in tuberculosis in absence of miliary tuberculosis is rare. This study was performed to analyse the spectrum and response to treatment of hepatic tuberculosis in the absence of miliary abdominal tuberculosis. Retrospective analysis of seven cases of hepatic tuberculosis without miliary abdominal tuberculosis who presented at the single tertiary referral center were analyzed. All patients presented with fever and hepatomegaly. Five of them had pain in upper abdomen and vomiting. HIV serology was positive in one patient. All patients had normocytic normochromic anaemia, raised erythrocyte sedimentation rate (Mean 65). Mild elevation of liver enzymes and low albumin (Mean 2.4 gm%) with reversal of albumin globulin ratio (Mean 0.6) were seen in all. Two had jaundice. Prothrombin time was normal in all and lactate dehydrogenase values were elevated in all (Mean 794 IU/L). On ultrasonography, 2 had multiple hypodense lesion, 1 had coarse echotexture of liver, 1 had hyperechoic pattern and 3 had just hepatomegaly. Complete resolution of liver lesions on treatment with 4-drug anti-tuberculosis drug chemotherapy was seen. In conclusion, liver tuberculosis has protean manifestations with nonspecific alteration of liver function tests and is best diagnosed on liver biopsy. Overall response to therapy is satisfactory.

  12. [Severe hepatic veno-occlusive disease (VOD) which was successfully treated with supportive therapy, but subsequently developed late-recurrence].

    PubMed

    Matsuoka, S; Okamoto, S; Ishida, A; Wakui, M; Watanabe, R; Moriki, T; Ikeda, Y; Hirabayashi, N

    1998-02-01

    A 40-year-old man with chronic myelogenous leukemia in chronic phase received an allogeneic marrow graft from his HLA identical brother. He was conditioned with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). Graft-versus-host disease (GVHD) prophylaxis was attempted with cyclosporine A (CYA) and methotrexate. On day 30, weight gain, ascites and hepatomegaly developed in addition to an elevation of total bilirubin (TB). He was diagnosed as having veno-occlusive disease (VOD) and treated conservatively. The TB level increased up to 20.1 mg/dl on day 66, then reduced to 2.1 mg/dl on day 129. By that time ascites and hepatomegaly also had completely resolved. However, on day 134. The TB level started to increase again, when the lesions of chronic GVHD were observed in the eye, the mouth, and the skin. CYA was started on day 142, and FK506 was substituted for CYA on day 161. Despite the improvement of oral and skin lesions, TB level continued to rise, and he died of respiratory failure due to ARDS on day 186. Autopsy revealed both acute and old hepatic VOD lesions, suggesting the occurrence of late-onset VOD which probably contributed to the liver dysfunction observed after clinical resolution of the first episode of VOD.

  13. Epstein-Barr virus-associated cholestatic hepatitis.

    PubMed

    Salva, Inês; Silva, Inês Vaz; Cunha, Florbela

    2013-12-16

    Epstein-Barr virus infection is common in children, usually presenting as infectious mononucleosis, including fever, tonsillitis and lymphadenopathy associated with self-resolving increase in transaminases. Cholestasis is rare in children with only a few cases reported but it was described in up to 55% of the adult population affected. We present a case of a 6-year-old boy with fever, vomiting and choluria. The physical examination showed hepatomegaly and jaundice and was otherwise unremarkable. The laboratory studies revealed increased transaminases (aspartate aminotransferase 97 U/L, alanine aminotransferase 166 U/L), hyperbilirubinaemia (total bilirubin 3.2 mg/dL, direct bilirubin 2.89 mg/dL) and increased γ-glutamyl transpeptidase (114 mg/dL). Urine urobilinogen was increased. The abdominal ultrasound showed hepatomegaly. Epstein-Barr viral capsid antibody IgM was positive and IgG was negative. Serological studies for other viruses were negative. We underline the need to consider Epstein-Barr virus in the cholestatic hepatitis differential diagnosis, in order to avoid unnecessary investigations.

  14. Successful Treatment of Suspected Pulmonary Arterial Hypertension in a Mealy Amazon Parrot (Amazona farinose).

    PubMed

    Brady, Sean M; Burgdorf-Moisuk, Anne; Silverman, Sarah; Wack, Raymund F

    2016-12-01

    A 25-year-old, male mealy Amazon parrot (Amazona farinose) with a history of polycythemia, hepatomegaly, and epistaxis was evaluated for progressive lethargy and anorexia. Clinical laboratory testing revealed severe polycythemia (71%), hypophosphatemia (1.6 mg/dL), and mild hypokalemia (2.8 mEq/L). Radiographs showed marked hepatomegaly and loss of air sac space. Despite supportive treatments, the bird's condition deteriorated, and it developed ataxia, was unable to fly, and became oxygen dependent. An echocardiogram, including an air bubble study, revealed a right-to-left atrial shunt and presumed pulmonary arterial hypertension. The bird was started on periodic phlebotomy (5-10 mL/kg q6wk) to reduce packed cell volume and sildenafil citrate (2.5 mg/kg PO q8h) for treatment of suspected pulmonary arterial hypertension. One week later, the patient was weaned off oxygen, and 24 days after initial presentation, the parrot was returned to its outdoor exhibit. Intermittent periods of increased respiratory rate and effort have been reported but have resolved without additional treatments. Epistaxis, once common in this bird, has not been noted since initiating treatment with sildenafil citrate 15 months ago.

  15. Treatment-naïve Gaucher disease patients achieve therapeutic goals and normalization with velaglucerase alfa by 4years in phase 3 trials.

    PubMed

    Zimran, Ari; Elstein, Deborah; Gonzalez, Derlis E; Lukina, Elena A; Qin, Yulin; Dinh, Quinn; Turkia, Hadhami Ben

    2016-10-21

    Gaucher disease is an inherited metabolic disease characterized by β-glucocerebrosidase deficiency and commonly treated with enzyme replacement therapy (ERT). The efficacy of ERT with velaglucerase alfa was assessed based on the achievement of published therapeutic goals and the normalization of disease parameters in 39 treatment-naïve patients with type 1 Gaucher disease, 6 to 62years of age, enrolled in phase 3 clinical trials. After 4years of ERT, therapeutic goals for thrombocytopenia and splenomegaly had been achieved in 100% of patients; goals for anemia and hepatomegaly had been achieved in 95% and 94% of patients, respectively. Consistent with the goal for bone mineral density, lumbar spine bone density improved in 87% of patients ≥18years of age. At year 4, compared with clinical ranges for healthy individuals, 86% of patients with a low baseline hemoglobin concentration had normalized, 60% with a low baseline platelet count had normalized, 67% with baseline splenomegaly had normalized, 58% with hepatomegaly had normalized, and lumbar spine bone density had normalized in 53% of adults. The decade-old therapeutic goals do not reflect the potential for normalization of clinical parameters in ERT-treated patients. Goals consistent with normalization or near-normalization should be considered. ClinicalTrials.gov identifiers: NCT00430625, NCT00553631, NCT00635427.

  16. Primitive neuroectodermal tumor of the liver: a case report.

    PubMed

    Mani, Siddhartha; Dutta, Deep; De, Binay K

    2010-03-01

    Ewing sarcoma/primitive neuroectodermal tumor is a rare tumor of soft tissues of thoraco-pulmonary regions, pelvis and lower extremities. Involvement of visceral organs by primitive neuroectodermal tumor is even rarer, with the kidney being the most commonly involved organ. Involvement of the liver has been reported in the form of metastasis from other primary sources presenting as liver abscess. We report a 20-year-old lady presenting with massive hepatomegaly, with computed tomography scan evidence of diffuse hepatomegaly and a normal porta and intrahepatic biliary radicles. She subsequently underwent ultrasonography-guided true-cut needle biopsy of the liver. Histopathology of the liver revealed nests of small round blue tumor cells in the background of hepatocytes infiltrating the liver, which expressed Mic-2 and Fli-1, and were negative for cytokeratin, desmin, hepatocyte-specific antigen (OCHIE5), synaptophysin, chromogranin A and CD-20. Immunohistochemistry revealed CD-99-positive. Extensive search regarding any possible different site of involvement by the tumor was negative. The patient responded to a combination therapy of vincristine, adriamycin and cyclophosphamide alternating with ifosfamide and etoposide 3 weekly over 43 weeks and has been doing well even after 1 year of diagnosis. The clinical presentation, the macroscopic aspect, together with the histological pattern, the cytological characteristic and the cellular immunophenotype lead to the diagnosis of primary primitive neuroectodermal tumor of the liver which responded well to combination chemotherapy.

  17. Diagnosis of hepatic glycogenosis in poorly controlled type 1 diabetes mellitus.

    PubMed

    Giordano, Stefania; Martocchia, Antonio; Toussan, Lavinia; Stefanelli, Manuela; Pastore, Francesca; Devito, Antonio; Risicato, Marcello G; Ruco, Luigi; Falaschi, Paolo

    2014-12-15

    Hepatic glycogenosis (HG) in type 1 diabetes is a underrecognized complication. Mauriac firstly described the syndrome characterized by hepatomegaly with altered liver enzymes, growth impairment, delay puberty and Cushingoid features, during childhood. HG in adulthood is characterized by the liver disorder (with circulating aminotransferase increase) in the presence of poor glycemic control (elevation of glycated hemoglobin, HbA1c levels). The advances in the comprehension of the metabolic pathways driving to the hepatic glycogen deposition point out the role of glucose transporters and insulin mediated activations of glucokinase and glycogen synthase, with inhibition of glucose-6-phosphatase. The differential diagnosis of HG consists in the exclusion of causes of liver damage (infectious, metabolic, obstructive and autoimmune disease). The imaging study (ultrasonography and/or radiological examinations) gives information about the liver alterations (hepatomegaly), but the diagnosis needs to be confirmed by the liver biopsy. The main treatment of HG is the amelioration of glycemic control that is usually accompanied by the reversal of the liver disorder. In selected cases, more aggressive treatment options (transplantation) have been successfully reported.

  18. Glycogen storage diseases: New perspectives

    PubMed Central

    Özen, Hasan

    2007-01-01

    Glycogen storage diseases (GSD) are inherited metabolic disorders of glycogen metabolism. Different hormones, including insulin, glucagon, and cortisol regulate the relationship of glycolysis, gluconeogenesis and glycogen synthesis. The overall GSD incidence is estimated 1 case per 20000-43000 live births. There are over 12 types and they are classified based on the enzyme deficiency and the affected tissue. Disorders of glycogen degradation may affect primarily the liver, the muscle, or both. Type Ia involves the liver, kidney and intestine (and Ib also leukocytes), and the clinical manifestations are hepatomegaly, failure to thrive, hypoglycemia, hyperlactatemia, hyperuricemia and hyperlipidemia. Type IIIa involves both the liver and muscle, and IIIb solely the liver. The liver symptoms generally improve with age. Type IV usually presents in the first year of life, with hepatomegaly and growth retardation. The disease in general is progressive to cirrhosis. Type VI and IX are a heterogeneous group of diseases caused by a deficiency of the liver phosphorylase and phosphorylase kinase system. There is no hyperuricemia or hyperlactatemia. Type XI is characterized by hepatic glycogenosis and renal Fanconi syndrome. Type II is a prototype of inborn lysosomal storage diseases and involves many organs but primarily the muscle. Types V and VII involve only the muscle. PMID:17552001

  19. Protective effect of Trillium tschonoskii saponin on CCl4-induced acute liver injury of rats through apoptosis inhibition.

    PubMed

    Wu, Hao; Qiu, Yong; Shu, Ziyang; Zhang, Xu; Li, Renpeng; Liu, Su; Chen, Longquan; Liu, Hong; Chen, Ning

    2016-12-01

    To explore hepatoprotective role and underlying mechanisms of Trillium tschonoskii Maxim (TTM), 36 rats were randomly divided into control, CCl4-induced liver injury model, and biphenyl dimethyl dicarboxylate (DDB) and low-, moderate-, and high-dose TTM treatment groups. After CCl4-induced model establishment, the rats from DDB and TTM groups were administrated with DDB at 0.2 g/kg per day and TTM at 0.1, 0.5, and 1.0 g/kg per day, while the rats from control and model groups were administrated with saline. After 5 days of treatments, all rats were sacrificed for determining serum ALT and AST levels and liver index, examining histopathological changes in liver through HE and TUNEL staining, and evaluating TNF-α and IL-6 mRNA expression by real-time PCR, and caspase-3, Bcl-2, and Bax expression by Western blot. Results indicated that CCl4 could induce acute liver injury and abnormal liver function in rats with obvious hepatomegaly, increased liver index, high ALT and AST levels, up-regulated TNF-α and IL-6, and overexpressed Bax and caspase-3. However, DDB and TTM could execute protective role in CCl4-induced liver injury in rats through reducing ALT and AST levels, rescuing hepatomegaly, down-regulating inflammatory factors and inhibiting hepatocyte apoptosis in a dose-dependent manner. Therefore, TTM has obvious protective role in CCl4-induced liver injury of rats through inhibiting hepatocyte apoptosis.

  20. Immunotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in a complex environmental mixture from the Love Canal.

    PubMed

    Silkworth, J B; Cutler, D S; Sack, G

    1989-02-01

    The organic phase of the leachate (OPL) from the Love Canal chemical dump site contains more than 100 organic compounds including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The immunotoxic potential of OPL was determined in two mouse strains which differ in their sensitivity to aromatic hydrocarbon (Ah) receptor-mediated toxicity. OPL was administered in corn oil in a single oral gavage to male BALB/cByJ (Ahb/Ahb) mice (0.5, 0.8, or 1.1 g/kg) and DBA/2J (Ahd/Ahd) mice (0.6, 0.9, or 1.3 g/kg). TCDD was similarly administered at 0.25, 1.0, 4.0, or 16.0 micrograms/kg. Two days later all mice were immunized with sheep erythrocytes (SRBC). The antibody response (PFC) and organ weights were evaluated 4 days later. OPL produced thymic atrophy and hepatomegaly in both strains at all dose levels. The PFC/spleen in BALB/cByJ mice was significantly reduced at the three doses to 34, 13, and 15%, respectively, of the control response. Serum anti-SRBC antibody levels and relative spleen weights were also reduced. The only immune effect in the DBA/2J mice was a decrease of the PFC/spleen to 58% of the control at the highest dose. TCDD decreased the relative thymus and spleen weights only in BALB/cByJ mice. However, TCDD produced hepatomegaly, a decrease in serum antibody, and a decrease in PFC/spleen in both BALB/cByJ and DBA/2J mice to 3 and 15%, respectively, at 16 micrograms/kg. Thus, the TCDD dose required to cause a 50% suppression (ED50) of PFC/spleen for the BALB/cByJ and DBA/2J strains was 1.84 and 3.89 micrograms/kg, respectively. The ED50 for OPL was 0.24 g/kg in BALB/cByJ mice. The TCDD concentration in the OPL was estimated to be 7.6 ppm, which agrees closely with the chemical analysis (3 ppm). The results suggest that the immunosuppression caused by OPL in BALB/cByJ mice was primarily due to TCDD, that the non-TCDD components of OPL diminished the TCDD immunotoxicity in the DBA/2J strain, and that the thymic atrophy and hepatomegaly were caused primarily by the non

  1. Veno-occlusive disease (VOD) of the liver in Korean patients following allogeneic bone marrow transplantation (BMT): efficacy of recombinant human tissue plasminogen activator (rt-PA) treatment.

    PubMed

    Lee, J H; Lee, K H; Choi, J S; Zang, D Y; Kim, S B; Kim, S W; Suh, C; Lee, J S; Kim, W K; Lee, Y S; Kim, S H

    1996-04-01

    Veno-occlusive disease (VOD) of the liver is a clinical syndrome characterized by hyperbilirubinemia, painful hepatomegaly, and fluid retention. In the bone marrow transplantation (BMT) setting, VOD is caused by dose-intensive chemotherapy and/or radiotherapy used to prepare patients for transplant. VOD occurs in up to 50% of the patients who undergo BMT and is usually associated with a high mortality rate. Until recently, there was no proven effective medical therapy for this condition once it was clinically apparent. We report here on the frequency and treatment result of VOD with rt-PA in our allogeneic BMT patients. Eight patients (median age 28.5 years) underwent allogeneic BMT from December, 1993 to June, 1995 in Asan Medical Center. Six leukemia patients were prepared for BMT with busulfan and cyclophosphmide, while two aplastic anemia patients received cyclophosphamide and antithymocyte globulin. VOD was defined as having two of the following features before day 20 posttransplant: jaundice (bilirubin > or = 2 mg/dL), tender hepatomegaly and/or right upper quadrant pain, ascites and/or unexplained weight gain (> 2% from baseline). All patients who were diagnosed with VOD received rt-PA (10-20 mg/day) and heparin (10,000 U/day). Three (37.5%) of the eight patients developed VOD that occurred between 6 and 10 days posttransplant. All three patients developed jaundice, weight gain, and tender hepatomegaly. Ascites and renal insufficiency occurred in two patients and pleural effusion in one patient. rt-PA and heparin were begun 6 to 26 days posttransplant and rt-PA was administered for 7 to 14 days. All three patients responded to the therapy; bilirubin levels began to decrease at 4 to 13 days from the start of therapy. They are all alive at day 111, 316, and 548 days posttransplant. None of the patients had significant hemorrhagic complications after rt-PA treatment. Prolonged administration of rt-PA was feasible without bleeding episode and it seems that rt

  2. Strong diabetes

    PubMed Central

    Young, James; Anwar, Aresh

    2007-01-01

    The case of a 36‐year‐old male professional bodybuilder is reported. He presented to the accident and emergency department with right upper quadrant pain. This was on the background of a 15‐year history of anabolic steroid and growth hormone misuse. Examination revealed mild hepatomegaly and a random blood sugar of 30.2 mmol/l. There was no evidence of ketonuria or acidosis. Biochemical evidence of hepatitis was found, and the patient was in acute renal failure. He was given a sliding scale of insulin and an intravenous infusion of crystalloid. The hepatitis and hyperglycaemia settled with conservative treatment. It is believed that this is the first reported case of frank diabetes precipitated by supraphysiological recreational growth hormone misuse. PMID:17324962

  3. Strong diabetes

    PubMed Central

    Young, James; Anwar, Aresh

    2009-01-01

    The case of a 36-year-old male professional bodybuilder is reported. He presented to the accident and emergency department with right upper quadrant pain. This was on the background of a 15-year history of anabolic steroid and growth hormone misuse. Examination revealed mild hepatomegaly and a random blood sugar of 30.2 mmol/l. There was no evidence of ketonuria or acidosis. Biochemical evidence of hepatitis was found, and the patient was in acute renal failure. He was given a sliding scale of insulin and an intravenous infusion of crystalloid. The hepatitis and hyperglycaemia settled with conservative treatment. It is believed that this is the first reported case of frank diabetes precipitated by supraphysiological recreational growth hormone misuse. PMID:21686671

  4. Radionuclide imaging of the liver in human fascioliasis

    SciTech Connect

    Rivera, J.V.; Bermudez, R.H.

    1984-08-01

    The clinical, laboratory, and scintigraphic findings in four cases of human fascioliasis are described. Acute onset of fever, abdominal pain, and weight loss in a person who has ingested watercress constitutes the clinical syndrome often seen. Eosinophilia and alteration in liver function tests, particularly alkaline phosphatase are frequent. Tc-99m sulfur colloid images showed hepatomegaly in four patients, focal defects in two, splenomegaly in three, and increased splenic uptake in two. Gallium citrate (Ga 67) images show increased uptake in the focal lesions in two of two. Sonographic imaging showed focal lucent abnormality in one of three. Liver biopsy findings were nonspecific. The differential diagnosis from other invasive parasitic diseases is discussed. A possible role of hepatic imaging in the evaluation of fascioliasis is suggested.

  5. Carnitine deficiency: clinical, morphological, and biochemical observations in a fatal case.

    PubMed Central

    Engel, A G; Banker, B Q; Eiben, R M

    1977-01-01

    A fatal case of carnitine deficiency is described. The patient had intermittent metabolic acidosis, fluctuating hepatomegaly, and progressive muscle weakness since 22 months of age. One of two liver biopsies revealed lipid accumulation in the hepatocytes, and a muscle biopsy at age 5 years showed a lipid storage myopathy. Type 1 fibres were the most severely affected. Satellite and vascular endothelial cells also contained abnormal lipid deposits. Quantitative electron microscopy demonstrated an approximately 50-fold increase in lipid material, and a twofold increase in mitochondria in myofibres. The muscle carnitine level was less than one-seventh of the lowest value encountered in 74 biopsies from non-weak or neuromuscular disease controls. The basic abnormality in this patient is assumed to be a defect in carnitine biosynthesis. Images PMID:874508

  6. Probable epizootic chlamydiosis in wild California (Larus californicus) and ring-billed (Larus delawarensis) gulls in North Dakota

    USGS Publications Warehouse

    Franson, J.C.; Pearson, J.E.

    1995-01-01

    During the summer of 1986, more than 400 California gulls (Larus californicus) and ring-billed gulls (Larvus delawarensis), primarily fledglings, died on an island in Lake Sakakawea near New Town, North Dakota (USA). Mortality was attributed largely to chlamydiosis. Necropsy findings in nine carcasses included splenomegaly (n = 9), hepatomegaly (n = 4), and pericarditis (n = 1). Livers from three California gulls and two ring-billed gulls, and spleens from the same five birds plus a third ring-billed gull were positive for Chlamydia psittaci by the direct immunofluorescence test. Chlamydia psittaci was isolated from separate pools of liver and spleen from one California gull and one ring-billed gull. This is believed to be the first record of epizootic chlamydiosis in gulls and the second report of epizootic chlamydial mortality in wild birds in North America.

  7. Clinical manifestations of Eosinophilic meningitis due to infection with Angiostrongylus cantonensis in children.

    PubMed

    Sawanyawisuth, Kittisak; Chindaprasirt, Jarin; Senthong, Vichai; Limpawattana, Panita; Auvichayapat, Narong; Tassniyom, Sompon; Chotmongkol, Verajit; Maleewong, Wanchai; Intapan, Pewpan M

    2013-12-01

    Eosinophilic meningitis, caused by the nematode Angiostrongylus cantonensis, is prevalent in northeastern Thailand, most commonly in adults. Data regarding clinical manifestations of this condition in children is limited and may be different those in adults. A chart review was done on 19 eosinophilic meningitis patients aged less than 15 years in Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand. Clinical manifestations and outcomes were reported using descriptive statistics. All patients had presented with severe headache. Most patients were males, had fever, nausea or vomiting, stiffness of the neck, and a history of snail ingestion. Six patients had papilledema or cranial nerve palsies. It was shown that the clinical manifestations of eosinophilic meningitis due to A. cantonensis in children are different from those in adult patients. Fever, nausea, vomiting, hepatomegaly, neck stiffness, and cranial nerve palsies were all more common in children than in adults.

  8. Typhoid fever in Malaysian children.

    PubMed

    Malik, A S; Malik, R H

    2001-12-01

    A prospective study of 102 children with bacteriologically confirmed typhoid fever, admitted to Hospital Universiti Sains Malaysia over 5 years was conducted. The average age at presentation was 91.3 (range 6 - 159) months. Fever (900%), abdominal pain (56%) and diarrhoea (44%) were common symptoms. Findings included: hepatomegaly (85.3%), splenomegaly (27.5%), anaemia (31%), leukopenia (15%). thrombocytopenia (26%), positive Widal (62.5%) and Typhidot test (96%). Patients were treated with ampicillin (n = 54) or chloramphenicol (n = 49) and 1/3 developed complications like hepatitis (n = 19), bone marrow suppression (n = 8) and paralytic ileus (n = 7). A patient with splenomegaly, thrombocytopenia or leukopenia was at higher risk of developing complications.

  9. Severe Hunter syndrome (mucopolysaccharidosis II) phenotype secondary to large deletion in the X chromosome encompassing IDS, FMR1, and AFF2 (FMR2).

    PubMed

    Burruss, Day M; Wood, Tim C; Espinoza, Lesby; Dwivedi, Alka; Holden, Kenton R

    2012-06-01

    A 2-year-old boy with an initial diagnosis of Hunter syndrome (mucopolysaccharidosis II) had a more severe phenotype than expected, which warranted further evaluation. The patient had severe infantile global neurodevelopmental delays, macrocephaly with a prominent forehead, coarse facial features with clear corneas, chronic congestion with snoring, wide-spaced teeth, short thick neck, hepatomegaly, an inguinal hernia repaired, early clawhand deformities, and severe generalized hypotonia. X chromosome microarray revealed a large deletion encompassing the genes IDS, FMR1, and AFF2 (FMR2) confirming the diagnoses of both Hunter and fragile X syndromes. This case is also a reminder to clinicians that for optimum patient care, further diagnostic testing is warranted if there is concern that a patient's phenotype is more severe or complex than would be expected for the initial neurogenetic diagnosis.

  10. Natural history, clinicoradiologic correlates, and response to triclabendazole in acute massive fascioliasis.

    PubMed

    Marcos, Luis A; Tagle, Martin; Terashima, Angelica; Bussalleu, Alejandro; Ramirez, Cesar; Carrasco, Carlos; Valdez, Luis; Huerta-Mercado, Jorge; Freedman, David O; Vinetz, Joseph M; Gotuzzo, Eduardo

    2008-02-01

    Fascioliasis is highly endemic in the Andean region of South America. Newer serological assays have improved our ability to diagnose acute fascioliasis. The diagnosis was established by Fasciola hepatica serology (Fas2-ELISA or Western blot) in 10 patients. Identifiable exposure included ingestion of watercress (N = 8), alfalfa juice (N = 5), and lettuce (N = 1). Computed tomography of the abdomen showed hepatomegaly (N = 9), track-like hypodense lesions with subcapsular location (N = 8), and subcapsular hematoma (N = 2). Radiologic sequelae included cyst calcifications detectable at least 3 years after treatment. Stool examinations were negative for F. hepatica eggs; serology was positive (Arc II [N = 2], Fas2-ELISA [N = 6], Western blot [N = 2]). The syndrome of eosinophilia, fever, and right upper quadrant pain, elevated transaminases without jaundice, hypodense liver lesions on CT, and an appropriate exposure history suggests acute fascioliasis. Fascioliasis is specifically treatable with a single dose of triclabendazole.

  11. [Hepatosplenic localization of cat scratch disease in immunocompetent adults. Two cases].

    PubMed

    Le Tallec, Véronique; Abgueguen, Pierre; Pichard, Eric; Chennebault, Jean-Marie; Bellec, Véronique; Delbos, Valérie; Rousselet, Marie-Christine; Dib, Nina; Boyer, Jean

    2003-02-01

    The infective agent responsible for cat scratch disease, Bartonella henselae, is a rare cause of hepatic granulomatosis in immunocompetent adults. Clinical features include a prolonged fever or more typical symptoms such as lymphadenopathy associated with painful hepatomegaly and a fever following a cat scratch or bite. Images of micronodular hepatosplenic lesions on abdominal ultrasonography or computed tomography scan along with epithelioid granulomas in a liver biopsy can suggest this diagnosis. It is established with a serology by indirect immunofluorescence or by ELISA and/or the presence of Bartonella henselae DNA evidenced by PCR in the liver biopsy. We report two cases of hepatosplenic localizations of cat scratch disease in a 41-year-old woman and a 44-year-old man presenting asthenia and fever associated with a biological inflammatory syndrome and elevated liver enzymes.

  12. Lymphosarcoma with leukemic blood profile in a Savannah monitor lizard (Varanus exanthematicus).

    PubMed

    Schultze, A E; Mason, G L; Clyde, V L

    1999-03-01

    A 6-mo-old male Savannah monitor lizard (Varanus exanthematicus) was presented for lethargy and anorexia of 7 days duration. Physical examination revealed a slightly raised subcutaneous mass (1 cm diameter) in the left scapular area. Fine-needle aspiration cytology of the mass revealed a population of immature, pleomorphic lymphoid cells consistent with lymphosarcoma. A hemogram indicated marked leukocytosis (465,000 cells/microl) characterized by extreme lymphocytosis and many circulating lymphoid blast cells. The lizard was euthanized at the owner's request. Necropsy revealed severe hepatomegaly and multiple raised, ulcerated mural masses in the gastrointestinal tract. There were many raised, poorly demarcated tan foci in all the parenchymal organs. Histopathologic examination confirmed infiltration of all parenchymal organs by neoplastic lymphoid cells. Transmission electron microscopic examination failed to identify viruses within the neoplastic cells. A literature review revealed few reports of squamate leukemia and lymphosarcoma and none in Savannah monitor lizards.

  13. Fatal toxoplasmosis in a vinaceous Amazon parrot (Amazona vinacea).

    PubMed

    Ferreira, Francisco Carlos; Donatti, Rogerio Venâncio; Marques, Marcus Vinícius Romero; Ecco, Roselene; Preis, Ingred Sales; Shivaprasad, H L; Vilela, Daniel Ambrózio da Rocha; Martins, Nelson Rodrigo da Silva

    2012-12-01

    Toxoplasmosis was diagnosed in a vinaceous Amazon parrot based on histopathology and immunohistochemistry. The bird was prostrate on the bottom of the cage and died. Necropsy revealed edema and congestion of the lungs, cloudy air sacs, and mild hepatomegaly. Histopathology revealed severe pulmonary congestion and edema and interstitial mononuclear cell inflammation associated with many cysts containing bradyzoites of Toxoplasma gondii scattered throughout. The heart had mild multifocal lymphocytic myocarditis and free tachyzoites in the muscle fibers, and the kidneys had mild interstitial nephritis and a few cysts containing bradyzoites of T. gondii. Immunohistochemistry was negative for Sarcocystis falcatula and Neospora caninum and confirmed the protozoa as T. gondii. This is the first description of T. gondii in an endangered species ofa Brazilian psittacine.

  14. Primarily isolated hepatic involvement of amyloidosis

    PubMed Central

    Ye, Lei; Shi, Hui; Wu, Hui-Min; Wang, Fang-Yu

    2016-01-01

    Abstract Background: Amyloidosis is particularly difficult to diagnose because the signs and symptoms are subtle. Additionally, there are no specific imaging or laboratory tests, except histopathology. Although it is considered to be a systemic disorder, a small portion of cases may be localized. Introduction of the case: A 54-year-old man presented with nonspecific symptoms (jaundice and back pruritus). Biochemical tests showed a high level of bilirubin and elevated serum tumor markers (CA19–9 and CA125). Routine imaging showed hepatomegaly without heterogeneous enhancement. Liver biopsy confirmed the diagnosis of hepatic amyloidosis. No cardiac or renal involvement was found. The patient accepted treatment involving oral chemotherapy. Conclusion: A rare and unique presentation of hepatic amyloidosis was highlighted in this case. PMID:28033255

  15. Hepatitis in children with acquired immune deficiency syndrome. Histopathologic and immunocytologic features.

    PubMed

    Duffy, L F; Daum, F; Kahn, E; Teichberg, S; Pahwa, R; Fagin, J; Kenigsberg, K; Kaplan, M; Fisher, S E; Pahwa, S

    1986-01-01

    Hepatic morphology and immunocytology were evaluated in 4 children with clinical and immunologic characteristics of the acquired immune deficiency syndrome or acquired immune deficiency syndrome related complex. All 4 children had hepatomegaly and increased serum alanine and aspartate aminotransferase activity. Both lobular and portal changes were noted. Lymphocytic infiltration, piecemeal necrosis, hepatocellular and bile duct damage, sinusoidal cell hyperplasia, and endothelialitis were prominent. Vesicular rosettes in sinusoidal lymphocytes and tubuloreticular structures in sinusoidal endothelial cells were demonstrated by electron microscopy. The lymphocytic infiltrate in both the lobular and portal spaces was characterized by a relative increase of cytotoxic/suppressor (T8) cells. Hepatitis may be a common feature of pediatric acquired immune deficiency syndrome and acquired immune deficiency syndrome-related complex. Although the histopathologic changes are consistent with chronic active hepatitis, the specific pathogenesis remains to be determined.

  16. Active viral B hepatitis in parenteral drug abusers with acquired immune deficiency syndrome (AIDS).

    PubMed

    Leevy, C B; Nurse, H; Kapila, R

    1989-01-01

    Eighty-percent of 47 parenteral drug abusers with hepatomegaly and acquired immunodeficiency syndrome had HBV DNA in serum, although only 27% were HBsAg or "e" antigen-positive by polyclonal radioimmunoassay. Liver biopsies from each of 37 HBV DNA seropositive patients showed HBV DNA and were HBcAg-positive. The absence of positive HBsAg and "e" antigen in HBV DNA-positive patients was attributable to the presence of immune complexes; after in vitro dissociation of these complexes there was an increase in HBsAg from 24% to 86%, and of "e" antigen from 19% to 62%. These data indicate that actively replicating hepatitis B virus is common in patients with AIDS, and that precautions should be taken to prevent its dissemination. Therapy in these patients should address both human immunodeficiency and hepatitis B virus infections.

  17. Dengue in children: a systematic review of clinical and laboratory factors associated with severity.

    PubMed

    Wakimoto, Mayumi Duarte; Camacho, Luiz Antonio Bastos; Guaraldo, Lusiele; Damasceno, Luana Santana; Brasil, Patrícia

    2015-01-01

    Dengue is a potentially life-threatening illness, and children are at higher risk of severity. This review aimed to systematize the identified clinical and laboratory parameters associated with severe dengue in children, as monitoring these signs and fluid-replacement therapy are actually the cornerstones of dengue treatment. Of the 527 studies initially reviewed, 21 were selected as follows: three cohort studies, three case-control studies, 14 cross-sectional studies and one not defined. Eighteen studies were carried out in Asia and three in the Americas. Hepatomegaly, lethargy, abdominal pain, bleeding, hemoconcentration and thrombocytopenia, all referenced as warning signs in the WHO 2009 Guidelines, were the clinical and laboratory parameters independently associated with severity in more than one study. The recognition of these known warning signs associated to severe dengue disease underlines the usefulness of the WHO 2009 classification.

  18. Involvement of endocrine system in a patient affected by glycogen storage disease 1b: speculation on the role of autoimmunity.

    PubMed

    Melis, Daniela; Della Casa, Roberto; Balivo, Francesca; Minopoli, Giorgia; Rossi, Alessandro; Salerno, Mariacarolina; Andria, Generoso; Parenti, Giancarlo

    2014-03-19

    Glycogen storage disease type 1b (GSD1b) is an inherited metabolic defect of glycogenolysis and gluconeogenesis due to mutations of the SLC37A4 gene and to defective transport of glucose-6-phosphate. The clinical presentation of GSD1b is characterized by hepatomegaly, failure to thrive, fasting hypoglycemia, and dyslipidemia. Patients affected by GSD1b also show neutropenia and/or neutrophil dysfunction that cause increased susceptibility to recurrent bacterial infections. GSD1b patients are also at risk for inflammatory bowel disease. Occasional reports suggesting an increased risk of autoimmune disorders in GSD1b patients, have been published. These complications affect the clinical outcome of the patients. Here we describe the occurrence of autoimmune endocrine disorders including thyroiditis and growth hormone deficiency, in a patient affected by GSD1b. This case further supports the association between GSD1b and autoimmune diseases.

  19. Transient abnormal myelopoiesis in a phenotypically normal newborn with polyclonal trisomy 21.

    PubMed

    Corazza, Francesco; Astolfi, Annalisa; Libri, Virginia; Franzoni, Monica; Serravalle, Salvatore; Alessandroni, Rosina; Melchionda, Fraia; Pession, Andrea

    2014-06-01

    We report a rare case of transient abnormal myelopoiesis (TAM) in a phenotypically normal neonate. The presence of a palpable hepatomegaly prompted in-depth laboratory tests, which revealed the presence of severe hyperleukocytosis, with blast cells present in a peripheral blood smear. Although no signs of Down syndrome were present, we suspected TAM. Further analysis identified a mutation in GATA1 along with the unique finding of two different trisomic cell lines, detected upon karyotyping; one with trisomy 21 only, and one with trisomies 21 and 22, which was present in a subpopulation of peripheral blood cells. These genetic abnormalities disappeared by the age of 6 months. The presence of two different trisomic clones may be an evidence of the polyclonal nature of TAM in this patient.

  20. DRESS and Ischemic Stroke.

    PubMed

    Cahyanur, Rahmat; Oktavia, Dina; Koesno, Sukamto

    2012-07-01

    DRESS (drug rash eosinophilia and systemic symptoms) is a life threatening condition characterized by skin rash, fever, leucocytosis with eosinophilia or atypical lymphocytosis, lymphadenopathy, and internal organ involvement. This case report would like to describe an interesting case of DRESS coincidence with ischemic stroke. A 38 year old woman had been admitted with skin rash and fever since four days before. Four weeks before admission she received antibiotic and multivitamin for one week. The patient looked ill, with body temperature 38.0°C. Marked physical findings were cervical lymphadenopathy and hepatomegaly. Dermatological examination finding was generalized exanthema. Laboratory evaluation showed leucocytosis, eosinophilia, and increased level of ALT and AST. During hospitalization the patient also suffered from ischemic stroke. Treatments administered in this patient were oxygen, adequate intravenous fluid, parenteral nutrition, methyl prednisolone, cethirizin bid, ranitidin bid, and antibiotic. The antibiotic treatment in this case was performed with graded challenge or test dosing.

  1. Anesthesia for gingivectomy and dental extractions in a child with I-cell disease--a case report.

    PubMed

    Mahfouz, Abdul Kader M; George, G

    2011-02-01

    I-cell disease (mucolipidosis II) is a rare metabolic disorder resulting from the deficiency of a specific lysosomal enzyme, N-acetylglucosamine-1-phosphotransferease. Developmental delay and growth failure are common presentations of I-cell disease. Psychomotor deterioration is rapid and progressive. Some physical signs, such as hip dislocations, inguinal hernia, hepatomegaly, joint limitation, and skin changes may be present at birth. Coarse facial features and skeletal abnormalities become more conspicuous with time. The life expectancy of children with this condition is poor, with death usually occurring around the fifth year. A case report of the anesthetic management of gingivectomy with multiple dental extractions in a 5 years old Omani female, with I-cell disease, is presented. The problems faced and their management during anesthesia are described.

  2. Columbid herpesvirus-1 in two Cooper's hawks (Accipiter cooperii) with fatal inclusion body disease.

    PubMed

    Pinkerton, Marie E; Wellehan, James F X; Johnson, April J; Childress, April L; Fitzgerald, Scott D; Kinsel, Michael J

    2008-07-01

    We report two separate naturally occurring cases of fatal herpesviral disease in Cooper's Hawks (Accipiter cooperii). Gross lesions included splenomegaly and hepatomegaly, with diffuse pale mottling or scattered small white foci. Histologic lesions included splenic and hepatic necrosis associated with eosinophilic intranuclear inclusion bodies characteristic of herpesvirus. In one case, necrosis and inclusions were also noted in bone marrow, thymus, bursa of Fabricius, thyroid gland, parathyroid gland, ceca, and the enteric system. Transmission electron microscopy demonstrated viral particles typical of herpesvirus within hepatocyte nuclei and budding from the nuclear membrane. Herpesviral DNA was amplified via polymerase chain reaction (PCR) of paraffin-embedded liver and spleen, and sequence data were consistent with columbid herpesvirus-1, an alphaherpesvirus of Rock Pigeons (Columba livia). PCR results provide evidence that this disease is transmitted to raptors via Rock Pigeons, most likely through ingestion of Rock Pigeons as prey.

  3. Senile cardiac amyloidosis: an underappreciated cause of heart failure

    PubMed Central

    Shah, Shreena; Dungu, Jason; Dubrey, Simon William

    2013-01-01

    This case presents a patient with biopsy-proven, wild-type transthyretin (TTR) senile amyloidosis. The case was that of a man in his early 70s who presented with gradually progressive symptoms and signs of heart failure. The recent history included an episode of severe pancreatitis secondary to cholelithiasis and subsequently (and incidentally) noted hepatomegaly and marked ascites. Further evaluation of the aetiology of the heart failure, through echocardiography, coronary angiography and endomyocardial biopsy, led to an exact diagnosis of SSA. The patient is being treated with conventional heart failure medications while consideration is given to the use of diflusinal as an antiamyloidogenic small molecular stabiliser of TTR. Monitoring and further management advice are being coordinated by the National Amyloidosis Centre. PMID:23391947

  4. The pathology and pathogenicity of a novel Haemoproteus spp. infection in wild Little Penguins (Eudyptula minor).

    PubMed

    Cannell, B L; Krasnec, K V; Campbell, K; Jones, H I; Miller, R D; Stephens, N

    2013-10-18

    One hundred and thirty four Little Penguin (Eudyptula minor) carcases found since 2004 in south west Australia were necropsied. The livers and spleens from ten of the penguins exhibited varying degrees of multifocal, randomly scattered areas of necrosis and varying numbers of parasites were associated with these areas. Hepatomegaly and splenomegaly were noted in many of these ten cases. Necrosis and parasites were also observed in the cardiac muscle of four of the cases and in the lung tissue in one of the penguins. Using PCR, the parasites were positively identified in four of the cases as Haemoproteus spp. and morphologically identical tissue stage parasites associated with histopathological changes were observed in all ten dead penguins. This is the first study to demonstrate both the in situ presence of the Haemoproteus parasite in any member of the Sphensicidae family and mortality due to its presence. We postulate the involvement of anomalous environmental conditions in a potential increase in local vectors.

  5. Study on impression smears of hepatic coccidiosis in rabbits.

    PubMed

    Sivajothi, S; Reddy, B Sudhakara; Rayulu, V C

    2016-09-01

    Hepatic coccidiosis is a contagious and lethal disease condition in rabbits. The disease was recorded in six rabbits suffering with watery diarrhoea. Clinically, affected rabbits showed decreased growth rate, anorexia, debilitation, diarrhea and rough hair coat. Examination of the faecal samples revealed the presence of unsporulated oocysts of Eimeria spp. After sporulation Eimeria stiedae oocysts were identified. Postmortem examination revealed hepatomegaly with presence of discrete yellowish-white nodules on the surface of the liver. Impression smears from the liver revealed the presence of numerous developmental stages of E. stiedae corresponding with the stage of the liver lesion and also represent the histological changes of the liver. Rabbits were treated with a combination of sulphaquinoxaline and diaveridine for five days.

  6. Hereditary fructose intolerance mimicking a biochemical phenotype of mucolipidosis: A review of the literature of secondary causes of lysosomal enzyme activity elevation in serum.

    PubMed

    Ferreira, Carlos R; Devaney, Joseph M; Hofherr, Sean E; Pollard, Laura M; Cusmano-Ozog, Kristina

    2017-02-01

    We describe a patient with failure to thrive, hepatomegaly, liver dysfunction, and elevation of multiple plasma lysosomal enzyme activities mimicking mucolipidosis II or III, in whom a diagnosis of hereditary fructose intolerance (HFI) was ultimately obtained. She presented before introduction of solid foods, given her consumption of a fructose-containing infant formula. We present the most extensive panel of lysosomal enzyme activities reported to date in a patient with HFI, and propose that multiple enzyme elevations in plasma, especially when in conjunction with a normal plasma α-mannosidase activity, should elicit a differential diagnosis of HFI. We also performed a review of the literature on the different etiologies of elevated lysosomal enzyme activities in serum or plasma. © 2016 Wiley Periodicals, Inc.

  7. Hepatic Primary and Secondary Cholesterol Deposition and Damage in Niemann-Pick Disease.

    PubMed

    Bosch, Marta; Fajardo, Alba; Alcalá-Vida, Rafael; Fernández-Vidal, Andrea; Tebar, Francesc; Enrich, Carlos; Cardellach, Francesc; Pérez-Navarro, Esther; Pol, Albert

    2016-03-01

    Niemann-Pick C disease is a neurovisceral disorder caused by mutations in the NPC gene that result in systemic accumulation of intracellular cholesterol. Although neurodegeneration defines the disease's severity, in most patients it is preceded by hepatic complications such as cholestatic jaundice or hepatomegaly. To analyze the contribution of the hepatic disease in Niemann-Pick C disease progression and to evaluate the degree of primary and secondary hepatic damage, we generated a transgenic mouse with liver-selective expression of NPC1 from embryonic stages. Hepatic NPC1 re-expression did not ameliorate the onset and progression of neurodegeneration of the NPC1-null animal. However, the mice showed reduced hepatomegalia and dramatic, although not complete, reduction of hepatic cholesterol and serum bile salts, bilirubin, and transaminase levels. Therefore, hepatic primary and secondary cholesterol deposition and damage occur simultaneously during Niemann-Pick C disease progression.

  8. Polysplenia syndrome with congenital agenesis of dorsal pancreas presenting as acute pancreatitis and the role of endoscopic ultrasonography in its diagnosis.

    PubMed

    Jeong, Jae Hoon; Kim, Gwang Ha; Song, Geun Am; Lee, Dong Gun; Moon, Ji Yoon; Cheong, Jae Hoon; Kim, Suk

    2012-07-01

    A 49-year-old female was admitted to our hospital for acute pancreatitis. The abdomen CT scan incidentally showed midline liver with hepatomegaly, centrally located gallbladder, pancreas truncation, right sided small bowel, left sided large bowel, interruption of the inferior vena cava with azygos continuation, preduodenal portal vein, and multiple spleens in the left upper quadrant. In MRCP, the head of pancreas was enlarged and short main pancreatic duct without accessory duct was showed. EUS revealed enlarged ventral pancreas with a main pancreatic duct of normal caliber, absence of the accessory pancreatic duct and the dorsal pancreas. She was diagnosed as polysplenia syndrome with agenesis of dorsal pancreas. It is a rare congenital anomaly frequently associated with various visceral anomalies including multiple spleens, impaired visceral lateralization, congenital heart diseases, gastrointestinal abnormalities and azygos continuation of the inferior vena cava. We report a case of polysplenia syndrome with agenesis of dorsal pancreas presenting acute pancreatitis.

  9. Neonatal Abdominal Hemangiomatosis: Propranolol beyond Infantile Hemangioma.

    PubMed

    Nip, Siu Ying Angel; Hon, Kam Lun; Leung, Wing Kwan Alex; Leung, Alexander K C; Choi, Paul C L

    2016-01-01

    Hemangioma is the most common vascular tumor of infancy; presentation is often as cutaneous infantile hemangioma (IH). Cutaneous hemangioma is a clinical diagnosis. Most IHs follow a benign course, with complete involution without treatment in the majority of cases. Visceral hemangioma often involves the liver and manifests as a life-threatening disorder. Hepatic hemangiomas may be associated with high output cardiac failure, coagulopathy, and hepatomegaly which generally develop between 1 and 16 weeks of age. Mortality has been reportedly high without treatment. We report a rare case of a male infant with neonatal hemangiomatosis with diffuse peritoneal involvement, which mimicked a malignant-looking tumor on imaging, and discuss therapeutic options and efficacy. Propranolol is efficacious for IH but generally not useful for other forms of vascular hemangiomas, tumors, and malformations. In our case of neonatal peritoneal hemangiomatosis, propranolol appears to have halted the growth and possibly expedite the involution of the hemangiomatosis without other treatments.

  10. Upper gastrointestinal bleeding in a young patient with Budd Chiari syndrome due to a mutation of factor V Leiden: a case report.

    PubMed

    Dina, Ion; Iacobescu, Claudia; Goldis, Adrian

    2013-06-01

    Budd Chiari syndrome or hepatic venous outflow obstruction is a complex entity with multiple etiologies and various clinical manifestations. It is often difficult to establish the diagnosis. The most common cause is a hypercoagulable state due to either genetic disorders of blood coagulation or several acquired conditions such as hematological diseases, tumors, infections, chronic inflammatory diseases, pregnancy. The most common clinical presentation is hepatomegaly, abdominal pain and ascites, but the onset can also be dramatical and life threatening with upper digestive bleeding due to portal hypertension through postsinusoidal blockage. We report the case of a young patient with a coagulation disorder secondary to a mutation of factor V Leiden, who presented with upper digestive bleeding as the first manifestation of Budd Chiari syndrome and who also was associated with myocardial infarction in his past medical history.

  11. Mechanisms underlying the hepatotoxic effects of ecstasy.

    PubMed

    Carvalho, Márcia; Pontes, Helena; Remião, Fernando; Bastos, Maria L; Carvalho, Félix

    2010-08-01

    3,4-Methylenedioxymethamphetamine (MDMA or ecstasy) is a worldwide illegally used amphetamine-derived designer drug known to be hepatotoxic to humans. Jaundice, hepatomegaly, centrilobular necrosis, hepatitis and fibrosis represent some of the adverse effects caused by MDMA in the liver. Although there is irrefutable evidence of MDMA-induced hepatocellular damage, the mechanisms responsible for that toxicity remain to be thoroughly clarified. One well thought-of mechanism imply MDMA metabolism in the liver into reactive metabolites as responsible for the MDMA-elicited hepatotoxicity. However, other factors, including MDMA-induced hyperthermia, the increase in neurotransmitters efflux, the oxidation of biogenic amines, polydrug abuse pattern, and environmental features accompanying illicit MDMA use, may increase the risk for liver complications. Liver damage patterns of MDMA in animals and humans and current research on the mechanisms underlying the hepatotoxic effects of MDMA will be highlighted in this review.

  12. Acute myelogenous leukemia and glycogen storage disease 1b.

    PubMed

    Pinsk, Maury; Burzynski, Jeffrey; Yhap, Margaret; Fraser, Robert B; Cummings, Brian; Ste-Marie, Micheline

    2002-12-01

    Glycogen storage disease 1b (GSD 1b) is caused by a deficiency of glucose-6-phosphate translocase and the intracellular accumulation of glycogen. The disease presents with failure to thrive, hepatomegaly, hypoglycemia, lactic acidosis, as well as neutropenia causing increased susceptibility to pyogenic infections. We present a case of a young woman with GSD 1b who developed acute myelogenous leukemia while on long-term granulocyte colony-stimulating factor therapy. The presence of two rare diseases in a single patient raises suspicion that GSD 1b and acute myelogenous leukemia are linked. Surveillance for acute myelogenous leukemia should become part of the long-term follow-up for GSD 1b.

  13. Extra-articular features in early rheumatoid disease.

    PubMed Central

    Fleming, A; Dodman, S; Crown, J M; Corbett, M

    1976-01-01

    One hundred and two patients who presented with rheumatoid disease within the first year of onset were studied prospectively every four months for a mean 4.5 years to assess the incidence of extra-articular features. The features that seemed to be common in the early stages included hand-muscle wasting, carpal tunnel syndrome, lymphadenopathy, non-specific ankle swelling, and rheumatoid nodules, and to a lesser extent hepatomegaly, being underweight, conjunctivitis, skin transparency, and a palpable thyroid gland. Those features which seldom occurred early included scleromalacia, temporal artery inolvement, salivary gland enlargement, distal-motor neuropathy, splenomegaly, digital vasculitis, and pulmonary and cardiac complications. Being underweight indicated a significantly more severe outcome. PMID:1083759

  14. Sister Mary Joseph nodule as the presenting sign of disseminated prostate carcinoma.

    PubMed

    Deb, Prabal; Rai, Radhey Shyam; Rai, Rahul; Gupta, Ekawali; Chander, Yogesh

    2009-01-01

    Sister Mary Joseph's nodule is referred to as metastasis of visceral malignancy to the umbilicus. Most common primaries are in the gastrointestinal or genital tract, while other locations are rare. We recently encountered a 76-year-old male who was referred to the surgery clinic with an erythematous nodule in the umbilicus measuring 6 cm in diameter with complaints of painless profuse hematuria. History revealed severe obstructive voiding symptoms of 2-year duration, along with significant loss of weight and difficulty in walking. A detailed examination showed hard nodular hepatomegaly, along with grade IV prostatomegaly. Serum prostate-specific antigen was 3069 ng/ml. A pelvic radiograph displayed multiple osteolytic lesions, while ultrasonography showed multiple iso- and hypoechoic lesions in both lobes of the liver, suggestive of metastasis. Histopathology of a Tru-cut biopsy of the prostate confirmed an adenocarcinoma (Gleason score 9) with umbilical metastasis. The patient was on regular follow-up and died 3 months later.

  15. Defibrotide for the treatment of hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation.

    PubMed

    Corbacioglu, Selim; Kernan, Nancy; Lehmann, Leslie; Brochstein, Joel; Revta, Carolyn; Grupp, Stephan; Martin, Paul; Richardson, Paul G

    2012-06-01

    Hepatic veno-occlusive disease (VOD) is a serious complication of stem cell transplantation in children. VOD is characterized by rapid weight gain, hepatomegaly, hyperbilirubinemia and ascites. The pathogenesis of VOD is thought to involve chemotherapy and radiation-induced damage to the sinusoidal endothelium, resulting in endothelial injury, microthrombosis, subendothelial damage and cytokine activation. These processes lead to concomitant progressive hepatocellular dysfunction and subsequent fluid retention and renal impairment. Severe VOD is typically associated with multiorgan failure and high mortality. A number of possible strategies for the prevention and/or treatment of VOD in children have been investigated. The most promising agent to date is defibrotide, a novel polydeoxyribonucleotide with fibrinolytic properties but no major bleeding risk. Numerous studies, including Phase II/III trials, have shown clinical benefit in pediatric patients with the use of defibrotide treatment and prophylaxis. This review discusses VOD in children and focuses on therapeutic options, including defibrotide, in this patient population.

  16. Late-onset hepatic veno-occlusive disease post autologous peripheral stem cell transplantation successfully treated with oral defibrotide.

    PubMed

    Shah, Mithun S; Jeevangi, Nandish Kumar S; Joshi, Amit; Khattry, Navin

    2009-01-01

    Hepatic veno-occlusive disease (VOD) remains one of the commonest and most serious complications after myeloablative hematopoietic stem cell transplantation (HSCT). Clinical diagnosis of hepatic VOD is based on the finding of the triad of painful hepatomegaly, hyperbilirubinemia, and unexplained fluid retention occurring within 21 days of the transplant. However, the uncommon clinical entity of late-onset VOD can occur even beyond 20 days and should be considered in the differential diagnosis of any liver disease of more than 3 weeks' duration. While mild cases usually resolve spontaneously, severe VOD is associated with a grim prognosis. Defibrotide, a polydisperse mixture of single-stranded oligonucleotide with antithrombotic and fibrinolytic effects on microvascular endothelium, has emerged as an effective and safe therapy for patients with severe VOD. We describe a patient who presented 55 days post transplant with clinical features suggestive of VOD. Upon treatment with oral defibrotide, he showed complete resolution of the VOD.

  17. Veno-occlusive disease in hematopoietic stem cell transplantation recipients.

    PubMed

    Sosa, Elisabeth C

    2012-10-01

    Veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic stem cell transplantation that affects the liver, as well as other organs. Although mild cases resolve on their own, severe cases of VOD carry a high mortality rate. The diagnosis usually is clinically based, with nonspecific signs such as weight gain, ascites, hepatomegaly, right upper quadrant abdominal pain, and elevated serum bilirubin. Although studies are ongoing, no U.S. Food and Drug Administration-approved treatments for VOD exist to date. Therefore, supportive care is a critical part of the treatment plan. Oncology nurses should be familiar with the risk factors and clinical signs of VOD so that patients can be monitored closely for its occurrence. Accurate and timely recognition of VOD is crucial for appropriate treatment.

  18. Edema, anemia, hypoproteinemia, and acrodermatitis enteropathica: an uncommon initial presentation of cystic fibrosis.

    PubMed

    Muñiz, Antonio E; Bartle, Sam; Foster, Robin

    2004-02-01

    Cystic fibrosis is a genetic disorder characterized by chronic obstructive pulmonary disease, pancreatic exocrine deficiency, and abnormally high sweat electrolyte concentrations. Less frequently, the presenting features in infants may include edema, anemia, hypoproteinemia, and acrodermatitis enteropathica. Liver involvement may produce hepatomegaly and mild elevation of transaminases. This clinical symptom usually presents within the first 6 months of life and is associated with a high morbidity and mortality. Early recognition and institution of appropriate nutritional supplementation and pancreatic enzymes is essential to improve outcome. Since the sweat test may be falsely negative, emergency physicians must maintain a high index of suspicion to make the diagnosis of cystic fibrosis in an infant who presents with edema, anemia, hypoproteinemia, and acrodermatitis enteropathica.

  19. Typhoid fever: case report and literature review.

    PubMed

    Sanhueza Palma, Natalia Carolina; Farías Molina, Solange; Calzadilla Riveras, Jeannette; Hermoso, Amalia

    2016-06-21

    Typhoid fever remains a major health problem worldwide, in contrast to Chile, where this disease is an isolated finding. Clinical presentation is varied, mainly presenting with fever, malaise, abdominal discomfort, and nonspecific symptoms often confused with other causes of febrile syndrome. We report a six-year-old, male patient presenting with fever of two weeks associated with gastrointestinal symptoms, malaise, hepatomegaly and elevated liver enzymes. Differential diagnoses were considered and a Widal reaction and two blood cultures were requested; both came back positive, confirming the diagnosis of typhoid fever caused by Salmonella typhi. Prior to diagnosis confirmation, empirical treatment was initiated with ceftriaxone and metronidazole, with partial response; then drug therapy was adjusted according to ciprofloxacin susceptibility testing with a favorable clinical response. We discuss diagnostic methods and treatment of enteric fever with special emphasis on typhoid fever.

  20. Lessons from Hepatocyte-Specific Cyp51 Knockout Mice: Impaired Cholesterol Synthesis Leads to Oval Cell-Driven Liver Injury

    NASA Astrophysics Data System (ADS)

    Lorbek, Gregor; Perše, Martina; Jeruc, Jera; Juvan, Peter; Gutierrez-Mariscal, Francisco M.; Lewinska, Monika; Gebhardt, Rolf; Keber, Rok; Horvat, Simon; Björkhem, Ingemar; Rozman, Damjana

    2015-03-01

    We demonstrate unequivocally that defective cholesterol synthesis is an independent determinant of liver inflammation and fibrosis. We prepared a mouse hepatocyte-specific knockout (LKO) of lanosterol 14α-demethylase (CYP51) from the part of cholesterol synthesis that is already committed to cholesterol. LKO mice developed hepatomegaly with oval cell proliferation, fibrosis and inflammation, but without steatosis. The key trigger was reduced cholesterol esters that provoked cell cycle arrest, senescence-associated secretory phenotype and ultimately the oval cell response, while elevated CYP51 substrates promoted the integrated stress response. In spite of the oval cell-driven fibrosis being histologically similar in both sexes, data indicates a female-biased down-regulation of primary metabolism pathways and a stronger immune response in males. Liver injury was ameliorated by dietary fats predominantly in females, whereas dietary cholesterol rectified fibrosis in both sexes. Our data place defective cholesterol synthesis as a focus of sex-dependent liver pathologies.

  1. Hereditary fructose intolerance presenting as Reye's-like syndrome: report of one case.

    PubMed

    Yang, T Y; Chen, H L; Ni, Y H; Hwu, W L; Chang, M H

    2000-01-01

    Hereditary fructose intolerance (HFI) is an autosomal recessive disease caused by catalytic deficiency of aldolase B (fructose-1, 6-bisphosphate aldolase). Herein we report on a case of hereditary fructose intolerance with initial presentation of episodic unconsciousness, seizure, hypoglycemia, hepatomegaly, and abnormal liver function since the patient was 11 months old. She was diagnosed as Reye's-like syndrome according to a liver biopsy done at 20 months of age. As she grew up, cold sweating, abdominal pain or gastrointestinal discomfort shortly after the intake of fruits was noted and she developed an aversion to fruits, vegetables and sweet-tasting foods. At 9 years of age, a fructose tolerance test signified a positive result that induced hypoglycemia, transient hypophosphatemia, hyperuricaemia, elevation of serum magnesium, and accumulation of lactic acid. Appropriate dietary management and precautions were recommended. The patient has been symptom-free and exhibited normal growth and development when followed up to 12 years of age.

  2. High liver glycogen in hereditary fructose intolerance.

    PubMed

    Cain, A R; Ryman, B E

    1971-11-01

    A case of hereditary fructose intolerance is reported in a girl aged 2 years at the time of her death. She had apparently progressed normally until the age of 14 months. At 19 months she was admitted to hospital with failure to thrive, hepatomegaly, and superficial infections. Investigations revealed hypoglycaemia, persistent acidosis, aminoaciduria, and a high liver glycogen level which suggested that she had glycogen storage disease. There was also some evidence of malabsorption. At necropsy the liver enzyme estimations showed that fructose 1-phosphate aldolase activity was absent and that fructose 1,6-diphosphate aldolase activity was reduced. Hereditary fructose intolerance and glycogen storage disease have been confused in the past on clinical grounds, but a high liver glycogen level has not previously been reported in hereditary fructose intolerance.

  3. A Novel Frameshift Mutation of the ALDOB Gene in a Korean Girl Presenting with Recurrent Hepatitis Diagnosed as Hereditary Fructose Intolerance.

    PubMed

    Choi, Hae-Won; Lee, Yeoun Joo; Oh, Seak Hee; Kim, Kyung Mo; Ryu, Jeong-Min; Lee, Beom Hee; Kim, Gu-Hwan; Yoo, Han-Wook

    2012-01-01

    Hereditary fructose intolerance is an autosomal recessive disorder that is caused by a deficiency in fructose-1-phosphate aldolase (Aldolase B). Children can present with hypoglycemia, jaundice, elevated liver enzymes and hepatomegaly after intake of dietary fructose. Long-term intake of fructose in undiagnosed patients can result in hepatic failure or renal failure. We experienced a case of hereditary fructose intolerance presenting as recurrent hepatitis-like episodes. Detailed evaluation of her dietary habits revealed her avoidance of sweetened foods and fruits. Genetic analysis of ALDOB revealed that she is a homozygote for a novel frameshifting mutation c[758_759insT]+[758_759insT] (p.[val25 3fsX24]+[val253fsX24]). This report is the first of a Korean patient diagnosed with hereditary fructose intolerance using only molecular testing without undergoing intravenous fructose tolerance test or enzyme assay.

  4. Protective altruistic phlebotomy: hereditary haemochromatosis presenting as hepatocellular carcinoma in a non-cirrhotic 83-year-old man.

    PubMed

    Ooka, Kohtaro; Onyiuke, Ifeyinwa; Zhang, Xuchen; Taddei, Tamar Hamosh

    2016-09-02

    Hereditary haemochromatosis is a multisystem disorder of iron metabolism. Hepatic manifestations include hepatomegaly, cirrhosis and hepatocellular carcinoma. Hepatocellular carcinoma is almost always preceded by cirrhosis. We present a case of an 83-year-old man without history of liver disease or iron overload who presented with abdominal pain. Workup revealed mildly elevated transaminases, ferritin of 3996 and a solitary liver tumour. Biopsy was consistent with hepatocellular carcinoma in a background of haemosiderosis without cirrhosis. He was diagnosed with hereditary haemochromatosis and hepatocellular carcinoma. He underwent a partial hepatectomy and was started on routine phlebotomy and surveillance imaging. He has improved and has not had signs of recurrence or new complications of haemochromatosis. We suggest a possible reason for his unique and late presentation.

  5. Factors affecting Brucella spp. blood cultures positivity in children.

    PubMed

    Apa, Hurşit; Devrim, Ilker; Memur, Seyma; Günay, Ilker; Gülfidan, Gamze; Celegen, Mehmet; Bayram, Nuri; Karaarslan, Utku; Bağ, Ozlem; Işgüder, Rana; Oztürk, Aysel; Inan, Seyhan; Unal, Nurrettin

    2013-03-01

    Brucella infections have a wide spectrum of symptoms especially in children, making the diagnosis a complicated process. The gold standard for the final diagnosis for brucellosis is to identify the Brucella spp. isolated from blood or bone marrow cultures. The main purpose of this work was to evaluate the factors affecting the isolation of Brucella spp. from blood cultures. In our study, the ratio of fever, presence of hepatomegaly, and splenomegaly were found to be higher in the bacteremic group. In addition, C-reactive protein levels and liver function enzymes were found to be higher in the bacteremic group. In our opinion, while evaluating the febrile child with suspected Brucella infection, we highly recommend sampling blood cultures regardless of the history of previous antimicrobial therapy and duration of the symptoms.

  6. Sphingomyelin lipidosis (Niemann-Pick disease) in a juvenile raccoon (Procyon lotor).

    PubMed

    Vapniarsky, N; Wenger, D A; Scheenstra, D; Mete, A

    2013-01-01

    A wild caught juvenile male raccoon with neurological disease was humanely destroyed due to poor prognosis. Necropsy examination revealed hepatomegaly, splenomegaly and multicentric lymphadenomegaly with diffuse hepatic pallor and pulmonary consolidation with pinpoint pale subpleural foci. Microscopically, there was marked pale cytoplasmic swelling of the central and peripheral neurons as well as the glial cells in the brain, accompanied by multiorgan infiltration by abundant foamy macrophages. Ultrastructural investigation revealed accumulation of concentrically arranged lamellar material within lysosomes of the affected neurons, macrophages and endothelial cells. Biochemical enzymatic analysis detected sphingomyelinase deficiency and lysosomal storage disease consistent with sphingomyelin lipidosis (Niemann-Pick disease [NPD]) was diagnosed. This is the first report of NPD in a raccoon.

  7. Primary amyloidosis and severe intrahepatic cholestatic jaundice.

    PubMed Central

    Peters, R A; Koukoulis, G; Gimson, A; Portmann, B; Westaby, D; Williams, R

    1994-01-01

    Liver involvement in systemic amyloidosis is frequent but is rarely of clinical importance. Five patients with severe cholestatic jaundice are described and an additional 20 from published reports are reviewed. The most frequent presenting symptoms were lethargy and abdominal pain, which were present for a median of 11 months before the onset of jaundice. Hepatomegaly, usually marked, was present in 92%, with ascites in 56% of the cases. The serum bilirubin concentration was noticeably high and the serum globulin low. Histology of the liver showed considerable perisinusoidal deposition with a slight predilection for the periportal area. Two patients presented with predominant centrilobular deposition. Congo red staining was not uniformly positive. A variety of treatment regimens was tried but median survival was only three months from the onset of jaundice. PMID:7959246

  8. [NASH: REPORT OF THE FIRST CASES AT THE GUILLERMO ALMENARA HOSPITAL

    PubMed

    Padilla Machaca, P. Martín; Torreblanca Nava, Juan; Ferrándiz Quiroz, Jorge; Asato Higa, Carmen

    2000-01-01

    The biochemical, clinical and histological findings are described in nine patients of the Gastroenterology Service of the Guillermo Almenara Irigoyen National Hospital - EsSALUD, with diagnosis of nonalcoholic steatohepatitis (NASH) between January 1996 and April 1998.They did not have significant differences in relation to sex prevalence (5 males and 4 women). Five patients were obese, 2 patients had diabetes mellitus, 5 hyperlipidemic values and a patient was taking prednisone for more than 2 years. Only 2 patients were asymptomatic at the moment of the study; while 4 patients presented with abdominal discomfort, 2 patient had pain in the right upper quadrant (RUQ), 5 patients referred fatigue and hepatomegaly was found on clinical examination. All the patients presented high levels of aminotransferases at the study. All the patients had steatohepatitis in the histology with different combinations of injury to the hepatocyte. Fibrosis and cirrhosis were found in 3 patients. Our results were compared with that described by other authors.

  9. Neonatal Jaundice with Splenomegaly: Not a Common Pick.

    PubMed

    Gotti, Giacomo; Marseglia, Antonio; De Giacomo, Costantino; Iascone, Maria; Sonzogni, Aurelio; D'Antiga, Lorenzo

    2016-01-01

    The most common conditions causing cholestatic jaundice in infants are biliary atresia, neonatal hepatitis, and Alagille syndrome. In these disorders, the clinical presentation includes jaundice, pale stools, dark urine and hepatomegaly. Splenomegaly is not an early feature since it is due to portal hypertension, a later event. The finding of cholestatic jaundice and a large spleen usually raises the suspicion of Niemann-Pick type C disease (NP-C), a lysosomal storage disorder. We present and discuss here a case of an infant with liver disease and splenomegaly that were not ascribed to NP-C, but to Gaucher disease type 2. Liver biopsy, enzymatic studies and whole exome sequencing allowed to make the diagnosis. Although rare, Gaucher disease can cause neonatal hepatitis. A prompt recognition is advocated.

  10. Polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS syndrome): a paraneoplastic syndrome

    PubMed Central

    Kumar, Sunil; Sharma, Shruti

    2015-01-01

    POEMS syndrome (Crow–Fukase syndrome) is a rare paraneoplastic disorder. It is characterized by peripheral neuropathy, elevated vascular endothelial growth factors (VEGFs), monoclonal gammopathy, sclerotic bone lesions and Castleman disease. Other important clinical features are organomegaly, edema, ascites, papilledema, endocrinopathy, skin changes and thrombocytosis. A high index of suspicion, a detailed clinical history and examination followed by appropriate laboratory investigations like VEGF level, radiological skeletal survey and bone marrow biopsy are required to diagnose POEMS syndrome. We report a case of POEMS syndrome who presented with insidious onset, progressive sensorimotor polyneuropathy, pedal edema, ascites, hepatomegaly, skin changes and hypothyroidism. X-ray of the pelvis showed osteosclerotic lesions. Immunoelectrophoresis using the immunofixation method revealed lambda chain monoclonal gammopathy. The patient was given radiotherapy, followed by a combination therapy of melphalan and dexamethasone. We emphasize the importance of recognizing a challenging diagnosis of a rare disease, which is shown to be treatment responsive. PMID:26634133

  11. Hepatic capillariasis in a Cape ground squirrel (Xerus inaurus).

    PubMed

    Erlwanger, K H; De Witt, B A; Fick, L G; Hetem, R S; Meyer, L C R; Mitchell, D; Wilson, W A; Mitchell, B

    2009-12-01

    We report, for the first time, an incidental finding of Calodium hepaticum infestation in a sub-adult female Cape ground squirrel (Xerus inaurus). Post mortem examination of the squirrel revealed severe haemoperitoneum, splenomegaly and hepatomegaly with miliary white spots distributed diffusely throughout the hepatic parenchyma. Histologically the portal tracts in the liver showed granulomatous inflammation with fibrosis and numerous giant cells. Occasional adult worms were identified and there were multiple C. hepaticum eggs distributed diffusely throughout the portal tracts and the parenchyma. The spleen also contained C. hepaticum eggs. The genus Rattus is the primary host and reservoir of C. hepaticum, but C. hepaticum infections have been reported previously in other Sciuridae. Based on our findings, people should be cautious of the zoonotic potential of C. hepaticum, when they come into contact with the Cape ground squirrel.

  12. A case of advanced second-degree atrioventricular block in a ferret secondary to lymphoma

    PubMed Central

    Menicagli, F.; Lanza, A.; Sbrocca, F.; Baldi, A.; Spugnini, E.P.

    2016-01-01

    A female ferret was referred as an emergency for severe respiratory distress symptoms. At presentation, the patient was listlessness, dyspnoeic, and hyper-responsive. The clinical examination evidenced dyspnea with cyanosis, altered cardiac rhythm, and hepatomegaly. Electrocardiography showed an advanced second-degree atrioventricular (AV) block. The liver aspirate was diagnostic for lymphoma. The patient did not respond to supportive therapy and rapidly died. Post-mortem exams confirmed the presence of lymphoma with hepatic involvement. Moreover, a pericardial lymphocytic infiltration and a widespread myocardial nodular localization of lymphoma were evidenced as well. This condition was probably the cause of the cardiac arrhythmia. To the best of our knowledge, ours is the first report of cardiac lymphoma causing heart block in ferrets. PMID:27200273

  13. Imaging Features of Pediatric Pentastomiasis Infection: a Case Report

    PubMed Central

    Wang, Xi Qun; Lin, Long; Gao, De Chun; Zhang, Hong Xi; Zhang, Yi Ying; Zhou, Yin Bao

    2010-01-01

    We report here a case of pentastomiasis infection in a 3-year-old girl who had high fever, abdominal pain, abdominal tension and anemia. Ultrasound scanning of the abdomen revealed disseminated hyperechoic nodules in the liver and a small amount of ascites. Abdominal MRI showed marked hepatomegaly with disseminated miliary nodules of high signal intensity throughout the hepatic parenchyma on T2-weighted images; retroperitoneal lymphadenopathy and disseminated miliary nodules on the peritoneum were also noted. Chest CT showed scattered small hyperdense nodules on both sides of the lungs. The laparoscopy demonstrated diffuse white nodules on the liver surface and the peritoneum. After the small intestinal wall and peritoneal biopsy, histological examination revealed parenchymal tubercles containing several larvae of pentastomids and a large amount of inflammatory cell infiltration around them. The pathological diagnosis was parasitic granuloma from pentastomiasis infection. PMID:20592934

  14. Case Report: Congenital Erythroleukemia in a Premature Infant with Dysmorphic Features.

    PubMed

    Helin, Heidi; van der Walt, Jon; Holder, Muriel; George, Simi

    2016-01-01

    We present a case of pure erythroleukemia, diagnosed at autopsy, in a dysmorphic premature infant who died of multiorgan failure within 24 hours of birth. Dysmorphic features included facial and limb abnormalities with long philtrum, microagnathia, downturned mouth, short neck as well as abnormal and missing nails, missing distal phalanx from the second toe, and overlapping toes. Internal findings included gross hepatomegaly and patchy hemorrhages in the liver, splenomegaly, and cardiomegaly; and subdural, intracerebral, and intraventricular hemorrhages. Histology revealed infiltration of bone marrow, kidney, heart, liver, adrenal, lung, spleen, pancreas, thyroid, testis, thymus, and placenta by pure erythroleukemia. Only 6 cases of congenital erythroleukemia have been previously reported with autopsy findings similar to those of this case. The dysmorphic features, although not fitting any specific syndrome, make this case unique. Congenital erythroleukemia and possible syndromes suggested by the dysmorphic features are discussed.

  15. Radiographic features of plasma cell leukemia in the maxilla: A case report

    PubMed Central

    Wong, Phillip; Kashtwari, Deeba

    2016-01-01

    Plasma cell leukemia (PCL) is an aggressive form of multiple myeloma where there is hematogenous spread of abnormal plasma cells into the periphery. This is opposed to multiple myeloma, where the abnormal plasma cells stay in the bone marrow. PCL is more common in males than females, and is also more common in African-Americans than Caucasians. Signs and symptoms of PCL include, but are not limited to, renal insufficiency, hypercalcemia, anemia, lytic bone lesions, thrombocytopenia, hepatomegaly, and splenomegaly. Here, we discussed a case of a 71-year-old Caucasian female recently diagnosed with primary PCL with radiographic features of this disease throughout the body, with an emphasis on the maxillofacial skeleton and relevance from a dental standpoint. PMID:28035306

  16. Hepatic toxocariasis: a rare cause of right upper abdominal pain in the emergency department.

    PubMed

    Coşkun, Figen; Akıncı, Emine

    2013-01-01

    Toxocara canis and Toxocara cati are common helminths that reside in the intestinal tract of cats and dogs. Toxocariasis and, commonly, T. canis, is a disease commonly seen in children, which is characterised by hypereosinophilia, hepatomegaly, fever, transient pulmonary infiltration, and hypergammaglobulinaemia. Humans, who are not the actual host for these parasitic worms, are infected following oral intake of the infective eggs. Radiological differentiation of hepatic toxocariasis can be difficult, as liver lesions, which present as multiple hypoechoic lesions with regular borders, can look like a tumour, an infarction or an infection. We report on a case that presented to our emergency department (ED) with abdominal pain. During the initial review, the pathology in the liver was thought to be an infarction or an infection; however, the patient was diagnosed with hepatic toxocariasis following further evaluation.

  17. A study of the toxicity of imidocarb dipropionate in cattle.

    PubMed

    Adams, L G; Corrier, D E; Williams, J D

    1980-03-01

    The toxic effects of imidocarb dipropionate (3,3'-bis[2-imidazolin-2-yl] carbanilide dipropionate) were studied in calves injected twice intramuscularly with 0, 5, 10 or 20 mg/kg dosages. Transient, dosage dependent signs of toxicosis consisted of excessive salivation, serous nasal discharge, diarrhoea and dyspnoea. Elevations in blood urea nitrogen concentrations and serum glutamic oxalacetic transaminase activities were related to dosage and markedly increased at the high dosage. Renal hyperaemia, hepatomegaly, pulmonary congestion and oedema, hydrothorax, hydroperitoneum, hydropericardium and mortality occurred at the 20 mg/kg dosage. Microscopic lesions observed at the high dosage included acute severe renal tubular necrosis and focal hepatocellular necrosis. Injection site reactions varied from microscopic areas of necrotising myositis at the 5 mg/kg dosage to focal grossly visible areas of necrosis, encapsulated by granulation tissue and surrounded by fascial oedema at the 20 mg/kg dosage.

  18. High-output heart failure in a newborn.

    PubMed

    Mascarenhas, Maria Inês; Moniz, Marta; Ferreira, Sofia; Goulão, Augusto; Barroso, Rosalina

    2012-07-10

    High-output cardiac failure is rare in newborns. Emergent diagnosis and management of this pathology is crucial. We report the case of a child, currently 12-months old; obstetric background is non-contributory. Clinic observation on D1 was normal except for the presence of a systolic cardiac murmur; cardiological evaluation revealed mild ventricular dysfunction of the right ventricle. On the third day of life, she developed cardiac failure with gallop rhythm, hepatomegaly and a murmur in the anterior fontanel; an echocardiogram confirmed clinic aggravation with biventricular dysfunction and right cavities and superior vena cava dilatation. The cranial MRI confirmed the presence of a pial arteriovenous malformation (AVM) involving the anterior and middle cerebral arteries with an associated fronto-parietal ischaemic lesion. The infant underwent embolisations of AVM with successful flow reduction and cardiac failure improvement. The multidisciplinary follow-up showed no cardiac dysfunction or permanent lesions but confirmed a severe psycho-motor delay and left hemiparesia.

  19. A preterm infant with secondary carnitine deficiency due to MCT formula--effective treatment of L-carnitine.

    PubMed

    Ishida, A; Goto, A; Takahashi, Y; Nakajima, W; Arai, H; Tazawa, Y; Takada, G

    1994-01-01

    We report a preterm infant who was prescribed an MCT formula and subsequently developed carnitine deficiency with liver dysfunction and an elevation of serum CK level. A male infant who had been born at 24 weeks' gestation with birth weight 799 g, was fed with an MCT formula containing 76.8% of all kinds of lipids, because of his steatorrhea after the 30th day. On the 100th day, he was noted hepatomegaly and elevation of serum levels of AST, ALT and CK. The needle biopsy of the liver indicated the existence of the liver damage. He showed low serum carnitine with high urinary loss of acylcarnitine and dicarboxylic aciduria. Administration of L-carnitine was an effective treatment. The carnitine deficiency might be exaggerated by an increased urinary loss of acylcarnitine. We should be cautious of the risk of carnitine deficiency in preterm infants during prolonged use of MCT formula.

  20. [Abdominal tomometry. Application to study of the liver. Experimental study, initial clinical results and perspectives in the exploration of tumour pathology (author's transl)].

    PubMed

    Lamarque, J L; Bruel, J M; Dondelinger, R; Sénac, J P; Rabischong, P; Bonnel, F; Laval-Jeantet, M; Laval-Jeantet, A M

    1977-04-01

    Over a period of two months, 120 patients were studied using an Acta-Scanner tomometer for various hepatic disorders. In parallel, comparative tomometric and pathological studies were carried out in cadavers and isolated livers. These made possible the recognition of normal structures in tomometry and the identification of certain hepatic images which might be potential sources of error. Serial axial transverse sections were used to reconstruct the volume of the liver in space, thus making in possible to eliminate certain forms of pseudo-tumoural hepatomegaly. Systematic densitometric analysis was made by radiological anatomical study and in hepatic pathology. This new type of analysis led to a quantified diagnosis of certain diffuse hepatic diseases and a histological approach to tumour lesions. Hepatography using liposoluble agents in very low dosage was used in hepatic tomometry after animal experimentation. The method, free of untoward effects, makes possible the diagnosis of hepato-splenic tumor lesions less than one centimetre in diameter.

  1. Autoimmune hepatitis in a teenage boy: 'overlap' or 'outlier' syndrome--dilemma for internists.

    PubMed

    Talukdar, Arunansu; Khanra, Dibbendhu; Mukherjee, Kabita; Saha, Manjari

    2013-02-08

    An 18-year-old boy presented with upper gastrointestinal bleeding and jaundice. Investigations revealed coarse hepatomegaly, splenomegaly and advanced oesophageal varices. Blood reports showed marked rise of alkaline phosphatase and more than twofold rise of transaminases and IgG. Liver histology was suggestive of piecemeal necrosis, interphase hepatitis and bile duct proliferation. Antinuclear antibody was positive in high titre along with positive antismooth muscle antibody and antimitochondrial antibody. The patient was positive for human leukocyte antigen DR3 type. Although an 'overlap' syndrome exists between autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), a cholestatic variant of AIH, a rare 'outlier' syndrome could not be excluded in our case. Moreover, 'the chicken or the egg', AIH or PBC, the dilemma for the internists continued. The patient was put on steroid and ursodeoxycholic acid with unsatisfactory response. The existing international criteria for diagnosis of AIH are not generous enough to accommodate its variant forms.

  2. Mosaic "tetrasomy" 8p: case report and review of the literature.

    PubMed

    Winters, J; Markello, T; Nance, W; Jackson-Cook, C

    1995-10-01

    A male infant presenting with multiple anomalies including a midline cleft palate, anasarca, hepatomegaly, pulmonary edema, agenesis of the corpus collosum, and complex congential cardiac anomalies was found to have mosaicism for an additional chromosome that appeared (following GTG-banding and FISH) to be a monocentric isochromosome of the short arm of chromosome 8 (46,XY/47,XY, +i(8p)). Nine other cases of mosaicism for an additional i(8p) were reviewed. Considerable phenotypic variation was noted. Consistent features were identified including agenesis of the corpus callosum, cardiac malformations, and minor facial dysmorphology. The phenotype of these patients partially overlaps those of trisomy 8 and trisomy 8p. By studying additional individuals with this condition, mosaic tetrasomy 8p may emerge as a recognizable clinical phenotype.

  3. Tophaceous gout in a female premenopausal patient with an unexpected diagnosis of glycogen storage disease type Ia: a case report and literature review.

    PubMed

    Zhang, Bingqing; Zeng, Xuejun

    2016-11-01

    A young female with recurrent tophaceous gout and infertility presented to our clinic. On clinical evaluation, hypoglycaemia, hypertriglyceridaemia, lactic acidosis, and hepatomegaly were noted. Targeted gene sequencing revealed a novel composite heterozygous c.190G>T/c.508C>T mutation in the G6PC gene of the patient, leading to a diagnosis of glycogen storage disease type Ia. Her father possessed a heterozygous c.190G>T mutation, and her mother possessed a heterozygous c.508C>T mutation. A search of the previous literature revealed 16 reported cases of glycogen storage disease type Ia with gout. Here, we describe a female patient with gout, review previous cases, and discuss the mechanisms of gout and hyperuricaemia in glycogen storage disease type Ia.

  4. Metabolic and structural consequences of ethanol and chloroquin administration during gestation on the developing fetus

    SciTech Connect

    Sharma, A.; Rawat, A.K.

    1987-05-01

    In the present study the effects of ethanol and chloroquin administration during gestation have been investigated on the developing rat fetus. Ethanol was given in liquid Sustacal diet as 30% of calories and controls were fed isocaloric sucrose-diet. Chloroquin was given intragastrically corresponding controls received saline. Chloroquin resulted in prenatal growth retardation leading to maximum decrease of 46% in body weight of the fetus. It also resulted in 30% higher incidence of hepatomegaly; 15% higher incidence of liquification of visceral organs; 34% decrease in the ossification of sternum; 9% higher defects of cleft palate, wrist drop, clubbed foot and brain liquification compared to the corresponding controls. Ethanol resulted in pre and post-natal growth retardation, cleft palate, still births and lowered brain weights. Fetuses from the ethanol-fed group also showed inhibited protein synthesis, RNA and DNA synthesis in the brain compared to the controls.

  5. Hb Lansing (HBA2: c.264C > G) and a new β promoter transversion [-52 (G > T)]: an attempt to define the phenotype of two mutations found in the Omani population.

    PubMed

    Hassan, Suha M; Harteveld, Cornelis L; Bakker, Engbert; Giordano, Piero C

    2015-01-01

    We report two examples showing how problematic it can be to define the phenotype of new or rare globin genes mutations. We describe two mutations observed for the first time in the Omani population: the first was found in the consanguineous parents of a deceased newborn with hepatomegaly, cardiomegaly and severe hemolytic anemia, putatively homozygous for the rare Hb Lansing (HBA2: c.264C > G) variant. The second is a novel β-globin gene promoter mutation [-52 (G > T)] observed in four independent patients. Two with borderline/elevated Hb A2, α-thalassemia (α-thal) and hypochromic red cell indices, and two heterozygotes for Hb S (HBB: c.20A > T), α-thal and with Hb A/Hb S ratios possibly indicating a very mild β(+)-thalassemia (β(+)-thal) mutation.

  6. Early manifestations of multiple sulfatase deficiency.

    PubMed

    Burk, R D; Valle, D; Thomas, G H; Miller, C; Moser, A; Moser, H; Rosenbaum, K N

    1984-04-01

    We describe two boys, presenting by 1 year of age, with developmental delay from birth, mildly coarse facial features, and hepatomegaly. These clinical features were most suggestive of a mucopolysaccharidosis, particularly MPS II. Biochemical studies, including sulfate incorporation in fibroblasts and lysosomal enzyme analyses in fibroblasts, leukocytes, and serum, showed abnormalities in both sulfatide and mucopolysaccharide metabolism and led to the diagnosis of multiple sulfatase deficiency. With time, both patients developed an ichthyotic rash and profound intellectual deterioration. We conclude that findings in the first year of life in some patients with MSD may closely resemble those in patients with a MPS disorder rather than the late infantile form of metachromatic leukodystrophy, as is classically described. Thus, MSD should be considered in the young patient suspected of having a MPS disorder.

  7. Opisthorchis viverrini: The carcinogenic human liver fluke

    PubMed Central

    Kaewpitoon, Natthawut; Kaewpitoon, Soraya J; Pengsaa, Prasit; Sripa, Banchob

    2008-01-01

    Opisthorchiasis caused by Opisthorchis viverrini remains a major public health problem in many parts of Southeast Asia, including Thailand, Lao PDR, Vietnam and Cambodia. The infection is associated with a number of hepatobiliary diseases, including cholangitis, obstructive jaundice, hepatomegaly, cholecystitis and cholelithiasis. Multi-factorial etiology of cholangiocarcinoma, mechanical damage, parasite secretions, and immunopathology may enhance cholangiocarcinogenesis. Moreover, both experimental and epidemiological evidences strongly implicate liver fluke infection as the major risk factor in cholangiocarcinoma, cancer of the bile ducts. The liver fluke infection is induced by eating raw or uncooked fish products that is the tradition and popular in the northeastern and northern region, particularly in rural areas, of Thailand. The health education programs to prevent and control opisthorchiasis are still required in the high-risk areas. PMID:18205254

  8. Glycogen storage disease type III in the Irish population.

    PubMed

    Crushell, Ellen; Treacy, Eileen P; Dawe, J; Durkie, M; Beauchamp, Nicholas J

    2010-12-01

    Glycogen storage disease type III (GSD III) results from mutations of the AGL gene encoding the glycogen debrancher enzyme. The disease has clinical and biochemical heterogeneity reflecting the severity of the AGL mutations. We sought to characterise the molecular defects in our cohort of Irish patients with GSD III. Fifteen patients from eight unrelated Irish families were identified: six males and nine females. The age ranged from 2-39 years old, and all presented in the first 3 years of life. Four patients (of three families) had mild disease with hepatomegaly, mild hypoglycaemia and normal creatine kinase (CK) levels. Five families had more severe disease, with liver and skeletal muscle involvement and elevated CK. Eleven different mutations were identified amongst the eight families. Of the 11, six were novel: p.T512fs, p.S736fs, p.A1400fs, p.K1407fs, p.Y519X and p.D627Y. The family homozygous for p.A1400fs had the most severe phenotype (early-onset hypoglycaemia, massive hepatomegaly, myopathy and hypertrophic cardiomyopathy before age 2 years), which was not halted by aggressive carbohydrate and protein supplementation. Conversely, the only missense mutation identified in the cohort, p.D627Y, was associated with a mild phenotype. The phenotypic diversity in our GSD III cohort is mirrored by the allelic heterogeneity. We describe two novel null mutations in exon 32 in two families with severe GSD III resistant to current treatment modalities. Knowledge of the specific mutations segregating in this cohort may allow for the development of new therapeutic interventions.

  9. Anti-diabetic and hypolipidemic effects of Sargassum yezoense in db/db mice

    SciTech Connect

    Kim, Su-Nam; Lee, Woojung; Bae, Gyu-Un; Kim, Yong Kee

    2012-08-10

    Highlights: Black-Right-Pointing-Pointer Sargassum yezoense (SY) treatment improved glucose and lipid impairment in vivo. Black-Right-Pointing-Pointer This pharmacological action is associated with PPAR{alpha}/{gamma} dual activation. Black-Right-Pointing-Pointer It decreases the expression of G6Pase for gluconeogenesis in liver. Black-Right-Pointing-Pointer It increases the expression of UCP3 for lipid metabolism in adipose tissue. Black-Right-Pointing-Pointer There are no significant side effects such as body weight gain and hepatomegaly. -- Abstract: Peroxisome proliferator-activated receptors (PPARs) have been considered to be desirable targets for metabolic syndrome, even though their specific agonists have several side effects including body weight gain, edema and tissue failure. Previously, we have reported in vitro effects of Sargassum yezoense (SY) and its ingredients, sargaquinoic acid (SQA) and sargahydroquinoic acid (SHQA), on PPAR{alpha}/{gamma} dual transcriptional activation. In this study, we describe in vivo pharmacological property of SY on metabolic disorders. SY treatment significantly improved glucose and lipid impairment in db/db mice model. More importantly, there are no significant side effects such as body weight gain and hepatomegaly in SY-treated animals, indicating little side effects of SY in liver and lipid metabolism. In addition, SY led to a decrease in the expression of G6Pase for gluconeogenesis in liver responsible for lowering blood glucose level and an increase in the expression of UCP3 in adipose tissue for the reduction of total and LDL-cholesterol level. Altogether, our data suggest that SY would be a potential therapeutic agent against type 2 diabetes and related metabolic disorders by ameliorating the glucose and lipid metabolism.

  10. [Autoimmune lymphoproliferative syndrome: a case report and literature review].

    PubMed

    Sun, Jia-peng; Lu, Xin-tian; Zhao, Wei-hong; Hua, Ying

    2015-12-18

    We described 1 case of autoimmune lymphoproliferative syndrome (ALPS), first diagnosed in our hospital, and reviewed the recent literature. The 11-month old male patient presented with a history of splenomegaly and hepatomegaly since 1 month after birth. He suffered recurrent infectious diseases including cytomegalovirus infection, parvovirus B19 infection and chronic diarrhea disease. Besides, his symptoms included hemolytic anemia and thrombocytopenia. The laboratory abnormality indicated an expanded population of alpha/beta double-negative T cells (DNTs) (27.18% of lymphocytes, 35.16% of CD3+ T lymphocytes) in peripheral blood, and autoantibodies including antinuclear antibody, double-stranded DNA and rheumatic factor were positive. Hyper gamma globulinemia and positive direct Coombs tests were seen in the patient. His parents were both healthy and denied autoimmune diseases. We identified a heterozygous point mutation in exon 3 of the FAS gene carrying c.309 A>C, resulting in a single base pair substitution in exon 3 of FAS gene which changed the codon of Arg103 to Ser103. Unfortunately, we were unable to obtain the gene results of the child's parents. The patient was treated with glucocorticoids in our hospital and with mycophenolatemofetil in other hospital. And we were informed that his anemia condition relieved through the telephone follow-up, but he still suffered recurrent infections, hepatomegaly and splenomegaly still existed. As we all know ALPS is characterized by defective lymphocyte apoptosis, and thus cause lymphoproliferative disease and autoimmune disease, and increase the risk of lymphoma. It is more likely to be misdiagnosed as other diseases. ALPS should be suspected in the case of chronic lymphadenopathy, splenomegaly and autoimmune features. Flow cytometry approach is helpful for the diagnosis. Immunosuppressive drugs are the necessary treatment.

  11. Weight change therapy as a potential treatment for end-stage ovarian carcinoma

    PubMed Central

    Oshakbayev, Kuat Pernekulovich; Alibek, Kenneth; Ponomarev, Igor Olegovich; Uderbayev, Nurlybek Nurlanovich; Dukenbayeva, Bibazhar Abayevna

    2014-01-01

    Patient: Female, 41 Final Diagnosis: Ovarian carcinoma Symptoms: Ascites • hepatomegaly • weight loss Medication: — Clinical Procedure: — Specialty: Oncology Objective: Unusual or unexpected effect of treatment Background: The aim of this case report is to present the results of treatment of end-stage ovarian carcinoma in a 41-year-old women using weight loss therapy. Case Report: We describe the case of a female aged 41 years with epithelial invasive ovarian cancer of III–IV stage, T3N2M1. Concurrent diseases were: abdominal carcinomatosis; hepatomegaly; ascites; condition after laparocentesis and skin-abdominal fistula; condition after 6 courses of neo-adjuvant polychemotherapy; hypertension II stage, risk factor of 3–4; dyslipidemia; and metabolic syndrome. A weight loss method based on a very-low-calorie diet and physical activity was used. Body weight was reduced from 74 kg to 53 due to loss of adipose tissue after 6 months of therapy. At the same time, the percentages of water and muscle tissue were increased significantly. While overweight was reducing, clinical, laboratory, and instrumental results were improving. As a result of the weight loss therapy, about ≈100 mm-sized ovarian cancer was transformed into smaller-sized ovarian cysts. Conclusions: An analgesic effect was also achieved without use of narcotic or non-narcotic analgesics. These cyto-reversible processes were documented by laboratory and instrumental data. The mechanisms behind these differences remain to be elucidated. Future research with a larger study cohort and longer follow-up is needed to further investigate the role of caloric restriction diet in cancer cell changes in ovarian cancer. PMID:24847411

  12. Dengue Infection in Children in Ratchaburi, Thailand: A Cohort Study. II. Clinical Manifestations

    PubMed Central

    Sirivichayakul, Chukiat; Limkittikul, Kriengsak; Chanthavanich, Pornthep; Jiwariyavej, Vithaya; Chokejindachai, Watcharee; Pengsaa, Krisana; Suvannadabba, Saravudh; Dulyachai, Wut; Letson, G. William; Sabchareon, Arunee

    2012-01-01

    Background Dengue infection is one of the most important mosquito-borne diseases. More data regarding the disease burden and the prevalence of each clinical spectrum among symptomatic infections and the clinical manifestations are needed. This study aims to describe the incidence and clinical manifestations of symptomatic dengue infection in Thai children during 2006 through 2008. Study Design This study is a school-based prospective open cohort study with a 9,448 person-year follow-up in children aged 3–14 years. Active surveillance for febrile illnesses was done in the studied subjects. Subjects who had febrile illness were asked to visit the study hospital for clinical and laboratory evaluation, treatment, and serological tests for dengue infection. The clinical data from medical records, diary cards, and data collection forms were collected and analyzed. Results Dengue infections were the causes of 12.1% of febrile illnesses attending the hospital, including undifferentiated fever (UF) (49.8%), dengue fever (DF) (39.3%) and dengue hemorrhagic fever (DHF) (10.9%). Headache, anorexia, nausea/vomiting and myalgia were common symptoms occurring in more than half of the patients. The more severe dengue spectrum (i.e., DHF) had higher temperature, higher prevalence of nausea/vomiting, abdominal pain, rash, diarrhea, petechiae, hepatomegaly and lower platelet count. DHF cases also had significantly higher prevalence of anorexia, nausea/vomiting and abdominal pain during day 3–6 and diarrhea during day 4–6 of illness. The absence of nausea/vomiting, abdominal pain, diarrhea, petechiae, hepatomegaly and positive tourniquet test may predict non-DHF. Conclusion Among symptomatic dengue infection, UF is most common followed by DF and DHF. Some clinical manifestations may be useful to predict the more severe disease (i.e., DHF). This study presents additional information in the clinical spectra of symptomatic dengue infection. PMID:22389735

  13. Negative screening tests in classical galactosaemia caused by S135L homozygosity.

    PubMed

    Crushell, E; Chukwu, J; Mayne, P; Blatny, J; Treacy, E P

    2009-06-01

    Classical galactosaemia is relatively common in Ireland due to a high carrier rate of the Q188R GALT mutation. It is screened for using a bacterial inhibition assay (BIA) for free galactose. A Beutler assay on day one of life is performed only in high risk cases (infants of the Traveller community and relatives of known cases). A 16-month-old Irish-born boy of Nigerian origin was referred for investigation of developmental delay, and failure to thrive. He had oral aversion to solids and his diet consisted of cow's milk and milk-based cereal mixes. He was found to have microcephaly, weight <2nd percentile, hepatomegaly and bilateral cataracts. Coagulation screen was normal and transaminases were slightly elevated. His original newborn screen was reviewed and confirmed to have been negative; urinary reducing substances on three separate occasions were negative. Beutler assay demonstrated "absent" red cell galactose-1-phosphate uridyltransferase (GALT) activity. GALT enzyme activity was <0.5 gsubs/h per gHb confirming classical galactosaemia. Gal-1-P was elevated at 1.88 micromol/gHb. Mutation analysis of the GALT gene revealed S135L homozygosity. S135L/S135L galactosaemia is associated with absent red cell GALT activity but with approximately 10% activity in other tissues such as the liver and intestines, probably explaining the negative screening tests and the somewhat milder phenotype associated with this genotype. The patient was commenced on galactose-restricted diet; on follow-up at 2 years of age, growth had normalized but there was global developmental delay. In conclusion, galactosaemia must be considered in children who present with poor growth, hepatomegaly, developmental delay and cataracts and GALT enzyme analysis should be a first line test in such cases. Non-enzymatic screening methods such as urinary reducing substances and BIA for free galactose are not reliable in S135L homozygous galactosaemia.

  14. Immunotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in a complex environmental mixture from the Love Canal

    SciTech Connect

    Silkworth, J.B.; Cutler, D.S.; Sack, G.

    1989-02-01

    The organic phase of the leachate (OPL) from the Love Canal chemical dump site contains more than 100 organic compounds including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The immunotoxic potential of OPL was determined in two mouse strains which differ in their sensitivity to aromatic hydrocarbon (Ah) receptor-mediated toxicity. OPL was administered in corn oil in a single oral gavage to male BALB/cByJ (Ahb/Ahb) mice (0.5, 0.8, or 1.1 g/kg) and DBA/2J (Ahd/Ahd) mice (0.6, 0.9, or 1.3 g/kg). TCDD was similarly administered at 0.25, 1.0, 4.0, or 16.0 micrograms/kg. Two days later all mice were immunized with sheep erythrocytes (SRBC). The antibody response (PFC) and organ weights were evaluated 4 days later. OPL produced thymic atrophy and hepatomegaly in both strains at all dose levels. The PFC/spleen in BALB/cByJ mice was significantly reduced at the three doses to 34, 13, and 15%, respectively, of the control response. Serum anti-SRBC antibody levels and relative spleen weights were also reduced. The only immune effect in the DBA/2J mice was a decrease of the PFC/spleen to 58% of the control at the highest dose. TCDD decreased the relative thymus and spleen weights only in BALB/cByJ mice. However, TCDD produced hepatomegaly, a decrease in serum antibody, and a decrease in PFC/spleen in both BALB/cByJ and DBA/2J mice to 3 and 15%, respectively, at 16 micrograms/kg. Thus, the TCDD dose required to cause a 50% suppression (ED50) of PFC/spleen for the BALB/cByJ and DBA/2J strains was 1.84 and 3.89 micrograms/kg, respectively. The ED50 for OPL was 0.24 g/kg in BALB/cByJ mice. The TCDD concentration in the OPL was estimated to be 7.6 ppm, which agrees closely with the chemical analysis (3 ppm).

  15. Decline in infection-related morbidities following drug-mediated reductions in the intensity of Schistosoma infection: A systematic review and meta-analysis

    PubMed Central

    Andrade, Gisele; Bertsch, David J.; Gazzinelli, Andrea

    2017-01-01

    Background Since 1984, WHO has endorsed drug treatment to reduce Schistosoma infection and its consequent morbidity. Cross-sectional studies suggest pre-treatment correlation between infection intensity and risk for Schistosoma-related pathology. However, evidence also suggests that post-treatment reduction in intensity may not reverse morbidity because some morbidities occur at all levels of infection, and some reflect permanent tissue damage. The aim of this project was to systematically review evidence on drug-based control of schistosomiasis and to develop a quantitative estimate of the impact of post-treatment reductions in infection intensity on prevalence of infection-associated morbidity. Methodology/Principal findings This review was registered at inception with PROSPERO (CRD42015026080). Studies that evaluated morbidity before and after treatment were identified by online searches and searches of private archives. Post-treatment odds ratios or standardized mean differences were calculated for each outcome, and these were correlated to treatment-related egg count reduction ratios (ERRs) by meta-regression. A greater ERR correlated with greater reduction in odds of most morbidities. Random effects meta-analysis was used to derive summary estimates: after treatment of S. mansoni and S. japonicum, left-sided hepatomegaly was reduced by 54%, right-sided hepatomegaly by 47%, splenomegaly by 37%, periportal fibrosis by 52%, diarrhea by 53%, and blood in stools by 75%. For S. haematobium, hematuria was reduced by 92%, proteinuria by 90%, bladder lesions by 86%, and upper urinary tract lesions by 72%. There were no consistent changes in portal dilation or hemoglobin levels. In sub-group analysis, age, infection status, region, parasite species, and interval to follow-up were associated with meaningful differences in outcome. Conclusion/Significance While there are challenges to implementing therapy for schistosomiasis, and praziquantel therapy is not fully

  16. Mucopolysaccharidosis type I.

    PubMed

    Wraith, J E; Jones, Simon

    2014-09-01

    Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of the lysosomal hydrolase a-L-Iduronidase leading to accumulation of the GAGs, dermatan sulfate, and heparan sulphate, The disease spectrum includes a disorder with severe involvement and CNS disease Hurler disease (HPS I H) a chronic disease without CNS disease Scheie disease (HPS I S5) and the intermediate Hurler/Scheie disease(HPS I HIS).The urine GAGs pattern. confirmed by Iduronidase enzyme assay is diagnostic. Over 200 mutations exist. Genotype / phenotype correlation is poor but two nonsense mutations results in Hurler disease.The skeletal disease dysostosis multiplex (DM) is seen in severe variants of MPS I. The hypoplastic odontoid putting these patients at high risk of cervical cord damage. MPS IH (Hurler Disease) affected infants develop a spinal 'gibbus' deformity, persistent nasal discharge, middle ear effusions and frequent upper respiratory infection. They have "coarse", facial features, and an enlarged tongue. . Progressive upper airway disease leads to obstructive sleep apnoea. Corneal clouding and cognitive impairment appears, growth ceases. Joint stiffness and contractures limit mobility. Cardiac disease is universal. Death occurs before 10 years. SCHEIE patients are diagnosed as teenagers with hepatomegaly, joint contractures, cardiac valve abnormalities and corneal clouding . Prolonged survival with considerable disability without cognitive impairment is usual. MPS IH/S Hurler/Scheie. is diagnosed by 6.5 years, with variable skeletal and visceral manifestations without cognitive involvement. Joint stiffness, corneal clouding, , umbilical hernia, abnormal facies, hepatomegaly, joint contractures, and cervical myelopathy occur. Patients die in their 20s .Haematopoietic stem cell transplantation (HSCT) the standard treatment of MPS IH for 30 years is unpredictable .When performed before 2 years it can stabilize cognitive impairment. Hepatosplenomegaly, urine GAGs excretion, upper

  17. Macrophage activation syndrome in a patient with systemic onset of the juvenile idiopathic arthritis.

    PubMed

    Jain, Deepak; Aggarwal, Hari K; Rao, Avinash; Mittal, Anshul; Jain, Promil

    2016-01-01

    Systemic onset juvenile idiopathic arthritis (sJIA) is defined as arthritis affecting one or more joint usually in the juvenile age group (< 16 years of age) with or preceded by fever of at least 2 weeks duration that is documented to be daily ("quotidian") for at least 3 days which may be associated with evanescent (non-fixed) erythematous rash or generalized lymph node enlargement or hepatomegaly/splenomegaly/both or serositis. Macrophage activation syndrome (MAS) is a life-threatening complication of sJIA marked by sudden onset of non-remitting high fever, profound depression in all three blood cell lines (i.e. leukopenia, anemia, and thrombocytopenia), hepatosplenomegaly, lymphadenopathy, and elevated serum liver enzyme levels. In children with systemic juvenile idiopathic arthritis, the clinical picture may mimic sepsis or an exacerbation of the underlying disease. We report a case of a 16-year-old female patient presenting with high grade fever with joint pains and generalized weakness which proved to be systemic onset juvenile idiopathic arthritis with macrophage activation syndrome after ruling out all other differential diagnoses and responded well to intravenous steroids.

  18. Self-healing juvenile cutaneous mucinosis.

    PubMed

    Kołodziejczyk, Beata; Gazda, Agnieszka; Hernik, Elżbieta; Szczygielska, Izabela; Rutkowska-Sak, Lidia; Koprowska, Marta Legatowicz

    2017-01-01

    Girl, aged 4 years old, began the disease with pain of the lower extremities, fever up to 38°C and signs of upper airway infection. Then the patient developed oedema and redness of the whole face, thickened skin, subcutaneous nodular foldings of the frontal, occipital, cervical and axillary regions, extensor areas of the joints; fine, hard whitish nodules in the frontal region and over interphalangeal joints of the hands, pruritus; oedemas of the ankles, knees and joints of the hands, cervical lymphadenopathy and hepatomegaly. Blood tests at the moment of the diagnosis revealed elevation of markers of inflammation as ESR and CRP, leukocytosis, thrombocytosis, hypoalbuminemia, and hyper-alfa-2-globulinemia. Histopathological examination of the skin biopsy specimen and subcutaneous tissue revealed myxoid subcutaneous tissue located under the dermis and a section consisting of myxoid mesenchymal tissue with inflammatory infiltration by histiocytic cells. The presence of acid mucopolysaccharides in fields of the myxoid tissue was also observed. The self-healing juvenile cutaneous mucinosis (SJCM) was diagnosed.

  19. Apigenin Ameliorates Dyslipidemia, Hepatic Steatosis and Insulin Resistance by Modulating Metabolic and Transcriptional Profiles in the Liver of High-Fat Diet-Induced Obese Mice.

    PubMed

    Jung, Un Ju; Cho, Yun-Young; Choi, Myung-Sook

    2016-05-19

    Several in vitro and in vivo studies have reported the anti-inflammatory, anti-diabetic and anti-obesity effects of the flavonoid apigenin. However, the long-term supplementary effects of low-dose apigenin on obesity are unclear. Therefore, we investigated the protective effects of apigenin against obesity and related metabolic disturbances by exploring the metabolic and transcriptional responses in high-fat diet (HFD)-induced obese mice. C57BL/6J mice were fed an HFD or apigenin (0.005%, w/w)-supplemented HFD for 16 weeks. In HFD-fed mice, apigenin lowered plasma levels of free fatty acid, total cholesterol, apolipoprotein B and hepatic dysfunction markers and ameliorated hepatic steatosis and hepatomegaly, without altering food intake and adiposity. These effects were partly attributed to upregulated expression of genes regulating fatty acid oxidation, tricarboxylic acid cycle, oxidative phosphorylation, electron transport chain and cholesterol homeostasis, downregulated expression of lipolytic and lipogenic genes and decreased activities of enzymes responsible for triglyceride and cholesterol ester synthesis in the liver. Moreover, apigenin lowered plasma levels of pro-inflammatory mediators and fasting blood glucose. The anti-hyperglycemic effect of apigenin appeared to be related to decreased insulin resistance, hyperinsulinemia and hepatic gluconeogenic enzymes activities. Thus, apigenin can ameliorate HFD-induced comorbidities via metabolic and transcriptional modulations in the liver.

  20. “Caught by the Eye of Sound” – Epigastric Swelling due to Xiphisternal Tuberculosis

    PubMed Central

    Grover, Shabnam Bhandari; Arora, Sumit; Kumar, Amit; Grover, Hemal; Katyan, Amit; Nair, Deepthi Mohan

    2017-01-01

    Summary Background Common causes of an epigastric mass include hepatomegaly, pancreatic pseudocyst and epigastric hernia, less common causes being carcinoma of the stomach or pancreas, whereas diseases of the sternum presenting as an epigastric swelling is extremely uncommon. We report a case of tubercular infection of the sternum located in the xiphoid process resulting in its presentation as an epigastric swelling. Case Report A 30-year-old immunocompetent woman with complaints of an epigastric swelling and undocumented pyrexia for four months was referred for sonographic evaluation with a clinical suspicion of an incompletely treated liver abscess. The patient was examined with ultrasound, sternal radiographs, CT and MRI. Ultrasound revealed a heterogeneous epigastric collection with linear echogenic components suggestive of bone fragments. These appearances suggested chronic infective osteomyelitis of the xiphoid process of the sternum. Lateral chest radiograph demonstrated lytic destruction of the xiphisternum. Tubercular etiology was considered and further evaluation with Multidetector Computed tomography (MDCT) and Magnetic Resonance Imaging (MRI) demonstrated erosive osteomyelitis of the xiphoid process with enhancing inflammation and collection in the adjoining soft tissue. Ultrasound-guided aspiration, PCR and Amplified Mycobacterium tuberculosis DNA test confirmed tubercular infection. Conclusions We report a new case of osteo-articular tuberculosis localized to the xiphisternum, a rare clinical entity with an extremely unusual clinical presentation as an epigastric mass. The role of ultrasound in primary diagnosis and as an interventional diagnostic modality for guided aspiration is highlighted. PMID:28217237

  1. Disseminated penicilliosis due to Penicillium chrysogenum in a pediatric patient with Henoch-Schönlein syndrome.

    PubMed

    Avilés-Robles, Martha; Gómez-Ponce, Carlos; Reséndiz-Sánchez, Jesús; Rodríguez-Tovar, Aída Verónica; Ceballos-Bocanegra, Adrián; Martínez-Rivera, Ángeles

    2016-10-01

    A case of disseminated infection caused by Penicillium chrysogenum in a 10-year-old boy with a history of Henoch-Schönlein purpura and proliferative glomerulonephritis, treated with immunosuppressors, is reported herein. The patient had a clinical picture of 2 weeks of fever that did not respond to treatment with broad-spectrum antibiotics and amphotericin B. Computed tomography imaging showed diffuse cotton-like infiltrates in the lungs, hepatomegaly, mesenteric lymphadenopathy, and multiple well-defined round hypodense lesions in the spleen. His treatment was changed to caspofungin, followed by voriconazole. One month later, a splenic biopsy revealed hyaline septate hyphae of >1μm in diameter. Fungal growth was negative. However, molecular analysis showed 99% identity with P. chrysogenum. A therapeutic splenectomy was performed, and treatment was changed to amphotericin B lipid complex and caspofungin. The patient completed 2 months of treatment with resolution of the infection. P. chrysogenum is a rare causative agent of invasive fungal infections in immunocompromised patients, and its diagnosis is necessary to initiate the appropriate antifungal treatment.

  2. Systemic Correction of Storage Disease in MPS I NOD/SCID Mice Using the Sleeping Beauty Transposon System

    PubMed Central

    Aronovich, Elena L; Bell, Jason B; Khan, Shaukat A; Belur, Lalitha R; Gunther, Roland; Koniar, Brenda; Schachern, Patricia A; Parker, Josh B; Carlson, Cathy S; Whitley, Chester B; McIvor, R Scott; Gupta, Pankaj; Hackett, Perry B

    2009-01-01

    The Sleeping Beauty (SB) transposon system is a nonviral vector that directs transgene integration into vertebrate genomes. We hydrodynamically delivered SB transposon plasmids encoding human α-L-iduronidase (hIDUA) at two DNA doses, with and without an SB transposase gene, to NOD.129(B6)-Prkdcscid IDUAtm1Clk/J mice. In transposon-treated, nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with mucopolysaccharidosis type I (MPS I), plasma IDUA persisted for 18 weeks at levels up to several hundred–fold wild-type (WT) activity, depending on DNA dose and gender. IDUA activity was present in all examined somatic organs, as well as in the brain, and correlated with both glycosaminoglycan (GAG) reduction in these organs and level of expression in the liver, the target of transposon delivery. IDUA activity was higher in the treated males than in females. In females, omission of transposase source resulted in significantly lower IDUA levels and incomplete GAG reduction in some organs, confirming the positive effect of transposition on long-term IDUA expression and correction of the disease. The SB transposon system proved efficacious in correcting several clinical manifestations of MPS I in mice, including thickening of the zygomatic arch, hepatomegaly, and accumulation of foamy macrophages in bone marrow and synovium, implying potential effectiveness of this approach in treatment of human MPS I. PMID:19384290

  3. Glycogen storage disease type 1b: an early onset severe phenotype associated with a novel mutation (IVS4) in the glucose 6-phosphate translocase (SLC37A4) gene in a Turkish patient.

    PubMed

    Oguz, M M; Aykan, E; Yilmaz, G; Aytekin, C; Karaer, K; Açoğlu, E A

    2014-01-01

    Glycogen storage disease type I (GSD-I) is a group of autosomal recessive disorders that include types Ia and Ib. GSD-Ib is caused by a deficiency in the glucose-6-phosphate transporter (G6PT) caused by a mutation in the SLC37A4 gene coding for G6PT. Glycogen storage disease is characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver and chronic neutropenia. Herein we describe a 4-month-old Turkish patient with early onset and severe typical clinical features of GSD-1b in which a novel mutation in the SLC37A4 gene was detected. After the bone marrow examination parenteral antibiotic therapy and subcutaneous granulocyte colony-stimulating factor (G-CSF) were started. Due to the severe neutropenia the patient had developed nosocomial sepsis and the dose of G-CSF was increased. After 2 months later from the initial treatment of the G-CSF he developed splenomegaly and urinary complications. Despite maximal therapy he had an extremely poor quality of life and life-threatening complications due to impaired bone marrow function. As the patient required continual hospitalization he was schedule for bone marrow transplantation.

  4. Investigation and management of the hepatic glycogen storage diseases.

    PubMed

    Bhattacharya, Kaustuv

    2015-07-01

    The glycogen storage diseases (GSD) comprise a group of disorders that involve the disruption of metabolism of glycogen. Glycogen is stored in various organs including skeletal muscle, the kidneys and liver. The liver stores glycogen to supply the rest of the body with glucose when required. Therefore, disruption of this process can lead to hypoglycaemia. If glycogen is not broken down effectively, this can lead to hepatomegaly. Glycogen synthase deficiency leads to impaired glycogen synthesis and consequently the liver is small. Glycogen brancher deficiency can lead to abnormal glycogen being stored in the liver leading to a quite different disorder of progressive liver dysfunction. Understanding the physiology of GSD I, III, VI and IX guides dietary treatments and the provision of appropriate amounts and types of carbohydrates. There has been recent re-emergence in the literature of the use of ketones in therapy, either in the form of the salt D,L-3-hydroxybutyrate or medium chain triglyceride (MCT). High protein diets have also been advocated. Alternative waxy maize based starches seem to show promising early data of efficacy. There are many complications of each of these disorders and they need to be prospectively surveyed and managed. Liver and kidney transplantation is still indicated in severe refractory disease.

  5. Cx3cr1 deficiency in mice attenuates hepatic granuloma formation during acute schistosomiasis by enhancing the M2-type polarization of macrophages.

    PubMed

    Ran, Lin; Yu, Qilin; Zhang, Shu; Xiong, Fei; Cheng, Jia; Yang, Ping; Xu, Jun-Fa; Nie, Hao; Zhong, Qin; Yang, Xueli; Yang, Fei; Gong, Quan; Kuczma, Michal; Kraj, Piotr; Gu, Weikuan; Ren, Bo-Xu; Wang, Cong-Yi

    2015-07-01

    Acute schistosomiasis is characterized by pro-inflammatory responses against tissue- or organ-trapped parasite eggs along with granuloma formation. Here, we describe studies in Cx3cr1(-/-) mice and demonstrate the role of Cx3cr1 in the pathoetiology of granuloma formation during acute schistosomiasis. Mice deficient in Cx3cr1 were protected from granuloma formation and hepatic injury induced by Schistosoma japonicum eggs, as manifested by reduced body weight loss and attenuated hepatomegaly along with preserved liver function. Notably, S. japonicum infection induced high levels of hepatic Cx3cr1 expression, which was predominantly expressed by infiltrating macrophages. Loss of Cx3cr1 rendered macrophages preferentially towards M2 polarization, which then led to a characteristic switch of the host immune defense from a conventional Th1 to a typical Th2 response during acute schistosomiasis. This immune switch caused by Cx3cr1 deficiency was probably associated with enhanced STAT6/PPAR-γ signaling and increased expression of indoleamine 2,3-dioxygenase (IDO), an enzyme that promotes M2 polarization of macrophages. Taken together, our data provide evidence suggesting that CX3CR1 could be a viable therapeutic target for treatment of acute schistosomiasis.

  6. Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia.

    PubMed

    Crane, B; Luo, X; Demaster, A; Williams, K D; Kozink, D M; Zhang, P; Brown, T T; Pinto, C R; Oka, K; Sun, F; Jackson, M W; Chan, L; Koeberl, D D

    2012-04-01

    Glycogen storage disease type Ia (GSD-Ia) stems from glucose-6-phosphatase (G6Pase) deficiency and causes hypoglycemia, hepatomegaly, hypercholesterolemia and lactic acidemia. Three dogs with GSD-Ia were initially treated with a helper-dependent adenovirus encoding a human G6Pase transgene (HDAd-cG6Pase serotype 5) on postnatal day 3. Unlike untreated dogs with GSD-Ia, all three dogs initially maintained normal blood glucose levels. After 6-22 months, vector-treated dogs developed hypoglycemia, anorexia and lethargy, suggesting that the HDAd-cG6Pase serotype 5 vector had lost efficacy. Liver biopsies collected at this time revealed significantly elevated hepatic G6Pase activity and reduced glycogen content, when compared with affected dogs treated only by frequent feeding. Subsequently, the HDAd-cG6Pase serotype 2 vector was administered to two dogs, and hypoglycemia was reversed; however, renal dysfunction and recurrent hypoglycemia complicated their management. Administration of a serotype 2 HDAd vector prolonged survival in one GSD-Ia dog to 12 months of age and 36 months of age in the other, but the persistence of long-term complications limited HDAd vectors in the canine model for GSD-Ia.

  7. A case of peripheral T-cell lymphoma, not otherwise specified in a HCV and HTLV-II-positive patient, diagnosed by abdominal fluid cytology

    PubMed Central

    Parekh, Trisha M.; Qian, You-Wen; Elghetany, M. Tarek; Schnadig, Vicki; Nawgiri, Ranjina

    2016-01-01

    Background Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) is a rare neoplasm that typically presents as generalized lymphadenopathy. PTCL, NOS presenting as malignant ascites is rare. Methods A 61-year-old African-American man with past medical history of HCV, cryoglobulinemia, and cryptococcal pneumonia was admitted for dyspnea on exertion over a period of 1 month and new onset of abdominal distension. Results Ascites, splenomegaly, hepatomegaly and extensive lymphadenopathy were found by imaging. Paracentesis obtained 1.3 liter of abdominal fluid, the cytologic evaluation showed a monomorphic population of intermediate-sized lymphoid cells with irregular to convoluted nuclear contours. Fluid sent for flow cytometry showed an abnormal T-lymphocyte population expressing CD4, weak surface CD3 and absence of CD7. PCR studies of ascitic fluid detected a clonal T-lymphocyte population with T-cell receptor gamma gene rearrangement. Serologic testing for human T lymphotropic virus (HTLV) was positive for HTLV-II. Subsequent bone marrow biopsy revealed lymphomatous involvement. CD30 and ALK-1 immunostaining were negative. This case was classified as PTCL, NOS. Conclusions PTCL, NOS can have unusual clinical presentation such as ascites and pleural effusion, and may also occur as a complication of immunodeficiency state. Further studies are needed to determine if HCV or HTLV-II viral infection is associated with PTCL. PMID:27034820

  8. Factors Associated with Growth Retardation in Children Suffering from Sickle Cell Anemia: First Report from Central Africa

    PubMed Central

    Ngiyulu, René Makuala; Gini-Ehungu, Jean Lambert; Mbuyi-Muamba, Jean Marie

    2017-01-01

    Background. The aim of this study was to investigate and determine the risk factors associated with poor growth among SCA children. Methods. A cross-sectional study was conducted in Kinshasa, the capital's country. The nutritional status was assessed using the Z scores of the anthropometric indices. Results. We gathered data on the 256 patients, 138 females (53.9%), who entered the study. The mean age at presentation was 8.4 ± 4.9 years of age. Underweight, stunting, and wasting were found, respectively, in 47.7%, 10.5%, and 50.3% of SCA children. A history of hand-foot syndrome, more than 3 blood transfusions, being less than 12 months of age when receiving the first transfusion, more than two severe sickle crises per year, a medical history of severe infections, and the presence of hepatomegaly were associated with poor growth. When comparing sickle cell patients under 12 years of age (n = 159) to a group of 296 age-matched children with normal Hb-AA, a significantly higher proportion of subjects with stunting and underweight were found among SCA. Conclusion. Nutritional status encountered in Congolese sickle cell children has been described for the first time in this study. A high prevalence of poor growth in SCA children was found in our study. PMID:28250985

  9. Fetal neuroblastoma: ultrasonography and magnetic resonance imaging findings in the prenatal and postnatal IV-S stage

    PubMed Central

    Werner, Heron; Daltro, Pedro; Davaus, Taisa

    2016-01-01

    We report a case of a fetus with an ultrasonography diagnosis of a neuroblastoma during a routine third trimester fetal scan, which presented as a hyperechogenic nodule located above the right kidney. No other abnormalities were found in the ultrasonography scan; however, the follow-up ultrasonography during the 36th week of gestation revealed that the lesion had doubled in size. At the same time, magnetic resonance imaging demonstrated a round mass in the topography of the right adrenal gland with a low signal on T1-weighted images and slightly high signal on T2-weighted images, causing a slight inferior displacement of the kidney. The liver had enlarged and had heterogeneous signal intensity, predominantly hypointense on T2-weighted sequences. Based on these findings, a diagnosis of congenital adrenal neuroblastoma with liver metastases was suggested. A newborn male was delivered by cesarean section 2 weeks later. The physical examination of the neonate revealed abdominal distention and hepatomegaly. The infant had a clinical follow-up in which no surgical or medical intervention was required. At 5 months of age, the infant was asymptomatic with a normal physical examination. PMID:27668206

  10. Properties of a fluorescent bezafibrate derivative (DNS-X). A new tool to study peroxisome proliferation and fatty acid beta-oxidation.

    PubMed

    Berlot, J P; Lutz, T; Cherkaoui Malki, M; Nicolas-Frances, V; Jannin, B; Latruffe, N

    2000-12-01

    The first peroxisome proliferator-activated receptor (PPAR) was cloned in 1990 by Issemann and Green. Many studies have reported the importance of this receptor in the control of gene expression of enzymes involved in lipid metabolic pathways including mitochondrial and peroxisomal fatty acid beta-oxidation, lipoprotein structure [apolipoprotein (apo) A2, apo CIII], and fatty acid synthase. By using radiolabeled molecules, it was shown that peroxisome proliferators bind and activate PPAR. As an alternative method, we developed a fluorescent dansyl (1-dimethylaminonaphthalene-5-sulfonyl) derivative peroxisome proliferator from bezafibrate (DNS-X), a hypolipidemic agent that exhibits an in vitro peroxisome proliferative activity on rat Fao-hepatic derived cultured cells. However, until now, the effect of this new compound on the liver of animals and subcellular localization was unknown. In addition to in vivo rat studies, we present a more efficient large-scale technique of DNS-X purification. Treating rats (DNS-X in the diet at 0.3% w/w) for 6 d leads to a hepatomegaly and a marked increase in liver peroxisomal palmitoyl-CoA oxidase activity. We also developed a method to localize and quantify DNS-X in tissues or cell compartment organelles. The primarily cytosolic distribution of DNS-X was confirmed by direct visualization using fluorescence microscopy of cultured Fao cells. Finally, transfection assay demonstrated that DNS-X enhanced the PPAR alpha activity as well as other peroxisome proliferators do.

  11. Yap reprograms glutamine metabolism to increase nucleotide biosynthesis and enable liver growth

    PubMed Central

    Brown, Kristin K.; Evason, Kimberley; Beltz, Sebastian; Tsomides, Allison; O'Connor, Keelin; Galli, Giorgio G.; Yimlamai, Dean; Chhangawala, Sagar; Yuan, Min; Lien, Evan C.; Wucherpfennig, Julia; Nissim, Sahar; Minami, Akihiro; Cohen, David E.; Camargo, Fernando D.; Asara, John M.; Houvras, Yariv; Stainier, Didier Y.R.; Goessling, Wolfram

    2016-01-01

    The Hippo pathway is an important regulator of organ size and tumorigenesis. It is unclear, however, how Hippo signaling provides the cellular building blocks required for rapid growth. Here, we demonstrate that transgenic zebrafish expressing an activated form of the Hippo pathway effector Yap1 (also known as YAP) develop enlarged livers and are prone to liver tumor formation. Transcriptomic and metabolomic profiling identify that Yap1 reprograms glutamine metabolism. Yap1 directly enhances glutamine synthetase (glul) expression and activity, elevating steady-state levels of glutamine and enhancing the relative isotopic enrichment of nitrogen during de novo purine and pyrimidine biosynthesis. Genetic or pharmacological inhibition of GLUL diminishes the isotopic enrichment of nitrogen into nucleotides, suppresses hepatomegaly and the growth of liver cancer cells. Consequently, Yap-driven liver growth is susceptible to nucleotide inhibition. Together, our findings demonstrate that Yap1 integrates the anabolic demands of tissue growth during development and tumorigenesis by reprogramming nitrogen metabolism to stimulate nucleotide biosynthesis. PMID:27428308

  12. Role of macrophages and stellate cells in the pathogenesis of veno-occlusive disease: an electron microscopic case study.

    PubMed

    Tang, Wendell; Ziring, David; Gershman, George; French, Samuel

    2003-12-01

    Veno-occlusive disease (VOD) is an entity described as a triad of pathologic findings including ascites, tender hepatomegaly, and elevated liver enzymes. The prognosis of patients suffering from VOD is highly variable, ranging from slow resolution to the need for liver transplant. The histopathology of VOD has been described by light and electron microscopy. However, the pathogenesis of VOD is still largely unclear. In the present case study, we report the significant findings in a case of pediatric VOD following chemotherapy. We studied the liver biopsy by light and electron microscopes. In addition to previous reported findings of occlusion of the central vein with endothelial cell damage, proliferation and activation of stellate cells, and collagen deposition in the central vein wall, there were prominent activated macrophages within the lumen and wall of central veins. The following mechanism of VOD was proposed: Tissue damage activates monocytes through monocyte chemoattractant protein-1. The secretory macrophages release TGF-beta, which promotes proliferation of stellate cells to cause collagenous thickening of the central vein. The activated stellate cells produce collagen. The normal drainage of the Space of Disse and sinusoids draining into the central vein are blocked by the fibrosis. This leads to extravasated RBCs trapped within the thickened central vein wall and impaction of RBCs in the sinusoids.

  13. 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

  14. Very Early Presentation of Extrahepatic Portal Vein Obstruction Causing Portal Hypertension in an Infant: Uncertainties in the Management and Therapeutic Limitations

    PubMed Central

    Khodayar-Pardo, Parisá; Peña Aldea, Andrés; Ramírez González, Ana; Meseguer Carrascosa, Adela; Calabuig Bayo, Cristina

    2016-01-01

    Extrahepatic portal vein obstruction, although rare in children, is a significant cause of portal hypertension (PHT) leading to life-threatening gastrointestinal bleeding in the pediatric age group. PHT may also lead to other complications such as hyperesplenism, cholangyopathy, ascites, and even hepatopulmonary syndrome and portopulmonary hypertension that may require organ transplantation. Herein we report the case of an asymptomatic 11-month-old infant wherein a hepatomegaly and cavernous transformation of the portal vein was detected by liver ultrasound. Neither signs of thrombosis in arteriovenous system, nor affectation of biliary tract were identified in the magnetic resonance imaging study. A significant enlargement of the caudate lobe of the liver was reported. No risk factors were detected. The differential diagnosis performed was extensive. Inherited thrombophilia and storage disorders were especially considered. Liver biopsy was normal. Upper gastrointestinal esophagogastroduodenoscopy detected two small varicose cords on the distal third of the esophagus. Finding a cavernous transformation of the portal vein with evidence of collateral circulation in such an early age is a challenging condition for professionals, since PHT may lead to severe complications during childhood and can compromise growth and development. Evidence-based guidelines for the management of PHT in adults have been published. However, follow-up and treatment of pediatric patients have not yet been standardized. Moreover, management of PHT in infants faces particular difficulties such as technical restrictions that could hinder their treatment. PMID:27504083

  15. Protein malnutrition in South India

    PubMed Central

    Rao, K. Someswara; Swaminathan, M. C.; Swarup, S.; Patwardhan, V. N.

    1959-01-01

    A protein malnutrition survey was carried out in ten areas of four States of South India among children under 5 years of age in families with a monthly income of less than Rs 100, estimated to constitute 85% of the population. The agricultural situation and socio-economic conditions are described. The diets investigated consisted largely of cereals, with small quantities of pulses and green vegetables; milk, meat and eggs were little eaten. The survey covered investigation of infant care, feeding and weaning practices, clinical examinations, anthropometric measurements, determinations of haemoglobin and serum protein, and analysis of hospital records. Although infants were usually breast-fed for a long time, the quantity of breast milk was found to be low after 6 months, at which time supplementary foods were introduced, but these were usually inadequate. Extreme growth retardation was seen after weaning. Diarrhoea was complained of in some 20% of children. Such deficiency signs as dyschromotrichia, hepatomegaly, moon face, angular stomatitis and xerophthalmia were frequently seen. Frank cases of kwashiorkor and marasmus were observed in 1% and 1.7% respectively of children at home. These findings and others clearly show protein malnutrition to be a problem of very considerable magnitude in the poorer communities of South India. A comparison is made with the results of surveys conducted in Africa and in Central America. ImagesFIG. 6FIG. 7FIG. 2 PMID:14436226

  16. Glutaric aciduria type 2 presenting with acute respiratory failure in an adult

    PubMed Central

    Ersoy, Ebru Ortac; Rama, Dorina; Ünal, Özlem; Sivri, Serap; Topeli, Arzu

    2015-01-01

    Glutaric aciduria (GTA) type II can be seen as late onset form with myopathic phenotype. We present a case of a 19-year old female with progressive muscle weakness was admitted in intensive care unit (ICU) with respiratory failure and acute renal failure. Patient was unconscious. Pupils were anisocoric and light reflex was absent. She had hepatomegaly. The laboratory results showed a glucose level of 70 mg/dl and the liver enzymes were high. The patient also had hyponatremia (117 mEq/L) and lactate level of 3.9 mmol/L. Tandem MS and organic acid analysis were compatible with GTA type II. Carnitine 1gr, riboflavin 100 mg and co-enzymeQ10 100 mg was arranged. After four months from beginning of treatment tandem MS results are improved. Respiratory failure, acute renal failure due to profound proximal myopathy can be due to glutaric aciduria type II that responded rapidly to appropriate therapy. PMID:26236614

  17. T-cell-rich B-cell lymphoma: a clinicopathologic study of 21 cases and comparison with 43 cases of diffuse large B-cell lymphoma.

    PubMed

    Aki, Hilal; Tuzuner, Nukhet; Ongoren, Seniz; Baslar, Zafer; Soysal, Teoman; Ferhanoglu, Burhan; Sahinler, Ismet; Aydin, Yildiz; Ulku, Birsen; Aktuglu, Gulten

    2004-03-01

    Clinicopathologic features of 21 patients with T-cell-rich B-cell lymphoma (TCRBCL) were reviewed and compared to 43 patients with diffuse large B-cell lymphoma (DLBCL) to determine if there were distinguishing clinical characteristics and differences in response or survival to CHOP therapy. For the diagnosis of TCRBCL, the current WHO criteria was used. In all of our cases, the majority of cells are non-neoplastic T cells and <10% large neoplastic B cells are present. The initial pathologic diagnosis was nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) in two cases. Patients with TCRBCL were significantly younger (median: 46 years) and had a significantly higher incidence of B symptoms (62%), hepatomegaly (33%) and marrow infiltration (33%) at presentation when compared to DLBCL (P<0.03). The CR rate after treatment was 48% for TCRBCL patients versus 79% for the DLBCL (P<0.003). Although the CR rates in between the two groups are significant, the difference in 3 years survival rates in each CR groups was insignificant (80% versus 77%). The overall survival time in the two groups was 17 months. Event-free survival time in TCRBCL was 12 months, compared with 17 months in the DLBCL (P>0.05). The frequency of patients with TCRBCL achieving CR was 52.6% whereas that of patients with DLBCL was 79% (P<0.003). The TCRBCL 3 years event-free survival 48% and overall survival 64% were 63 and 72% for DLBCL, respectively.

  18. A high risk critical mitral valve stenosis with emergency management at Apollo Hospitals Dhaka.

    PubMed

    Zahangir, N M; Hoque, K Z; Khan, M H; Haque, M A; Haider, M Z

    2013-10-01

    Heart valve surgery in high-risk patients with severe jaundice, congestive hepatomegaly and renal impairment is associated with considerable morbidity and mortality. Without operation the consequences are invariably grave. A 35 years old gentleman with congestive cardiac failure was initially treated in coronary care unit (CCU). Mitral valve area was 0.5cm², pulmonary arterial systolic pressure (PASP) was 110mmHg, serum bilirubin was 20mg/dl, SGPT & SGOT were 1024iu/l and 1027iu/l respectively. Serum creatinine was 3.35mmol/l. Serum bilirubin gradually diminished to 3.1mg/dl after 12 days treatment in Coronary Care Unit but next day it increased to 3.6mg/dl. Mitral valve was replaced on an emergency basis. Echocardiogram on the 5th post operative day showed well functioning prosthetic mitral valve in situ. Serum bilirubin decreased to 2.2mg/dl, SGPT, SGOT and serum creatinine to 43iu/l, 40iu/l and 1.34mmol/l respectively. After 8 weeks of postoperative follow up his serum bilirubin decreased to 0.8mg/dl.

  19. [Fascioliasis in children. A study of 10 cases].

    PubMed

    Alvarez-Chacón, R; García-Rosales, J J; de la Cruz-Otero, M C; Wong-Chío, M; Cabrera-Bravo, M; Gómez-Gómez, J V; Gamez-Aranda, V

    1992-06-01

    These are the observation found in ten children with fascioliasis diagnosis at the Servicio de Parasitología, of the Instituto Nacional de Pediatría, from 1979 to 1990; six children in scholar age; one prescholar and three teenagers; only one was female. Four of them lined at the State of Mexico; three at Morelos; one at Puebla, another one at Oaxaca and the other one at Mexico City. In nine of the watercress eaten was confirmed. The most important clinic manifestations were: fever, weight lose, paleness, hepatomegaly, hiporexia, right hypochondrium pain and diarrhoea. Diagnosis was established by: counterimmunoelectrophoresis, indirect haemagglutination and there were found eggs by simple sedimentation, Ritchie's method and microscopic study of duodenal sample. Leukocytes counts were between 11,000 and 34,000/mm3. Eosinophils were to 77% with 24,430 totals. Only in three of them haemoglobin was found under 9 g/dL. All of them had hypergammaglobulinemia. In nine patients the alkaline phosphatase was found in higher levels; only in three of them, transaminase, oxalacetic and glutamic piruvic were found in higher levels. The most effective drug in the treatment was dehidroemetine.

  20. Molecular and immunological diagnosis of echinococcosis.

    PubMed Central

    Gottstein, B

    1992-01-01

    Echinococcosis is an infectious disease of humans caused by the larval (metacestode) stage of the cestode species Echinococcus granulosus (cystic echinococcosis or hydatid disease) or Echinococcus multilocularis (alveolar echinococcosis or alveolar hydatid disease). Clinical manifestations depend primarily on localization and size of hepatic lesions and may include hepatomegaly, obstructive jaundice, or cholangitis. Prognostically, alveolar echinococcosis is considered similar to liver malignancies, including a lethality rate of 90% for untreated cases. Diagnosis is based on imaging techniques coupled with immunodiagnostic procedures. Antibody detection tests for E. multilocularis have markedly improved with the use of affinity-purified Em2 antigen and recombinant antigen II/3-10 in enzyme immunoassays. Antigens of corresponding quality for E. granulosus are still unavailable. The detection of circulating antigens and immune complexes in the sera of patients with cystic echinococcosis, the demonstration of in vitro lymphocyte proliferation in response to stimulation with Echinococcus antigens, and the discrimination of serum immunoglobulin isotype activity to various Echinococcus antigens in both cystic and alveolar echinococcosis have been suggested for diagnostic purposes as well as for monitoring patients after treatment. New diagnostic molecular tools include DNA probes for Southern hybridization tests and polymerase chain reaction for the amplification of E. multilocularis and E. granulosus species-specific DNA fragments. Images PMID:1498767

  1. Liver complications in lymphomas treated with a combination of chemotherapy and radiotherapy: preliminary results

    SciTech Connect

    Haddad, E.; Le Bourgeois, J.P.; Kuentz, M.; Lobo, P.

    1983-09-01

    From May 1978 to May 1981, a total of 20 patients (18 patients with Non Hodgkin Lymphomas + 2 patients with Stage IV Hodgkin's disease) were treated with chemotherapy and whole or upper abdominal radiotherapy. All the patients were in complete remission at the time of irradiation. Shielding of the kidneys was effected at the start of treatment and the right lobe of the liver was shielded after a dose of 20 Gy was delivered. As of January 1982, 17 of the patients were alive and free of disease with a follow-up ranging from 6 to 32 months (mean follow-up of 18.5 months). Two patients were dead from their disease. Alterations in liver chemistry were observed in 5 patients, clinical jaundince or transient hepatomegaly along with changes in liver chemistry in 4 patients, classical veno-occlusive disease in 2 patients and 7 of the patients did not develop any complication. No death from complications were observed. The contribution of the following factors such as radiotherapy dose to the liver, drugs, nutritional status and associated medical conditions, towards the development of complications have been analyzed in detail.

  2. Hairy-cell leukemia: a rare blood disorder in Asia.

    PubMed

    Josephine, F P; Nissapatorn, V

    2006-01-01

    We report a 68-year-old Indian man who was referred to the Hematology Unit for investigation for thrombocytopenia, an incidental finding during a pre-operative screening for prostatectomy. Physical examination was unremarkable. There was no splenomegaly, hepatomegaly or lymphadenopathy. Complete blood counts showed normal hemoglobin and total white cell count with moderate thrombocytopenia. Hairy-cell leukemia was diagnosed based on peripheral blood film, bone-marrow aspirate and trephine biopsy findings, supported by immunophenotyping results by flow cytometry. The purpose of this report is to create awareness of this uncommon presentation and to emphasize that a single-lineage cytopenia or absence of splenomegaly does not exclude the diagnosis of hairy-cell leukemia. Careful attention to morphological detail is important for early diagnosis, especially when low percentages of "hairy" cells are present in the peripheral blood and bone marrow. Early diagnosis is important to ensure that patients obtain maximum benefit from the newer therapeutic agents that have greatly improved the prognosis in this rare disorder.

  3. Clinical and chemotherapeutic study of hepatocellular carcinoma in Malaysia: a comparison with African and American patients.

    PubMed

    Joishy, S K; Bennett, J M; Balasegaram, M; MacIntyre, J M; Falkson, G; Moertel, C; Carbone, P P

    1982-09-15

    Twenty Malaysian patients with unresectable primary liver cell cancer were prospectively studied at the General Hospital, Kuala Lampur, and were compared for clinical features with an equal number each of African and American patients being studied by the Eastern Cooperative Oncology Group. The patients received intravenous 5-FU and oral MeCCNU which was used for the first time in an Asian country. Most of the Malaysian patients were Chinese, belonged to younger age groups, and presented with massive hepatomegaly, jaundice, and fever. Toxicity to MeCCNU invariably occurred in the form of leukopenia or thrombocytopenia, but none life threatening. Partial response was seen in 20% of Malaysians as compared to 16% in Americans and none in Africans. Malaysians achieved a median survival of 16 weeks compared to 28 weeks in Americans and only eight weeks in Africans. Malaysian Chinese patients were all HBc Ab + ve. Other factors which may have played an etiologic role in the induction of primary liver cancer included alcohol, Chinese herbal medicines, aflatoxin and habitual use of medicated rubbing oils.

  4. Clinical and laboratory characteristics of infectious mononucleosis by Epstein-Barr virus in Mexican children

    PubMed Central

    2012-01-01

    Background Infectious mononucleosis (IM) or Mononucleosis syndrome is caused by an acute infection of Epstein-Barr virus. In Latin American countries, there are little information pertaining to the clinical manifestations and complications of this disease. For this reason, the purpose of this work was to describe the clinical and laboratory characteristics of infection by Epstein-Barr virus in Mexican children with infectious mononucleosis. Methods A descriptive study was carried out by reviewing the clinical files of patients less than 18 years old with clinical and serological diagnosis of IM by Epstein-Barr virus from November, 1970 to July, 2011 in a third level pediatric hospital in Mexico City. Results One hundred and sixty three cases of IM were found. The most frequent clinical signs were lymphadenopathy (89.5%), fever (79.7%), general body pain (69.3%), pharyngitis (55.2%), hepatomegaly (47.2%). The laboratory findings were lymphocytosis (41.7%), atypic lymphocytes (24.5%), and increased transaminases (30.9%), there were no rupture of the spleen and no deaths among the 163 cases. Conclusions Our results revealed that IM appeared in earlier ages compared with that reported in industrialized countries, where adolescents are the most affected group. Also, the order and frequency of the clinical manifestations were different in our country than in industrialized ones. PMID:22818256

  5. Drug Reaction With Eosinophilia and Systemic Symptoms Induced by Valproic Acid: A Case Report

    PubMed Central

    Darban, Mahboubeh; Bagheri, Bahador

    2016-01-01

    Introduction Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but life-threatening reaction to drugs such as carbamazepine and allopurinol. The condition is characterized by skin rashes, fever, hematological disturbances, lymphadenopathy, and organ failure, most probably hepatic dysfunction. To date, only a few cases of valproate-induced DRESS syndrome have been reported. Case Presentation We report on the case of a 60-year-old man who had been treated with valproic acid some time before being referred to Kowsar Hospital, Semnan, Iran in December 2015. He was given valproic acid 1000 mg PO, and after 20 days, he had developed widespread rashes, fever, esophagitis, cervical lymphadenopathy, and tender hepatomegaly. Laboratory results at Kowsar showed a drop in hemoglobin, in addition to lymphocytosis, thrombocytopenia, and elevated serum transaminases. DRESS was diagnosed, and corticosteroid therapy was initiated. Administration of the culprit drug to the patient was also stopped. Intravenous immunoglobulin (IVIG) improved the general condition of the patient. Conclusions Only a small number of case reports have described valproic acid-induced DRESS syndrome; therefore, the condition is difficult to prevent. Rechallenge with valproic acid should be avoided in patients with a history of reaction to the drug. PMID:28144463

  6. A 3-Year-Old Girl with Recurrent Infections and Autoimmunity due to a STAT1 Gain-of-Function Mutation: The Expanding Clinical Presentation of Primary Immunodeficiencies

    PubMed Central

    Aldave Becerra, Juan Carlos; Cachay Rojas, Enrique

    2017-01-01

    We report a 3-year-old Peruvian girl, born to non-consanguineous parents. At the age of 8 months, she had a severe pneumonia complicated with empyema that required thoracic drainage and mechanical ventilation. Although no microorganisms were isolated, the patient recovered with broad-spectrum antibiotics. Since that date, she has presented multiple episodes of pneumonia and recurrent episodes of bronchospasm. At 1 year 5 months of age, the patient began with recurrent episodes of oropharyngeal, vaginal, and skin candidiasis, which improved transiently after using oral azole drugs. At 2.5 years of age, she was admitted with lupus-like syndrome, including serositis, hemolytic anemia, thrombocytopenia, and positive antinuclear (1:80) and dsDNA (1:10) autoantibodies. Available immunologic testing was not contributory. Imaging studies revealed bilateral ethmoidal sinusitis and mild hepatomegaly. Bone marrow analysis did not showed evidence of leukemia or myelodysplasia, while renal biopsy concluded mild mesangial proliferation. Genetic studies revealed a pathogenic heterozygous signal transducer and activator of transcription 1 gain-of-function mutation (WT/P293L). The clinical status and lung function of the patient has worsened progressively. She has not achieved an optimal response to therapy, including high-dose intravenous immunoglobulin, GM-CSF, prophylactic antibiotics and antifungal drugs, so we plan to perform hematopoietic stem cell transplantation. PMID:28367431

  7. Radiologic evaluation of the liver and gastrointestinal tract in rats infected with Taenia taeniaeformis.

    PubMed

    Perry, R L; Williams, J F; Carrig, C B; Kaneene, J B; Schillhorn van Veen, T W

    1994-08-01

    In rats infected with the cestode Taenia taeniaeformis, hepatomegaly results from development of parasitic cysts in the liver. Diffuse nodular mucosal hyperplasia in the glandular region (corpus and antrum) of the stomach, and gross thickening of the intestinal mucosa also result. Between postinfection days (PID) 21 and 84, radiologic observations were made after oral administration of a barium sulfate suspension in T taeniaeformis-infected rats and in age/sex-matched controls. There was radiographic evidence of hepatic enlargement at PID 21. Enlargement of the gastric folds was first observed along the greater curvature of the stomach at PID 35. Fimbriation of small intestinal mucosal surfaces resulted from thickening of the intestinal villi and was observed in the duodenum at PID 21. Intestinal motility was assessed, and contractions were counted, using image intensification fluoroscopy, then were recorded on videotape. There were no significant differences between control and infected rats for gastric emptying time, intestinal transit time, and number of intestinal contractions per minute. Barium contrast radiography clearly indicated large gastric folds, thickening of the small intestinal villi, and hepatic enlargement, and was useful for assessing gastrointestinal motility.

  8. Novel treatment options for lysosomal acid lipase deficiency: critical appraisal of sebelipase alfa

    PubMed Central

    Su, Kim; Donaldson, Emma; Sharma, Reena

    2016-01-01

    Lysosomal acid lipase deficiency (LAL-D) is a rare disorder of cholesterol metabolism with an autosomal recessive mode of inheritance. The absence or deficiency of the LAL enzyme gives rise to pathological accumulation of cholesterol esters in various tissues. A severe LAL-D phenotype manifesting in infancy is associated with adrenal calcification and liver and gastrointestinal involvement with characteristic early mortality. LAL-D presenting in childhood and adulthood is associated with hepatomegaly, liver fibrosis, cirrhosis, and premature atherosclerosis. There are currently no curative pharmacological treatments for this life-threatening condition. Supportive management with lipid-modifying agents does not ameliorate disease progression. Hematopoietic stem cell transplantation as a curative measure in infantile disease has mixed success and is associated with inherent risks and complications. Sebelipase alfa (Kanuma) is a recombinant human LAL protein and the first enzyme replacement therapy for the treatment of LAL-D. Clinical trials have been undertaken in infants with rapidly progressive LAL-D and in children and adults with later-onset LAL-D. Initial data have shown significant survival benefits in the infant group and improvements in biochemical parameters in the latter. Sebelipase alfa has received marketing authorization in the United States and Europe as long-term therapy for all affected individuals. The availability of enzyme replacement therapy for this rare and progressive disorder warrants greater recognition and awareness by physicians. PMID:27799810

  9. Cx3cr1 deficiency in mice attenuates hepatic granuloma formation during acute schistosomiasis by enhancing the M2-type polarization of macrophages

    PubMed Central

    Ran, Lin; Yu, Qilin; Zhang, Shu; Xiong, Fei; Cheng, Jia; Yang, Ping; Xu, Jun-Fa; Nie, Hao; Zhong, Qin; Yang, Xueli; Yang, Fei; Gong, Quan; Kuczma, Michal; Kraj, Piotr; Gu, Weikuan; Ren, Bo-Xu; Wang, Cong-Yi

    2015-01-01

    ABSTRACT Acute schistosomiasis is characterized by pro-inflammatory responses against tissue- or organ-trapped parasite eggs along with granuloma formation. Here, we describe studies in Cx3cr1−/− mice and demonstrate the role of Cx3cr1 in the pathoetiology of granuloma formation during acute schistosomiasis. Mice deficient in Cx3cr1 were protected from granuloma formation and hepatic injury induced by Schistosoma japonicum eggs, as manifested by reduced body weight loss and attenuated hepatomegaly along with preserved liver function. Notably, S. japonicum infection induced high levels of hepatic Cx3cr1 expression, which was predominantly expressed by infiltrating macrophages. Loss of Cx3cr1 rendered macrophages preferentially towards M2 polarization, which then led to a characteristic switch of the host immune defense from a conventional Th1 to a typical Th2 response during acute schistosomiasis. This immune switch caused by Cx3cr1 deficiency was probably associated with enhanced STAT6/PPAR-γ signaling and increased expression of indoleamine 2,3-dioxygenase (IDO), an enzyme that promotes M2 polarization of macrophages. Taken together, our data provide evidence suggesting that CX3CR1 could be a viable therapeutic target for treatment of acute schistosomiasis. PMID:26035381

  10. Clinicopathological and ultrasonographic findings in 40 water buffaloes (Bubalus bubalis) with traumatic pericarditis.

    PubMed

    Mohamed, T

    2010-11-20

    Forty buffaloes with traumatic pericarditis were examined to characterise the ultrasonographic findings in buffaloes with traumatic pericarditis, determine the extent of the lesions and assess the prognosis. The most noticeable clinical presentations were presternal oedema (73 per cent) and jugular and mammary vein distension (88 per cent). Laboratory findings included neutrophilic leucocytosis, elevated total protein concentration, hypoalbuminaemia, hypergammaglobulinaemia and increased concentration of free fatty acids. Ultrasonographically, fluid in the pericardium appeared as either mild or massive anechoic accumulations containing fibrin threads or were imaged as homogenous, echogenic pericardial effusions. Moderate to severe corrugation of the reticular wall was observed. Deposits of fibrinous tissue interspersed with fluid pockets were seen between the reticulum, dorsal ruminal sac and diaphragm. Perireticular and mediastinal abscesses were imaged and appeared as echogenic lines with anechoic, echogenic, homogenous or heterogeneous contents. Additional ultrasonographic findings included hepatomegaly, dilation of the caudal vena cava, hepatic and portal veins, ascites, echogenic pleural effusions and vegetations of the tricuspid, mitral and pulmonary valves. The ultrasonographic findings were confirmed at postmortem examination.

  11. Self-healing juvenile cutaneous mucinosis

    PubMed Central

    Kołodziejczyk, Beata; Gazda, Agnieszka; Hernik, Elżbieta; Szczygielska, Izabela; Koprowska, Marta Legatowicz

    2017-01-01

    Girl, aged 4 years old, began the disease with pain of the lower extremities, fever up to 38°C and signs of upper airway infection. Then the patient developed oedema and redness of the whole face, thickened skin, subcutaneous nodular foldings of the frontal, occipital, cervical and axillary regions, extensor areas of the joints; fine, hard whitish nodules in the frontal region and over interphalangeal joints of the hands, pruritus; oedemas of the ankles, knees and joints of the hands, cervical lymphadenopathy and hepatomegaly. Blood tests at the moment of the diagnosis revealed elevation of markers of inflammation as ESR and CRP, leukocytosis, thrombocytosis, hypoalbuminemia, and hyper-alfa-2-globulinemia. Histopathological examination of the skin biopsy specimen and subcutaneous tissue revealed myxoid subcutaneous tissue located under the dermis and a section consisting of myxoid mesenchymal tissue with inflammatory infiltration by histiocytic cells. The presence of acid mucopolysaccharides in fields of the myxoid tissue was also observed. The self-healing juvenile cutaneous mucinosis (SJCM) was diagnosed. PMID:28386144

  12. 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.

  13. Mortality of captive whooping cranes caused by eastern equine encephalitis virus.

    PubMed

    Dein, F J; Carpenter, J W; Clark, G G; Montali, R J; Crabbs, C L; Tsai, T F; Docherty, D E

    1986-11-01

    Of 39 captive whooping cranes (Grus americana), 7 died during a 7-week period (Sept 17 through Nov 4, 1984) at the Patuxent Wildlife Research Center, Laurel, Md. Before their deaths, 4 cranes did not develop clinical signs, whereas the other 3 cranes were lethargic and ataxic, with high aspartate transaminase, gamma-glutamyl transferase, and lactic acid dehydrogenase activities, and high uric acid concentrations. Necropsies indicated that the birds had ascites, intestinal mucosal discoloration, fat depletion, hepatomegaly, splenomegaly, and visceral gout. Microscopically, extensive necrosis and inflammation were seen in many visceral organs; the CNS was not affected. Eastern equine encephalitis (EEE) virus was isolated from specimens of the livers, kidneys, lungs, brains, and intestines of 4 of the 7 birds that died, and EEE virus-neutralizing antibody was detected in 14 (44%) of the 32 surviving birds. Other infectious or toxic agents were not found. Morbidity or mortality was not detected in 240 sandhill cranes (Grus canadensis) interspersed among the whooping cranes; however, 13 of the 32 sandhill cranes evaluated had EEE virus-neutralizing antibody. Of the 41 wild birds evaluated in the area, 3 (4%) had EEE virus-neutralizing antibody. Immature Culiseta melanura (the most probable mosquito vector) were found in scattered foci 5 km from the research center.

  14. Fatal hemoprotozoal infections in multiple avian species in a zoological park.

    PubMed

    Ferrell, Shannon T; Snowden, Karen; Marlar, Annajane B; Garner, Michael; Lung, Nancy P

    2007-06-01

    Over a 3-yr span, two juvenile lesser flamingos (Phoeniconaias minor), two green jays (Cyanocorax yncas glaucescens), and two Montezuma oropendolas (Psarocolius montezuma) died peracutely with no premonitory signs at a zoological park in the southern United States. At necropsy, the birds were in excellent body condition. Except for one green jay, the coelomic cavities were filled with a dark serosanguineous fluid. Splenomegaly and hepatomegaly were present. The livers were tan to purple with numerous, randomly distributed red-to-black foci, ranging in size from 1 to 4 mm. The predominant histopathologic finding, except in one green jay, was large protozoal cysts in the hepatic parenchyma. Histologically, the protozoal cysts were restricted to the liver, and none were identified in the skeletal muscle, spleen, or other tissues. Frozen tissue samples harvested at necropsy had a nested polymerase chain reaction assay performed to amplify the mitochondrial cytochrome B gene of the protozoa. The amplified gene sequences were compared with reference cytochrome B gene sequences for avian Plasmodium spp., Haemoproteus spp., and Leucocytozoon spp. The protozoal parasite within the hepatic parenchyma from the Montezuma oropendolas and the lesser flamingos was identified as Haemoproteus spp. Both green jays had Plasmodium spp. isolated from the submitted tissue samples. The peracute nature of the infections precluded any successful medical intervention, making prevention by exclusion the principal means to control hemoprotozoal transmission. There are no reports in the literature documenting identified fatal hemoprotozoal infections in oropendolas, green jays, or lesser flamingos.

  15. Multidrug resistant citrobacter: an unusual cause of liver abscess.

    PubMed

    Kumar, Prabhat; Ghosh, Soumik; Rath, Deepak; Gadpayle, A K

    2013-04-22

    Liver abscesses are infectious, space occupying lesions in the liver, the two most common abscesses being pyogenic and amoebic. A pyogenic liver abscess (PLA) is a rare condition with a reported incidence of 20 per 100 000 hospital admissions in the western population. The right lobe of the liver is the most common site in both types of liver abscess. Clinical presentation is elusive with complaints of fever, right upper quadrant pain in the abdomen and hepatomegaly with or without jaundice. The aetiology of PLA has changed in the past few decades and may be of biliary, portal, arterial or traumatic origin, but many cases are still cryptogenic. The most common organisms causing PLA are Gram-negative aerobes, especially Escherichia coli and Klebsiella pneumoniae. Studies have shown a high degree of antimicrobial susceptibility of isolated organism resulting in an overall lower mortality in PLA. Here, we present a case of PLA caused by multidrug-resistant Citrobacter freundii, which is an unusual organism to be isolated.

  16. An Animal Model for the Juvenile Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis.

    PubMed

    Marin, Veronica; Rosso, Natalia; Dal Ben, Matteo; Raseni, Alan; Boschelle, Manuela; Degrassi, Cristina; Nemeckova, Ivana; Nachtigal, Petr; Avellini, Claudio; Tiribelli, Claudio; Gazzin, Silvia

    2016-01-01

    Non Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome; worrisome is the booming increase in pediatric age. To recreate the full spectrum of juvenile liver pathology and investigate the gender impact, male and female C57Bl/6 mice were fed with high fat diet plus fructose in the drinking water (HFHC) immediately after weaning (equal to 3-years old human), and disease progression followed for 16 weeks, until adults (equal to 30-years old human). 100% of subjects of both genders on HFHC diet developed steatosis in 4weeks, and some degree of fibrosis in 8weeks, with the 86% of males and 15% of females presenting a stage 2 fibrosis at 16weeks. Despite a similar final liver damage both groups, a sex difference in the pathology progression was observed. Alterations in glucose homeostasis, dyslipidemia, hepatomegaly and obese phenotype were evident from the very beginning in males with an increased hepatic inflammatory activity. Conversely, such alterations were present in females only at the end of the HFHC diet (with the exception of insulin resistance and the hepatic inflammatory state). Interestingly, only females showed an altered hepatic redox state. This juvenile model appears a good platform to unravel the underlying gender dependent mechanisms in the progression from NAFLD to NASH, and to characterize novel therapeutic approaches.

  17. Clinical and pathologic findings of the liver in the acquired immune deficiency syndrome (AIDS).

    PubMed

    Glasgow, B J; Anders, K; Layfield, L J; Steinsapir, K D; Gitnick, G L; Lewin, K J

    1985-05-01

    Clinical data and histologic sections of the liver, including immunohistochemical studies for hepatitis B surface and core antigens, were reviewed in 42 autopsy cases of the acquired immune deficiency syndrome (AIDS). Hepatomegaly, elevation of serum transaminases, and mild elevation of alkaline phosphatase were commonly observed clinical and biochemical abnormalities. Mildly elevated alkaline phosphatase and normal bilirubin levels were present in patients with Mycobacterium avium-intracellulare (MAI) infection, cytomegalovirus (CMV) infection, and Kaposi's sarcoma (KS). Histologic sections demonstrated liver involvement by MAI in eight cases; KS in six cases; cryptococcus in three cases; and CMV in two cases. One case of MAI infection was associated with marked central vein sclerosis, a finding previously unreported. Thirty-two (76%) of 42 cases had serologic or pathologic evidence of hepatitis exposure. Two patients had histologic evidence of chronic active hepatitis. The pathologic processes involving the liver appeared to be secondary to the infections and neoplasms for which this population is susceptible and did not significantly contribute to morbidity or mortality. No findings specific or pathognomic for AIDS were identified in the liver.

  18. Serological evidence of infection with rodent-borne hepatitis E virus HEV-C1 or antigenically related virus in humans

    PubMed Central

    SHIMIZU, Kenta; HAMAGUCHI, Sugihiro; NGO, Cuong Chi; LI, Tian-Cheng; ANDO, Shuji; YOSHIMATSU, Kumiko; YASUDA, Shumpei P.; KOMA, Takaaki; ISOZUMI, Rie; TSUDA, Yoshimi; FUJITA, Hiromi; PHAM, Thuy Thanh; LE, Mai Quynh; DANG, Anh Duc; NGUYEN, Tuan Quang; YOSHIDA, Lay-Myint; ARIYOSHI, Koya; ARIKAWA, Jiro

    2016-01-01

    Zoonotic potential of a rat-derived hepatitis E virus (HEV), designated as HEV-C1, remains unknown. To evaluate the risk for HEV-C1 infection in humans, paired sera of 208 hospitalized febrile patients collected from 2001 to 2003 in Hanoi, Vietnam, were examined for IgG antibodies to HEV-C1 and genotype 1 HEV (HEV-1), which is common in humans. IgG antibodies to virus-like particles (VLPs) of HEV-C1 and/or HEV-1 were detected from 99 of the 208 convalescent sera in enzyme-linked immunosorbent assay (ELISA). IgG antibody titers to HEV-C1 antigen in 3 of the 99 sera were more than 8-fold higher than those to HEV-1 antigen. IgM antibodies to HEV-C1 antigen were detected in acute sera from 2 of the 3 patients in ELISA and Western blotting. However, no HEV genome was detected. Clinical information was available for 1 of the 2 patients. Hepatic enzymes, aspartate aminotransferase and alanine aminotransferase, were mildly elevated (156 IU/l and 68 IU/l, respectively), and hepatomegaly was detected by ultrasonography. The patient recovered from the illness after 17 days. These results indicated that HEV-C1 or its variants infect humans in Vietnam and may cause acute febrile illness with mild liver dysfunction. PMID:27499185

  19. Liver disease in rheumatoid arthritis and Sjøgren's syndrome. Prospective study using biochemical and serological markers of hepatic dysfunction.

    PubMed Central

    Webb, J; Whaley, K; MacSween, R N; Nuki, G; Dick, W C; Buchanan, W W

    1975-01-01

    Inter-relationships of biochemical and immunological tests of liver function have been studied in a prospective study of 216 patients with rheumatoid arthritis (RA), 32 patients with Sjogren's syndrome, and 27 patients with the sicca syndrome, and these results have been compared with those obtained 289 patients with osteoarthrosis or with a form of seronegative polyarthropathy. In general the prevalence of abnormalities in serum alkaline phosphatase, bromsulphthalein excretion, smooth muscle antibody, and mitochondrial antibody in the former three groups was higher than in patients with osteoarthrosis. Patients with Sjogren's syndrome with RA had a higher prevalence of abnormalities of bromsulphthalein excretion, salivary duct antibody than patients with the sicca syndrome. Patients with RA had a higher pervalence of rheumatoid factor than those with the sicca syndrome. Patients with a positive smooth muscle or mitochondrial antibody were found to have a higher prevalence of hepatomegaly and splenomegaly, of abnormal liver function tests, of other autoantibodies, and of histological abnromalitis of liver than those in whom these tests were negative. PMID:1092275

  20. 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

  1. Investigation and management of the hepatic glycogen storage diseases

    PubMed Central

    2015-01-01

    The glycogen storage diseases (GSD) comprise a group of disorders that involve the disruption of metabolism of glycogen. Glycogen is stored in various organs including skeletal muscle, the kidneys and liver. The liver stores glycogen to supply the rest of the body with glucose when required. Therefore, disruption of this process can lead to hypoglycaemia. If glycogen is not broken down effectively, this can lead to hepatomegaly. Glycogen synthase deficiency leads to impaired glycogen synthesis and consequently the liver is small. Glycogen brancher deficiency can lead to abnormal glycogen being stored in the liver leading to a quite different disorder of progressive liver dysfunction. Understanding the physiology of GSD I, III, VI and IX guides dietary treatments and the provision of appropriate amounts and types of carbohydrates. There has been recent re-emergence in the literature of the use of ketones in therapy, either in the form of the salt D,L-3-hydroxybutyrate or medium chain triglyceride (MCT). High protein diets have also been advocated. Alternative waxy maize based starches seem to show promising early data of efficacy. There are many complications of each of these disorders and they need to be prospectively surveyed and managed. Liver and kidney transplantation is still indicated in severe refractory disease. PMID:26835382

  2. Relationship between plasma lipids and palmitoyl-CoA hydrolase and synthetase activities with peroxisomal proliferation in rats treated with fibrates.

    PubMed Central

    Alegret, M.; Ferrando, R.; Vázquez, M.; Adzet, T.; Merlos, M.; Laguna, J. C.

    1994-01-01

    1. The time-course of the effect of clofibrate (CFB), bezafibrate (BFB) and gemfibrozil (GFB) on lipid plasma levels and palmitoyl-CoA hydrolase and synthetase activities, as well as the correlations with the peroxisomal proliferation phenomenon have been studied in male Sprague-Dawley rats. 2. The administration of the three drugs caused a significant reduction in body weight gain, accompanied with a paradoxical increase in food intake in groups treated with BFB and GFB. 3. Drug treatment produced gross hepatomegaly and increase in peroxisomal beta-oxidation, and these parameters were strongly correlated. The order of potency was BFB > CFB > or = GFB. 4. Both plasma cholesterol (BFB approximately CFB > GFB) and triglyceride (BFB approximately GFB > CFB) levels were reduced in treated animals. There was an inverse correlation between these parameters and peroxisomal beta-oxidation, although the peroxisomal proliferation seemed to explain only a small part of the hypolipidemic effect observed. 5. Cytosolic and microsomal (but not mitochondrial) palmitoyl-CoA hydrolase activities were increased by the three drugs (BFB > CFB > GFB), probably by inducing the hydrolase I isoform, which is insensitive to inhibition by fibrates in vitro. The increased hydrolase activities were directly and strongly correlated with peroxisomal beta-oxidation. 6. Palmitoyl-CoA synthetase activity was also increased by the treatment with fibrates (BFB > CFB > GFB), probably as a consequence of the enhancement of hydrolase activities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7915611

  3. Hepatic disease in patients with acquired immunodeficiency syndrome (AIDS).

    PubMed

    Lodenyo, Hudson; Segal, Issy

    2004-01-01

    The acquired immunodeficiency syndrome is now the leading cause of death in the world. Liver involvement in opportunistic infections and neoplasms affecting patients with human immunodeficiency disease syndrome are common. Many of these patients also take many medicines and toxins that are potentially harmful to the liver. This is an overview on the aetiology and possible diagnostic guide to determine liver involvement in patients with HIV infection. A literature review was performed on major published series on the liver and HIV infection between 1985 and 1999, both years inclusive. Data and opinions from 5 general reviews and 31 original articles from MEDLINE on liver disease in patients with HIV infection regarding aetiology, pathology, presentation and patient evaluation are summarised. The liver is frequently affected in patients with AIDS. The majority of the patients have hepatomegaly and abnormal liver enzymes secondary to involvement with opportunities infections, AIDS associated neoplasms and drug therapy. Most of the infections reach the liver by lymphohaematogeneous spread from other sites in the body. Methodical approach in patient evaluation is therefore essential for prompt diagnosis and treatment to minimise morbidity and early mortality.

  4. RB tumor suppressive function in response to xenobiotic hepatocarcinogens.

    PubMed

    Reed, Christopher; Hutcheson, Jack; Mayhew, Christopher N; Witkiewicz, Agnieszka K; Knudsen, Erik S

    2014-06-01

    Diverse etiologic events are associated with the development of hepatocellular carcinoma. During hepatocarcinogenesis, genetic events likely occur that subsequently cooperate with long-term exposures to further drive the progression of hepatocellular carcinoma. In this study, the frequent loss of the retinoblastoma (RB) tumor suppressor in hepatocellular carcinoma was modeled in response to diverse hepatic stresses. Loss of RB did not significantly affect the response to a steatotic stress as driven by a methionine- and choline-deficient diet. In addition, RB status did not significantly influence the response to peroxisome proliferators that can drive hepatomegaly and tumor development in rodents. However, RB loss exhibited a highly significant effect on the response to the xenobiotic1,4-Bis-[2-(3,5-dichloropyridyloxy)] benzene. Loss of RB yielded a unique proliferative response to this agent, which was distinct from both regenerative stresses and genotoxic carcinogens. Long-term exposure to 1,4-Bis-[2-(3,5-dichloropyridyloxy)] benzene yielded profound tumor development in RB-deficient livers that was principally absent in RB-sufficient tissue. These data demonstrate the context specificity of RB and the key role RB plays in the suppression of hepatocellular carcinoma driven by xenobiotic stress.

  5. The Syndrome of Veno-occlusive Disease After Blood or Marrow Transplantation.

    PubMed

    Carreras, E; Rozman, C

    1998-01-01

    Veno-occlusive disease of the liver (VOD) was originally described in patients who drank infusions made with plants containing pyrrolizidine alkaloids [1]. This disease was characterized, histologically, by a progressive and concentric non-thrombotic narrowing of the lumina of small intrahepatic veins. Later, VOD was related to other pathogens such as alcohol, contraceptives, toxic oil, liver radiation and several antineoplastic drugs [2-3]. The first case of veno-occlusive disease following bone marrow transplantation (BMT) was reported in 1979 [4]. Since then, BMT has proved to be the main cause of VOD which is one of the leading causes of morbidity and mortality after transplant [5-7]. Clinical manifestations of VOD are very characteristic (jaundice, painful hepatomegaly and fluid retention) but indistinguishable from those produced by other regime-related morphological changes on zone 3 of the liver acinus. For this reason, the term "syndrome of veno-occlusive disease of the liver" has been adopted to designate the clinical manifestations of conditioning regimen toxicity on this zone [8]. This review focuses on the present knowledge of VOD syndrome after BMT.

  6. Hodgkin's disease presenting as a cholestatic febrile illness: incidence and main characteristics in a series of 421 patients.

    PubMed

    Cervantes, F; Briones, J; Bruguera, M; Font, C; Grau, J M; Rozman, C; Montserrat, E

    1996-06-01

    In order to determine the frequency and characteristics of patients with liver abnormalities as the presenting manifestation of Hodgkin's disease (HD), 421 consecutive HD patients were studied. Six patients in the series (1.4%) presented with liver abnormalities that led to of a liver biopsy and the subsequent diagnosis of HD. All had fever prior to HD diagnosis, four frank jaundice, and one hepatic failure. No patient had pruritus. Moderate hepatomegaly was present in four patients. Cholestasis was observed in all cases; in most patients a moderate increase in the transaminase activity was also seen. Two patients had a mild rise in the serum LDH, four had leukopenia, and one eosinophilia. At liver histologic study, Reed-Sternberg cells were demonstrated in four patients; in the remaining two, the presence of atypical histiocytes, lymphocytes, and eosinophils was highly suggestive of HD, the latter diagnosis being confirmed by subsequent study of bone marrow and/or retroperitoneal lymphadenopathies. In three of the six patients, HD was not demonstrated in sites other than the liver. Three patients older than 60 years died shortly after HD diagnosis. By contrast, three patients younger than 40 years showed a dramatic response to chemotherapy: two of them had a further relapse, and one is considered cured after 14 years of continuous remission. Liver disease constitutes an infrequent form of HD presentation which must be included in the differential diagnosis of any patient with fever of unknown origin.

  7. The changing profile of idiopathic myelofibrosis: a comparison of the presenting features of patients diagnosed in two different decades.

    PubMed

    Cervantes, F; Pereira, A; Esteve, J; Cobo, F; Rozman, C; Montserrat, E

    1998-02-01

    In an attempt to ascertain whether the presenting features of idiopathic myelofibrosis (IM) have changed in recent years, 2 groups of patients diagnosed with IM in a single institution in different time periods were compared. The first group included 53 patients diagnosed from 1975 to 1986, and the second included 56 patients diagnosed from 1987 to 1997. No significant differences were observed between the two groups with regard to age, gender, delay from first symptoms to disease diagnosis, peripheral blood hematological values and serum biochemical parameters. Patients diagnosed prior to 1987 presented more often with constitutional symptoms (fever, night sweats, weight loss), but the difference did not reach statistical significance. These latter patients had, however, a higher frequency of splenomegaly (91% vs. 73%, p=0.01) and hepatomegaly (79% vs. 48%, p=0.002), and were more often in the osteosclerotic phase at diagnosis (p=0.05) than patients more recently diagnosed. Finally, no significant differences were found between both groups in either the distribution by prognostic scores or survival. The above results seem to indicate a trend towards a less florid clinical picture of IM at presentation in recent years. This, however, does not result in a longer patient survival.

  8. Evaluation of childhood brucellosis in the central Black Sea region.

    PubMed

    Çıraklı, Sevgi; Karlı, Arzu; Şensoy, Gülnar; Belet, Nurşen; Yanık, Keramettin; Çıraklı, Alper

    2015-01-01

    Brucellosis is a systemic infectious disease that leads to various clinical pictures and is still a significant health problem in Turkey. In this study, 52 pediatric patients diagnosed with brucellosis between January 2008 and December 2013 were examined. Clinical and laboratory findings, response to treatment, prognosis and complications were evaluated. Diagnosis of brucellosis was made based on a clinical picture compatible with the disease, together with standard tube agglutination test (SAT) positivity (1/160 or higer titer) or isolation of Brucella spp. in a sterile body fluid culture. The cases comprised 10 females and 42 males. In 75% of cases, there was a history of consumption of unpasteurized milk or dairy products. The most commonly seen symptoms and findings were fever (75%), arthralgia (54%), fatigue (19%), splenomegaly (44%), hepatomegaly (42%) and arthritis (19%). Atypical presentations were seen in one case of epidydymo-orchitis and three cases of bleeding of the nose and gums. In the laboratory examinations, anemia was determined in 56% of cases, leukopenia in 40% and thrombocytopenia in 27%. In blood cultures taken from 41 patients, Brucella spp. were isolated in 23 (56.1%). All patients recovered, and sequelae were seen only in a patient with osteoarthritis. In conclusion, although brucellosis leads to many different clinical pictures, a very good response to treatment can be obtained. If effective treatment cannot be implemented in time, the disease may become chronic, and complications and relapses may be encountered. Therefore, early diagnosis and treatment is of great importance.

  9. A PELAGIC OUTBREAK OF AVIAN CHOLERA IN NORTH AMERICAN GULLS: SCAVENGING AS A PRIMARY MECHANISM FOR TRANSMISSION?

    PubMed

    Wille, Michelle; McBurney, Scott; Robertson, Gregory J; Wilhelm, Sabina I; Blehert, David S; Soos, Catherine; Dunphy, Ron; Whitney, Hugh

    2016-10-01

    Avian cholera, caused by the bacterium Pasteurella multocida , is an endemic disease globally, often causing annual epizootics in North American wild bird populations with thousands of mortalities. From December 2006 to March 2007, an avian cholera outbreak caused mortality in marine birds off the coast of Atlantic Canada, largely centered 300-400 km off the coast of the island of Newfoundland. Scavenging gulls ( Larus spp.) were the primary species detected; however, mortality was also identified in Black-legged Kittiwakes ( Rissa tridactyla ) and one Common Raven ( Corvus corax ), a nonmarine species. The most common gross necropsy findings in the birds with confirmed avian cholera were acute fibrinous and necrotizing lesions affecting the spleen, air sacs, and pericardium, and nonspecific hepatomegaly and splenomegaly. The etiologic agent, P. multocida serotype 1, was recovered from 77 of 136 carcasses examined, and confirmed or probable avian cholera was diagnosed in 85 cases. Mortality observed in scavenging gull species was disproportionately high relative to their abundance, particularly when compared to nonscavenging species. The presence of feather shafts in the ventricular lumen of the majority of larid carcasses diagnosed with avian cholera suggests scavenging of birds that died from avian cholera as a major mode of transmission. This documentation of an outbreak of avian cholera in a North American pelagic environment affecting primarily scavenging gulls indicates that offshore marine environments may be a component of avian cholera dynamics.

  10. Identification and functional analysis of a defect in the human ALG9 gene: definition of congenital disorder of glycosylation type IL.

    PubMed

    Frank, Christian G; Grubenmann, Claudia E; Eyaid, Wafaa; Berger, Eric G; Aebi, Markus; Hennet, Thierry

    2004-07-01

    Defects of lipid-linked oligosaccharide assembly lead to alterations of N-linked glycosylation known as "type I congenital disorders of glycosylation" (CDG). Dysfunctions along this stepwise assembly pathway are characterized by intracellular accumulation of intermediate lipid-linked oligosaccharides, the detection of which contributes to the identification of underlying enzymatic defects. Using this approach, we have found, in a patient with CDG, a deficiency of the ALG9 alpha 1,2 mannosyltransferase enzyme, which causes an accumulation of lipid-linked-GlcNAc(2)Man(6) and -GlcNAc(2)Man(8) structures, which was paralleled by the transfer of incomplete oligosaccharides precursors to protein. A homozygous point-mutation 1567G-->A (amino acid substitution E523K) was detected in the ALG9 gene. The functional homology between the human ALG9 and Saccharomyces cerevisiae ALG9, as well as the deleterious effect of the E523K mutation detected in the patient with CDG, were confirmed by a yeast complementation assay lacking the ALG9 gene. The ALG9 defect found in the patient with CDG--who presented with developmental delay, hypotonia, seizures, and hepatomegaly--shows that efficient lipid-linked oligosaccharide synthesis is required for proper human development and physiology. The ALG9 defect presented here defines a novel form of CDG named "CDG-IL."

  11. Ocular and multicentric lymphoma in a young racehorse.

    PubMed

    Germann, Stephanie E; Richter, Marianne; Schwarzwald, Colin C; Wimmershoff, Julia; Spiess, Bernhard M

    2008-09-01

    A 6-year-old thoroughbred gelding was presented with a history of blepharospasm and opacity in the OS of 1 weeks' duration. Ophthalmic examination findings were consistent with acute uveitis in the OS, and traditional treatment was initiated with systemic antibiotics and anti-inflammatory drugs, topical mydriatics, and corticosteroids. During the total treatment period of 4 weeks response to treatment was weak and the horse developed further problems such as cellulitis of the right hind limb with fever and eventually weight loss and dependent edema. Blood work was indicative of liver disease. Abdominal sonography revealed severe splenomegaly and slight hepatomegaly, and a liver biopsy confirmed malignant T-cell lymphoma. The horse was euthanized due to deteriorating general condition and subsequently underwent postmortem examination. Necropsy and histologic examination revealed a multicentric lymphoma with involvement of spleen, mesenteric lymph nodes, and OU. The findings in this case demonstrate that the differential diagnosis of intraocular and systemic lymphoma should be considered in any horse presenting with anterior uveitis, especially when uveitis is unresponsive to treatment and when additional systemic signs of illness such as lethargy, fever, weight loss, or dependent edema arise. Cytological examination of aqueous humor may provide a rapid diagnosis of intraocular lymphoma in eyes with clinical uveitis.

  12. Forced expression of fibroblast growth factor 21 reverses the sustained impairment of liver regeneration in hPPARα(PAC) mice due to dysregulated bile acid synthesis.

    PubMed

    Liu, Hui-Xin; Hu, Ying; French, Samuel W; Gonzalez, Frank J; Wan, Yu-Jui Yvonne

    2015-01-01

    Peroxisome proliferator activated receptor α (PPARα) stimulates hepatocellular proliferation is species-specific. Activation of mouse, but not human, PPARα induces hepatocellular proliferation, hepatomegaly, and liver cancer. Here we tested the hypothesis that human and mouse PPARα affects liver regeneration differentially. PPARα-humanized mice (hPPARα(PAC)) were similar to wild type mice in responding to fasting-induced PPARα signaling. However, these mouse livers failed to regenerate in response to partial hepatectomy (PH). The liver-to-body weight ratios did not recover even 3 months after PH in hPPARα(PAC). The mouse PPARα-mediated down-regulation of let-7c was absent in hPPARα(PAC), which might partially be responsible for impaired proliferation. After PH, hPPARα(PAC) displayed steatosis, necrosis, and inflammation mainly in periportal zone 1, which suggested bile-induced toxicity. Quantification of hepatic bile acids (BA) revealed BA overload with increased hydrophobic BA in hPPARα(PAC). Forced FGF21 expression in partial hepatectomized hPPARα(PAC) reduced hepatic steatosis, prevented focal necrosis, and restored liver mass. Compared to mouse PPARα, human PPARα has a reduced capacity to regulate metabolic pathways required for liver regeneration. In addition, FGF21 can compensate for the reduced ability of human PPARα in stimulating liver regeneration, which suggests the potential application of FGF21 in promoting hepatic growth in injured and steatotic livers in humans.

  13. An outbreak of Chlamydophila psittaci in an outdoor colony of Magellanic penguins (Spheniscus magellanicus).

    PubMed

    Jencek, Jacqueline E; Beaufrère, Hugues; Tully, Thomas N; Garner, Michael M; Dunker, Freeland H; Baszler, Timothy V

    2012-12-01

    An outbreak of Chlamydophila psittaci occurred in an outdoor colony of 63 Magellanic penguins (Spheniscus magellanicus) at the San Francisco Zoo. Affected penguins presented with inappetence, lethargy, and light green urates. Hematologic and serum biochemical findings were consistent with chronic inflammation. Penguins did not respond to initial supportive and antimicrobial therapy, and 3 died. Necropsy results of the 3 birds revealed hepatomegaly and splenomegaly, and histologic lesions included necrotizing hepatitis, splenitis, and vasculitis. Chlamydophila psittaci infection was confirmed by results of Gimenez staining, immunohistochemistry, and tissue polymerase chain reaction assay. As additional birds continued to present with similar clinical signs, the entire colony of penguins was prophylactically treated with a 30-day minimum course of doxycycline, administered orally or intramuscularly or as a combination of both. Despite treatment, 9 additional penguins died during a 3-month period. Pathologic results from these birds revealed renal and visceral gout (n = 4), cardiac insufficiency (n = 2), sepsis from a suspected esophageal perforation (n = 2), and no gross lesions (n = 1). During the outbreak, 4 birds presented with seizures, 5 developed dermatitis, and nearly 90% of birds in the colony showed severe keratoconjunctivitis, believed to be related to drug therapy with doxycycline. We report the clinical and pathologic features of Chlamydophila psittaci infection in an outdoor colony of penguins and the associated challenges of treatment.

  14. Activating CAR and β-catenin induces uncontrolled liver growth and tumorigenesis.

    PubMed

    Dong, Bingning; Lee, Ju-Seog; Park, Yun-Yong; Yang, Feng; Xu, Ganyu; Huang, Wendong; Finegold, Milton J; Moore, David D

    2015-02-09

    Aberrant β-catenin activation contributes to a third or more of human hepatocellular carcinoma (HCC), but β-catenin activation alone is not sufficient to induce liver cancer in mice. Differentiated hepatocytes proliferate upon acute activation of either β-catenin or the nuclear xenobiotic receptor CAR. These responses are strictly limited and are tightly linked, since β-catenin is activated in nearly all of the CAR-dependent tumours generated by the tumour promoter phenobarbital. Here, we show that full activation of β-catenin in the liver induces senescence and growth arrest, which is overcome by combined CAR activation, resulting in uncontrolled hepatocyte proliferation, hepatomegaly and rapid lethality despite maintenance of normal liver function. Combining CAR activation with limited β-catenin activation induces tumorigenesis, and the tumours share a conserved gene expression signature with β-catenin-positive human HCC. These results reveal an unexpected route for hepatocyte proliferation and define a murine model of hepatocarcinogenesis with direct relevance to human HCC.

  15. Development of Dengue Infection Severity Score

    PubMed Central

    Pongpan, Surangrat; Tawichasri, Chamaiporn; Namwongprom, Sirianong

    2013-01-01

    Objectives. To develop a simple scoring system to predict dengue infection severity based on patient characteristics and routine clinical profiles. Methods. Retrospective data of children with dengue infection from 3 general hospitals in Thailand were reviewed. Dengue infection was categorized into 3 severity levels: dengue infection (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). Coefficients of significant predictors of disease severity under ordinal regression analysis were transformed into item scores. Total scores were used to classify patients into 3 severity levels. Results. Significant clinical predictors of dengue infection severity were age >6 years, hepatomegaly, hematocrit ≥40%, systolic pressure <90 mmHg, white cell count >5000 /μL, and platelet ≤50000 /μL. The derived total scores, which ranged from 0 to 18, classified patients into 3 severity levels: DF (scores <2.5, n = 451, 58.1%), DHF (scores 2.5–11.5, n = 276, 35.5%), and DSS (scores >11.5, n = 50, 6.4%). The derived score correctly classified patients into their original severity levels in 60.7%. An under-estimation of 25.7% and an over-estimation of 13.5% were clinically acceptable. Conclusions. The derived dengue infection severity score classified patients into DF, DHF, or DSS, correctly into their original severity levels. Validation of the score should be reconfirmed before application of routine practice. PMID:24324896

  16. Liver dysfunction in residents exposed to leachate from a toxic waste dump.

    PubMed

    Meyer, C R

    1983-02-01

    It has been estimated that there are some 30,000 chemical waste dumps in the United States. Many of these landfill operations were undertaken in the early 1950s and 1960s, when knowledge regarding the safe and prolonged containment of the waste buried was nonexistent or minimal at best. As a result, many of these dump sites were located in areas that were geologically unsuitable for toxic chemical wastes. The Love Canal area in Niagara Falls, NY, is probably the best known of these dump sites. While a few of these sites have attracted wide media coverage, the availability of objective scientific information regarding the health effects of such sites has been deficient. The present study of a large toxic waste dump located in Hardeman County, TN, its contamination of surface and underground aquifers and the health effects on the area residents exposed via ingestion of contaminated water, offers the first objective evidence of organ dysfunction in such a human population. During this study comprehensive evaluation of that population revealed multiple symptoms, evidence of hepatomegaly and elevated liver function tests apparently caused by ingestion of water contaminated by numerous organic chemicals, many of which are known to be hepatotoxins.

  17. Platynosomum fastosum-induced chronic intrahepatic cholangitis and Spirometra spp. infections in feral cats from Grand Cayman.

    PubMed

    Headley, S A; Gillen, M A; Sanches, A W D; Satti, M Z

    2012-06-01

    The occurrence of platynosomiasis and intestinal sparganosis is described in feral cats from Grand Cayman, Cayman Islands. Spirometra spp. was observed within the intestine of 18.18% (10/55) of cats; 1.18% (1/55) of cats demonstrated gross and histological manifestation of parasitism by Platynosomum fastosum, but 14.5% (8/55) of cats had the characteristic pathological manifestations of P. fastosum-induced intrahepatic cholangitis without the concomitant presence of the intraductal trematode. Combined parasitism (Spirometra spp. and P. fastosum) was observed in 9.09% (5/55) of feral cats. Significant pathological findings were only associated with the hepatic fluke, P. fastosum, and were grossly characterized by moderate hepatomegaly with enlarged and dilated bile ducts. Examples of cestodes with morphological features characteristic of Spirometra spp. were observed within the small intestine without any associated pathological lesion. The histopathological evaluation of liver fragments revealed chronic intrahepatic cholangitis with and without the associated intraductal trematode, and was characterized by marked periductal fibrosis, adenomatous proliferation of bile duct epithelium, dilation of intrahepatic bile ducts and portal accumulations of inflammatory cells. The occurrence of the cestode in feral cats coupled with factors that are unique to Grand Cayman makes this island the ideal location for sporadic cases of human sparganosis.

  18. Successful treatment of severe cardiomyopathy in glycogen storage disease type III With D,L-3-hydroxybutyrate, ketogenic and high-protein diet.

    PubMed

    Valayannopoulos, Vassili; Bajolle, Fanny; Arnoux, Jean-Baptiste; Dubois, Sandrine; Sannier, Nathalie; Baussan, Christiane; Petit, François; Labrune, Philippe; Rabier, Daniel; Ottolenghi, Chris; Vassault, Anne; Broissand, Christine; Bonnet, Damien; de Lonlay, Pascale

    2011-12-01

    Glycogen storage disease type III (GSD III) due to debranching enzyme deficiency presenting usually with hepatomegaly and hypoglycemia may be responsible for severe cardiomyopathy which is often fatal. Current treatment of GSD III is based on frequent high-carbohydrate meals that have no effect on the cardiomyopathy. We describe a 2-mo-old infant presenting with a familial form of GSD III complicated with cardiomyopathy. As conventional treatment was unable to improve his sister's cardiomyopathy who was deceased at age 11 mo, we proposed an experimental treatment combining the use of synthetic ketone bodies (D,L-3-OH butyrate) as an alternative energy source, 2:1 ketogenic diet to reduce glucose intake and high-protein diet to enhance gluconeogenesis. Twenty-four months after the onset of this treatment, echocardiography showed an improvement of cardiomyopathy. Growth and liver size remained normal, and no side effects were observed. Blood glucose levels remained within the normal range and insulin levels decreased. These findings show that synthetic ketone bodies as well as low-carbohydrate, high-lipid, and high-protein diet may be a more beneficial therapeutic choice therapeutic choice for GSD III patients with cardiomyopathy. These encouraging data need to be confirmed in more GSD III patients presenting with cardiac or muscular symptoms.

  19. Mixed Hepatoblastoma in a Young Male Adult: A Case Report and Literature Review

    PubMed Central

    Fiaschetti, Valeria; Fiori, Roberto; Gaspari, Eleonora; Crusco, Sonia; Simonetti, Giovanni

    2010-01-01

    Hepatoblastoma (HB) is a rare malignant tumour of the liver and usually occurs in the first three years of life. Most of these tumours arise in the embryo; hence it seems to be unusual that hepatoblastoma occurs in adults and is an exceptional cause of primary malignant liver tumour in adult patients. The diagnosis is often overlooked, and patients might be diagnosed at late stages of the disease at risk of increased mortality. In this paper we report a case of a 30-year-old man with mixed hepatoblastoma and abdominal pain, hepatomegaly and fever. The patient under went noninvasive diagnostic methods: duplex scanning, Computed Tomography (CT), and Magnetic Resonance imaging (MRI). In our experience, despite the important role of histological sample provided by biopsy in defining the diagnosis, very important was the role of MRI, more than ultrasonography and enhanced CT. The MRI detects tumor features as size, margins, and ratio with neighboring organs in order to get the best surgical approach. PMID:21113306

  20. Community-Acquired Methicillin-Resistant Pyogenic Liver Abscess

    PubMed Central

    Cherian, Joel; Singh, Rahul; Varma, Muralidhar; Vidyasagar, Sudha; Mukhopadhyay, Chiranjay

    2016-01-01

    Pyogenic liver abscesses are rare with an incidence of 0.5% to 0.8% and are mostly due to hepatobiliary causes (40% to 60%). Most are polymicrobial with less than 10% being caused by Staphylococcus aureus. Of these, few are caused by methicillin-resistant Staphylococcus aureus (MRSA) and fewer still by a community-acquired strain. Here we present a case study of a patient with a community-acquired MRSA liver abscess. The patient presented with fever since 1 month and tender hepatomegaly. Blood tests revealed elevated levels of alkaline phosphatase, C-reactive protein, erythrocyte sedimentation rate, and neutrophilic leukocytosis. Blood cultures were sterile. Ultrasound of the abdomen showed multiple abscesses, from which pus was drained and MRSA isolated. Computed tomography of the abdomen did not show any source of infection, and an amebic serology was negative. The patient was started on vancomycin for 2 weeks, following which he became afebrile and was discharged on oral linezolid for 4 more weeks. Normally a liver abscess is treated empirically with ceftriaxone for pyogenic liver abscess and metronidazole for amebic liver abscess. However, if the patient has risk factors for a Staphylococcal infection, it is imperative that antibiotics covering gram-positive organisms be added while waiting for culture reports. PMID:27540556

  1. An obscure case of hepatic subcapsular hematoma.

    PubMed

    Ndzengue, Albert; Hammoudeh, Fadi; Brutus, Pierre; Ajah, Ofem; Purcell, Roland; Leadon, Joseph; Rafal, Richard B; Balmir, Simon; Enriquez, Danilo A; Posner, Gerald L; Jaffe, Eric A; Chandra, Pradeep

    2011-04-13

    Spontaneous liver bleeding is often reported in preeclampsia. It is otherwise rare and has been linked to gross anatomical lesions and coagulopathy. We report a case of subcapsular hematoma of the liver without any apparent lesion and in the absence of coagulopathy. A 41-year-old male, paraplegic for 16 years, presented to the emergency department 3 days after sudden onset of right upper quadrant and shoulder pain. He had been on vitamins and 5,000 units subcutaneous heparin 12-hourly at the nursing home for the last month. He was in no distress, afebrile, with stable vitals. Physical examination showed a diverting colostomy, tender hepatomegaly and sacral decubiti. A fecal occult blood test was negative. There was spastic paraplegia below the level of T12. Two days after admission, the patient was afebrile and hemodynamically stable. PTT, PT, liver profile, BUN and creatinine were all normal, however his hemoglobin had dropped from 11.3 to 7.6 g/dl. An abdominal CT scan revealed an isolated 9.0 × 1.8 cm subcapsular hematoma. The patient received blood transfusion in the intensive care unit and was discharged 7 days later. In conclusion, spontaneous liver hemorrhage occurs in the nonobstetrical population in the setting of gross anatomical lesions or coagulopathy. This is the first report of an isolated subcapsular liver hematoma.

  2. Computed tomography findings of hepatic veno-occlusive disease caused by Sedum aizoon with histopathological correlation

    PubMed Central

    Shao, H.; Chen, H. Z.; Zhu, J. S.; Ruan, B.; Zhang, Z. Q.; Lin, X.; Gan, M. F.

    2015-01-01

    This study investigated the value of computed tomography (CT) in the diagnosis and treatment of hepatic veno-occlusive disease (HVOD) caused by Sedum aizoon (SA). The clinical manifestations, treatment results, imaging findings, and histological findings of the liver were analyzed in 39 patients with HVOD caused by SA. Hepatomegaly, liver dysfunction, abdominal effusion, and geographic density changes on liver CT scans were found in all 39 patients. The pathological findings of histological liver examination included swelling and point-like necrosis of liver cells, significant expansion and congestion of the sinuses, endothelial swelling, and wall thickening with incomplete lumen occlusion of small liver vessels. CT geographic density changes were confirmed by histological examination of the liver in 18 patients. Sixteen patients with small amounts of ascites that started within 4 weeks of treatment recovered completely or significantly improved after symptomatic and supportive treatment. However, only 43.75% of the patients with larger amounts of ascites improved following symptomatic and supportive treatment. In conclusion, liver CT examination is a valuable, safe, and noninvasive tool for the diagnosis of HVOD caused by SA. In selected cases, liver CT examination may replace liver biopsy and histological analysis. PMID:26517336

  3. Production of interleukins 4 and 10 in children with hepatic involvement in the course of Toxocara spp. infection.

    PubMed

    Mazur-Melewska, K; Figlerowicz, M; Cwalińska, A; Mikoś, H; Jończyk-Potoczna, K; Lewandowska-Stachowiak, M; Służewski, W

    2016-02-01

    Toxocara spp. infestations present with a wide spectrum of symptoms, from general inflammation of internal organs with eosinophilic granuloma formulation through ocular or brain involvement. There is also an asymptomatic form. The known factors that influence the clinical form of the disease are the intensity of the infestation, the localization of the larvae, the age of the patient, the efficiency of the immune system and the history of reinfection. The aim of our study was to evaluate the production of interleukins 4 (IL-4) and 10 (IL-10) in children in the course of Toxocara spp. infections with hepatic involvement. The analysis of peripheral leucocytes, eosinophils, immunoglobulin E, and IL-4 and IL-10 concentrations presented significantly higher values in children with radiologically confirmed liver granuloma than in uncomplicated hepatomegaly. Based on statistical analysis, we confirmed the IL-4/IL-10 ratio variation in the analysed groups: patients with liver lesions showed a ratio of <1, while children without granulomas had a ratio of >2. The relevant analysis confirmed a positive statistical correlation in both seropositive groups for IgE and IL-4, and only in the granuloma group for IgE and IL-10.

  4. Ethical issues of unrelated hematopoietic stem cell transplantation in adult thalassemia patients

    PubMed Central

    2011-01-01

    Background Beta thalassemia major is a severe inherited form of hemolytic anemia that results from ineffective erythropoiesis. Allogenic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative therapy. Unfortunately, the subgroup of adult thalassemia patients with hepatomegaly, portal fibrosis and a history of irregular iron chelation have an elevated risk for transplantation-related mortality that is currently estimated to be about 29 percent. Discussion Thalassemia patients may be faced with a difficult choice: they can either continue conventional transfusion and iron chelation therapy or accept the high mortality risk of HSCT in the hope of obtaining complete recovery. Throughout the decision making process, every effort should be made to sustain and enhance autonomous choice. The concept of conscious consent becomes particularly important. The patient must be made fully aware of the favourable and adverse outcomes of HSCT. Although it is the physician's duty to illustrate the possibility of completely restoring health, considerable emphasis should be put on the adverse effects of the procedure. The physician also needs to decide whether the patient is eligible for HSCT according to the "rule of descending order". The patient must be given full details on self-care and fundamental lifestyle changes and be fully aware that he/she will be partly responsible for the outcome. Summary Only if all the aforesaid conditions are satisfied can it be considered reasonable to propose unrelated HSCT as a potential cure for high risk thalassemia patients. PMID:21385429

  5. [Results of the treatment of nonlymphoblastic acute leukemia in a pediatric population].

    PubMed

    Rivera Luna, R; Ajuria Gottwald, E; Silva Sosa, M; González Chirinos, P

    1977-01-01

    On a prospective fashion during approximately two years, 22 pediatric patients with acute non lymphocytic leukemia were evaluated. Of this population the majority had acute mielocytic leukemia, followed by acute myelomonocytic leukemia. Absolutely all patients at the time of diagnosis and subsequently every 4 to 6 weeks had a bone marrow aspiration test. When the patients were first seen, 54% of them presented fever; lymph node enlargement was not a common finding. Only few of this patients presented splenomegaly and/or hepatomegaly. In regards to complete blood counts the most outstanding of its was the presence of leukocyte count above 20000/mm.3 in 8 of this patients. From the 22 patients studied only 21 are evaluable. All 21 patients were treated with a 4 drug combination (modified COAP). Sixteen patients (76%) achieved bone marrow remission, of which only 15 patients (71%) achieved complete remission. The median duration remission was of 9.2 months with a range of 2 to 26 months. At the present time only 7 patients (33%) are alive and on remission. Two more patients are alive but in full relapse. The mortality rate of this study is of 59%. The review of recent chemotherapy reports is presented and the need for further trials is emphasized especially in view of recent papers published in which it appears that better results are being obtained at last in children's acute non lymphocitic leukemia.

  6. Cyst infection in autosomal dominant polycystic kidney disease: causative microorganisms and susceptibility to lipid-soluble antibiotics.

    PubMed

    Suwabe, T; Araoka, H; Ubara, Y; Kikuchi, K; Hazue, R; Mise, K; Hamanoue, S; Ueno, T; Sumida, K; Hayami, N; Hoshino, J; Imafuku, A; Kawada, M; Hiramatsu, R; Hasegawa, E; Sawa, N; Takaichi, K

    2015-07-01

    Cyst infection is a frequent and serious complication of autosomal dominant polycystic kidney disease (ADPKD). Lipid-soluble antibiotics like fluoroquinolones show good penetration into cysts and are recommended for cyst infection, but causative microorganisms are often resistant to these agents. This study investigated the profile of the microorganisms causing cyst infection in ADPKD, their susceptibility to lipid-soluble antibiotics, and clinical outcomes. This retrospective study reviewed all ADPKD patients admitted to Toranomon Hospital with a diagnosis of cyst infection from January 2004 to March 2014. All patients who underwent cyst drainage and had positive cyst fluid cultures were enrolled. Patients with positive blood cultures who satisfied our criteria for cyst infection or probable infection were also enrolled. There were 99 episodes with positive cyst fluid cultures and 93 episodes with positive blood cultures. The majority of patients were on dialysis. The death rate was high when infection was caused by multiple microorganisms or when there were multiple infected cysts. Gram-negative bacteria accounted for 74-79 % of the isolates in all groups, except for patients with positive hepatic cyst fluid cultures. The susceptibility of Escherichia coli to fluoroquinolones was very low in patients with hepatic cyst infection, especially those with frequent episodes and those with hepatomegaly. Fungi were detected in two episodes. Fluoroquinolone-resistant microorganisms showed a high prevalence in cyst infection. It is important to identify causative microorganisms to avoid the overuse of fluoroquinolones and to improve the outcome of cyst infection in ADPKD.

  7. Primary hepatic amyloidosis: A case report and review of literature

    PubMed Central

    Sonthalia, Nikhil; Jain, Samit; Pawar, Sunil; Zanwar, Vinay; Surude, Ravindra; Rathi, Praveen M

    2016-01-01

    We describe a case of 42-year-old female presenting with abdominal pain associated with loss of weight and fever for 8 mo. On evaluation she had gross hepatomegaly with raised alkaline phosphatase and raised GGT levels with normal transaminases and bilirubin. On imaging she had diffuse enlargement of liver with heterogeneous contrast uptake in liver. Her viral marker and autoimmune markers were negative. Liver biopsy depicted massive deposition of amyloid in peri-sinusoidal spaces which revealed apple green birefringence on polarizing microscopy after Congo red staining. Cardiac and renal evaluation was unremarkable. Abdominal fat pad and rectum biopsy was negative for amyloid deposit. There was no evidence of primary amyloidosis as bone marrow examination was normal. Serum and urine immunofixation electrophoresis were normal. Immunoperoxidase staining for serum amyloid associated protein for secondary amyloidosis was negative from liver biopsy. We present this rare case of primary hepatic amyloidosis and review the literature regarding varied presentations of hepatic involvement in amyloidosis. PMID:26962400

  8. Toxic effects in C57B1/6 and DBA/2 mice following consumption of halogenated aromatic hydrocarbon-contaminated Great Lakes coho salmon (Oncorhynchus kisutch Walbaum).

    PubMed Central

    Cleland, G B; Leatherland, J F; Sonstegard, R A

    1987-01-01

    Diets containing coho salmon (Oncorhynchus kisutch Walbaum) from the Pacific Ocean or from Lakes Erie, Michigan, and Ontario [containing a gradation from low to high of halogenated aromatic hydrocarbons, (HAHs)] were fed to C57B1/6 and DBA/2 mice. Following a 4-month dietary exposure to Lake Ontario salmon, both strains of mice demonstrated hepatomegaly. The ethoxyresorufin-O-deethylase (ERR) enzyme levels were elevated in livers of C57B1/6 mice fed diets of salmon from all of the Great Lakes studied, with exceptionally high levels detected in C57B1/6 mice fed Lake Ontario salmon. Induction of ERR enzyme levels was detected in DBA/2 mice only following dietary exposure to Lake Ontario salmon. Serum levels of L-thyroxine (T4) and triiodo-L-thryonine (T3) were suppressed in C57B1/6 mice following consumption of Lake Ontario coho salmon, but T3 and T4 levels remained unchanged in DBA/2 mice. In general, pathobiological effects correlated with both dietary HAH exposure level and Ah receptor status. PMID:3691436

  9. [SOME CLINICAL AND CYTOKINE FEATURES OF THE CLINICAL COURSE OF RECURRENT RESPIRATORY SYSTEM DISEASES IN CHILDREN WITH THE TOXOCARIASIS INVASION].

    PubMed

    Dralova, A; Usachova, E

    2015-12-01

    The aim of the present study was to analyze clinical and cytokine features of recurrent respiratory system diseases in children with toxocariasis. 50 children aged 1 to 17 years (mean age - 10±5 years) with recurrent current of respiratory system disorders were studied. During the survey such clinical manifestations of the respiratory system disorders as obstructive bronchitis (50%), bronchial asthma (30%), pneumonia (10%) and laryngotracheitis (10%) have been revealed. Statistical analysis of the results was performed using the software package STATISTICA 6.1 (SNANSOFT). We have shown that the disorders of respiratory system in case of toxocariasis invasion often occur with severe intoxication and bronchial obstruction syndromes, temperature reaction, respiratory insufficiency and hepatomegaly. A prolonged course of the disease has been noted. "Inflammatory" indicators of general blood analysis, such as leukocytosis and increased of ESR have been recorded in patients with respiratory system disorders in children with T.canis infection significantly more often, significant "allergic" laboratory changes were in the form of eosinophilia. High average levels of pro-inflammatory IL-6, as well as low levels of IL 5 have been determined in children suffering from the respiratory system disorders and with toxocariasis invasion in the anamnesis. The obtained findings require further study.

  10. Biliary Atresia: 50 Years after the First Kasai

    PubMed Central

    Wildhaber, Barbara E.

    2012-01-01

    Biliary atresia is a rare neonatal disease of unknown etiology, where obstruction of the biliary tree causes severe cholestasis, leading to biliary cirrhosis and death in the first years of life, if the condition is left untreated. Biliary atresia is the most frequent surgical cause of cholestatic jaundice in neonates and should be evoked whenever this clinical sign is associated with pale stools and hepatomegaly. The treatment of biliary atresia is surgical and currently recommended as a sequence of, eventually, two interventions. During the first months of life a hepatoportoenterostomy (a “Kasai,” modifications of which are discussed in this paper) should be performed, in order to restore the biliary flow to the intestine and lessen further damage to the liver. If this fails and/or the disease progresses towards biliary cirrhosis and life-threatening complications, then liver transplantation is indicated, for which biliary atresia represents the most frequent pediatric indication. Of importance, the earlier the Kasai is performed, the later a liver transplantation is usually needed. This warrants a great degree of awareness of biliary atresia, and the implementation of systematic screening for this life-threatening pathology. PMID:23304557

  11. 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

  12. Senescent case of cholesterol ester storage disease that progressed to liver cirrhosis with a novel mutation (N250H) of lysosomal acid lipase gene.

    PubMed

    Kojima, Seiichiro; Watanabe, Norihito; Takashimizu, Shinji; Kagawa, Tatehiro; Shiraishi, Koichi; Koizumi, Jun; Hirabayashi, Ken-Ichi; Ohkubo, Tomoichi; Kamiguchi, Hiroshi; Tsuda, Michio; Mine, Tetsuya

    2013-12-01

    The patient, a 69-year-old man, had a chief complaint of hepatomegaly. The liver was palpated four fingerbreadths below the costal margin, and the spleen was three fingerbreadths below the costal margin. There were no other abnormal findings. Laparoscopy showed that the liver resembled an orange-yellow crayon in appearance and was nodular. The pathological findings of the liver biopsy tissue were consistent with liver cirrhosis. Inside the fibrous septum was an apparent aggregation of enlarged macrophages that phagocytosed lipid components, as well as enlarged Kupffer cells that phagocytosed lipid droplets. Electron microscopy showed the lipid droplets to have a moth-eaten appearance. Using monocytes extracted from the peripheral blood, acid lipase activity was measured by fluorescence spectrometry using 4-methylumbelliferone palmitate as a substrate. This patient's human lysosomal acid lipase activity was 0.020 nM/min per 10(6)  cells, corresponding to 5.9% of that in healthy subjects (0.332 ± 0.066 nM/min per 10(6)  cells). Cholesterol ester storage disease was therefore diagnosed. The acid lipase A base sequence obtained from leukocytes by direct sequencing was compared with a library. This patient had a point mutation of N250H/N250H in exon 7, a novel gene abnormality that has not previously been reported.

  13. Adenovirus-Mediated Somatic Genome Editing of Pten by CRISPR/Cas9 in Mouse Liver in Spite of Cas9-Specific Immune Responses.

    PubMed

    Wang, Dan; Mou, Haiwei; Li, Shaoyong; Li, Yingxiang; Hough, Soren; Tran, Karen; Li, Jia; Yin, Hao; Anderson, Daniel G; Sontheimer, Erik J; Weng, Zhiping; Gao, Guangping; Xue, Wen

    2015-07-01

    CRISPR/Cas9 derived from the bacterial adaptive immunity pathway is a powerful tool for genome editing, but the safety profiles of in vivo delivered Cas9 (including host immune responses to the bacterial Cas9 protein) have not been comprehensively investigated in model organisms. Nonalcoholic steatohepatitis (NASH) is a prevalent human liver disease characterized by excessive fat accumulation in the liver. In this study, we used adenovirus (Ad) vector to deliver a Streptococcus pyogenes-derived Cas9 system (SpCas9) targeting Pten, a gene involved in NASH and a negative regulator of the PI3K-AKT pathway, in mouse liver. We found that the Ad vector mediated efficient Pten gene editing even in the presence of typical Ad vector-associated immunotoxicity in the liver. Four months after vector infusion, mice receiving the Pten gene-editing Ad vector showed massive hepatomegaly and features of NASH, consistent with the phenotypes following Cre-loxP-induced Pten deficiency in mouse liver. We also detected induction of humoral immunity against SpCas9 and the potential presence of an SpCas9-specific cellular immune response. Our findings provide a strategy to model human liver diseases in mice and highlight the importance considering Cas9-specific immune responses in future translational studies involving in vivo delivery of CRISPR/Cas9.

  14. [An elderly case of idiopathic dilatation of the right atrium in which right-sided heart failure was exacerbated by drug-induced bradyarrhythmia].

    PubMed

    Kodama-Takahashi, K; Ohshima, K; Yamamoto, K; Iwata, T

    2001-07-01

    We describe an elderly case of idiopathic dilatation of the right atrium in which right-sided heart failure was exacerbated by drug-induced bradyarrhythmia. An 84-year-old man, who had a 10-year history of episodic edema, was treated with proscillaridin and verapamil hydrochloride at another hospital. He had experienced a poor appetite and general malaise 2 months previously, and exertional dyspnea 10 days previously. On admission, he had jugular venous dilatation, systemic edema, and hepatomegaly. On auscultation, a third heart sound originating from the right ventricle and systolic murmur of tricuspid regurgitation were heard. An admission electrocardiogram showed an atrial standstill and junctional escape rhythm with a QRS rate of 31 beats/minute. Chest roentgenogram revealed a bilateral pleural effusion and cardiomegaly with a cardiothoracic ratio of 76%, but no pulmonary congestion. Echocardiogram disclosed idiopathic dilatation of the right atrium and secondary tricuspid regurgitation. He was given a diagnosis of right-sided heart failure due to idiopathic dilatation of the right atrium exacerbated by bradyarrhythmia, which was suspected to derive from the side effects of proscillaridin and verapamil hydrochloride. Thus, these agents were withheld. In addition, the patient reduced sodium intake and was treated with diuretics and beta-adrenergic agonist. Thereafter, right-sided heart failure markedly improved. At the time of the last follow-up 16 months after discharge, he felt well.

  15. Novel Synergistic Protective Efficacy of Atovaquone and Diclazuril on Fetal-Maternal Toxoplasmosis

    PubMed Central

    Oz, Helieh S.

    2014-01-01

    Over 1 billion people globally are estimated to be infected with Toxoplasma gondii with severe or unknown consequences and no safe and effective therapies are available against congenital or persistent chronic infection. We propose that atovaquone and diclazuril synergistically protect against fetal-maternal toxoplasmosis. Methods Programmed pregnant mice were treated with atovaquone and diclazuril monotherapy, or combined (atovaquone + diclazuril) therapy and infected with tachyzoites (0, 300, 600) and the course of infection was studied. Results Infected dams with low dose (300) developed moderate toxoplasmosis complications and treatments were similarly effective with minor differences between monotherapies. In contrast, major differences were observed amongst varied treatments during high-dose (600) infection and severe related- toxoplasmosis complications as follows. Dams developed hydrothorax, ascities and excess weight gain. Combined therapy (P < 0.01) and to a lesser extent diclazuril monotherapy (P < 0.05) protected dams from excess weight, hydrothorax, and ascities. Infected dams exhibited splenomegaly, hepatomegaly and severe hepatitis. Combined therapy synergistically normalized pathology (P < 0.001) and to a lesser degree monotherapy (diclazuril P < 0.01, and atovaquone P < 0.05) protected dams from hepatitis and splemomegaly. Additionally, behavioral response to pain stimuli and fetal weight and fetal numbers were significantly preserved in treated dams Conclusions This is the first report describing combined atovaquone and diclazuril therapy (a) to be safe in pregnancy, (b) to exert novel synergistic effects, and (c) to protect dams and their nested fetuses against adverse effects of severe toxoplasmosis. PMID:25210646

  16. Proteinuric nephropathy in acquired and congenital generalized lipodystrophy: baseline characteristics and course during recombinant leptin therapy.

    PubMed

    Javor, Edward D; Moran, Stephanie Ann; Young, Janice Ryan; Cochran, Elaine K; DePaoli, Alex M; Oral, Elif Arioglu; Turman, Martin A; Blackett, Piers R; Savage, David B; O'Rahilly, Stephen; Balow, James E; Gorden, Phillip

    2004-07-01

    Generalized lipodystrophy is characterized by adipose tissue absence, hypoleptinemia, hypertriglyceridemia, insulin resistance, diabetes, hepatomegaly, and nonalcoholic steatohepatitis. In the course of recruiting patients for treatment with recombinant leptin, we were struck by the frequency and severity of proteinuria. We evaluated 25 patients with generalized lipodystrophy. Eighteen were treated with recombinant leptin, and we have followed 15 on leptin for 4-36 months. We followed renal parameters at baseline and during follow-up visits. Renal biopsies were performed as clinically indicated. At baseline, 22 of 25 patients (88%) had elevated urine albumin excretion (>30 mg/24 h), 15 (60%) had macroalbuminuria (>300 mg/24 h), and five (20%) had nephrotic-range proteinuria (>3500 mg/24 h). Twenty-three (92%) had elevated creatinine clearance (>125 ml/min.1.73 m(2)). Eleven of 15 patients (73%) treated with recombinant leptin exhibited reduction in proteinuria, associated with reduction of hyperfiltration. Four patients who did not improve are discussed individually. Renal biopsy findings were remarkable for focal segmental glomerulosclerosis in four patients, membranoproliferative glomerulonephritis in two patients, and diabetic nephropathy in one patient. In conclusion, generalized lipodystrophy is associated with proteinuria and unique renal pathologies, including focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis. The majority treated with recombinant leptin demonstrated reduction in proteinuria and hyperfiltration.

  17. Giant hepatic metastasis in a patient with coin-like small cell lung carcinoma incidentally diagnosed at autopsy

    PubMed Central

    Fodor, Decebal; Gurzu, Simona; Contac, Anca Otilia; Jung, Ioan

    2017-01-01

    Abstract Rationale: Encephalopathy is a rare complication of hepatic metastases. In this paper we present a case of a patient with lung cancer and metastatic-related giant hepatomegaly. Patient concerns: A 78-year-old previously healthy male was admitted in the Emergency room in hepatic coma. Diagnoses: The abdominal CT scan examination revealed a huge liver filled with solid nodules. Interventions: No interventions were performed. Outcomes: The patient died at few hours after hospitalization. The autopsy showed a 6.5 kilograms liver with several whitish metastatic nodules and an occult prostate adenocarcinoma. The hilum of both lungs was free of tumor and a 10 mm white nodule was identified surrounding a small bronchus. No peripheral nodules were macroscopically identified. Under microscope, cluster of small cells were observed encasing a small bronchus with multiple minute coin-shaped subpleural foci. A massive intrapulmonary angiolymphatic invasion and metastases from small cell carcinoma in liver, lymph nodes and iliac crest bone marrow were also diagnosed. Lessons: This case highlights the difficulty of diagnosis of aggressive lung carcinomas and the necessity of checking for metachronous tumors. The encephalopathy might be the result of metastatic damage of the liver parenchyma combined with the paraneoplastic effect of the tumor cells. Few than 25 cases of SCLCs with diffuse liver metastases and fulminant liver failure were reported to December 2016. This is the first reported case with a synchronous prostate cancer and a “coin-like” aspect of the SCLC. PMID:28296775

  18. Clinico-pathological studies of Plasmodium falciparum and Plasmodium vivax - malaria in India and Saudi Arabia.

    PubMed

    Khan, Wajihullah; Zakai, Haytham A; Umm-E-Asma

    2014-06-01

    Malaria is one of the most devastating diseases of tropical countries with clinical manifestations such as anaemia, splenomegaly, thrombocytopenia, hepatomegaly and acute renal failures. In this study, cases of thrombocytopenia and haemoglobinemia were more prominent in subjects infected with Plasmodium falciparum (Welch, 1897) than those with Plasmodium vivax (Grassi et Feletti, 1890). However, anaemia, jaundice, convulsions and acute renal failure were significantly high (3-4 times) in subjects infected with P. falciparum than those infected with P. vivax. The incidence of splenomegaly and neurological sequelae were 2 and 6 times higher in P. falciparum infections compared to the infections of P. vivax. Both in P. vivax and P. falciparum malaria, the cases of splenomegaly, jaundice and neurological sequelae were almost double in children (<10 years) compared to older patients. The liver enzymes were generally in normal range in cases of low and mild infections. However, the AST, ALT, ALP activities and serum bilirubin, creatinine, and the urea content were increased in P. falciparum and P. vivax malaria patients having high parasitaemia, confirming liver dysfunction and renal failures in few cases of severe malaria both in India and Saudi Arabia.

  19. Fatty liver and kidney syndrome in chicks. I. Effect of biotin in diet.

    PubMed

    Pearson, J A; Johnson, A R; Hood, R L; Fogerty, A C

    1976-12-01

    Fatty liver and kidney syndrome, a disorder of young chicks, was studied under laboratory conditions. Affected chicks had enlarged livers (hepatomegaly), an increased content of lipid in the liver, and an increased level of palmitoleic acid in the liver lipids. The disorder was observed mainly in chicks from young parent flocks, and was associated either with commerical diets which were subsequently found to be low in biotin, or with specially formulated low-biotin diets. A third factor, imposition of stress, was required to initiate the disorder. There was evidence of increased lipogenesis causing an increase of triacylglycerols in the liver lipids and an increased production of saturated fatty acids, particularly palmitic acid. Increased levels of palmitoleic acid resulted from an increased desaturation of palmitic acid. Under stress, affected chicks had low blood glucose levels, suggesting that gluconeogenesis was impaired. Since biotin-dependent enzymes are involved in both gluconeogenesis and lipogenesis, it would appear that the relevant enzymes respond differently to a deficiency of biotin.

  20. A pelagic outbreak of avian cholera in North American gulls: Scavenging as a primary mechanism for transmission?

    USGS Publications Warehouse

    Wille, Michelle; McBurney, Scott; Robertson, Gregory J.; Wilhelm, Sabine; Blehert, David; Soos, Catherine; Dunphy, Ron; Whitney, Hugh

    2016-01-01

    Avian cholera, caused by the bacterium Pasteurella multocida, is an endemic disease globally, often causing annual epizootics in North American wild bird populations with thousands of mortalities. From December 2006 to March 2007, an avian cholera outbreak caused mortality in marine birds off the coast of Atlantic Canada, largely centered 300–400 km off the coast of the island of Newfoundland. Scavenging gulls (Larus spp.) were the primary species detected; however, mortality was also identified in Black-legged Kittiwakes (Rissa tridactyla) and one Common Raven (Corvus corax), a nonmarine species. The most common gross necropsy findings in the birds with confirmed avian cholera were acute fibrinous and necrotizing lesions affecting the spleen, air sacs, and pericardium, and nonspecific hepatomegaly and splenomegaly. The etiologic agent, P. multocida serotype 1, was recovered from 77 of 136 carcasses examined, and confirmed or probable avian cholera was diagnosed in 85 cases. Mortality observed in scavenging gull species was disproportionately high relative to their abundance, particularly when compared to nonscavenging species. The presence of feather shafts in the ventricular lumen of the majority of larid carcasses diagnosed with avian cholera suggests scavenging of birds that died from avian cholera as a major mode of transmission. This documentation of an outbreak of avian cholera in a North American pelagic environment affecting primarily scavenging gulls indicates that offshore marine environments may be a component of avian cholera dynamics.

  1. [Veno-occlusive disease of the liver].

    PubMed

    Rybicka, Malwina; Krysiak, Robert; Okopień, Bogusław

    2009-01-01

    Veno-occlusive disease (VOD) is seen most often in the group of bone marrow transplant recipients. The essence of this disease is the obstruction of the hepatic sinusoidal and centrolobular venous outflow, because of the injury to the endothelium of the liver vessels. It results in congestion of the liver and hepatomegaly. The typical clinical symptoms of VOD are: jaundice, portal hypertension with peripheral oedemas and the weight gain. Depending on the extent of the injury of the hepatic vessels, VOD is divided into three grades: mild, moderate and severe. The clinical markers that inform about the severity of the disease are: the rate of the serum bilirubin growth and the rate of the weight gain growth within the first 2 weeks since the beginning of the disease. Severe VOD is the third of the most often cause of death among people who underwent bone marrow transplantation. The mortality rate is diverse and depends on severity of the disease. The effectiveness of the VOD therapy is limited, so it is worth putting greater pressure on the prophylaxis of VOD or on finding more effective modes of treatment.

  2. Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: review and update on the use of defibrotide.

    PubMed

    Ho, Vincent T; Linden, Erica; Revta, Carolyn; Richardson, Paul G

    2007-06-01

    Veno-occlusive disease (VOD) of the liver remains one of the most feared complications associated with high-dose chemotherapy and hematopoietic stem cell transplantation (SCT). As a clinical syndrome characterized by fluid retention, hyperbilirubinemia, and painful hepatomegaly, VOD incidence varies widely, but it is universally recognized that severe cases of VOD have an extremely poor prognosis, with mortality at day 100 after SCT in excess of 80%. Systemic anticoagulant and thrombolytic therapies have been tested extensively in this disease, but are largely ineffective and are associated with significant bleeding complications. In recent years, defibrotide (DF; a polydisperse oligonucleotide derived from porcine intestinal mucosa with antithrombotic and protective properties on the microvasculature but minimal hemorrhagic risk) has emerged as a promising therapy for VOD. In large, multicenter, international phase I/II trials targeting patients with severe VOD, DF has been associated with complete response rates between 36 and 60%, survival past transplant day 100 in the range of 32 to 50%, and few significant attributable side effects. On the basis of these encouraging results, a pivotal, prospective, multinational, phase III trial of DF is underway in patients with severe VOD, and should provide validation of this agent as a therapy for established disease with a high risk of mortality. This article reviews our current understanding of hepatic VOD after SCT and provides a summary of the data to date on the use of DF as both therapy and prophylaxis for this disease.

  3. Cardiomyopathy in captive African hedgehogs (Atelerix albiventris).

    PubMed

    Raymond, J T; Garner, M M

    2000-09-01

    From 1994 to 1999, 16 captive African hedgehogs (Atelerix albiventris), from among 42 necropsy cases, were diagnosed with cardiomyopathy. The incidence of cardiomyopathy in this study population was 38%. Fourteen of 16 hedgehogs with cardiomyopathy were males and all hedgehogs were adult (>1 year old). Nine hedgehogs exhibited 1 or more of the following clinical signs before death: heart murmur, lethargy, icterus, moist rales, anorexia, dyspnea, dehydration, and weight loss. The remaining 7 hedgehogs died without premonitory clinical signs. Gross findings were cardiomegaly (6 cases), hepatomegaly (5 cases), pulmonary edema (5 cases), pulmonary congestion (4 cases), hydrothorax (3 cases), pulmonary infarct (1 case), renal infarcts (1 case), ascites (1 case), and 5 cases showed no changes. Histologic lesions were found mainly within the left ventricular myocardium and consisted primarily of myodegeneration, myonecrosis, atrophy, hypertrophy, and disarray of myofibers. All hedgehogs with cardiomyopathy had myocardial fibrosis, myocardial edema, or both. Other common histopathologic findings were acute and chronic passive congestion of the lungs, acute passive congestion of the liver, renal tubular necrosis, vascular thrombosis, splenic extramedullary hematopoiesis, and hepatic lipidosis. This is the first report of cardiomyopathy in African hedgehogs.

  4. Prenatal detection of Fraser syndrome without cryptophthalmos: case report and review of the literature.

    PubMed

    Berg, C; Geipel, A; Germer, U; Pertersen-Hansen, A; Koch-Dörfler, M; Gembruch, U

    2001-07-01

    Fraser syndrome (cryptophthalmos-syndactyly syndrome) is an autosomal recessive multiple malformation syndrome whose major manifestations are cryptophthalmos, syndactyly, laryngeal atresia and urogenital defects. Enlarged hyperechogenic lungs contrasted by oligohydramnios, non-visualization of the kidneys and microphthalmia were sonographic markers leading to the prenatal detection of this rare autosomal recessive disorder in earlier reports. We report a case of Fraser syndrome diagnosed at 16 weeks' gestational age in a woman whose previous pregnancy was terminated because of multiple fetal malformations. Abnormal sonographic findings included bilateral agenesis of the kidneys, dilated trachea and main bronchi (suggestive of high airway obstruction), hyperechogenic lungs, syndactyly of the fingers, hepatomegaly, oligohydramnios and hydrops placentae. Face and cerebral structures appeared normal. These findings together with those of the previously affected child led to the diagnosis of Fraser syndrome. The parents elected to terminate the pregnancy. Autopsy results were confirmatory. In conclusion, prenatal diagnosis of Fraser syndrome is possible in the hands of an expert, but due to the great variety of possible malformations the diagnosis will remain doubtful in most cases in which no previous child is affected.

  5. Apigenin Ameliorates Dyslipidemia, Hepatic Steatosis and Insulin Resistance by Modulating Metabolic and Transcriptional Profiles in the Liver of High-Fat Diet-Induced Obese Mice

    PubMed Central

    Jung, Un Ju; Cho, Yun-Young; Choi, Myung-Sook

    2016-01-01

    Several in vitro and in vivo studies have reported the anti-inflammatory, anti-diabetic and anti-obesity effects of the flavonoid apigenin. However, the long-term supplementary effects of low-dose apigenin on obesity are unclear. Therefore, we investigated the protective effects of apigenin against obesity and related metabolic disturbances by exploring the metabolic and transcriptional responses in high-fat diet (HFD)-induced obese mice. C57BL/6J mice were fed an HFD or apigenin (0.005%, w/w)-supplemented HFD for 16 weeks. In HFD-fed mice, apigenin lowered plasma levels of free fatty acid, total cholesterol, apolipoprotein B and hepatic dysfunction markers and ameliorated hepatic steatosis and hepatomegaly, without altering food intake and adiposity. These effects were partly attributed to upregulated expression of genes regulating fatty acid oxidation, tricarboxylic acid cycle, oxidative phosphorylation, electron transport chain and cholesterol homeostasis, downregulated expression of lipolytic and lipogenic genes and decreased activities of enzymes responsible for triglyceride and cholesterol ester synthesis in the liver. Moreover, apigenin lowered plasma levels of pro-inflammatory mediators and fasting blood glucose. The anti-hyperglycemic effect of apigenin appeared to be related to decreased insulin resistance, hyperinsulinemia and hepatic gluconeogenic enzymes activities. Thus, apigenin can ameliorate HFD-induced comorbidities via metabolic and transcriptional modulations in the liver. PMID:27213439

  6. Fatal hepatic sarcocystosis in a puppy with eosinophilia and eosinophilic peritoneal effusion.

    PubMed

    Allison, Robin; Williams, Philip; Lansdowne, Jennifer; Lappin, Michael; Jensen, Tracey; Lindsay, David

    2006-09-01

    A 3-month-old male Golden Retriever puppy was evaluated for lethargy and fever of 2-days duration. Results of a CBC and biochemical profile revealed marked eosinophilia (6.3 X 10(3)/microL; reference interval 0.1-1.2 X 10(3)/microL), moderate thrombocytopenia, and increased activities of alanine aminotransferase, aspartate aminotransferase, and creatine kinase. Hepatomegaly and peritoneal effusion were found using abdominal ultrasound. Peritoneal fluid analysis revealed eosinophilic inflammation (23,000 nucleated cells/microL with 88% eosinophils). Despite supportive treatment the puppy's condition deteriorated rapidly; euthanasia was requested, and a necropsy performed. Microscopically, there was marked necrosuppurative and eosinophilic hepatitis with vasculitis. Numerous hepatocytes contained protozoal organisms suspected to be Toxoplasma gondii or Neospora caninum. However, serum was negative for both T gondii and N caninum antibodies; polymerase chain reaction assay on hepatic tissue was negative for both organisms; and immunohistochemical evaluation of hepatic tissue using serum raised against T gondii, N caninum, and Sarcocystis neurona also was negative. Schizont morphology suggested that merozoites replicated by endopolygeny, forming rosettes around a central residual body. Transmission electron microscopy revealed that merozoites lacked rhoptries. These findings were consistent with a diagnosis of Sarcocystis canis, an apicomplexan parasite with an unknown life cycle.

  7. Molecular epidemiology of Brucella genotypes in patients at a major hospital in central Peru.

    PubMed

    Nöckler, Karsten; Maves, Ryan; Cepeda, David; Draeger, Angelika; Mayer-Scholl, Anne; Chacaltana, Jesus; Castañeda, María; Espinosa, Benjamin; Castillo, Rosa; Hall, Eric; Al Dahouk, Sascha; Gilman, Robert H; Cabeza, Franco; Smits, Henk L

    2009-10-01

    The multiple-locus variable-number repeat analysis of 90 human Brucella melitensis isolates from a large urban area in central Peru revealed variations at 4 (Bruce07, Bruce09, Bruce18, and Bruce42) out of 16 loci investigated, of which 1 (Bruce42) also is used for species identification. Ten genotypes were identified, separated by the number of Bruce42 repeats into two groups that may have distinct phenotypic characteristics. Whereas genotypes with five or six Bruce42 repeats were cultured mainly from adult patients, genotypes with three Bruce42 repeats were isolated from children and young adolescents as well as from adults. In addition, the isolates with three Bruce42 repeats were obtained more often from patients with splenomegaly (P = 0.02) or hepatomegaly (P = 0.006). An annual variation in the diversity of genotypes was observed, possibly reflecting changes in sources of fresh dairy products, supply routes to city shops and markets, and the movement of infected dairy goat herds.

  8. The first Korean case of mucopolysaccharidosis IIIC (Sanfilippo syndrome type C) confirmed by biochemical and molecular investigation.

    PubMed

    Huh, Hee Jae; Seo, Ja Young; Cho, Sung Yoon; Ki, Chang-Seok; Lee, Soo-Youn; Kim, Jong-Won; Park, Hyung-Doo; Jin, Dong-Kyu

    2013-01-01

    Mucopolysaccharidosis (MPS) III has 4 enzymatically distinct forms (A, B, C, and D), and MPS IIIC, also known as Sanfilippo C syndrome, is an autosomal recessive lysosomal storage disease caused by a deficiency of heparan acetyl-CoA:alpha-glucosaminide N-acetyltransferase (HGSNAT). Here, we report a case of MPS IIIC that was confirmed by molecular genetic analysis. The patient was a 2-yr-old girl presenting with skeletal deformity, hepatomegaly, and delayed motor development. Urinary excretion of glycosaminoglycan (GAG) was markedly elevated (984.4 mg GAG/g creatinine) compared with the age-specific reference range (<175 mg GAG/g creatinine), and a strong band of heparan sulfate was recognized on performing thin layer chromatography. HGSNAT enzyme activity in leukocytes was 0.7 nmol/17 hr/mg protein, which was significantly lower than the reference range (8.6-32 nmol/17 hr/mg protein). PCR and direct sequencing of the HGSNAT gene showed 2 mutations: c.234+1G>A (IVS2+1G>A) and c.1150C>T (p.Arg384*). To the best of our knowledge, this is the first case of MPS IIIC to be confirmed by clinical, biochemical, and molecular genetic findings in Korea.

  9. Subacute intramuscular toxicity of the acetylcholinesterase reactivating agent Hi-6 in rats and dogs. (Reannouncement with new availability information)

    SciTech Connect

    Levine, B.S.; Tomlinson, M.J.

    1993-12-31

    Studies herein describe the toxicity of HI-6 in Sprague-Dawley rats and Beagle dogs following i.m. injection for 14 days. Dose levels were 0, 50, 150, and 450 mg/kg/day for 10 rats/sex/dose and 0, 35, 70, and 140 mg/kg/day for 4 dogs/sex/dose. Three rats at the high dose, 2 males and 1 female, died prior to scheduled sacrifice. Reduced weight gain, decreased activity, tremors, hunched posture,and poor grooming were seen in high dose survivors. Increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities at the mid and high doses suggested hepatotoxicity, although liver weights and histology were normal. Hematology parameters were unaffected except for slight, dose-related increases of platelets in both sexes. Injection site inflammation was seen; however, serum creatine kinase activity was not altered. In dogs, slight weight loss, vomiting, salivation, and diarrhea occurred at the high dose, but no deaths were observed at any of the doses. As with rats, dose-related increases in ALT and AST activities occurred at the mid and high doses, and were, in this case, accompanied at the high dose by hepatomegaly and hepatocellular vacuolization. Cardiotoxicity was evidenced by increased relative heart weights and subtle ECG changes, the latter of which occurred almost exclusively at the highest dose. Injection site inflammation, which was accompanied by dose-related elevations in serum CK-MM2 activity, was also observed.

  10. Activating CAR and β-Catenin Induces Uncontrolled Liver Growth and Tumorigenesis

    PubMed Central

    Dong, Bingning; Lee, Ju-Seog; Park, Yun-Yong; Yang, Feng; Xu, Ganyu; Huang, Wendong; Finegold, Milton; Moore, David D.

    2014-01-01

    Aberrant β-catenin activation contributes to a third or more of human hepatocellular carcinoma (HCC), but β-catenin activation alone is not sufficient to induce liver cancer in mice. Differentiated hepatocytes proliferate upon acute activation of either β-catenin or the nuclear xenobiotic receptor CAR. These responses are strictly limited and are tightly linked, since β-catenin is activated in nearly all of the CAR-dependent tumors generated by the tumor promoter phenobarbital. Here we show that full activation of β-catenin in the liver induces senescence and growth arrest, which is overcome by combined CAR activation, resulting in uncontrolled hepatocyte proliferation, hepatomegaly, and rapid lethality despite maintenance of normal liver function. Combining CAR activation with limited β-catenin activation induces tumorigenesis, and the tumors share a conserved gene expression signature with β-catenin positive human HCC. These results reveal an unexpected route for hepatocyte proliferation and define a murine model of hepatocarcinogenesis with direct relevance to human HCC. PMID:25661872

  11. Natural Progression of Canine Glycogen Storage Disease Type IIIa

    PubMed Central

    Brooks, Elizabeth D; Yi, Haiqing; Austin, Stephanie L; Thurberg, Beth L; Young, Sarah P; Fyfe, John C; Kishnani, Priya S; Sun, Baodong

    2016-01-01

    Glycogen storage disease type IIIa (GSD IIIa) is caused by a deficiency of glycogen debranching enzyme activity. Hepatomegaly, muscle degeneration, and hypoglycemia occur in human patients at an early age. Long-term complications include liver cirrhosis, hepatic adenomas, and generalized myopathy. A naturally occurring canine model of GSD IIIa that mimics the human disease has been described, with progressive liver disease and skeletal muscle damage likely due to excess glycogen deposition. In the current study, long-term follow-up of previously described GSD IIIa dogs until 32 mo of age (n = 4) and of family-owned GSD IIIa dogs until 11 to 12 y of age (n = 2) revealed that elevated concentrations of liver and muscle enzyme (AST, ALT, ALP, and creatine phosphokinase) decreased over time, consistent with hepatic cirrhosis and muscle fibrosis. Glycogen deposition in many skeletal muscles; the tongue, diaphragm, and heart; and the phrenic and sciatic nerves occurred also. Furthermore, the urinary biomarker Glc4, which has been described in many types of GSD, was first elevated and then decreased later in life. This urinary biomarker demonstrated a similar trend as AST and ALT in GSD IIIa dogs, indicating that Glc4 might be a less invasive biomarker of hepatocellular disease. Finally, the current study further demonstrates that the canine GSD IIIa model adheres to the clinical course in human patients with this disorder and is an appropriate model for developing novel therapies. PMID:26884409

  12. Gastrointestinal system manifestations in juvenile systemic lupus erythematosus.

    PubMed

    Sönmez, Hafize Emine; Karhan, Asuman Nur; Batu, Ezgi Deniz; Bilginer, Yelda; Gümüş, Ersin; Demir, Hülya; Yüce, Aysel; Özen, Seza

    2017-02-16

    Systemic lupus erythematosus (SLE) is an autoimmune disease which may involve gastrointestinal system (GIS). The aim of this study was to present GIS manifestations of pediatric SLE patients. The medical files of 69 children with SLE followed between January 2011 and January 2016 were reviewed. All fulfilled the Systemic Lupus International Collaborating Clinics criteria. All patients (≤18 years of age) with GIS manifestations were included. GIS manifestations were observed in 19 (27.5%) out of 69 SLE patients and present at the time of SLE diagnosis in 13 (68.4%). The GIS manifestations due to SLE were autoimmune hepatitis (AIH) (n = 8) and lupus enteritis (n = 1). Manifestations associated with SLE were hepatomegaly and hypertransaminasemia due to macrophage activation syndrome (MAS) (n = 3) and hepatic steatosis (n = 1). GIS manifestations as a result of the adverse events of drugs were as follows: toxic hepatitis (n = 3; associated with methotrexate and nonsteroidal anti-inflammatory drugs in one, methotrexate in another, and azathioprine in another patient), azathioprine-induced cholestatic hepatitis (n = 1), and gastritis associated with corticosteroid (n = 1). In one patient, acute appendicitis occurred as a coincidence. In this study, one of every five pediatric SLE patients had GIS-related manifestations. GIS involvement may occur as an initial manifestation of the disease.

  13. IgD multiple myeloma: Clinical, biological features and prognostic value of the serum free light chain assay.

    PubMed

    Djidjik, R; Lounici, Y; Chergeulaïne, K; Berkouk, Y; Mouhoub, S; Chaib, S; Belhani, M; Ghaffor, M

    2015-09-01

    IgD multiple myeloma (MM) is a rare subtype of myeloma, it affects less than 2% of patients with MM. To evaluate the clinical and prognostic attributes of serum free light chains (sFLCs) analysis, we examined 17 cases of IgD MM. From 1998 to 2012, we obtained 1250 monoclonal gammapathies including 590 multiple myeloma and 17 patients had IgD MM. With preponderance of men patients with a mean age at diagnosis of: 59±12years. Patients with IgD MM have a short survival (Median survival=9months). The presenting features included: bone pain (75%), lymphadenopathy (16%), hepatomegaly (25%), splenomegaly (8%), associated AL amyloidosis (6%), renal impairment function (82%), infections (47%), hypercalcemia (37%) and anemia (93%). Serum electrophoresis showed a subtle M-spike (Mean=13.22±10g/L) in all patients associated to a hypogammaglobulinemia. There was an over-representation of Lambda light chain (65%); high serum β2-microglobulin in 91% and Bence Jones proteinuria was identified in 71%. The median rate of sFLCs κ was 19.05mg/L and 296.75mg/L for sFLCs λ. sFLCR was abnormal in 93% of patients and it showed concordance between baseline sFLCR and the survival (P=0.034). The contribution of FLC assay is crucial for the prognosis of patients with IgD MM.

  14. Clinical characteristics and follow-up analysis of adult-onset Still's disease complicated by hemophagocytic lymphohistiocytosis.

    PubMed

    Zhang, Yun; Yang, Yingyun; Bai, Yujia; Yang, Dan; Xiong, Yangyang; Zeng, Xuejun

    2016-05-01

    We evaluated clinical characteristics and prognosis for adult-onset Still's disease (AOSD) complicated by hemophagocytic lymphohistiocytosis (HLH). We retrospectively identified cases of AOSD with (n = 10) and without (n = 305) HLH complications. We reviewed their medical records, completed follow-up through outpatient clinic and telephone interviews, and analyzed their clinical symptoms, signs, laboratory test results, treatments, and prognosis. More AOSD patients with HLH developed hepatomegaly, bleeding, serositis, and neurologic symptoms than those without HLH, and they more commonly presented with leukopenia, thrombocytopenia, severe anemia, severe liver function abnormalities, decreased fibrinogen, elevated immunoglobulin, and bone marrow hemophagocytosis. The ten patients with AOSD complicated by HLH were treated with high-dose steroids or pulse steroid therapy, and eight of them also received cytotoxic drugs, while biological agents showed poor response. Follow-up results indicated that AOSD patients overall had good prognosis, while those with HLH showed worse prognosis, including higher relapse and readmission rates and increased mortality. In patients with AOSD, unexplained decreased blood cells, severe liver dysfunction, and/or hemophagocytosis in the bone marrow should be considered as signs of HLH complication. Patients with AOSD complicated by HLH have worse prognosis and higher relapse rates compared to AOSD patients without HLH complications. Thus, these patients should undergo frequent and careful follow-up.

  15. [Use of hepatocytes in primary cultures to predict potential hepatocarcinogenicity of compounds

    PubMed

    Bieri, F.; Muakkassah-Kelly, S.; Bentley, P.

    1990-01-01

    Short-term tests for genotoxic activity will detect a variety of potential carcinogens. However, experience over the last few years has shown that many chemical carcinogens are not detected in these tests. A large proportion of these non-mutagenic (non-genotoxic) carcinogens induce tumors in the rodent liver after life-long feeding. One class of such carcinogens are the hypolipidemic drugs many of which induce a characteristic hepatomegaly upon subchronic treatment. Typically this liver enlargement is accompanied by increased mitotic activity and a proliferation of the hepatic peroxisome compartment. Results also suggest a correlation between the degree and the nature of the hepatomegalic response to a compound, and its hepatocarcinogenic potency, but it remains unclear whether the growth stimulation and/or the peroxisome proliferation is correlated with the carcinogenicity. Both, the induction of peroxisomal enzyme and of replicative DMA synthesis may be measured in primary cultures of adult rat hepatocytes following in vitro exposition. Moreover, the ability of the compounds tested to induce in vitro replicative DNA synthesis in primary cultures of adult rat hepatocytes correlated well with the potency of the hepatomegalic response induced in vivo in treated rodents. Consequently, studies using such cultures might be useful to characterize and possibly predict in vitro the hepatocarcinogenic potency of some new compounds. The early recognition of the possible carcinogenic property of a new substance might accordingly contribute to the reduction of a number of life-long studies.

  16. A Novel Nonsense Mutation of the AGL Gene in a Romanian Patient with Glycogen Storage Disease Type IIIa

    PubMed Central

    Zimmermann, Anca; Rossmann, Heidi; Bucerzan, Simona; Grigorescu-Sido, Paula

    2016-01-01

    Background. Glycogen storage disease type III (GSDIII) is a rare metabolic disorder with autosomal recessive inheritance, caused by deficiency of the glycogen debranching enzyme. There is a high phenotypic variability due to different mutations in the AGL gene. Methods and Results. We describe a 2.3-year-old boy from a nonconsanguineous Romanian family, who presented with severe hepatomegaly with fibrosis, mild muscle weakness, cardiomyopathy, ketotic fasting hypoglycemia, increased transaminases, creatine phosphokinase, and combined hyperlipoproteinemia. GSD type IIIa was suspected. Accordingly, genomic DNA of the index patient was analyzed by next generation sequencing of the AGL gene. For confirmation of the two mutations found, genetic analysis of the parents and grandparents was also performed. The patient was compound heterozygous for the novel mutation c.3235C>T, p.Gln1079⁎ (exon 24) and the known mutation c.1589C>G, p.Ser530⁎ (exon 12). c.3235 >T, p.Gln1079⁎ was inherited from the father, who inherited it from his mother. c.1589C>G, p.Ser530⁎ was inherited from the mother, who inherited it from her father. Conclusion. We report the first genetically confirmed case of a Romanian patient with GSDIIIa. We detected a compound heterozygous genotype with a novel mutation, in the context of a severe hepatopathy and an early onset of cardiomyopathy. PMID:26885414

  17. Histoplasmosis: a new endemic fungal infection in China? Review and analysis of cases.

    PubMed

    Pan, Bo; Chen, Min; Pan, Weihua; Liao, Wanqing

    2013-05-01

    Histoplasmosis occurs in specific endemic areas, including the mid-western United States, Africa and most of Latin America. Sporadic cases have also been reported in China. The aim of this study was to summarise the epidemiological and clinical data of histoplasmosis in China. We searched the PubMed, CBMdisk and CNKI databases to identify publications related to histoplasmosis in China. Case reports/series on patients with histoplasmosis were included. A comprehensive literature review identified additional cases. The relevant material was evaluated and reviewed. Overall, 300 cases of histoplasmosis were reported in China from 1990 to 2011, and 75% were from regions through which the Yangtze River flows. Most of the patients were autochthonous infections. Of these, 43 patients had pulmonary histoplasmosis and 257 patients had disseminated histoplasmosis. Common underlying diseases included HIV infection, diabetes mellitus and liver diseases. Fever was the most frequently reported clinical feature in disseminated histoplasmosis, followed by splenomegaly and hepatomegaly. Cases of histoplasmosis had a prominent geographical distribution in China. Histoplasmosis should be considered in the diagnosis of patients with relevant symptoms and a history of travel to or residence in these areas.

  18. A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments

    PubMed Central

    Stirnemann, Jérôme; Belmatoug, Nadia; Camou, Fabrice; Serratrice, Christine; Froissart, Roseline; Caillaud, Catherine; Levade, Thierry; Astudillo, Leonardo; Serratrice, Jacques; Brassier, Anaïs; Rose, Christian; Billette de Villemeur, Thierry; Berger, Marc G.

    2017-01-01

    Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. In the general population, its incidence is approximately 1/40,000 to 1/60,000 births, rising to 1/800 in Ashkenazi Jews. The main cause of the cytopenia, splenomegaly, hepatomegaly, and bone lesions associated with the disease is considered to be the infiltration of the bone marrow, spleen, and liver by Gaucher cells. Type-1 Gaucher disease, which affects the majority of patients (90% in Europe and USA, but less in other regions), is characterized by effects on the viscera, whereas types 2 and 3 are also associated with neurological impairment, either severe in type 2 or variable in type 3. A diagnosis of GD can be confirmed by demonstrating the deficiency of acid glucocerebrosidase activity in leukocytes. Mutations in the GBA1 gene should be identified as they may be of prognostic value in some cases. Patients with type-1 GD—but also carriers of GBA1 mutation—have been found to be predisposed to developing Parkinson’s disease, and the risk of neoplasia associated with the disease is still subject to discussion. Disease-specific treatment consists of intravenous enzyme replacement therapy (ERT) using one of the currently available molecules (imiglucerase, velaglucerase, or taliglucerase). Orally administered inhibitors of glucosylceramide biosynthesis can also be used (miglustat or eliglustat). PMID:28218669

  19. Constrictive pericarditis versus restrictive cardiomyopathy: challenges in diagnosis and management.

    PubMed

    Chinnaiyan, Kavitha M; Leff, Carrie B; Marsalese, Dominic L

    2004-01-01

    This is the case of a patient who presented with severe right-sided heart failure due to diastolic dysfunction that caused a dilemma of differential diagnosis between restrictive cardiomyopathy and constrictive pericarditis. Restrictive cardiomyopathy was diagnosed based on noninvasive and invasive hemodynamic testing. However, the patient did not respond to therapy and succumbed to worsening heart failure and multiple comorbidities. Clinical features of right heart failure with edema, ascites, jugular venous distention, and tender hepatomegaly are commonly seen in clinical practice. When systolic function is determined to be normal, diastolic causes of heart failure must be ruled out. These include myocardial disorders with a broad range of pathologies leading to restrictive physiology, of which amyloidosis is a prototype. Pericardial disorders leading to diastolic heart failure are usually in the form of constrictive physiology, when pericardial tamponade is ruled out. Differentiation between restrictive and constrictive pathologies is often difficult and requires careful attention to hemodynamic and Doppler echocardiographic features. We report a case of severe right heart failure illustrating some of the complexities in decision-making and the importance of meticulous hemodynamic and ancillary testing in the diagnosis and treatment of this often fatal condition.

  20. Paragonimiasis in Chinese Children: 58 Cases Analysis

    PubMed Central

    Xu, Hong Zhen; Tang, Lan Fang; Zheng, Xiao Ping; Chen, Zhi Min

    2012-01-01

    Objective To analyze the clinical and radiological features of paragonimiasis in children and raise the awareness of this disease. Methods A total of 58 paragonimiasis patients were reviewed. They were 42 boys and 16 girls aged 2.0 to 15.3 years. Findings Among these patients, 20 were diagnosed in the recent 5 years, 46 with a history of raw water or food ingestion. Except 2 patients without any complaint, the most common features involved the systemic (41, 70.7%) and respiratory systems (43, 74.1%), followed by abdominal, cardiac and nervous systems, with rash and mass. Eosinophilia was noted in 46 (79.3%) patients, granulocytosis in 45 (77.6%), anemia in 14 (24.1%), and thrombocytopenia in 3. Imageology showed pneumonia in 26 (44.8%) patients, pleurisy in 28 (48.3%), hydropericardium in 17 (29.3%), ascites in 16 (27.6%), and celiac lymphadenitis in 13 (22.4%). Besides hepatomegaly and splenomegaly, calcification and multiple lamellar low echogenic areas in the liver were noted, each in one patient. Abnormal brain imaging was noted in 4 of 10 patients. Karyocyte hyperplasia with eosinophilia was noted in all the 19 patients who received bone marrow puncture. Conclusion Paragonimiasis should be considered in the differential diagnosis of patients with multiple organs or system lesions, especially those with eosinophilia, serous cavity effusion, respiratory, cardiac, digestive system, nervous system abnormality, and/or mass. Healthy eating habit is helpful for paragonimiasis prevention. PMID:23430310

  1. Viral infections associated with haemophagocytic syndrome.

    PubMed

    Maakaroun, Nadine Rouphael; Moanna, Abeer; Jacob, Jesse T; Albrecht, Helmut

    2010-03-01

    Haemophagocytic syndrome (HPS) or haemophagocytic lymphohistiocytosis (HLH) is a rare disease caused by a dysfunction of cytotoxic T cells and NK cells. This T cell/NK cell dysregulation causes an aberrant cytokine release, resulting in proliferation/activation of histiocytes with subsequent haemophagocytosis. Histiocytic infiltration of the reticuloendothelial system results in hepatomegaly, splenomegaly, lymphadenopathy and pancytopenia ultimately leading to multiple organ dysfunctions. Common clinical features include high fevers despite broad spectrum antimicrobials, maculopapular rash, neurological symptoms, coagulopathy and abnormal liver function tests. Haemophagocytic syndrome can be either primary, i.e. due to an underlying genetic defect or secondary, associated with malignancies, autoimmune diseases (also called macrophage activation syndrome) or infections. Infectious triggers are most commonly due to viral infections mainly of the herpes group, with EBV being the most common cause. HPS can be fatal if untreated. Early recognition of the clinical presentation and laboratory abnormalities associated with HPS and prompt initiation of treatment can be life saving. HPS triggered by viral infections generally does not respond to specific antiviral therapy but may be treated with immunosuppressive/immunomodulatory agents and, in refractory cases, with bone marrow transplantation.

  2. Discovery and epidemiology of PCB poisoning in Taiwan: a four-year followup

    SciTech Connect

    Hsu, S.T.; Ma, C.I.; Hsu, S.K.H.; Wu, S.S.; Hsu, N.H.M.; Yeh, C.C.; Wu, S.B.

    1985-02-01

    An outbreak of polychlorinated biphenyl (PCB) poisoning from the consumption of contaminated rice oil, covering four counties in central Taiwan, was investigated. There were 1843 cases by the end of 1980. The highest frequency of incidence occurred during the period from March to July 1979. The severity of clinical manifestations varied. Most patients showed symptoms of mild or moderate severity. The major age group affected was between 11 and 20 years old. Most of the victims were students and factor workers. The amount of PCB intake in each victim was estimated to be 0.7 to 1.84 g and the latent period from the time of intake to the onset of clinical manifestations was approximately 3 to 4 months. The patients blood PCB concentrations ranged from 3 ppb to 1156 ppb; 44.27% of 613 patients had levels of 51 to 100 ppb and 27.6% PCB blood levels over 100 ppb. In the course of 3.5 years, 2061 persons were determined to be PCB poisoning victims. Now, except for a few severe cases, their skin symptoms are very much improved. Thirty-nine babies showing hyperpigmentation were born from PCB-poisoned mothers. The fatality rate was high: eight of them died. Another 24 deaths were reported among the PCB-poisoned group, almost half of them (12) from hepatoma, liver cirrhosis or liver diseases with hepatomegaly.

  3. Clinical and laboratory findings in primary generalized and multiple-myeloma-related amyloidosis.

    PubMed Central

    Pruzanski, W.; Katz, A.

    1976-01-01

    Thirty-four patients with primary generalized amyloidosis (PGA) and 14 with multiple-myeloma-related amyloidosis (MRA) were studied. The commonest clinical manifestations in PGA were nephrotic syndrome, hepatomegaly and congestive heart failure, and in MRA, low back pain, plasmacytoma and rheumatoid-arthritis-like syndrome. Eight patients with PGA had limited clinical expression of the disease, such as involvement of only kidneys, joints, parotid glands or gastrointestinal tract; in one patient amyloidosis was limited to lymph nodes. Low serum concentrations of total protein and albumin were common. M components were detected in the serum of 91% of patients with PGA and 92% of patients with MRA: 70% of the M components in PGA and 25% of those in MRA had lambda light chains. Bence Jones proteinemia was detected in 56% of the patients with PGA and in 77% of those with MRA. The serum concentration of immunoglobulins was decreased substantially in more than two thirds of the patients with PGA. Proteinuria (greater than 250 mg/24 h) was observed in 78% of patients with PGA and in 93% of patients with MRA. Bence Jones proteinuria was noted in 75 and 77% of patients, respectively. Plasmacytic infiltration of the bone marrow was found in 90% of the patients with PGA. The mean survival time of the patients with PGA was 28 months and of those with MRA, 29 months from the time of diagnosis. PMID:1268776

  4. GADD45β, an anti-tumor gene, inhibits avian leukosis virus subgroup J replication in chickens

    PubMed Central

    Zhang, Xinheng; Yan, Zhuanqiang; Li, Xinjian; Lin, Wencheng; Dai, Zhenkai; Yan, Yiming; Lu, Piaopiao; Chen, Weiguo; Zhang, Huanmin; Chen, Feng; Ma, Jingyun; Xie, Qingmei

    2016-01-01

    Avian leukosis virus subgroup J (ALV-J) is a retroviruses that induces neoplasia, hepatomegaly, immunosuppression and poor performance in chickens. The tumorigenic and pathogenic mechanisms of ALV-J remain a hot topic. To explore anti-tumor genes that promote resistance to ALV-J infection in chickens, we bred ALV-J resistant and susceptible chickens (F3 generation). RNA-sequencing (RNA-Seq) of liver tissue from the ALV-J resistant and susceptible chickens identified 216 differentially expressed genes; 88 of those genes were up-regulated in the ALV-J resistant chickens (compared to the susceptible ones). We screened for significantly up-regulated genes (P < 0.01) of interest in the ALV-J resistant chickens, based on their involvement in biological signaling pathways. Functional analyses showed that overexpression of GADD45β inhibited ALV-J replication. GADD45β could enhance defense against ALV-J infection and may be used as a molecular marker to identify ALV-J infections. PMID:27655697

  5. Aerococcus christensenii native aortic valve subacute bacterial endocarditis (SBE) presenting as culture negative endocarditis (CNE) mimicking marantic endocarditis.

    PubMed

    Jose, Anita; Cunha, Burke A; Klein, Natalie C; Schoch, Paul E

    2014-01-01

    This is a case report of an adult who presented with apparent culture negative endocarditis (CNE) thought to be marantic endocarditis due to a B-cell lymphoproliferative disorder. This was a most perplexing case and was eventually diagnosed as subacute bacterial endocarditis (SBE) due to a rare slow growing organism. Against the diagnosis of SBE was the lack of fever, hepatomegaly, peripheral manifestations and microscopic hematuria. Also, against a diagnosis of SBE was another explanation for the patient's abnormal findings, e.g., elevated ferritin levels, elevated α1/α2 globulins on SPEP, an elevated alkaline phosphatase, flow cytometry showing B-lymphocytes expressing CD5, and a bone lesion in the right iliac. Findings compatible with both SBE and marantic endocarditis due to a B-cell lymphoproliferative disorder included an elevated ESR, and splenomegaly. Blood cultures eventually became positive during hospitalization. We report a case of native aortic valve (AV) subacute bacterial endocarditis (SBE) due to Aerococcus christensenii mimicking marantic endocarditis due to a B-cell lymphoproliferative disorder. To the best of our knowledge, this is the first reported case of native AV SBE due to A. christensenii presenting as marantic endocarditis.

  6. [Toxocariasis under the present conditions].

    PubMed

    Uspenskiĭ, A V; Peshkov, R A; Gorokhov, V V; Gorokhova, E V

    2011-01-01

    Toxocariasis is today the most widespread zoonotic, helminthic infection in Russia and other countries of the world. A large population of Toxocara has recently inhabited the urban populations of dogs and cats. Therefore toxocariasis canis and toxocariasis cati have shifted from rural areas to cities and megalopolises where Toxocara canis infestation amounts to as much as 100%, without excluding that in the rural populations of dogs. Due to the fact that the number of dogs and cats has considerably increased (20% of adult dogs and 80% of puppies are infected with Toxocara) in our megalopolises, cities, and urban communities as in foreign countries, this substantially increases the risk of toxacariasis. From the above reasoning, environmental contamination with Toxacara eggs creates an important reservoir of infestation for humans and animals (the contamination rates in different regions of Russia ranges from 1-3 to 50-60%, with the infestation rates of 1 - 10 eggs per 100 g of soil). Human toxocariasis is polymorphic, from its subclinical course to significant organ pathology, and detectable as a manifestation of eosinophilia, fever, hepatomegaly, hyperglobulinemia, lung and central nervous system lesions, myocarditis, and skin rash. The diagnosis of toxocariasis is established by its clinical presentation and serological findings. It is important in the history that children have spent much time with dogs or cats.

  7. Intestinal brucellosis associated with celiac artery and superior mesenteric artery stenosis and with ileum mucosa and submucosa thickening

    PubMed Central

    Wang, Miaoqian; Zhu, Qingli; Yang, Qian; Li, Wenbo; Wang, Xinning; Liu, Wei; Zhou, Baotong; Li, Zhenghong; Yang, Hong

    2017-01-01

    Abstract Rationale: Brucellosis is a multisystem infection found worldwide that has a broad range of characteristics, which range from acute fever and hepatomegaly to chronic infections that most commonly affect the central nervous system, cardiovascular system, or skeletal system. Gastrointestinal and splanchnic artery involvements in brucellosis are relatively uncommon. Patient concerns: We report a case of brucellosis in an adolescent presenting as intermittent abdominal pain, diarrhea, and fever, with intestinal tract involvement. And stenosis of the celiac artery and the superior mesenteric artery was found after exposed to risk factors of Brucella infection. Splanchnic vessels stenosis and an endothelial lesion may exacerbate the prevalent symptom of abdominal pain, as a form of colic pain, occurring after eating. Diagnoses: The patient was diagnosed as brucellosis. The narrowing of the SMA and CA was suspected to be vasculitis secondary to the brucellosis. Interventions: The patient was treated with minocycline and rifampicin for 12 weeks totally. Outcomes: The gastrointestinal manifestations of brucellosis recovered rapidly under intensive treatment. However, follow-up imaging revealed that the superior mesenteric artery and celiac artery stenosis was unimproved. Lessons: In brucellosis, gastrointestinal manifestations may be the only observable features of the disease. Splanchnic arterial stenosis is a rare complication of brucellosis. Sonography and computed tomography may be useful for both diagnosis and follow-up. PMID:28079834

  8. Hepatocellular adenomas associated with anabolic androgenic steroid abuse in bodybuilders: a report of two cases and a review of the literature.

    PubMed

    Socas, L; Zumbado, M; Pérez-Luzardo, O; Ramos, A; Pérez, C; Hernández, J R; Boada, L D

    2005-05-01

    Anabolic androgenic steroids (AAS) are used illicitly at high doses by bodybuilders. The misuse of these drugs is associated with serious adverse effects to the liver, including cellular adenomas and adenocarcinomas. We report two very different cases of adult male bodybuilders who developed hepatocellular adenomas following AAS abuse. The first patient was asymptomatic but had two large liver lesions which were detected by ultrasound studies after routine medical examination. The second patient was admitted to our hospital with acute renal failure and ultrasound (US) studies showed mild hepatomegaly with several very close hyperecogenic nodules in liver, concordant with adenomas at first diagnosis. In both cases the patients have evolved favourably and the tumours have shown a tendency to regress after the withdrawal of AAS. The cases presented here are rare but may well be suggestive of the natural course of AAS induced hepatocellular adenomas. In conclusion, sportsmen taking AAS should be considered as a group at risk of developing hepatic sex hormone related tumours. Consequently, they should be carefully and periodically monitored with US studies. In any case, despite the size of the tumours detected in these two cases, the possibility of spontaneous tumour regression must also be taken in account.

  9. High-output heart failure in a newborn

    PubMed Central

    Mascarenhas, Maria Inês; Moniz, Marta; Ferreira, Sofia; Goulão, Augusto; Barroso, Rosalina

    2012-01-01

    High-output cardiac failure is rare in newborns. Emergent diagnosis and management of this pathology is crucial. We report the case of a child, currently 12-months old; obstetric background is non-contributory. Clinic observation on D1 was normal except for the presence of a systolic cardiac murmur; cardiological evaluation revealed mild ventricular dysfunction of the right ventricle. On the third day of life, she developed cardiac failure with gallop rhythm, hepatomegaly and a murmur in the anterior fontanel; an echocardiogram confirmed clinic aggravation with biventricular dysfunction and right cavities and superior vena cava dilatation. The cranial MRI confirmed the presence of a pial arteriovenous malformation (AVM) involving the anterior and middle cerebral arteries with an associated fronto-parietal ischaemic lesion. The infant underwent embolisations of AVM with successful flow reduction and cardiac failure improvement. The multidisciplinary follow-up showed no cardiac dysfunction or permanent lesions but confirmed a severe psycho-motor delay and left hemiparesia. PMID:22783011

  10. Teratogenic effect of cisplatin in rats and the protective role of sodium selenate.

    PubMed

    Hassan, Mohammed S; Morgan, Ashraf M; Mekawy, Mohey M; Zaki, Amr R; Ghazi, Zeinab M

    2016-05-01

    Eighty pregnant Sprague-Dawley rats were used in this study. They were allotted to four equal groups. The first group served as a control without any treatment while the other groups were given cisplatin, sodium selenate, and cisplatin+sodium selenate, respectively. Cisplatin was injected intraperitoneally in a dose of 5mg/kgb wt. on the 12th day of gestation while sodium selenate was administered orally in a dose of 0.5mg/kgb wt throughout gestation. Animals were sacrificed on the 20th day of gestation for fetal examination. Cisplatin produced significant elevation in the percentages of late resorption sites and dead foetuses compared with the control group. The mean foetal and placental weights were significantly reduced. Dwarf foetuses and subcutaneous (s/c) haemorrhage were also recorded in cisplatin-treated group. Visceral abnormalities were revealed in the form of dilated nares, anophthalmia and/or microphthalmia, dilated brain ventricles, hypertrophy of the heart, hypoplasia of the lung, hepatomegaly and dilated renal pelvis. Skeletal examination showed wide open fontanel, incomplete ossification of parietal and interparietal bones, incomplete ossification of sternum, reduction in the number or even complete absence of phalanges, sacral and/or caudal vertebrae. Histopathological examination of placentas in cisplatin-treated group revealed severe pathological alterations. Administration of sodium selenate significantly alleviated the afore-mentioned adverse effects of cisplatin on the fetuses and their placentas so we conclude that sodium selenate as an antioxidant has an effective protective role in cisplatin teratogenic effects.

  11. Plasma cholesterol-lowering and transient liver dysfunction in mice lacking squalene synthase in the liver.

    PubMed

    Nagashima, Shuichi; Yagyu, Hiroaki; Tozawa, Ryuichi; Tazoe, Fumiko; Takahashi, Manabu; Kitamine, Tetsuya; Yamamuro, Daisuke; Sakai, Kent; Sekiya, Motohiro; Okazaki, Hiroaki; Osuga, Jun-ichi; Honda, Akira; Ishibashi, Shun

    2015-05-01

    Squalene synthase (SS) catalyzes the biosynthesis of squalene, the first specific intermediate in the cholesterol biosynthetic pathway. To test the feasibility of lowering plasma cholesterol by inhibiting hepatic SS, we generated mice in which SS is specifically knocked out in the liver (L-SSKO) using Cre-loxP technology. Hepatic SS activity of L-SSKO mice was reduced by >90%. In addition, cholesterol biosynthesis in the liver slices was almost eliminated. Although the hepatic squalene contents were markedly reduced in L-SSKO mice, the hepatic contents of cholesterol and its precursors distal to squalene were indistinguishable from those of control mice, indicating the presence of sufficient centripetal flow of cholesterol and/or its precursors from the extrahepatic tissues. L-SSKO mice showed a transient liver dysfunction with moderate hepatomegaly presumably secondary to increased farnesol production. In a fed state, the plasma total cholesterol and triglyceride were significantly reduced in L-SSKO mice, primarily owing to reduced hepatic VLDL secretion. In a fasted state, the hypolipidemic effect was lost. mRNA expression of liver X receptor α target genes was reduced, while that of sterol-regulatory element binding protein 2 target genes was increased. In conclusion, liver-specific ablation of SS inhibits hepatic cholesterol biosynthesis and induces hypolipidemia without increasing significant mortality.

  12. EWS/FLI-1 induces rapid onset of myeloid/erythroid leukemia in mice.

    PubMed

    Torchia, Enrique C; Boyd, Kelli; Rehg, Jerold E; Qu, Chunxu; Baker, Suzanne J

    2007-11-01

    EWS/FLI-1 is a chimeric oncogene generated by chromosomal translocation in Ewing tumors, a family of poorly differentiated pediatric tumors arising predominantly in bone but also in soft tissue. The fusion gene combines sequences encoding a strong transactivating domain from the EWS protein with the DNA binding domain of FLI-1, an ETS transcription factor. A related fusion, TLS/ERG, has been found in myeloid leukemia. To determine EWS/FLI-1 function in vivo, we engineered mice with Cre-inducible expression of EWS/FLI-1 from the ubiquitous Rosa26 locus. When crossed with Mx1-cre mice, Cre-mediated activation of EWS/FLI-1 resulted in the rapid development of myeloid/erythroid leukemia characterized by expansion of primitive mononuclear cells causing hepatomegaly, splenomegaly, severe anemia, and death. The disease could be transplanted serially into naïve recipients. Gene expression profiles of primary and transplanted animals were highly similar, suggesting that activation of EWS/FLI-1 was the primary event leading to disease in this model. The Cre-inducible EWS/FLI-1 mouse provides a novel model system to study the contribution of this oncogene to malignant disease in vivo.

  13. 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.

  14. An Animal Model for the Juvenile Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis

    PubMed Central

    Marin, Veronica; Rosso, Natalia; Dal Ben, Matteo; Raseni, Alan; Boschelle, Manuela; Degrassi, Cristina; Nemeckova, Ivana; Nachtigal, Petr; Avellini, Claudio; Tiribelli, Claudio; Gazzin, Silvia

    2016-01-01

    Non Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome; worrisome is the booming increase in pediatric age. To recreate the full spectrum of juvenile liver pathology and investigate the gender impact, male and female C57Bl/6 mice were fed with high fat diet plus fructose in the drinking water (HFHC) immediately after weaning (equal to 3-years old human), and disease progression followed for 16 weeks, until adults (equal to 30-years old human). 100% of subjects of both genders on HFHC diet developed steatosis in 4weeks, and some degree of fibrosis in 8weeks, with the 86% of males and 15% of females presenting a stage 2 fibrosis at 16weeks. Despite a similar final liver damage both groups, a sex difference in the pathology progression was observed. Alterations in glucose homeostasis, dyslipidemia, hepatomegaly and obese phenotype were evident from the very beginning in males with an increased hepatic inflammatory activity. Conversely, such alterations were present in females only at the end of the HFHC diet (with the exception of insulin resistance and the hepatic inflammatory state). Interestingly, only females showed an altered hepatic redox state. This juvenile model appears a good platform to unravel the underlying gender dependent mechanisms in the progression from NAFLD to NASH, and to characterize novel therapeutic approaches. PMID:27391242

  15. Case of hepatocellular carcinoma in a patient with hereditary tyrosinemia in the post-newborn screening era

    PubMed Central

    Imseis, Essam M; Bynon, John S; Thornhill, Chad

    2017-01-01

    Hereditary tyrosinemia type 1 (HT-1) is a metabolic disorder caused by a defect in tyrosine degradation. Without treatment, symptoms of hepatomegaly, renal tubular dysfunction, growth failure, neurologic crises resembling porphyrias, rickets and possible hepatocellular carcinoma can develop. The use of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione and early diagnosis through newborn screening initiatives have resulted in a sharp decline in morbidity and mortality associated with this disease. We present a case report of a 7-year-old patient with HT-1 who was born prior to the addition of tyrosinemia to the newborn screening in her birth area. At her time of diagnosis, the patient had developed many of the symptoms associated with her disease, including chronic kidney disease, rickets, and myopathy that left her non-ambulatory. During her initial evaluation, she was also noted to have hepatocellular carcinoma. With cadaveric liver transplantation and nutritional support, her symptoms all either resolved or stabilized. Her case illustrates the severity of the disease if left untreated, the need for vigilance in populations who do not routinely receive newborn screens, and the markedly improved outcomes in patients following transplant.

  16. Cardiac Tamponade Associated with the Presentation of Anaplastic Large Cell Lymphoma in a 2-Year-Old Child

    PubMed Central

    Mira-Perceval Juan, Gema; Alcalá Minagorre, Pedro J.; Huertas Sánchez, Ana M.; Segura Sánchez, Sheila; López Iniesta, Silvia; De León Marrero, Francisco J.; Costa Navarro, Estela; Niveiro de Jaime, María

    2015-01-01

    The anaplastic large cell lymphoma is a rare entity in pediatric patients. We present an unusual case of pericardial involvement, quite uncommon as extranodal presentation of this type of disorder, that provoked a life-risk situation requiring an urgent pericardiocentesis. To our knowledge, this is the first report on a child with pericardial involvement without an associated cardiac mass secondary to anaplastic large cell lymphoma in pediatric age. We report the case of a 21-month-old Caucasian male infant with cardiac tamponade associated with the presentation of anaplastic large cell lymphoma. Initially, the child presented with 24-day prolonged fever syndrome, cutaneous lesions associated with hepatomegaly, inguinal adenopathies, and pneumonia. After a 21-day asymptomatic period, polypnea and tachycardia were detected in a clinical check-up. Chest X-ray revealed a remarkable increase of the cardiothoracic index. The anaplastic large cell lymphoma has a high incidence of extranodal involvement but myocardial or pericardial involvements are rare. For this reason, we recommend a close monitoring of patients with a differential diagnosis of anaplastic large cell lymphoma. PMID:26435869

  17. A centronuclear myopathy--dynamin 2 mutation impairs autophagy in mice.

    PubMed

    Durieux, Anne-Cécile; Vassilopoulos, Stéphane; Lainé, Jeanne; Fraysse, Bodvaël; Briñas, Laura; Prudhon, Bernard; Castells, Josiane; Freyssenet, Damien; Bonne, Gisèle; Guicheney, Pascale; Bitoun, Marc

    2012-06-01

    Dynamin 2 (Dnm2) is involved in endocytosis and intracellular membrane trafficking through its function in vesicle formation from distinct membrane compartments. Heterozygous (HTZ) mutations in the DNM2 gene cause dominant centronuclear myopathy or Charcot-Marie-Tooth neuropathy. We generated a knock-in Dnm2R465W mouse model expressing the most frequent human mutation and recently reported that HTZ mice progressively developed a myopathy. We investigated here the cause of neonatal lethality occurring in homozygous (HMZ) mice. We show that HMZ mice present at birth with a reduced body weight, hypoglycemia, increased liver glycogen content and hepatomegaly, in agreement with a defect in neonatal autophagy. In vitro studies performed in HMZ embryonic fibroblasts point out to a decrease in the autophagy flux prior to degradation at the autolysosome. We show that starved HMZ cells have a higher number of immature autophagy-related structures probably due to a defect of acidification. Our results highlight the role of Dnm2 in the cross talk between endosomal and autophagic pathways and evidence a new role of Dnm2-dependent membrane trafficking in autophagy which may be relevant in DNM2-related human diseases.

  18. GADD45β, an anti-tumor gene, inhibits avian leukosis virus subgroup J replication in chickens.

    PubMed

    Zhang, Xinheng; Yan, Zhuanqiang; Li, Xinjian; Lin, Wencheng; Dai, Zhenkai; Yan, Yiming; Lu, Piaopiao; Chen, Weiguo; Zhang, Huanmin; Chen, Feng; Ma, Jingyun; Xie, Qingmei

    2016-10-18

    Avian leukosis virus subgroup J (ALV-J) is a retroviruses that induces neoplasia, hepatomegaly, immunosuppression and poor performance in chickens. The tumorigenic and pathogenic mechanisms of ALV-J remain a hot topic. To explore anti-tumor genes that promote resistance to ALV-J infection in chickens, we bred ALV-J resistant and susceptible chickens (F3 generation). RNA-sequencing (RNA-Seq) of liver tissue from the ALV-J resistant and susceptible chickens identified 216 differentially expressed genes; 88 of those genes were up-regulated in the ALV-J resistant chickens (compared to the susceptible ones). We screened for significantly up-regulated genes (P < 0.01) of interest in the ALV-J resistant chickens, based on their involvement in biological signaling pathways. Functional analyses showed that overexpression of GADD45β inhibited ALV-J replication. GADD45β could enhance defense against ALV-J infection and may be used as a molecular marker to identify ALV-J infections.

  19. C57BL/6 and A/J Mice Have Different Inflammatory Response and Liver Lipid Profile in Experimental Alcoholic Liver Disease

    PubMed Central

    Bavia, Lorena; de Castro, Íris Arantes; Isaac, Lourdes

    2015-01-01

    Alcoholic liver disease (ALD) is an important worldwide public health issue characterized by liver steatosis, inflammation, necrosis, and apoptosis of hepatocytes with eventual development of fibrosis and cirrhosis. Comparison of murine models with different inflammatory responses for ALD is important for an evaluation of the importance of genetic background in the interpretation of ethanol-induced phenotypes. Here, we investigated the role of inflammation and genetic background for the establishment of ALD using two different mouse strains: C57BL/6 (B6) and A/J. B6 and A/J mice were treated with a high fat diet containing ethanol (HFDE) and compared to the controls for 10 weeks. Hepatomegaly and steatohepatitis were similar in B6 and A/J mice, but only A/J mice were resistant to weight gain. On the other hand, HFDE-fed B6 accumulated more triglycerides (TG) and cholesterol and presented more intense cellular infiltrate in the liver when compared to HFDM-fed mice. Liver inflammatory environment was distinct in these two mouse strains. While HFDE-fed B6 produced more liver IL-12, A/J mice increased the TNF-α production. We concluded that mouse genetic background could dictate the intensity of the HFDE-induced liver injury. PMID:26448681

  20. Acne Fulminans: Case Series and Review of the Literature.

    PubMed

    Alakeel, Abdullah; Ferneiny, Marie; Auffret, Nicole; Bodemer, Christine

    2016-11-01

    Acne fulminans (AF) is a rare manifestation and the most severe form of the entire clinical spectrum of acne. The disease is destructive and is characterized by the sudden onset of painful and ulcerative pustules and systemic symptoms including high fever, hepatomegaly, polyarthralgia, leukocytosis, plaquetose, and increased inflammatory markers and transaminases. Osteolytic lesions in multiple skeletal sites could also be associated. The use of isotretinoin is considered a related trigger, as well as the use and cessation of testosterone, although a bacterial infection, a drug-induced disease, or an intake of anabolic androgenic steroids has been suggested. The treatment of AF is challenging and controversial. The recommended treatment is aggressive and consists of a combination of oral steroids and low doses of isotretinoin, with no consensus at this time. The patient may require several weeks of hospitalization to control the eruption. The cutaneous lesions usually leave scars and milia. We report on two boys and two girls presenting with AF, triggered by isotretinoin in three patients and by an antibiotic in one patient. All the patients treated with corticosteroids and isotretinoin with success.

  1. Very Early Presentation of Extrahepatic Portal Vein Obstruction Causing Portal Hypertension in an Infant: Uncertainties in the Management and Therapeutic Limitations.

    PubMed

    Khodayar-Pardo, Parisá; Peña Aldea, Andrés; Ramírez González, Ana; Meseguer Carrascosa, Adela; Calabuig Bayo, Cristina

    2016-01-01

    Extrahepatic portal vein obstruction, although rare in children, is a significant cause of portal hypertension (PHT) leading to life-threatening gastrointestinal bleeding in the pediatric age group. PHT may also lead to other complications such as hyperesplenism, cholangyopathy, ascites, and even hepatopulmonary syndrome and portopulmonary hypertension that may require organ transplantation. Herein we report the case of an asymptomatic 11-month-old infant wherein a hepatomegaly and cavernous transformation of the portal vein was detected by liver ultrasound. Neither signs of thrombosis in arteriovenous system, nor affectation of biliary tract were identified in the magnetic resonance imaging study. A significant enlargement of the caudate lobe of the liver was reported. No risk factors were detected. The differential diagnosis performed was extensive. Inherited thrombophilia and storage disorders were especially considered. Liver biopsy was normal. Upper gastrointestinal esophagogastroduodenoscopy detected two small varicose cords on the distal third of the esophagus. Finding a cavernous transformation of the portal vein with evidence of collateral circulation in such an early age is a challenging condition for professionals, since PHT may lead to severe complications during childhood and can compromise growth and development. Evidence-based guidelines for the management of PHT in adults have been published. However, follow-up and treatment of pediatric patients have not yet been standardized. Moreover, management of PHT in infants faces particular difficulties such as technical restrictions that could hinder their treatment.

  2. Clinical and Mutational Features of Three Chinese Children with Congenital Generalized Lipodystrophy

    PubMed Central

    Su, Xueying; Lin, Ruizhu; Huang, Yonglan; Sheng, Huiying; Li, Xiaofei; Ting, Tzer Hwu; Liu, Li; Li, Xiuzhen

    2017-01-01

    Objective: To investigate the clinical and molecular features of congenital generalized lipodystrophy (CGL) in three Chinese patients with various typical manifestations. Methods: Data on clinical symptoms, results of laboratory analyses, and previous treatments in three Chinese patients were collected by a retrospective review of medical records. All coding regions and adjacent exon–intron junction regions of AGPAT2 and BSCL2 genes were amplified by polymerase chain reaction and sequenced. Results: Generalized lipodystrophy, acanthosis nigricans, muscular hypertrophy, severe hypertriglyceridemia, and hepatomegaly were features in all three patients. Patient 1 developed diabetes mellitus at the early age of 2 months and he was the youngest CGL patient reported with overt diabetes. Patient 2 was found to have cardiomyopathy when she was aged 6 months. All of the patients were found to have mutations in the BSCL2 gene, but none of these was a novel mutation. We did not find any AGPAT2 mutation in our patients. Conclusion: All of our patients exhibited characteristic features of CGL due to mutations in the BSCL2 gene. PMID:27612026

  3. Diagnostic performance of Contrast-enhanced CT in Pyrrolizidine Alkaloids-induced Hepatic Sinusoidal Obstructive Syndrome

    PubMed Central

    Kan, Xuefeng; Ye, Jin; Rong, Xinxin; Lu, Zhiwen; Li, Xin; Wang, Yong; Yang, Ling; Xu, Keshu; Song, Yuhu; Hou, Xiaohua

    2016-01-01

    Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by pyrrolizidine alkaloids(PAs)-containing herbals. Since PAs exposure is obscure and clinical presentation of HSOS is unspecific, it is challenge to establish the diagnosis of PAs-induced HSOS. Gynura segetum is one of the most wide-use herbals containing PAs. The aim of our study is to describe the features of contrast-enhanced computed tomography (CT) in gynura segetum-induced HSOS, and then determine diagnostic performance of radiological signs. We retrospectively analyzed medical records and CT images of HSOS patients (71 cases) and the controls (222 cases) enrolled from January 1, 2008, to Oct 31, 2015. The common findings of contrast CT in PAs-induced HSOS included: ascites (100%), hepatomegaly (78.87%), gallbladder wall thickening (86.96%), pleural effusion (70.42%), hepatic vein narrowing (87.32%), patchy liver enhancement (92.96%), and heterogeneous hypoattenuation (100%); of these signs, patchy enhancement and heterogeneous hypoattenuation were valuable features. Then, the result of diagnostic performance demonstrated that contrast CT possessed better performance in diagnosing PAs-induced HSOS compared with various parameters of Seattle criteria. In conclusion, the patients with PAs-induced HSOS display distinct radiologic features at CT-scan, which reveals that contrast-enhanced CT provides an effective noninvasive method for diagnosing PAs-induced HSOS. PMID:27897243

  4. Infantile hemangioendothelioma of the liver: a radiologic-pathologic-clinical correlation

    SciTech Connect

    Dachman, A.H.; Lichtenstein, J.E.; Friedman, A.C.; Hartman, D.S.

    1983-06-01

    Infantile hemangioendothelioma is the most common symptomatic vascular liver tumor of infancy. It is considered a benign tumor; however, aggressive behavior is occasionally seen microscopically, and rarely distant metastases have been reported. The exact incidence of infantile hemangioendothelioma is difficult to determine because often it has been either misdiagnosed or mislabeled as cavernous hemangioma in the literature. Cavernous hemangioma is the most common primary liver tumor in older age groups but is rarely found in infants as a clinically significant tumor. Levick and Rubie were the first to recognize an association between hemangioendothelioma of the liver and congestive heart failure, and there were subsequent reports substantiating this association. However, it is our impression and the finding of others that congestive heart failure is distinctly less common than abdominal mass or hepatomegaly as the presenting sign in infantile hemangioendothelioma. Congestive heart failure is rarely a feature of cavernous hemangioma. Because of the errors in terminology and questions regarding clinical presentation, a radiologic-pathologic-clinical correlation study of infantile hemangioendothelioma and review of the literature was undertaken.

  5. Molecular diagnosis of Eimeria stiedae in hepatic tissue of experimentally infected rabbits.

    PubMed

    Hassan, Khaled M; Arafa, Waleed M; Mousa, Waheed M; Shokier, Khaled A M; Shany, Salama A; Aboelhadid, Shawky M

    2016-10-01

    The early detection of Eimeria stiedae in the hepatic tissue of experimentally infected rabbits was investigated using molecular assay. Forty 6-week-old male New Zealand rabbits were divided into two groups. Group A (30 animals) was infected with 2.5 × 10(4) sporulated oocysts of E. stiedae per animal on Day 0 and Group B (10 animals) was used as the uninfected controls. Three animals from Group A and one from Group B were sacrificed at 0, 3, 6, 9, 12, 15, 18, 21, 24 and 27 days post infection (PI). Gross and microscopic post-mortem findings were recorded. Polymerase chain reaction (PCR) of the E. stiedae internal transcribed spacer 1 genomic region was conducted on blood, liver tissue, and feces from the Group A experimentally infected animals. Macroscopically, the liver showed irregular yellowish white nodules pathognomonic to E. stiedae infection beginning on Day 15 PI. Hepatomegaly and ascites were obvious from Day 21-24 PI. The presence of different E. stiedae schizonts and gametocytes in the histopathological sections of the biliary epithelium were evident on Day 15 PI. The E. stiedae PCR was first positive in liver tissues on Day 12 and in fecal samples on Day 18 PI, but the blood samples were negative. In conclusion, the PCR can be used for early diagnosis and control of E. stiedae schizonts before shedding of the oocysts in feces.

  6. Hepatoblastoma in adult age. A case report and literature review.

    PubMed

    Remes-Troche, José M; Montaño-Loza, Aldo; Meza-Junco, Judith; García-Leiva, Jorge; Torre-Delgadillo, Aldo

    2006-01-01

    Hepatoblastoma (HB) rarely occurs in adults. We report herein the unusual case of a 19-year-old, otherwise healthy woman with no history of liver disease who presented with upper abdominal pain and hepatomegaly. Tests for hepatitis B virus (HBV), hepatitis C virus (HCV) were negative, and AFP was normal. There was no evidence of liver cirrhosis. A welldemarcated solid mass of 14 cm in diameter, which was lobulated and partly necrotic, was detected in the liver by computed tomography (CT). At surgical exploration a large liver mass was detected occupying the entire right lobe. A right trisegmentectomy was performed with tumor grossly resected with microscopic residual disease (i.e positive margins). On microscopic examination the tumor was composed mainly of two components which were intermingled: epithelial and mesenchymal elements. The epithelial component was formed of small embryonal cells, grouped into nodules, scattered in cellular mesenchymal tissue. The diagnosis was mixed hepatoblastoma. The patient received 4 cycles of systemic chemotherapy with cisplatinum and adriamycin. Post-chemotherapy evaluation revealed recurrence of the hepatoblastoma in the remaining liver. She died 6 months later.

  7. Mortality of captive whooping cranes caused by eastern equine encephalitis virus

    USGS Publications Warehouse

    Dein, F.J.; Carpenter, J.W.; Clark, G.G.; Montali, R.J.; Crabbs, C.L.; Tsai, T.F.; Docherty, D.E.

    1986-01-01

    Of 39 captive whooping cranes (Grus americana), 7 died during a 7-week period (Sept 17 through Nov 4, 1984) at the Patuxent Wildlife Research Center, Laurel, Md. Before their deaths, 4 cranes did not develop clinical signs, whereas the other 3 cranes were lethargic and ataxic, with high aspartate transaminase, gamma-glutamyl transferase, and lactic acid dehydrogenase activities, and high uric acid concentrations. Necropsies indicated that the birds had ascites, intestinal mucosal discoloration, fat depletion, hepatomegaly, splenomegaly, and visceral gout. Microscopically, extensive necrosis and inflammation were seen in many visceral organs; the CNS was not affected. Eastern equine encephalitis (EEE) virus was isolated from specimens of the livers, kidneys, lungs, brains, and intestines of 4 of the 7 birds that died, and EEE virus-neutralizing antibody was detected in 14 (44%) of the 32 surviving birds. Other infectious or toxic agents were not found. Morbidity or mortality was not detected in 240 sandhill cranes (Grus canadensis) interspersed among the whooping cranes; however, 13 of the 32 sandhill cranes evaluated had EEE virus-neutralizing antibody. Of the 41 wild birds evaluated in the area, 3 (4%) had EEE virus-neutralizing antibody. Immature Culiseta melanura (the most probable mosquito vector) were found in scattered foci 5 km from the research center.

  8. Inhibiting heat shock protein 90 (HSP90) limits the formation of liver cysts induced by conditional deletion of Pkd1 in mice.

    PubMed

    Smithline, Zachary B; Nikonova, Anna S; Hensley, Harvey H; Cai, Kathy Q; Egleston, Brian L; Proia, David A; Seeger-Nukpezah, Tamina; Golemis, Erica A

    2014-01-01

    Polycystic liver disease (PLD) occurs in 75-90% of patients affected by autosomal dominant polycystic kidney disease (ADPKD), which affects 1∶400-1,000 adults and arises from inherited mutations in the PKD1 or PKD2 genes. PLD can lead to bile duct obstructions, infected or bleeding cysts, and hepatomegaly, which can diminish quality of life. At present, no effective, approved therapy exists for ADPKD or PLD. We recently showed that inhibition of the molecular chaperone heat shock protein 90 (HSP90) with a small molecule inhibitor, STA-2842, induced the degradation of multiple HSP90-dependent client proteins that contribute to ADPKD pathogenesis and slowed the progression of renal cystogenesis in mice with conditional deletion of Pkd1. Here, we analyzed the effects of STA-2842 on liver size and cystic burden in Pkd-/- mice with established PLD. Using magnetic resonance imaging over time, we demonstrate that ten weeks of STA-2842 treatment significantly reduced both liver mass and cystic index suggesting selective elimination of cystic tissue. Pre-treatment cystic epithelia contain abundant HSP90; the degree of reduction in cysts was accompanied by inhibition of proliferation-associated signaling proteins EGFR and others, and induced cleavage of caspase 8 and PARP1, and correlated with degree of HSP90 inhibition and with inactivation of ERK1/2. Our results suggest that HSP90 inhibition is worth further evaluation as a therapeutic approach for patients with PLD.

  9. Hepar lobatum carcinomatosum revealing an occult metastatic lobular carcinoma of the breast.

    PubMed

    Graber, Ivan; Dumortier, Jérôme; Poncet, Gilles; Queneau, Pierre-Edouard; Mathevet, Patrice; Scoazec, Jean-Yves

    2010-12-01

    Hepar lobatum carcinomatosum is an unusual cause of chronic liver failure, usually maskerading as cirrhosis. The pathogenesis of this syndrome is unclear. We report a case of liver failure revealing an occult lobular carcinoma of the breast, which offers the opportunity to gain further insight into the mechanisms of this rare cause of chronic liver disease. A 57-year-old woman, without history of malignancy, presented with hepatomegaly, ascites and altered liver tests (serum transaminase activity >5 N and hyperbilirubinemia). The transjugular liver biopsy performed at diagnosis showed an extensive fibrosis, containing scattered tumor cells, typical of metastatic lobular carcinoma of the breast. Four months later, after discovery of a rectal adenocarcinoma, a laparoscopy was performed; peritoneal carcinomatosis was discovered. A surgical biopsy of the liver was taken during the procedure: it showed histological features suggestive of chronic Budd-Chiari syndrome, with venocentric fibrosis and reversed lobulation. Intraluminal invasion of small hepatic veins and sinusoidal obstruction by neoplastic cells were observed. A small focus of lobular carcinoma was eventually discovered in the left mammary gland. The present case report expands the spectrum of clinical presentations associated with hepar lobatum carcinomatosum and points out to the importance of vascular injury in the pathogenesis of this rare cause of chronic liver disease.

  10. Current biochemical studies of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis suggest a new therapeutic approach.

    PubMed

    Hookman, Perry; Barkin, Jamie S

    2003-09-01

    The study population in this report by Lin et al. was ob/ob mice that have an inherited genetic deficiency of the appetite-suppressing hormone leptin. These mice develop hyperinsulinemia, insulin resistance, and fatty livers. Compared with their lean littermates and wild-type C57BL-6 mice, ob/ob mice have hepatomegaly. In this study, the authors compared three different groups of adult mice (aged 8-10 wk), including male ob/ob C57BL-6 mice, their lean littermates, and wild-type C57BL-6 mice of the same age and sex. The primary purpose of this study was to test the efficacy of metformin for treatment of fatty liver disease in obese, ob/ob mice that develop hyperinsulinemia or insulin resistance and fatty livers. Metformin therapy was found to eliminate fatty liver disease in this model. The potential mechanisms of the action of metformin were the inhibition of hepatic tumor necrosis factor (TNF)alpha and several TNF-inducible responses, which are likely to promote hepatic steatosis and necrosis. In these experiments, ob/ob mice were divided into three treatment groups. Group 1 consisted of eight mice that were treated with metformin and permitted to consume a nutritiously replete liquid mouse diet ad libitum. Mice in group 2 (n = 8) did not receive metformin but were pair-fed the same volume of liquid diet that the mice in the metformin-treated group had consumed on the previous day. Obese ob/ob mice in group 3 (n = 4) and lean mice received no metformin, as with the mice in group 2, but were permitted to consume the liquid diet ad libitum. Liquid diet was given to facilitate accurate daily comparison of food intake among the various treatment groups. All mice were weighed at the beginning of the study and weekly thereafter until killed and then sera, fat, and liver tissues were collected. Tissues were either fixed in buffered formalin and processed from the deceased mice for histology or snap frozen in liquid nitrogen and stored until RNA and proteins were isolated

  11. Vertebral osteomyelitis: clinical features and diagnosis.

    PubMed

    Eren Gök, S; Kaptanoğlu, E; Celikbaş, A; Ergönül, O; Baykam, N; Eroğlu, M; Dokuzoğuz, B

    2014-10-01

    We aimed to describe clinical and diagnostic features of vertebral osteomyelitis for differential diagnosis and treatment. This is a prospective observational study performed between 2002 and 2012 in Ankara Numune Education and Research Hospital in Ankara, Turkey. All the patients with vertebral osteomyelitis were followed for from 6 months to 3 years. In total, 214 patients were included in the study, 113 out of 214 (53%) were female. Out of 214 patients, 96 (45%) had brucellar vertebral osteomyelitis (BVO), 63 (29%) had tuberculous vertebral osteomyelitis (TVO), and 55 (26%) had pyogenic vertebral osteomyelitis (PVO). Mean number of days between onset of symptoms and establishment of diagnosis was greater with the patients with TVO (266 days) than BVO (115 days) or PVO (151 days, p <0.001). In blood cultures, Brucella spp. were isolated from 35 of 96 BVO patients (35%). Among 55 PVO patients, the aetiological agent was isolated in 11 (20%) patients. For tuberculin skin test >15 mm, sensitivity was 0.66, specificity was 0.97, positive predictive value was 0.89, negative predictive value was 0.88, and receiver operating characteristics area was 0.8. Tuberculous and brucellar vertebral osteomyelitis remained the leading causes of vertebral osteomyelitis with delayed diagnosis. In differential diagnosis of vertebral osteomyelitis, consumption of unpasteurized cheese, dealing with husbandry, sweating, arthralgia, hepatomegaly, elevated alanine transaminase, and lumbar involvement in magnetic resonance imaging were found to be predictors of BVO, thoracic involvement in magnetic resonance imaging and tuberculin skin test > 15 mm were found to be predictors of TVO, and history of spinal surgery and leucocytosis were found to be predictors of PVO.

  12. Glycogen storage disease type 1 and diabetes: learning by comparing and contrasting the two disorders.

    PubMed

    Rajas, F; Labrune, P; Mithieux, G

    2013-10-01

    Glycogen storage disease type 1 (GSD1) and diabetes may look at first like totally opposite disorders, as diabetes is characterized by uncontrolled hyperglycaemia, whereas GSD1 is characterized by severe fasting hypoglycaemia. Diabetes is due to a failure to suppress endogenous glucose production (EGP) in the postprandial state because of either a lack of insulin or insulin resistance. In contrast, GSD1 is characterized by a lack of EGP. However, both diseases share remarkably similar patterns in terms of pathophysiology such as the long-term progression of renal dysfunction and hepatic steatosis leading to renal failure and the development of hepatic tumours, respectively. Thus, much may be learned from considering the similarities between GSD1 and diabetes, especially in the metabolic pathways underlying nephropathy and fatty liver, and perhaps even more from their differences. In this review, the differences between diabetes and GSD1 are first highlighted, as both are characterized by alterations in EGP. The molecular pathways involved in liver pathologies, including steatosis, hepatomegaly (glycogenic hepatopathy) and the development of liver tumours are also compared. These pathologies are mainly due to the accumulation of lipids and/or glycogen in hepatocytes. Finally, the similar pathways leading to nephropathy in both diabetic and GSD1 patients are described. In conclusion, comparisons of these pathologies should lead to a better understanding of the crucial role of EGP in the control of glucose and energy homoeostasis. Moreover, it may highlight similar therapeutic targets for the two disorders. Thus, this review suggests that the treatment of adult patients with either GSD1 or diabetes could be carried out by the same specialists-diabetologists.

  13. Cloning of the canine glucose-6-phosphatase gene

    SciTech Connect

    Kishnani, P.; Bao, Y.; Brix, A.E.

    1994-09-01

    Two Maltese puppies with massive hepatomegaly and failure to thrive were found to have a markedly reduced Glucose-6-phosphatase (G-6-Pase) activity in the liver and kidney. Deficiency of G-6-Pase activity causes type 1a glycogen storage disease in humans. To further study the mutation responsible for the disease in dog, we cloned G-6-Pase canine cDNA from normal mixed breed dog liver RNA using reverse transcriptase and PCR amplification using primers derived from the published murine G-6-Pase gene sequence. Sequencing revealed an open reading frame of 1071 nucleotides that encodes a predicted 357 amino acid polypeptide in the canine G-6-Pase gene, same as mouse and human. We found more than 90% sequence homology between dog and human G-6-Pase sequence. Hydropathy analysis of the deduced canine G-6-Pase polypeptide shows six transmembrane-spanning segments similar to those seen in human and mouse. Endoplasmic reticulum (ER) localization is similarly predicted by the presence of the ER protein retention signal KK positioned 3 and 4 amino acids from the carboxy terminal. Potential asparagine-linked glycosylation sites are identified at positions 96, 203, and 276. Northern blot analysis revealed increased G-6-Pase mRNA in the deficient dog liver compared to control. This could possibly reflect upregulation of transcription due to the persistent hypoglycemic state. Further studies are directed at the identification of the mutation involved in this deficient dog strain. Characterization of the G-6-Pase gene and protein in the deficient dog model can pave the way for new understanding in the pathophysiology of this disease and for the trials of novel therapeutic approaches including gene therapy.

  14. Hepatic lentiviral gene transfer prevents the long-term onset of hepatic tumours of glycogen storage disease type 1a in mice.

    PubMed

    Clar, Julie; Mutel, Elodie; Gri, Blandine; Creneguy, Alison; Stefanutti, Anne; Gaillard, Sophie; Ferry, Nicolas; Beuf, Olivier; Mithieux, Gilles; Nguyen, Tuan Huy; Rajas, Fabienne

    2015-04-15

    Glycogen storage disease type 1a (GSD1a) is a rare disease due to the deficiency in the glucose-6-phosphatase (G6Pase) catalytic subunit (encoded by G6pc), which is essential for endogenous glucose production. Despite strict diet control to maintain blood glucose, patients with GSD1a develop hepatomegaly, steatosis and then hepatocellular adenomas (HCA), which can undergo malignant transformation. Recently, gene therapy has attracted attention as a potential treatment for GSD1a. In order to maintain long-term transgene expression, we developed an HIV-based vector, which allowed us to specifically express the human G6PC cDNA in the liver. We analysed the efficiency of this lentiviral vector in the prevention of the development of the hepatic disease in an original GSD1a mouse model, which exhibits G6Pase deficiency exclusively in the liver (L-G6pc(-/-) mice). Recombinant lentivirus were injected in B6.G6pc(ex3lox/ex3lox). SA(creERT2/w) neonates and G6pc deletion was induced by tamoxifen treatment at weaning. Magnetic resonance imaging was then performed to follow up the development of hepatic tumours. Lentiviral gene therapy restored glucose-6 phosphatase activity sufficient to correct fasting hypoglycaemia during 9 months. Moreover, lentivirus-treated L-G6pc(-/-) mice presented normal hepatic triglyceride levels, whereas untreated mice developed steatosis. Glycogen stores were also decreased although liver weight remained high. Interestingly, lentivirus-treated L-G6pc(-/-) mice were protected against the development of hepatic tumours after 9 months of gene therapy while most of untreated L-G6pc(-/-) mice developed millimetric HCA. Thus the treatment of newborns by recombinant lentivirus appears as an attractive approach to protect the liver from the development of steatosis and hepatic tumours associated to GSD1a pathology.

  15. The Upstream enhancer elements of the G6PC promoter are critical for optimal G6PC expression in murine glycogen storage disease type Ia

    PubMed Central

    Lee, Young Mok; Pan, Chi-Jiunn; Koeberl, Dwight D.; Mansfield, Brian C.; Chou, Janice Y.

    2013-01-01

    Glycogen storage disease type-Ia (GSD-Ia) patients deficient in glucose-6-phosphatase-α (G6Pase-α or G6PC) manifest impaired glucose homeostasis characterized by fasting hypoglycemia, growth retardation, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. Two efficacious recombinant adeno-associated virus pseudotype 2/8 (rAAV8) vectors expressing human G6Pase-α have been independently developed. One is a single-stranded vector containing a 2864-bp of the G6PC promoter/enhancer (rAAV8-GPE) and the other is a double-stranded vector containing a shorter 382-bp minimal G6PC promoter/enhancer (rAAV8-miGPE). To identify the best construct, a direct comparison of the rAAV8-GPE and the rAAV8-miGPE vectors was initiated to determine the best vector to take forward into clinical trials. We show that the rAAV8-GPE vector directed significantly higher levels of hepatic G6Pase-α expression, achieved greater reduction in hepatic glycogen accumulation, and led to a better toleration of fasting in GSD-Ia mice than the rAAV8-miGPE vector. Our results indicated that additional control elements in the rAAV8-GPE vector outweigh the gains from the double-stranded rAAV8-miGPE transduction efficiency, and that the rAAV8-GPE vector is the current choice for clinical translation in human GSD-Ia. PMID:23856420

  16. The upstream enhancer elements of the G6PC promoter are critical for optimal G6PC expression in murine glycogen storage disease type Ia.

    PubMed

    Lee, Young Mok; Pan, Chi-Jiunn; Koeberl, Dwight D; Mansfield, Brian C; Chou, Janice Y

    2013-11-01

    Glycogen storage disease type-Ia (GSD-Ia) patients deficient in glucose-6-phosphatase-α (G6Pase-α or G6PC) manifest impaired glucose homeostasis characterized by fasting hypoglycemia, growth retardation, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. Two efficacious recombinant adeno-associated virus pseudotype 2/8 (rAAV8) vectors expressing human G6Pase-α have been independently developed. One is a single-stranded vector containing a 2864-bp of the G6PC promoter/enhancer (rAAV8-GPE) and the other is a double-stranded vector containing a shorter 382-bp minimal G6PC promoter/enhancer (rAAV8-miGPE). To identify the best construct, a direct comparison of the rAAV8-GPE and the rAAV8-miGPE vectors was initiated to determine the best vector to take forward into clinical trials. We show that the rAAV8-GPE vector directed significantly higher levels of hepatic G6Pase-α expression, achieved greater reduction in hepatic glycogen accumulation, and led to a better toleration of fasting in GSD-Ia mice than the rAAV8-miGPE vector. Our results indicated that additional control elements in the rAAV8-GPE vector outweigh the gains from the double-stranded rAAV8-miGPE transduction efficiency, and that the rAAV8-GPE vector is the current choice for clinical translation in human GSD-Ia.

  17. A case of primary hepatic Burkitt's lymphoma.

    PubMed

    Lee, Seung Hyun; Kim, Hyung Joon; Mun, Jang Sik; Oh, Hyoung-Chul; Lee, Hyun Woong; Choi, Chang Hwan; Kim, Jeong Wook; Do, Jae Hyuk; Kim, Jae Gyu; Chang, Sae Kyung; Kim, Mi Kyung

    2008-04-01

    Burkitt's lymphoma is a rare disease that belongs to the aggressive non-Hodgkin's lymphoma. Herein, we report a case of primary hepatic Burkitt's lymphoma. A 19-year-old man visited the hospital for right upper quadrant pain. He felt fatigue for two months. Physical examination revealed hepatomegaly and no palpable lymph node. He had no fever, weight loss, or night sweating. Laboratory finding showed mild anemia (hemoglobin, 12.4 g/dL), mild elevated transaminase (ALT, 52 IU/L), elevated lactate dehydrogenase (LDH, 437 IU/L), and alkaline phosphatase (ALP, 129 IU/L). The viral marker was positive for HBsAg, HBeAg, anti-HBs, and anti-HBc (IgG), and negative for anti-HBe, anti-HCV, and anti-HIV. CEA, AFP, and CA19-9 levels were within normal ranges. The HBV DNA quantitation was 1.3 x 10(9) copies/ml. Abdominal-Pelvis CT scan and abdominal MRI finding were compatible with malignant lymphoma. Liver biopsy examination confirmed Burkitt's lymphoma. No metastasis was detected in the thoracic cavity, bone marrow, and spinal fluid. The patient was treated with the combination regimen of cyclophosphamide, doxorubicin, vincristine, prednisone and high dose methotrexate. Cytosine arabinoside and methotrexate were added for CNS prophylaxis by intrathecal installation. Chemotherapy was administered every 3 weeks for fifteen cycles. Serial follow-up CT scan showed a marked decrease in the size of hepatic lesions. Follow-up CT scan and PET-CT scan were performed 4 weeks after the final cycle disclosed no definite residual or active lesion confirming the state of complete remission.

  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. The etiology of hypertransaminasemia in Turkish children

    PubMed Central

    Serdaroglu, Filiz; Koca, Tugba; Dereci, Selim; Akcam, Mustafa

    2016-01-01

    The aim of this study was to investigate the causes of elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in children. We analyzed the medical records for children aged 3 months to 18 years who presented to the hospital with ALT >45 IU/L and/or AST >50 IU/L, between 2012 and 2014, for various reasons, including those not related to liver disease. In total, 281 children met the study criteria. This group comprised of 125 (44.5%) females and 156 (55.5%) males. At the presentation, the most common patient complaint was fatigue (53.4%), while 15.7% of the patients reported no symptoms. The most common findings on the physical examination were jaundice and hepatomegaly. In 15% of the cases, the findings were normal. According to the diagnosis, the most common cause of the elevated transaminases were infections (34%), with hepatitis A virus (HAV) infection as the leading cause (18.9%). Drug-induced liver injury (DILI) was the cause in 18.1% of the cases and non-alcoholic fatty liver disease (NAFLD) in 11.1%. The highest transaminase levels were associated with HAV infection, while DILI and NAFLD caused only slightly elevated transaminases. Overall, our results show that the elevated transaminases in children are most often caused by infections, DILI, and NAFLD. In a majority of cases, elevated ALT and AST indicate liver disease, however, they could also be associated with conditions other than liver damage. Additionally, the elevated enzymes can be detected in completely healthy individuals. PMID:26894285

  20. Circulating cytokines and chemokines associated with plasma leakage and hepatic dysfunction in Brazilian children with dengue fever.

    PubMed

    Ferreira, Ralph Antonio Xavier; de Oliveira, Solange Artimos; Gandini, Mariana; Ferreira, Laura da Cunha; Correa, Gladys; Abiraude, Fernanda Mattos; Reid, Mariana Mancebo; Cruz, Oswaldo Gonçalves; Kubelka, Claire Fernandes

    2015-09-01

    Dengue fever is usually a benign acute viral infection transmitted by arthropods but may evolve to severe clinical manifestations such as coagulation and/or hemodynamic disorders, caused mainly by an increase of vascular permeability. Deregulated circulating immunological factors have been associated with severity. In Brazil severe cases appeared in children only recently and we evaluated the profile of cytokine/chemokine kinetics in 134 hospitalized young patients during the epidemic in Rio de Janeiro in 2008. Inflammatory cytokines TNF and IFNγ were found elevated during the acute phase in children as well as the anti-inflammatory IL10 and chemokines MIF and CXCL10/IP10, all last three persisting longer during the recovery phase. Severe disease fitting the dengue hemorrhagic fever pattern (WHO, 1997) was associated with higher IL10 and CXCL10/IP10 circulating levels (peak levels at seven days with P<0.01 and P<0.001 respectively as compared to DF). These factors were higher in patients pulmonary effusion or ascites (P<0.05 for IL10 and P<0.01 for CXCL10/IP10). Both factors were also associated with liver changes such as AST increase correlated with CXCL10/IP10 (r=0.4300 with P<0.0001) and patients presenting painful hepatomegaly showed higher circulating levels of IL10 (P<0.01, at 7-9 days) and of CXCL10/IP10 (P<0.05, 4-6 days and P<0.001, 7-9 days) when compared to patients without apparent liver alterations. Most cases presented a history of prior infection (93%). This is the first study demonstrating cytokine and chemokine association with severity during dengue fever in Brazilian children. IL10 and CXCL10/IP10 play a role in the disease severity associated with induction of vascular leakage and a novel association with changes in liver dysfunction.

  1. Budd-Chiari Syndrome in a Patient with JAK-2 V617F and Factor V G1691A Mutations.

    PubMed

    Velarde-Félix, J S; Sanchez-Zazueta, J; Gonzalez-Ibarra, F P; González-Valdez, J A; Salcido-Gómez, B; Gallardo-Angulo, E; Murillo-Llanes, J

    2014-09-01

    Myeloproliferative neoplasms (MPN) are considered a risk factor for Budd-Chiari syndrome (BCS). The current classification of MPN by the World Health Organization is based on the presence of JAK-2 V617F somatic mutation, which is present in 40 to 60% of patients with BCS. Factor V Leiden mutation is found in around 53% of patients with BCS, representing the most common prothrombotic disease associated with the disorder. We describe a 48-year old woman with a past medical history of deep venous thrombosis in the left upper extremity and one episode in both lower extremities, one episode of transient ischaemic attack and essential thrombocythemia, who presented with jaundice, ascites and hepatomegaly. Budd-Chiari syndrome was diagnosed based on findings on Doppler ultrasound and liver biopsy. Doppler ultrasound showed narrowness of hepatic veins and inferior vena cava in its hepatic portion, diffuse echotexture and portal hypertension. Liver biopsy showed congestion of sinusoids and portal fibrosis. The patient was found to be a heterozygous carrier of Factor V and homozygous wild type G20210A prothrombin mutations. The JAK-2 V617F mutation was detected by allele-specific polymerase chain reaction (AS-PCR). The association of these mutations is rare, with only a few cases reported in the literature. The patient was treated with oral anticoagulation and antiplatelets with good results and proper follow-up. In conclusion, due to the possible coexistence of multiple prothrombotic factors in patients with Budd-Chiari syndrome, the approach to these patients must be focussed on searching for multiple factors and should include the JAK-2 V617F mutation.

  2. Shwachman's syndrome. A review of 21 cases.

    PubMed Central

    Aggett, P J; Cavanagh, N P; Matthew, D J; Pincott, J R; Sutcliffe, J; Harries, J T

    1980-01-01

    21 patients (10 male, 11 female) aged between 11 months and 29 years with Shwachman's syndrome are reviewed. All patients had exocrine pancreatic insufficiency. Haematological features included neutropenia in 19 (95%), anaemia in 10 (50%), and thrombocytopenia in 14 (70%); one patient developed erythroleukaemia. Severe infections occurred in 17 (85%) from which 3 (15%) died. Only one child exceeded the 3rd centile for height, and growth retardation was particularly evident in the older patients. All had skeletal abnormalities or delayed skeletal maturation, or both. Metaphyseal dyschondroplasia affected 13 of the older patients and was associated with skeletal deformities. Eight of 9 children under 2 1/2 years had rib abnormalities. Respiratory function tests in children under 2 years demonstrated reduced thoracic gas volume and chest wall compliance. Older patients had reduced forced expiratory volume and forced vital capacity. Neurological assessment showed developmental retardation or reduced IQ assessments, or both, in 85% of patients studied. Other neurological abnormalities included hypotonia, deafness, and retinitis pigmentosa. Neonatal problems had been present in 16 (80%) of the patients and 5 were of low birthweights. Hepatomegaly with biochemical evidence of liver involvement occurred in the younger patients and resolved with age. Other associated features included dental abnormalities, renal dysfunction, an icthyotic maculopapular rash in 13 (65%), delayed puberty, diabetes mellitus, and various dysmorphic features. These findings stress the diverse manifestations of the syndrome and extend knowledge on a number of aspects. Sibship segregation ratios support an autosomal mode of inheritance and an hypothesis for the pathophysiological basis of this syndrome is advanced. Images Fig. 2 Fig. 4(a) Fig. 4(b) Fig. 5 PMID:7436469

  3. Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease)

    PubMed Central

    Fan, Cathy Q.; Crawford, James M.

    2014-01-01

    Hepatic sinusoidal obstruction syndrome (SOS) is an obliterative venulitis of the terminal hepatic venules, which in its more severe forms imparts a high risk of mortality. SOS, also known as veno-occlusive disease (VOD), occurs as a result of cytoreductive therapy prior to hematopoietic stem cell transplantation (HSCT), following oxaliplatin-containing adjuvant or neoadjuvant chemotherapy for colorectal carcinoma metastatic to the liver and treated by partial hepatectomy, in patients taking pyrrolizidine alkaloid-containing herbal remedies, and in other particular settings such as the autosomal recessive condition of veno-occlusive disease with immunodeficiency (VODI). A central pathogenic event is toxic destruction of hepatic sinusoidal endothelial cells (SEC), with sloughing and downstream occlusion of terminal hepatic venules. Contributing factors are SEC glutathione depletion, nitric oxide depletion, increased intrahepatic expression of matrix metalloproteinases and vascular endothelial growth factor (VEGF), and activation of clotting factors. The clinical presentation of SOS includes jaundice, development of right upper-quadrant pain and tender hepatomegaly, ascites, and unexplained weight gain. Owing to the potentially critical condition of these patients, transjugular biopsy may be the preferred route for liver biopsy to exclude other potential causes of liver dysfunction and to establish a diagnosis of SOS. Treatment includes rigorous fluid management so as to avoid excessive fluid overload while avoiding too rapid diuresis or pericentesis, potential use of pharmaceutics such as defibrotide, coagulolytic agents, or methylprednisolone, and liver transplantation. Proposed strategies for prevention and prophylaxis include reduced-intensity conditioning radiation for HSCT, treatment with ursodeoxycholic acid, and inclusion of bevacizumab with oxaliplatin-based chemotherapeutic regimes. While significant progress has been made in understanding the pathogenesis

  4. A novel cystine based antioxidant attenuates oxidative stress and hepatic steatosis in diet-induced obese mice

    PubMed Central

    Sinha-Hikim, Indrani; Sinha-Hikim, Amiya P.; Shen, Ruoqing; Kim, H.; French, Samuel W.; Vazari, Nostrola D.; Crum, Albert; Rajavashisth, Tripathi B.; Norris, Keith C.

    2011-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver pathologies and is associated with obesity and the metabolic syndrome. Here, we investigated the molecular mechanisms by which a novel cystine based glutathione precursor with added selenomethionine (F1) prevents hepatic steatosis in a moderate high fat dietary model of NAFLD. Adult (8 weeks old), male apolipoprotein E (ApoE)−/− mice were fed with a normal diet (ND) or high fat diet (HFD), consisting of 21% fat and 0.21% cholesterol, with or without dietary supplementation of F1 (3 g/kg food) for 16 weeks. Compared with ApoE−/− mice fed with ND with or without F1, ApoE−/− mice fed with HFD exhibited significant weight gain, hepatomegaly, and increased serum cholesterol and triglycerides levels with no change in serum albumin levels. High resolution light and electron microscopy revealed micro-and macro-vesicular steatosis in ApoE−/− mice fed on a HFD. HFD- induced obesity also led to increased lipogenesis, oxidative stress, activation of c-Jun-NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), perturbation of the BAX/BCL-2 rheostat, hepatocyte apoptosis, and activation of caspases 9 and 3. F1 fully prevented the adverse effects of HFD on serum triglyceride levels, body and liver weights, and hepatic steatosis and substantially attenuated HFD-induced increase in lipogenesis, oxidative stress, kinase activation, apoptotic signaling, and hepatocyte ultrastructural abnormalities. These results demonstrate that administration of F1, a glutathione precursor, ameliorates HFD-induced hepatic steatosis in ApoE−/− mice and emphasizes the role of oxidative stress in diet-induced obesity and hepatic steatosis. PMID:21570964

  5. Autoimmune Manifestations in the 3xTg-AD Model of Alzheimer's Disease

    PubMed Central

    Marchese, Monica; Cowan, David; Head, Elizabeth; Ma, Donglai; Karimi, Khalil; Ashthorpe, Vanessa; Kapadia, Minesh; Zhao, Hui; Davis, Paulina; Sakic, Boris

    2015-01-01

    Background Immune system activation is frequently reported in patients with Alzheimer's disease (AD). However, it remains unknown whether this is a cause, a consequence, or an epiphenomenon of brain degeneration. Objective The present study examines whether immunological abnormalities occur in a well-established murine AD model and if so, how they relate temporally to behavioral deficits and neuropathology. Methods A broad battery of tests was employed to assess behavioral performance and autoimmune/inflammatory markers in 3xTg-AD (AD) mice and wild type controls from 1.5 to 12 months of age. Results Aged AD mice displayed severe manifestations of systemic autoimmune/inflammatory disease, as evidenced by splenomegaly, hepatomegaly, elevated serum levels of anti-nuclear/anti-dsDNA antibodies, low hematocrit, and increased number of double-negative T splenocytes. However, anxiety-related behavior and altered spleen function were evident as early as 2 months of age, thus preceding typical AD-like brain pathology. Moreover, AD mice showed altered olfaction and impaired “cognitive” flexibility in the first 6 months of life, suggesting mild cognitive impairment-like manifestations before general learning/memory impairments emerged at an older age. Interestingly, all of these features were present in 3xTg-AD mice prior to significant amyloid-β or tau pathology. Conclusion The results indicate that behavioral deficits in AD mice develop in parallel with systemic autoimmune/inflammatory disease. These changes antedate AD-like neuropathology, thus supporting a causal link between autoimmunity and aberrant behavior. Consequently, 3xTg-AD mice may be a useful model in elucidating the role of immune system in the etiology of AD. PMID:24150111

  6. Immunogenomics reveal molecular circuits of diclofenac induced liver injury in mice

    PubMed Central

    Lee, Eun-Hee; Oh, Jung-Hwa; Selvaraj, Saravanakumar; Park, Se-Myo; Choi, Mi-Sun; Spanel, Reinhard

    2016-01-01

    Diclofenac is a non-steroidal anti-inflammatory drug and its use can be associated with severe adverse reactions, notably myocardial infarction, stroke and drug-induced liver injury (DILI). In pursue of immune-mediated DILI mechanisms an immunogenomic study was carried out. Diclofenac treatment of mice at 30 mg/kg for 3 days caused significant serum ALT and AST elevations, hepatomegaly and degenerative changes including hepatic glycogen depletion, hydropic swelling, cholesterolosis and eosinophilic hepatocytes with one animal presenting subsegmental infarction due to portal vein thrombosis. Furthermore, portal/periportal induction of the rate limiting enzyme in ammonia detoxification, i.e. carbamoyl phosphate synthetase 1 was observed. The performed microarray studies informed on > 600 differential expressed genes of which 35, 37 and 50 coded for inflammation, 51, 44 and 61 for immune and 116, 129 and 169 for stress response, respectively after single and repeated dosing for 3 and 14 days. Bioinformatic analysis defined molecular circuits of hepatic inflammation with the growth hormone (Ghr)− and leptin receptor, the protein-tyrosine-phosphatase, selectin and the suppressor-of-cytokine-signaling (Socs) to function as key nodes in gene regulatory networks. Western blotting confirmed induction of fibronectin and M-CSF to hallmark tissue repair and differentiation of monocytes and macrophages. Transcript expression of the macrophage receptor with collagenous structure increased > 7-fold and immunohistochemistry of CD68 evidenced activation of tissue-resident macrophages. Importantly, diclofenac treatment prompted strong expression of phosphorylated Stat3 amongst individual animals and the associated 8- and 4-fold Soc3 and Il-6 induction reinforced Ghr degradation as evidenced by immunoblotting. Moreover, immunohistochemistry confirmed regulation of master regulatory proteins of diclofenac treated mice to suggest complex pro-and anti-inflammatory reactions in immune

  7. Ferrokinetic study of splenic erythropoiesis: Relationships among clinical diagnosis, myelofibrosis, splenomegaly, and extramedullary erythropoiesis

    SciTech Connect

    Beguin, Y.; Fillet, G.; Bury, J.; Fairon, Y. )

    1989-10-01

    Splenic erythropoiesis was demonstrated by surface counting of {sup 59}Fe in 129 of 1,350 ferrokinetic studies performed over a 15 year period. These 129 studies were carried out in 108 patients, including 40 with chronic myelogenous leukemia (CML), 24 with agnogenic myeloid metaplasia (AMM), 18 with polycythemia vera (PV), six with a myelodysplastic syndrome, five with acute leukemia, three with prostate or breast carcinoma, two each with aplastic anemia or Hodgkin's disease, and one each with idiopathic thrombocythemia, multiple myeloma, chronic renal failure, or treated hypopituitarism. Splenomegaly was present in 83% of the studies and hepatomegaly in 72%. Grade II-III myelofibrosis was demonstrated in 62% of the cases. Hepatic erythropoiesis was present in 77% of the studies (only 38% in PV), and marrow erythropoiesis was undetectable in 33%. Total erythropoiesis was about twice normal (range 0.2 to 8 times normal) but was ineffective to varying degrees in 86% of the studies. Relationships between organomegaly, myelofibrosis, and extramedullary erythropoiesis, as well as differences among clinical disorders, are discussed. Differences observed between CML in chronic or blastic phase suggested that the erythroid cell line was involved in the proliferative process. It is concluded that splenic erythropoiesis (1) is encountered in a variety of clinical conditions; (2) is not necessarily associated with splenomegaly or myelofibrosis, even in the myeloproliferative disorders; (3) is part of a predominantly extramedullary (in the liver as well as in the spleen), expanded, and largely inefficient total erythropoiesis; and (4) can be evaluated in a semiquantitative manner by surface counting.

  8. The PPAR alpha-humanized mouse: a model to investigate species differences in liver toxicity mediated by PPAR alpha.

    PubMed

    Yang, Qian; Nagano, Tomokazu; Shah, Yatrik; Cheung, Connie; Ito, Shinji; Gonzalez, Frank J

    2008-01-01

    To determine the impact of the species difference between rodents and humans in response to peroxisome proliferators (PPs) mediated by peroxisome proliferator-activated receptor (PPAR)alpha, PPAR alpha-humanized transgenic mice were generated using a P1 phage artificial chromosome (PAC) genomic clone bred onto a ppar alpha-null mouse background, designated hPPAR alpha PAC. In hPPAR alpha PAC mice, the human PPAR alpha gene is expressed in tissues with high fatty acid catabolism and induced upon fasting, similar to mouse PPAR alpha in wild-type (Wt) mice. Upon treatment with the PP fenofibrate, hPPAR alpha PAC mice exhibited responses similar to Wt mice, including peroxisome proliferation, lowering of serum triglycerides, and induction of PPAR alpha target genes encoding enzymes involved in fatty acid metabolism in liver, kidney, and heart, suggesting that human PPAR alpha (hPPAR alpha) functions in the same manner as mouse PPAR alpha in regulating fatty acid metabolism and lowering serum triglycerides. However, in contrast to Wt mice, treatment of hPPAR alpha PAC mice with fenofibrate did not cause significant hepatomegaly and hepatocyte proliferation, thus indicating that the mechanisms by which PPAR alpha affects lipid metabolism are distinct from the hepatocyte proliferation response, the latter of which is only induced by mouse PPAR alpha. In addition, a differential regulation of several genes, including the oncogenic let-7C miRNA by PPs, was observed between Wt and hPPAR alpha PAC mice that may contribute to the inherent difference between mouse and human PPAR alpha in activation of hepatocellular proliferation. The hPPAR alpha PAC mouse model provides an in vivo platform to investigate the species difference mediated by PPAR alpha and an ideal model for human risk assessment PPs exposure.

  9. Results of miconazole therapy in twenty-eight patients with paracoccidioidomycosis (South American blastomycosis).

    PubMed Central

    Negroni, R; Rubinstein, P; Herrmann, A; Gimenez, A

    1977-01-01

    Results are presented of treatment with miconazole, orally and intravenously, in patients with paracoccidioidomycosis. Twenty-eight male patients aged from 34 to 66 years and exhibiting various clinical forms of the disease were studied. Twenty-five came from endemic areas in north east Argentina (Chaco, Formosa, Misiones, Corrientes and northern Santa Fe) and the remaining three from Paraguay. Twenty patients were engaged in agricultural work or at woodmills. single or multiple lesions were observed in 24 cases. Thirteen were suffering from infection of the larynx and in two of them a tracheotomy was necessary. Twenty-three showed pulmonary lesions on X-rays. Twelve had ganglionic lesions, eight had cutaneous lesions and one patient had osteoarthritis of the knee. One patient had hepatomegaly which was unrelated to chronic alcoholism. Fourteen patients had received previous treatments such as sulphonamides and amphotericin B (7 cases); sulphonamides (3), sulphonamides and the combination sulfamethoxazole + trimethoprim (3), and one patient had received all three medications. All patients had relapsed before starting miconazole therapy. Diagnosis was established by the presence of P. brasiliensis in all cases, recovered either from cutaneous or mucosal biopsy samples or from the sputum. Complement fixation tests were positive in all patients at the onset of the treatment and the immunodiffusion reactions showed precipitation bands in 27/28 patients. Skin tests with P. brasiliensis antigens proved to be positive in 18 cases and negative in 10. The erythrocyte sedimentation rate was markedly accelerated in 22 patients (greater than 20 mm in the first hour).(ABSTRACT TRUNCATED AT 250 WORDS) Images p24-a Fig 1 Fig 2 PMID:122643

  10. X-linked lymphoreticular disease in the scurfy (sf) mutant mouse.

    PubMed

    Godfrey, V L; Wilkinson, J E; Russell, L B

    1991-06-01

    Scurfy (sf) is a spontaneous, sex-linked, recessive mutation that maps to the extreme proximal portion of the X chromosome, about 2 centimorgans from sparse fur (spf). Hemizygotes for sf manifest several clinical disorders, evident at 14 days of age, including scaliness and crusting of the eyelids, ears, and tail, runting, reddening and swelling of the genital papilla, anemia, cachexia, and early death (average, 24 days). Our studies indicate that the phenotype of hemizygous scurfy is not, as has been suggested, a model for human X-linked ichthyosis, but appears to be a disease primarily affecting the lymphoreticular, and possibly the hematopoietic, systems. Gross lesions include marked splenomegaly, hepatomegaly, enlarged lymph nodes, and variable thickening of the ears. The characteristic histologic lesion is a lymphohistiocytic proliferation and infiltration of peripheral lymph nodes, spleen, liver, and skin. In routine hematoxylin and eosin-stained sections, these lesions efface lymph node architecture, thicken the dermis, and form nodular portal infiltrates in the liver. Scurfy lesions characteristically contain a population of large blastlike cells with round to oval nuclei, a vesicular chromatin pattern, and prominent single nucleoli. Mixed perivascular infiltrates of lymphocytes, macrophages, and granulocytes sometimes are found in kidney, heart, pancreas, lung, and mesenteries. There is excessive hematopoiesis in the liver and spleen. Cells expressing B220 or Thy-1 antigens localize to appropriate areas in the lymph nodes and spleen, but are rare in the portal infiltrates and are absent from the skin. There is a marked, polyclonal increase in serum IgG, severe Coombs'-positive anemia, and leukocytosis with atypical mononuclear cells. Scurfy mice are negative for antinuclear antibodies. Despite their morphologically aberrant lymphoreticular system, scurfy mice can exist in a conventional environment without evidence of opportunistic infection. Raising

  11. Clearance of Hepatic Sphingomyelin by Olipudase Alfa Is Associated With Improvement in Lipid Profiles in Acid Sphingomyelinase Deficiency

    PubMed Central

    Wasserstein, Melissa P.; Jones, Simon A.; Schiano, Thomas D.; Cox, Gerald F.; Puga, Ana Cristina

    2016-01-01

    Acid sphingomyelinase deficiency (ASMD; Niemann-Pick disease type A and B) is a lysosomal storage disorder characterized by abnormal intracellular sphingomyelin (SM) accumulation. Prominent liver involvement results in hepatomegaly, fibrosis/cirrhosis, abnormal liver chemistries, and a proatherogenic lipid profile. Olipudase alfa (recombinant human ASM) is in clinical development as an investigational enzyme replacement therapy for the non-neurological manifestations of ASMD. In a phase 1b study conducted to evaluate the safety and tolerability of within-patient dose escalation with olipudase alfa, measurement of SM levels in liver biopsies was used as a pharmacodynamic biomarker of substrate burden. Five adult patients with non neuronopathic ASMD received escalating doses of olipudase alfa every 2 weeks for 26 weeks. Liver biopsies obtained at baseline and 26 weeks after treatment were evaluated for SM storage by histomorphometric analysis, biochemistry, and electron microscopy. Biopsies were also assessed for inflammation and fibrosis, and for the association of SM levels with liver volume, liver function tests, and lipid profiles. At baseline, SM storage present in Kupffer cells and hepatocytes ranged from 9.8% to 53.8% of the microscopic field. After 26 weeks of treatment, statistically significant reductions in SM (P<0.0001) measured by morphometry were seen in 4 patients with evaluable liver biopsies. The 26-week biopsy of the fifth patient was insufficient for morphometric quantitation. Posttreatment SM levels ranged from 1.2% to 9.5% of the microscopic field, corresponding to an 84% to 92% relative reduction from baseline. Improvements in liver volume, liver function tests, and lipid profiles were also observed. This study illustrates the utility of SM assessment by liver biopsy as a pharmacodynamic biomarker of disease burden in these patients. PMID:27340749

  12. Opuntia ficus indica (nopal) attenuates hepatic steatosis and oxidative stress in obese Zucker (fa/fa) rats.

    PubMed

    Morán-Ramos, Sofía; Avila-Nava, Azalia; Tovar, Armando R; Pedraza-Chaverri, José; López-Romero, Patricia; Torres, Nimbe

    2012-11-01

    Nonalcoholic fatty liver disease (NAFLD) is associated with multiple factors such as obesity, insulin resistance, and oxidative stress. Nopal, a cactus plant widely consumed in the Mexican diet, is considered a functional food because of its antioxidant activity and ability to improve biomarkers of metabolic syndrome. The aim of this study was to assess the effect of nopal consumption on the development of hepatic steatosis and hepatic oxidative stress and on the regulation of genes involved in hepatic lipid metabolism. Obese Zucker (fa/fa) rats were fed a control diet or a diet containing 4% nopal for 7 wk. Rats fed the nopal-containing diet had ∼50% lower hepatic TG than the control group as well as a reduction in hepatomegaly and biomarkers of hepatocyte injury such as alanine and aspartate aminotransferases. Attenuation of hepatic steatosis by nopal consumption was accompanied by a higher serum concentration of adiponectin and a greater abundance of mRNA for genes involved in lipid oxidation and lipid export and production of carnitine palmitoyltransferase-1 and microsomal TG transfer proteins in liver. Hepatic reactive oxygen species and lipid peroxidation biomarkers were significantly lower in rats fed nopal compared with the control rats. Furthermore, rats fed the nopal diet had a lower postprandial serum insulin concentration and a greater liver phosphorylated protein kinase B (pAKT):AKT ratio in the postprandial state. This study suggests that nopal consumption attenuates hepatic steatosis by increasing fatty acid oxidation and VLDL synthesis, decreasing oxidative stress, and improving liver insulin signaling in obese Zucker (fa/fa) rats.

  13. Risk Factors for Insulin Resistance, Metabolic Syndrome, and Diabetes in 248 HFE C282Y Homozygotes Identified by Population Screening in the HEIRS Study

    PubMed Central

    Barton, J. Clayborn; Adams, Paul C.; Acton, Ronald T.

    2016-01-01

    Abstract Background: We sought to identify risk factors for insulin resistance, metabolic syndrome (MetS), and diabetes mellitus in 248 non-Hispanic white HFE C282Y homozygotes identified by population screening. Methods: We analyzed observations obtained prospectively in a postscreening examination: age; sex; body mass index (BMI); systolic/diastolic blood pressure; metacarpophalangeal (MP) joint hypertrophy; hepatomegaly; complete blood counts; alanine/aspartate aminotransferase levels; elevated C-reactive protein (>0.5 mg/dL); transferrin saturation; serum ferritin; homeostasis model assessment-insulin resistance (HOMA-IR); and MetS. Results: Twenty-six participants (10.5%) had diabetes diagnoses. A significant trend across HOMA-IR quartiles was observed only for blood neutrophils. Logistic regression on HOMA-IR fourth quartile revealed positive associations: age (P = 0.0002); male sex (P = 0.0022); and BMI (P < 0.0001). HOMA-IR fourth quartile predicted MetS (P < 0.0001). Logistic regression on diabetes revealed positive associations: age (P = 0.0012); male sex (P = 0.0068); MP joint hypertrophy (P = 0.0167); neutrophils (P = 0.0342); and MetS (P = 0.0298). Serum ferritin did not predict HOMA-IR fourth quartile, MetS, or diabetes. Conclusions: In screening C282Y homozygotes, age, male sex, and BMI predicted HOMA-IR fourth quartile. HOMA-IR fourth quartile alone predicted MetS. Diabetes was associated with greater age, male sex, MP joint hypertrophy, greater blood neutrophil counts, and MetS. PMID:26771691

  14. New case of mitochondrial HMG-CoA synthase deficiency. Functional analysis of eight mutations.

    PubMed

    Ramos, Mónica; Menao, Sebastián; Arnedo, María; Puisac, Beatriz; Gil-Rodríguez, María Concepción; Teresa-Rodrigo, María Esperanza; Hernández-Marcos, María; Pierre, Germaine; Ramaswami, Uma; Baquero-Montoya, Carolina; Bueno, Gloria; Casale, Cesar; Hegardt, Fausto G; Gómez-Puertas, Paulino; Pié, Juan

    2013-08-01

    Mitochondrial HMG-CoA synthase deficiency is a rare inherited metabolic disorder that affects ketone-body synthesis. Acute episodes include vomiting, lethargy, hepatomegaly, hypoglycaemia, dicarboxylic aciduria, and in severe cases, coma. This deficiency may have been under-diagnosed owing to the absence of specific clinical and biochemical markers, limitations in liver biopsy and the lack of an effective method of expression and enzyme assay for verifying the mutations found. To date, eight patients have been reported with nine allelic variants of the HMGCS2 gene. We present a new method of enzyme expression and a modification of the activity assay that allows, for first time, the functional study of missense mutations found in patients with this deficiency. Four of the missense mutations (p.V54M, p.R188H, p.G212R and p.G388R) did not produce proteins that could have been detected in soluble form by western blot; three produced a total loss of activity (p.Y167C, p.M307T and p.R500H) and one, variant p.F174L, gave an enzyme with a catalytic efficiency of 11.5%. This indicates that the deficiency may occur with partial loss of activity of enzyme. In addition, we describe a new patient with this deficiency, in which we detected the missense allelic variant, c.1162G>A (p.G388R) and the nonsense variant c.1270C>T (p.R424X).

  15. Predictors of Non-alcoholic Fatty Liver Disease in Obese and Overweight Egyptian Children: Single Center Study

    PubMed Central

    El-Karaksy, Hanaa M.; El-Koofy, Nehal M.; Anwar, Ghada M.; El-Mougy, Fatma M.; El-Hennawy, Ahmed; Fahmy, Mona E.

    2011-01-01

    Background/Aim: Pediatric non-alcoholic fatty liver disease (NAFLD) is a global problem which has been increasingly recognized with the dramatic rise in pediatric obesity. The aim of the present study was to identify the clinical, sonographic, and biochemical predictors for NAFLD in obese children. Materials and Methods: Seventy-six children (2-15 years) were included after an informed consent. All were subjected to full anthropometric assessment (including height, weight, body mass index, subscapular skin fold thickness, waist and hip circumference and calculation of waist: hip ratio), biochemical assessment of liver function tests, lipid profile and insulin resistance and sonographic assessment of hepatic echogenicity. Liver biopsy when indicated, was done in 33 patients. Results: Sixteen patients (21%) had elevated ALT and 6 (7.9%) had elevated AST. Significant dyslipidemia (low HDL-c, high total cholesterol, high LDL-c and triglycerides) and higher insulin resistance were found in obese patients (P<0.01). The main sonographic findings were hepatomegaly in 20 patients (26.3%) and echogenic liver in 41 patients (53.9%). Liver biopsy showed simple steatosis in eight cases (24.2%) and non-alcoholic steatohepatitis (NASH) in seven cases (21.2%). Anthropometric measurements, increased hepatic echogenicty by ultrasound, insulin resistance and lipid profile were good predictors of NAFLD in obese children if assessed together. However, LDL-c was the only sensitive predictor (independent variable) for NAFLD in both uni- and multivariate logistic regression analyses. Conclusion: Dyslipidemia per se is a strong predictor of NAFLD among obese Egyptian children. PMID:21196652

  16. The etiology of hypertransaminasemia in Turkish children.

    PubMed

    Serdaroğlu, Filiz; Koca, Tuğba; Dereci, Selim; Akçam, Mustafa

    2016-02-19

    The aim of this study was to investigate the causes of elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in children. We analyzed the medical records for children aged 3 months to 18 years who presented to the hospital with ALT >45 IU/L and/or AST >50 IU/L, between 2012 and 2014, for various reasons, including those not related to liver disease. In total, 281 children met the study criteria. This group comprised of 125 (44.5%) females and 156 (55.5%) males. At the presentation, the most common patient complaint was fatigue (53.4%), while 15.7% of the patients reported no symptoms. The most common findings on the physical examination were jaundice and hepatomegaly. In 15% of the cases, the findings were normal. According to the diagnosis, the most common cause of the elevated transaminases were infections (34%), with hepatitis A virus (HAV) infection as the leading cause (18.9%). Drug-induced liver injury (DILI) was the cause in 18.1% of the cases and non-alcoholic fatty liver disease (NAFLD) in 11.1%. The highest transaminase levels were associated with HAV infection, while DILI and NAFLD caused only slightly elevated transaminases. Overall, our results show that the elevated transaminases in children are most often caused by infections, DILI, and NAFLD. In a majority of cases, elevated ALT and AST indicate liver disease, however, they could also be associated with conditions other than liver damage. Additionally, the elevated enzymes can be detected in completely healthy individuals.

  17. Radioembolization as Locoregional Therapy of Hepatic Metastases in Uveal Melanoma Patients

    SciTech Connect

    Klingenstein, A.; Haug, A. R.; Zech, C. J.; Schaller, U. C.

    2013-02-15

    To retrospectively evaluate the overall survival, safety, and efficacy of metastatic uveal melanoma patients after radioembolization as salvage therapy. Thirteen patients were treated with radioembolization of branches of the hepatic artery with resin-based yttrium-90 ({sup 90}Y)-labelled microspheres. Twelve patients underwent a single application, and 1 patient underwent 4 interventions. Dosages from 644 to 2,450 MBq (mean activity 1,780) were applied. Treatment response was evaluated by way of liver magnetic resonance imaging and computed tomography (CT) as well as whole-body fluorodeoxyglucose positron emission tomography (PET)/CT with evaluation of percentage changes in SUV{sub max} before and at 2-3 months after therapy. Kaplan-Meier analysis was calculated to determine overall survival. Partial remission (PR) was observed in 8 (62 %), stable disease (SD) in 2 (15 %), and progressive disease (PD) in 3 (23 %) patients under terms of standard criteria and PR in 3 (23 %), SD in 3 (23 %), and PD in 7 (54 %) patients according to PET criteria. Neither RECIST nor PET criteria showed a significant difference in predicting overall survival (P = 0.12 and 0.11, respectively). Median survival time after radioembolization was 7 months. No acute toxicity with in-hospital morbidity was observed. One patient developed hepatomegaly, and 1 patient developed gastric ulceration. Throughout follow-up, progression of extrahepatic metastases was observed. Radioembolization may be a promising therapy in uveal melanoma patients with predominant hepatic metastases. At first follow-up, we observed PR or SD in 77 % patients under terms of standard criteria with an acceptable toxicity profile.

  18. Duck viral enteritis in domestic muscovy ducks in Pennsylvania

    USGS Publications Warehouse

    Davison, S.; Converse, K.A.; Hamir, A.N.; Eckroade, R.J.

    1993-01-01

    Duck viral enteritis (DVE) outbreaks occurred at two different locations in Pennsylvania in 1991 and 1992. In the first outbreak, four ducks died out of a group of 30 domestic ducks; in the second outbreak, 65 ducks died out of a group of 114 domestic ducks, and 15 domestic geese died as well. A variety of species of ducks were present on both premises, but only muscovy ducks (Cairina moschata) died from the disease. On necropsy, gross lesions included hepatomegaly with petechial hemorrhages, petechial hemorrhages in the abdominal fat, petechial hemorrhages on the epicardial surface of the heart, and multifocal to coalescing areas of fibrinonecrotic material over the mucosal surface of the trachea, esophagus, intestine, and cloaca. Histologically, the liver had random multifocal areas of necrosis and eosinophilic intranuclear inclusion bodies in hepatocytes. DVE virus was isolated and identified using muscovy duck embryo fibroblast inoculation and virus neutralization. /// En dos sitios diferentes se presentaron brotes de enteritis viral de los patos en el estados de Pensilvania en los a??os 1991 y 1992. En el primer brote, cuatro de un lote de 30 patos murieron mientras que en el segundo brote murieron 65 patos de un lote de 114 patos y 15 gansos. En ambas localidades exist?-a una variedad de especies de patos, sin embargo, s??lamente los patos almizcleros (Cairina moschata) murieron. A la necropsia, las lesiones macrosc??picas incluyeron hepatomegalia con hemorragias petequiales, hemorragias petequiales en la grasa abdominal y en la superficie del epicardio, y ?!reas multifocales o coalescentes de material fibrinonecr??tico sobre la superficie de la mucosa de la tr?!quea, es??fago, intestino y cloaca. Histol??gicamente, el h?-gado mostraba ?!reas multifocales de necrosis y cuerpos de inclusi??n intranucleares eosinof?-licos en los hepatocitos. El virus de la enteritis viral de los patos fue aislado e identificado usando fibroblasto de embriones de pato almizclero

  19. Effect of Dietary Cocoa Tea (Camellia ptilophylla) Supplementation on High-Fat Diet-Induced Obesity, Hepatic Steatosis, and Hyperlipidemia in Mice

    PubMed Central

    Yang, Xiao Rong; Wat, Elaine; Wang, Yan Ping; Ko, Chun Hay; Koon, Chi Man; Siu, Wing Sum; Gao, Si; Cheung, David Wing Shing; Lau, Clara Bik San; Ye, Chuang Xing; Leung, Ping Chung

    2013-01-01

    Recent studies suggested that green tea has the potential to protect against diet-induced obesity. The presence of caffeine within green tea has caused limitations. Cocoa tea (Camellia ptilophylla) is a naturally decaffeinated tea plant. To determine whether cocoa tea supplementation results in an improvement in high-fat diet-induced obesity, hyperlipidemia and hepatic steatosis, and whether such effects would be comparable to those of green tea extract, we studied six groups (n = 10) of C57BL/6 mice that were fed with (1) normal chow (N); (2) high-fat diet (21% butterfat + 0.15% cholesterol, wt/wt) (HF); (3) a high-fat diet supplemented with 2% green tea extract (HFLG); (4) a high-fat diet supplemented with 4% green tea extract (HFHG); (5) a high-fat diet supplemented with 2% cocoa tea extract (HFLC); and (6) a high-fat diet supplemented with 4% cocoa tea extract (HFHC). From the results, 2% and 4% dietary cocoa tea supplementation caused a dose-dependent decrease in (a) body weight, (b) fat pad mass, (c) liver weight, (d) total liver lipid, (e) liver triglyceride and cholesterol, and (f) plasma lipids (triglyceride and cholesterol). These data indicate that dietary cocoa tea, being naturally decaffeinated, has a beneficial effect on high-fat diet-induced obesity, hepatomegaly, hepatic steatosis, and elevated plasma lipid levels in mice, which are comparable to green tea. The present findings have provided the proof of concept that dietary cocoa tea might be of therapeutic value and could therefore provide a safer and cost effective option for patients with diet-induced metabolic syndrome. PMID:23935682

  20. Antihyperglycemia and Antihyperlipidemia Effect of Protoberberine Alkaloids From Rhizoma Coptidis in HepG2 Cell and Diabetic KK-Ay Mice.

    PubMed

    Ma, Hang; Hu, Yinran; Zou, Zongyao; Feng, Min; Ye, Xiaoli; Li, Xuegang

    2016-06-01

    Preclinical Research Rhizoma Coptidis (RC), the root of Coptis chinensis Franch, a species in the genus Coptis (family Ranunculaceae), has been commonly prescribed for the treatment of diabetes in Chinese traditional herbal medicine applications. The present study is focused on the assessment of the antihyperglycemia and antidiabetic hyperlipidemia effect of five protoberberine alkaloids, berberine (BBR), coptisine (COP), palmatine (PAL), epiberberine (EPI), and jatrorrhizine (JAT), separated from R. Coptidis in hepatocellular carcinoma HepG2 cells and diabetic KK-Ay mice. Protoberberine alkaloids are effective in modulating hyperglycemia and hyperlipidemia. After adding BBR and COP to culture medium, glucose consumption of HepG2 cells was increased. In KK-Ay mice assays, suppressed fasting blood glucose level and ameliorated glucose tolerance were observed after BBR/COP administration. After treated with berberine and coptisine, in the same dose of 5 µg/mL, the glucose consumption of HepG2 cells were promoted and, respectively, reached 96.1% and 17.6%. Body weight, food consumption, water intake, and urinary output of KK-Ay mice were reduced after treated with EPI. Serum total cholesterol and triglyceride of mice were decreased after treated with palmatine and jatrorrhizine. Serum high-density lipoprotein cholesterol of mice was increased after palmatine, jatrorrhizine, and berberine administrated. Moreover, hepatomegaly was attenuated in JTR-treated mice. Suggested that these protoberberine alkaloids from R. Coptidis have potential curative effect for diabetes. Drug Dev Res 77 : 163-170, 2016.   © 2016 Wiley Periodicals, Inc.

  1. Deregulation of Fas ligand expression as a novel cause of autoimmune lymphoproliferative syndrome-like disease.

    PubMed

    Nabhani, Schafiq; Ginzel, Sebastian; Miskin, Hagit; Revel-Vilk, Shoshana; Harlev, Dan; Fleckenstein, Bernhard; Hönscheid, Andrea; Oommen, Prasad T; Kuhlen, Michaela; Thiele, Ralf; Laws, Hans-Jürgen; Borkhardt, Arndt; Stepensky, Polina; Fischer, Ute

    2015-09-01

    Autoimmune lymphoproliferative syndrome is frequently caused by mutations in genes involved in the Fas death receptor pathway, but for 20-30% of patients the genetic defect is unknown. We observed that treatment of healthy T cells with interleukin-12 induces upregulation of Fas ligand and Fas ligand-dependent apoptosis. Consistently, interleukin-12 could not induce apoptosis in Fas ligand-deficient T cells from patients with autoimmune lymphoproliferative syndrome. We hypothesized that defects in the interleukin-12 signaling pathway may cause a similar phenotype as that caused by mutations of the Fas ligand gene. To test this, we analyzed 20 patients with autoimmune lymphoproliferative syndrome of unknown cause by whole-exome sequencing. We identified a homozygous nonsense mutation (c.698G>A, p.R212*) in the interleukin-12/interleukin-23 receptor-component IL12RB1 in one of these patients. The mutation led to IL12RB1 protein truncation and loss of cell surface expression. Interleukin-12 and -23 signaling was completely abrogated as demonstrated by deficient STAT4 phosphorylation and interferon γ production. Interleukin-12-mediated expression of membrane-bound and soluble Fas ligand was lacking and basal expression was much lower than in healthy controls. The patient presented with the classical symptoms of autoimmune lymphoproliferative syndrome: chronic non-malignant, non-infectious lymphadenopathy, splenomegaly, hepatomegaly, elevated numbers of double-negative T cells, autoimmune cytopenias, and increased levels of vitamin B12 and interleukin-10. Sanger sequencing and whole-exome sequencing excluded the presence of germline or somatic mutations in genes known to be associated with the autoimmune lymphoproliferative syndrome. Our data suggest that deficient regulation of Fas ligand expression by regulators such as the interleukin-12 signaling pathway may be an alternative cause of autoimmune lymphoproliferative syndrome-like disease.

  2. Interferon-γ-induced protein 10 in Dengue Virus infection.

    PubMed

    Fallahi, P; Elia, G

    2016-01-01

    Dengue virus (DENV) infection causes dengue fever, dengue hemorrhagic fever, or dengue shock syndrome. Interferons (IFNs), and IFN-γ dependent chemokines, chemokine (C-X-C motif) ligand (CXCL)10/IFN-γ-induced protein 10 (IP-10), CXCL9/MIG and CXCL11/I-TAC, and their common receptor chemokine (C-X-C motif) receptor (CXCR)3 are induced by DENV infection; however it has been shown that the latter two could not compensate for the absence of IP-10. This paper reviews studies about DENV and IP-10. Evidences show the importance of IP-10 induction during DENV infection, in macrophages, lymphocytes, hepatic cells, denritic cells, in skin and in the brain. Furthermore it has been shown that chemokines IP-10, I-TAC and their receptor CXCR3 are involved in severity of dengue; in fact, pulmonary effusion or ascites, painful hepatomegaly or aspartate aminotransferase increase, are correlated with IP-10 levels. It has been also demonstrated that IP-10 was more elevated in subjects who subsequently developed dengue hemorrhagic fever or dengue shock syndrome. It has been also shown that IP-10 has a direct action in control of dengue viral replication. Furthermore IP-10 circulating levels may be used to discriminate dengue fever from other febbrile diseases. This is of particular importance in certain situations, for example to discriminate occupationally acquired dengue, in patients with febbrile disorders coming from endemic countries. These studies suggested that these chemokines can be used as potential biomarkers for differential diagnosis and the disease progression, while others can be used to control dengue viral replication, thus representing a viable targets for drug therapy.

  3. Inclusion body hepatitis associated with an outbreak of fowl adenovirus type 2 and type 8b in broiler flocks in South Africa.

    PubMed

    Maartens, Louis H; Joubert, Hilda W; Aitchison, Henry; Venter, Estelle H

    2014-12-02

    Inclusion body hepatitis is an acute disease of chickens ascribed to viruses of the genus Aviadenovirus and referred to as fowl adenovirus (FAdV). There are 12 FAdV types (FAdV1to FAdV8a and FAdV8b to FAdV11), classified into five species based on their genotype (designated FAdVA to FAdVE). A total of 218 000 chickens, 2-29 days of age, were affected over a 1-year period, all testing positive by microscopy, virus isolation and confirmation with polymerase chain reaction (PCR). Affected birds were depressed, lost body weight,were weak and had watery droppings. Pathological changes observed during necropsy indicated consistent changes in the liver, characterised by hepatomegaly, cholestasis and hepatitis. Lesions were also discernible in the spleen, kidney and gizzard wall and were characterised by splenomegaly, pinpoint haemorrhages, nephritis with haemorrhage,visceral gout and serosal ecchymosis of the gizzard wall. Histopathological lesions were most consistently observed in the liver but could also be seen in renal and splenic tissue. Virus isolation was achieved in embryonated eggs and most embryos revealed multifocalto diffuse hepatic necrosis, with a mixed cellular infiltrate of macrophages and heterophils(necro-granulomas), even in the absence of macroscopic pathology. Virus isolation results were verified by histopathology and PCR on embryonic material and further characterised by nucleotide sequence analysis. Two infectious bursal disease virus isolates were also made from the Klerksdorp flock. Nucleotide sequence analysis of the L1 hexon loop of all the FAdV isolates indicated homology (99%) with prototype strains P7-A for FAdV-2, as well as for FAdV-8b.

  4. Treatment of progressive familial intrahepatic cholestasis: liver transplantation or partial external biliary diversion.

    PubMed

    Ismail, H; Kaliciński, P; Markiewicz, M; Jankowska, I; Pawłowska, J; Kluge, P; Eliadou, E; Kamiński, A; Szymczak, M; Drewniak, T; Revillon, Y

    1999-08-01

    Progressive intrahepatic familial cholestasis (PFIC), previously called Byler's disease, is a syndrome in which children develop severe cholestasis progressing to biliary cirrhosis and chronic liver failure, usually during the first decade of life. Clinical features include jaundice, hepatomegaly, splenomegaly, growth retardation and severe pruritus. Laboratory tests demonstrate elevated bilirubin and bile acids, without an increase in serum gamma-glutamyl-transpeptidase or cholesterol. This study was performed to evaluate our experience with medical therapy as well as two types of surgical treatment used in children with PFIC, particularly partial external biliary diversion (PEBD) as an alternative method of therapy to liver transplantation (OLTx). Between 1979 and 1998 we have treated 46 children with PFIC (27 boys and 19 girls), aged 10 months to 19 yr (at the time of this study). Medical treatment with ursodeoxycholic (UDCA) was used in 39 patients for the period between 6 and 82 months. PEBD (cholecysto-jejuno-cutaneostomy) was performed in 16 patients, OLTx in eight children (including one after unsuccessful PEBD). Retrospective analysis of the clinical course and selected laboratory tests (bilirubin, ASPAT, ALAT, bile acids), and histopathological examinations were performed. Results of treatment were assessed by means of influence of the type of treatment on clinical symptoms, laboratory tests, progress of liver cirrhosis and hepatic failure, as well as physical development and survival. Medical therapy was effective in the long term in four (10%) of the patients resulting in clinical and biochemical normalization. Both surgical methods of therapy of PFIC, PEBD and OLTx, resulted in an 80% success rate and therefore should be used as complementary therapies. In patients before established liver cirrhosis, PEBD should be the first choice of treatment. Patients presenting with cirrhosis or after ineffective PEBD should qualify for OLTx. With this strategy

  5. Fbxw7 regulates lipid metabolism and cell fate decisions in the mouse liver

    PubMed Central

    Onoyama, Ichiro; Suzuki, Atsushi; Matsumoto, Akinobu; Tomita, Kengo; Katagiri, Hideki; Oike, Yuichi; Nakayama, Keiko; Nakayama, Keiichi I.

    2010-01-01

    E3 ubiquitin ligase complexes of the SCF type consist of ring-box 1 (Rbx1), cullin 1 (Cul1), S-phase kinase-associated protein 1 (Skp1), and a member of the F-box family of proteins. The identity of the F-box protein determines the substrate specificity of the complex. The F-box family member F-box– and WD repeat domain–containing 7 (Fbxw7; also known as Fbw7, SEL-10, hCdc4, and hAgo) targets for degradation proteins with wide-ranging functions, and uncovering its in vivo role has been difficult, because Fbxw7–/– embryos die in utero. Using two different Cre-loxP systems (Mx1-Cre and Alb-Cre), we generated mice with liver-specific null mutations of Fbxw7. Hepatic ablation of Fbxw7 resulted in hepatomegaly and steatohepatitis, with massive deposition of triglyceride, a phenotype similar to that observed in humans with nonalcoholic steatohepatitis. Both cell proliferation and the abundance of Fbxw7 substrates were increased in the Fbxw7-deficient liver. Long-term Fbxw7 deficiency resulted in marked proliferation of the biliary system and the development of hamartomas. Fbxw7 deficiency also skewed the differentiation of liver stem cells toward the cholangiocyte lineage rather than the hepatocyte lineage in vitro. This bias was corrected by additional loss of the Notch cofactor RBP-J, suggesting that Notch accumulation triggered the abnormal proliferation of the biliary system. Together, our results suggest that Fbxw7 plays key roles, regulating lipogenesis and cell proliferation and differentiation in the liver. PMID:21123947

  6. Methylmalonic acidemia mimicking diabetic ketoacidosis in an infant.

    PubMed

    Guven, A; Cebeci, N; Dursun, A; Aktekin, Eh; Baumgartner, Mr; Fowler, B

    2012-09-01

    Methylmalonic acidemia (MMA) is an inherited organic acidemia usually present with recurrent episodes of acute illness. A typical episode is ushered in with ketonuria and vomiting, followed by acidosis, dehydration, and lethargy, leading, in the absence of aggressive treatment, to coma and death. We report an infant with MMA presented with diabetes symptoms. A 13-month-old girl complained of polydipsia, diuresis, and loss of weight. She had clinical signs of diabetic ketoacidosis such as dehydration, deep sighing respiration, smell of ketones, lethargy, and vomiting. Laboratory analysis showed hyperglycemia with acidosis and ketonuria. She was treated with parenteral fluid, electrolyte, and insulin infusion. Two days after her discharge, after having a meal rich in protein, she was brought unconscious with hepatomegaly, severe acidosis, ketonuria, and mild hyperammonemia. The absence of hyperglycemia and the presence of neurologic findings suggested organic acidemia. MMA was diagnosed because of methylmalonic aciduria and elevated C3 carnitine esters. Cranial magnetic resonance imaging (MRI) showed increased uptake of radiocontrast material in the basal ganglia bilaterally. A homozygous mutation in exon 4 of the MMAA gene was found in mutation analysis and confirmed the diagnosis of cblA-deficient MMA. Neurologic regression was improved with treatment of low-protein diet, vitamin B12, and l-carnitine. In patients born to consanguineous parents who admit during infancy with severe acidosis refractory to treatment, organic acidemias should be kept in mind, even they have high blood glucose. The definitive diagnosis is important because it may allow a specific treatment and a favorable evolution to prevent the sequelae.

  7. Glycogen Storage Disease type 1a – a secondary cause for hyperlipidemia: report of five cases

    PubMed Central

    2013-01-01

    Background and aims Glycogen storage disease type Ia (GSD Ia) is a rare metabolic disorder, caused by deficient activity of glucose-6-phosphatase-α. It produces fasting induced hypoglycemia and hepatomegaly, usually manifested in the first semester of life. Besides, it is also associated with growth delay, anemia, platelet dysfunction, osteopenia and sometimes osteoporosis. Hyperlipidemia and hyperuricemia are almost always present and hepatocellular adenomas and renal dysfunction frequent late complications. Methods The authors present a report of five adult patients with GSD Ia followed in internal medicine appointments and subspecialties. Results Four out of five patients were diagnosed in the first 6 months of life, while the other one was diagnosed in adult life after the discovery of hepatocellular adenomas. In two cases genetic tests were performed, being identified the missense mutation R83C in one, and the mutation IVS4-3C > G in the intron 4 of glucose-6-phosphatase gene, not previously described, in the other. Growth retardation was present in 3 patients, and all of them had anemia, increased bleeding tendency and hepatocellular adenomas; osteopenia/osteoporosis was present in three cases. All but one patient had marked hyperlipidemia and hyperuricemia, with evidence of endothelial dysfunction in one case and of brain damage with refractory epilepsy in another case. Proteinuria was present in two cases and end-stage renal disease in another case. There was a great variability in the dietary measures; in one case, liver transplantation was performed, with correction of the metabolic derangements. Conclusions Hyperlipidemia is almost always present and only partially responds to dietary and drug therapy; liver transplantation is the only definitive solution. Although its association with premature atherosclerosis is rare, there have been reports of endothelial dysfunction, raising the possibility for increased cardiovascular risk in this group of

  8. Hepatobiliary manifestations of the acquired immune deficiency syndrome.

    PubMed

    Cappell, M S

    1991-01-01

    Patients with the acquired immune deficiency syndrome (AIDS) frequently develop hepatic dysfunction. Although hepatic injury may indirectly result from malnutrition, hypotension, administered medications, sepsis, or other conditions, the hepatic injury is frequently due to opportunistic hepatic infection, directly related to AIDS. Infection with Mycobacterium avium intracellulare typically occurs in patients with advanced immunocompromise and with systemic symptoms due to widely disseminated infection. In contrast, hepatic tuberculosis often occurs with less advanced immunocompromise. Cytomegaloviral infection may produce a hepatitis. Cytomegaloviral and cryptosporidial infections have been implicated as causes of acalculous cholecystitis and of a secondary sclerosing cholangitis. About 10-20% of patients with AIDS have chronic hepatitis B infection. These patients tend to develop minimal hepatic inflammation and necrosis. The clinical findings in patients with hepatic cryptococcal infection are usually due to concomitant extrahepatic infection. Hepatic histoplasmosis usually develops as part of a widely disseminated infection with systemic symptoms. Hepatic involvement by Kaposi's sarcoma is rarely documented ante mortem because an unguided liver biopsy is an insensitive diagnostic procedure. Patients with non-Hodgkin's lymphoma of the liver typically have lymphadenopathy, hepatomegaly, and systemic symptoms. As a pragmatic approach, patients with liver dysfunction and HIV-related disease should have a sonographic or computerized tomographic examination of the liver. Patients with dilated bile ducts should undergo endoscopic retrograde cholangiopancreatography because opportunistic infection may produce biliary obstruction. Patients with a focal hepatic lesion should be considered for a guided liver biopsy. Patients with a significantly elevated serum alkaline phosphatase level should be considered for a percutaneous liver biopsy. When performed for these

  9. Polyenylphosphatidylcholine attenuates alcohol-induced fatty liver and hyperlipemia in rats.

    PubMed

    Navder, K P; Baraona, E; Lieber, C S

    1997-09-01

    Chronic administration of a soybean-derived polyenylphosphatidylcholine (PPC) extract prevents the development of cirrhosis in alcohol-fed baboons. To assess whether this phospholipid also affects earlier changes induced by alcohol consumption (such as fatty liver and hyperlipemia), 28 male rat littermates were pair-fed liquid diets containing 36% of energy either as ethanol or as additional carbohydrate for 21 d, and killed 90 min after intragastric administration of the corresponding diets. Half of the rats were given PPC (3 g/l), whereas the other half received the same amount of linoleate (as safflower oil) and choline (as bitartrate salt). PPC did not affect diet or alcohol consumption [15.4 +/- 0.5 G/(kg.d)], but the ethanol-induced hepatomegaly and the hepatic accumulation of lipids (principally triglycerides and cholesterol esters) and proteins were about half those in rats not given PPC. The ethanol-induced postprandial hyperlipemia was lower with PPC than without, despite an enhanced fat absorption and no difference in the level of plasma free fatty acids. The attenuation of fatty liver and hyperlipemia was associated with correction of the ethanol-induced inhibition of mitochondrial oxidation of palmitoyl-1-carnitine and the depression of cytochrome oxidase activity, as well as the increases in activity of serum glutamate dehydrogenase and aminotransferases. Thus, PPC attenuates early manifestations of alcohol toxicity, at least in part, by improving mitochondrial injury. These beneficial effects of PPC at the initial stages of alcoholic liver injury may prevent or delay the progression to more advanced forms of alcoholic liver disease.

  10. New diagnostic and therapeutic techniques in the management of pyogenic liver abscesses.

    PubMed Central

    Ranson, J H; Madayag, M A; Localio, S A; Spencer, F C

    1975-01-01

    An unexplained increase in the frequency of pyogenic liver abscesses of unknown etiology has, fourtunately, been paralleled by significant advances in diagnostic and therapeutic methods. This report reviews experience with 14 patients operated upon at NYU Medical Center since 1971. Eight cases (57%) were cryptogenic. Other abscesses were associated with biliary disease (3); abdominal sepsis (2); and trauma (1). Abscesses were present on hospitalization in 12 patients. Clinical findings included fever (101-108 F); 100%; leucocytosis, 71%; anorexia and vomiting, 50%; localized tenderness and hepatomegaly, 50%; hypoalbuminemia, 86%; hypocholesterolemia, 78%; elevated SGOT, 71%; and elevated aikaline phosphatase, 43%. Technetium hepatic scintiscans showed focal defects in 10 of 12 patients (83%), but did not detect multiple abscesses in 2 of these. Hepatic arteriography performed in 10 patients was highly accurate, outlining single abscesses in 6 and multiple abscesses in 4. Furthermore, in one patient a false positive scintiscan was demonstrated by negative arteriography, confirmed by autopsy. In 4 patients, arteriography indicated an abscess in the posterior-superior area of the right hepatic lobe. With precise anatomical localization, a trans-thoracic approach permitted uncomplicated drainage in each case. This approach provides excellent exposure and direct drainage for abscesses in this area. An additional therapeutic adjunct in two patients, with 4 and 11 abscesses each, was postoperative intraportal infusion of antibiotics through the umbilical vein. Thirteen patients (83%) recovered, one dying from pulmonary embolism. Primary hepatic abscesses occur with increasing frequency. Primary hepatic abscesses occur with increasing frequency. Primary hepatic abscesses occur with increasing frequency. The methods described allow more precise preoperative diagnosis and direct surgical drainage. Images Fig. 1. Fig. 2. PMID:1130869

  11. Enhanced Gastrointestinal Expression of Cytosolic Malic Enzyme (ME1) Induces Intestinal and Liver Lipogenic Gene Expression and Intestinal Cell Proliferation in Mice

    PubMed Central

    Al-Dwairi, Ahmed; Brown, Adam R.; Pabona, John Mark P.; Van, Trang H.; Hamdan, Hamdan; Mercado, Charles P.; Quick, Charles M.; Wight, Patricia A.; Simmen, Rosalia C. M.; Simmen, Frank A.

    2014-01-01

    The small intestine participates in lipid digestion, metabolism and transport. Cytosolic malic enzyme 1 (ME1) is an enzyme that generates NADPH used in fatty acid and cholesterol biosynthesis. Previous work has correlated liver and adipose ME1 expression with susceptibility to obesity and diabetes; however, the contributions of intestine-expressed ME1 to these conditions are unknown. We generated transgenic (Tg) mice expressing rat ME1 in the gastrointestinal epithelium under the control of the murine villin1 promoter/enhancer. Levels of intestinal ME1 protein (endogenous plus transgene) were greater in Tg than wildtype (WT) littermates. Effects of elevated intestinal ME1 on body weight, circulating insulin, select adipocytokines, blood glucose, and metabolism-related genes were examined. Male Tg mice fed a high-fat (HF) diet gained significantly more body weight than WT male littermates and had heavier livers. ME1-Tg mice had deeper intestinal and colon crypts, a greater intestinal 5-bromodeoxyuridine labeling index, and increased expression of intestinal lipogenic (Fasn, Srebf1) and cholesterol biosynthetic (Hmgcsr, Hmgcs1), genes. The livers from HF diet-fed Tg mice also exhibited an induction of cholesterol and lipogenic pathway genes and altered measures (Irs1, Irs2, Prkce) of insulin sensitivity. Results indicate that gastrointestinal ME1 via its influence on intestinal epithelial proliferation, and lipogenic and cholesterologenic genes may concomitantly impact signaling in liver to modify this tissue’s metabolic state. Our work highlights a new mouse model to address the role of intestine-expressed ME1 in whole body metabolism, hepatomegaly, and crypt cell proliferation. Intestinal ME1 may thus constitute a therapeutic target to reduce obesity-associated pathologies. PMID:25402228

  12. Natural killer cell leukaemia.

    PubMed

    Gandhi, Jamish

    2009-01-01

    A 42-year-old white woman, who was a general practitioner referral to the medical team, presented with a 3-day history of left upper quadrant pain; an urgent private ultrasound scan had showed splenomegaly. She was initially admitted with sepsis without an obvious cause but with a differential diagnosis of a haematological malignancy. Her admission blood tests showed a mildly reduced white cell count and low platelets. Her symptoms progressed and she developed right upper quadrant pain. Her blood counts deteriorated showing a disseminated intravascular coagulation (DIC) picture and mildly deranged liver function tests. Blood films were non-diagnostic. A CT scan of the abdomen/pelvis showed splenomegaly and also hepatomegaly and ascites, not seen in her initial ultrasound scan. Multiple cultures of blood/urine/ascites and infective serology were unremarkable.She was transferred to a larger tertiary centre under the care of the surgeons with presumed abdominal sepsis and underwent an open laparotomy, which showed a big firm liver and spleen but no obvious cause for sepsis. The infectious disease team were unable to find a cause, and haematology became involved to investigate the possibility of a haematological malignancy. The patient underwent two bone marrow biopsies, a percutaneous liver biopsy and had flow cytometry of her ascitic fluid, which revealed the diagnosis of a natural killer cell leukaemia. After some slight improvement on steroids, the patient was given cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab (CHOP-R) chemotherapy. The patient had an initial response to chemotherapy, with reduction in ascitic volume and hepatosplenomegaly, and normalisation of her coagulation. This was accompanied by an overall improvement in her physical condition. She had a second cycle of CHOP-R, but unfortunately approximately 2 weeks after that, she deteriorated rapidly. She was too weak for salvage chemotherapy, so she was put on comfort care. She died

  13. Transcription coactivator PRIP, the peroxisome proliferator-activated receptor (PPAR)-interacting protein, is redundant for the function of nuclear receptors PParalpha and CAR, the constitutive androstane receptor, in mouse liver.

    PubMed

    Sarkar, Joy; Qi, Chao; Guo, Dongsheng; Ahmed, Mohamed R; Jia, Yuzhi; Usuda, Nobuteru; Viswakarma, Navin; Rao, M Sambasiva; Reddy, Janardan K

    2007-01-01

    Disruption of the genes encoding for the transcription coactivators, peroxisome proliferator-activated receptor (PPAR)-interacting protein (PRIP/ASC-2/RAP250/TRBP/NRC) and PPAR-binding protein (PBP/TRAP220/DRIP205/MED1), results in embryonic lethality by affecting placental and multiorgan development. Targeted deletion of coactivator PBP gene in liver parenchymal cells (PBP(LIV-/-)) results in the near abrogation of the induction of PPARalpha and CAR (constitutive androstane receptor)-regulated genes in liver. Here, we show that targeted deletion of coactivator PRIP gene in liver (PRIP(LIV-/-)) does not affect the induction of PPARalpha-regulated pleiotropic responses, including hepatomegaly, hepatic peroxisome proliferation, and induction of mRNAs of genes involved in fatty acid oxidation system, indicating that PRIP is not essential for PPARalpha-mediated transcriptional activity. We also provide additional data to show that liver-specific deletion of PRIP gene does not interfere with the induction of genes regulated by nuclear receptor CAR. Furthermore, disruption of PRIP gene in liver did not alter zoxazolamine-induced paralysis, and acetaminophen-induced hepatotoxicity. Studies with adenovirally driven EGFP-CAR expression in liver demonstrated that, unlike PBP, the absence of PRIP does not prevent phenobarbital-mediated nuclear translocation/retention of the receptor CAR in liver in vivo and cultured hepatocytes in vitro. These results show that PRIP deficiency in liver does not interfere with the function of nuclear receptors PPARalpha and CAR. The dependence of PPARalpha- and CAR-regulated gene transcription on coactivator PBP but not on PRIP attests to the existence of coactivator selectivity in nuclear receptor function.

  14. Thiamine deficiency in tachypnoeic Cambodian infants.

    PubMed

    Keating, Elizabeth M; Nget, Phot; Kea, Sreng; Kuong, Suy; Daly, Leng; Phearom, Seng; Enders, Felicity; Cheryk, Lynn A; Topazian, Mark; Fischer, Philip R; Kumar, Varun

    2014-10-27

    Background: Beriberi is endemic in South-east Asia. Diagnosis is based on clinical findings, but correlation of clinical features with blood thiamine concentrations is uncertain. Objectives: To investigate in tachypnoeic Cambodian infants the correlation between whole blood thiamine diphosphate (TDP) concentrations, clinical findings and blood TDP levels after therapy. Methods: Infants hospitalised with tachypnoea were enrolled from October 2011 to January 2012. Initial clinical features, diagnostic test results and final diagnoses were recorded. Blood for TDP determination was collected prior to treatment and at discharge. Matched infants from the general outpatient clinic with minor complaints were enrolled as controls. Thiamine was administered at the discretion of the treating paediatrician. Results: Of the 47 tachypnoeic and 47 control infants, median initial blood TDP concentrations were 83 and 93 nmol/L, respectively (P = 0·69), and were below the estimated limit of normal (<70 nmol/L) in 43% vs 34% (P = 0·40). Median initial TDP levels were 72 and 91 nmol/L in tachypnoeic infants who did or did not receive thiamine, respectively (P = 0·56); at hospital discharge, median TDP concentration had increased by 107 and 3·5 nmol/L in these two subgroups (P<0·001). Classical findings of beriberi such as dysphonia, tachycardia and hepatomegaly did not correlate with low initial TDP concentrations, but infant age, Tiger Balm use, absence of wheezing and low blood CRP levels were associated with low initial TDP levels. Use of infant formula was associated with higher initial TDP levels. Conclusions: Thiamine deficiency is common in tachypnoeic Cambodian infants, but routine clinical assessments do not accurately identify those with low blood TDP concentrations. Parenteral thiamine administration markedly increases TDP levels. Empirical thiamine treatment should be considered for tachypnoeic infants in regions with endemic thiamine deficiency.

  15. Relationship between plasma lipids and palmitoyl-CoA hydrolase and synthetase activities with peroxisomal proliferation in rats treated with fibrates.

    PubMed

    Alegret, M; Ferrando, R; Vázquez, M; Adzet, T; Merlos, M; Laguna, J C

    1994-06-01

    1. The time-course of the effect of clofibrate (CFB), bezafibrate (BFB) and gemfibrozil (GFB) on lipid plasma levels and palmitoyl-CoA hydrolase and synthetase activities, as well as the correlations with the peroxisomal proliferation phenomenon have been studied in male Sprague-Dawley rats. 2. The administration of the three drugs caused a significant reduction in body weight gain, accompanied with a paradoxical increase in food intake in groups treated with BFB and GFB. 3. Drug treatment produced gross hepatomegaly and increase in peroxisomal beta-oxidation, and these parameters were strongly correlated. The order of potency was BFB > CFB > or = GFB. 4. Both plasma cholesterol (BFB approximately CFB > GFB) and triglyceride (BFB approximately GFB > CFB) levels were reduced in treated animals. There was an inverse correlation between these parameters and peroxisomal beta-oxidation, although the peroxisomal proliferation seemed to explain only a small part of the hypolipidemic effect observed. 5. Cytosolic and microsomal (but not mitochondrial) palmitoyl-CoA hydrolase activities were increased by the three drugs (BFB > CFB > GFB), probably by inducing the hydrolase I isoform, which is insensitive to inhibition by fibrates in vitro. The increased hydrolase activities were directly and strongly correlated with peroxisomal beta-oxidation. 6. Palmitoyl-CoA synthetase activity was also increased by the treatment with fibrates (BFB > CFB > GFB), probably as a consequence of the enhancement of hydrolase activities. 7. Some of the effects of fibrate treatment can be explained, at least in part, in terms of peroxisomal induction and caution should be exercised in the extrapolation of these results to species, such as man,that are insensitive to peroxisomal proliferation.

  16. [Brucellosis as a cause of hemophagocytic syndrome].

    PubMed

    Aydın, Saliha; Günal, Özgür; Taşkın, Mehmet Hakan; Atilla, Aynur; Kılıç, Süleyman Sırrı

    2015-04-01

    Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of excessive inflammation and tissue destruction due to abnormal immune activation and inflammation. HLH can occur primarily due to genetic etiology, or secondarily associated with malignancies, autoimmmune diseases or infections. There are a number of reports that revealed the relationship of hemophagocytosis with brucellosis. In this report, we described a brucellosis-related HLH case. A 73-year-old male who work as farmer was admitted to our hospital with the complaints of fever continuing for 10 days, loss of appetite and back pain. Physical examination revealed right upper quadrant tenderness and hepatomegaly. Since the patient exhibited five of the diagnostic criteria for HLH (fever, hepatosplenomegaly, bicytopenia, hypertriglyceridemia and high ferritin level), he was diagnosed as secondary HLH. PCR, microscopic agglutination and indirect fluorescent antibody tests gave negative results for the diagnosis of Crimean-Congo hemorrhagic fever, leptospirosis and Q fever, respectively. On the other hand, Rose Bengal test for brucellosis was positive, while standard tube agglutination test (STA) was negative. The patient's serum yielded a very high positive (1/1280) result when Coombs' test was performed in terms of the possibility of blocking antibodies or prozone phenomenon. Additionally, B.melitensis was isolated from his blood culture on the sixth day. The patient was treated with doxycycline and rifampicin, and on the 10th day of antibiotic therapy the patient was discharged and recommended to complete his treatment up to 6 weeks. In conclusion, in patients with secondary HLH symptoms especially in the endemic areas, brucellosis should be considered as a predisposing infection.

  17. Comparison between azithromycin and cefixime in the treatment of typhoid fever in children.

    PubMed

    Begum, B; Haque, M A; Ahmed, M S; Islam, M N; Ahsan, M M; Khan, A H; Hasan, M M; Akhtaruzzaman, M; Hossain, M A; Khaleque, M A; Choudhury, A M; Khatun, A A

    2014-07-01

    An intervention study was carried out in the department of paediatrics of Mymensingh Medical College Hospital, Mymensingh to compare the clinical efficacy of Azithromycin in the treatment of childhood typhoid fever with that of cefixime for a period of one year from January 2011 to December 2011. A total of 60 cases of typhoid fever were enrolled in to a randomized clinical trial and was divided into two groups. The inclusion criteria of the cases were: Documented fever for more than 4 days plus two or more of the following clinical features: toxic physical appearance, intestinal complaints, coated tongue, ceacal gurgling, hepatomegaly and splenomegaly, diarrhoea and constipation plus positive Widal test and/or blood culture positivity. Patients who had complication like GIT heamorrhage; intestinal perforaion and/or shock were excluded from the study. Data were collected in a structured questionnaire. Azithromycin was given at a dose of 10mg/kg/day for a period of 07 days Cefixime was given at a dose of 20mg/kg/day in two divided dose for 14 days. The mean time of defervesence was 4.05+1.14 days with azithromycin and 3.41+0.95 with cefixime respectively. The minimum defervesence time was 02 days and maximum defervesence time was 07 days. Clinical cure rate was 87% in azithromycin group and 93% in cefixime group. No serious adverse effect was noted related to azithromycin and cefixime therapy except nausea, vomiting, diarrhoea and jaundice. It was found that azithromycin is almost as effective as cefixime in the treatment of typhoid fever.

  18. THE IMPACT OF MODE OF ACQUISITION ON BIOLOGICAL MARKERS OF PAEDIATRIC HEPATITIS C VIRUS INFECTION

    PubMed Central

    England, Kirsty; Thorne, Claire; Harris, Helen; Ramsay, Mary; Newell, Marie-Louise

    2012-01-01

    Background Despite the introduction of blood donor screening, worldwide, children continue to become infected with HCV via un-sterile medical injections, receipt of unscreened blood and isolated hospital contamination outbreaks. It is plausible that the natural history and disease progression in these children might differ from that of their vertically infected counterparts. Materials and Methods Vertically and parenterally HCV infected children were prospectively followed within the European Paediatric HCV Network and the UK National HCV Register respectively. Biological profiles were compared. Results Vertically and parenterally HCV infected children differed in terms of some key characteristics including the male:female ratio and the proportion of children receiving therapy. Parenterally infected children were more likely to have at least one hepatomegaly event during follow-up, 20% vs. 10%. Parenteral infection did not significantly affect the odds of being consistently viraemic, AOR 1.14 p=0.703 and there was no significant difference in the odds of having consistently elevated ALT levels and mode of acquisition, AOR 0.83 p=0.748. The proportion of children with 2 or more markers of HCV infection did not differ significantly by mode of acquisition, χ21.13 p=0.288. Conclusions This analysis does not support substantial differences between vertically and parenterally infected groups but there are specific mechanisms identified requiring further investigation. Given the continued parenteral infection of children worldwide it is vital that knowledge of disease progression in this group is accurate and that the differences in comparison to vertically infected children are clarified to inform more accurate and individualised clinical management. PMID:21762285

  19. Plasma cell leukemia.

    PubMed

    Albarracin, Flavio; Fonseca, Rafael

    2011-05-01

    Plasma cell leukemia (PCL) is a rare, yet aggressive plasma cell (PC) neoplasm, variant of multiple myeloma (MM), characterized by high levels of PCs circulating in the peripheral blood. PCL can either originate de novo (primary PCL) or as a secondary leukemic transformation of MM (secondary PCL). Presenting signs and symptoms are similar to those seen in MM such as renal insufficiency, hypercalcemia, lytic bone lesions, anemia, and thrombocytopenia, but can also include hepatomegaly and splenomegaly. The diagnostic evaluation of a patient with suspected PCL should include a review of the peripheral blood smear, bone marrow aspiration and biopsy, serum protein electrophoresis (SPEP) with immunofixation, and protein electrophoresis of an aliquot from a 24h urine collection (UPEP). The diagnosis is made when a monoclonal population of PCs is present in the peripheral blood with an absolute PC count exceeding 2000/μL and PC comprising 20% or more of the peripheral blood white cells. The prognosis of PCL is poor with a median survival of 7 to 11 months. Survival is even shorter (2 to 7 months) when PCL occurs in the context of refractory or relapsing MM. There have been no prospective randomized trials investigating the treatment of PCL. Recommendations are primarily based upon data from small retrospective series, case reports, and extrapolation of data from patients with MM. In general, patients are treated with induction therapy followed by hematopoietic cell transplantation (HCT) in those who are appropriate candidates for this approach. The best induction regimen for PCL is not known and there is great variability in clinical practice. Newer agents that are being incorporated into frontline and salvage therapy for MM have also demonstrated activity in PCL such as Immunomodulatory agents and the use of bortezomib with different combinations.

  20. Plasma cell leukemia

    PubMed Central

    Albarracin, Flavio; Fonseca, Rafael

    2014-01-01

    Plasma cell leukemia (PCL) is a rare, yet aggressive plasma cell (PC) neoplasm, variant of multiple myeloma (MM), characterized by high levels of PCs circulating in the peripheral blood. PCL can either originate de novo (primary PCL) or as a secondary leukemic transformation of MM (secondary PCL). Presenting signs and symptoms are similar to those seen in MM such as renal insufficiency, hypercalcemia, lytic bone lesions, anemia, and thrombocytopenia, but can also include hepatomegaly and splenomegaly. The diagnostic evaluation of a patient with suspected PCL should include a review of the peripheral blood smear, bone marrow aspiration and biopsy, serum protein electrophoresis (SPEP) with immunofixation, and protein electrophoresis of an aliquot from a 24h urine collection (UPEP). The diagnosis is made when a monoclonal population of PCs is present in the peripheral blood with an absolute PC count exceeding 2000/μL and PC comprising 20% or more of the peripheral blood white cells. The prognosis of PCL is poor with a median survival of 7 to 11 months. Survival is even shorter (2 to 7 months) when PCL occurs in the context of refractory or relapsing MM. There have been no prospective randomized trials investigating the treatment of PCL. Recommendations are primarily based upon data from small retrospective series, case reports, and extrapolation of data from patients with MM. In general, patients are treated with induction therapy followed by hematopoietic cell transplantation (HCT) in those who are appropriate candidates for this approach. The best induction regimen for PCL is not known and there is great variability in clinical practice. Newer agents that are being incorporated into frontline and salvage therapy for MM have also demonstrated activity in PCL such as Immunomodulatory agents and the use of bortezomib with different combinations. PMID:21295388

  1. Proinflammatory Liver and Antiinflammatory Intestinal Mediators Involved in Portal Hypertensive Rats

    PubMed Central

    Aller, Maria Angeles; Vara, Elena; Garcia, Cruz; Palma, Maria Dolores; Arias, Jorge L.; Nava, Maria Paz; Arias, Jaime

    2005-01-01

    Proinflammatory (TNF-α, IL-1β, and NO) and antiinflammatory (IL-10, CO) levels were assayed in serum, liver, and small bowel in order to verify a hypothetic inflammatory etiopathogeny of portal hypertension that could be the cause of its evolutive heterogeneity. Male Wistar rats were divided into one control group (n = 11) and one group with a triple stenosing ligation of the portal vein (n = 23) after 28 days of evolution. In one subgroup of portal hypertensive rats, portal pressure, collateral venous circulation, mesenteric vasculopathy, and liver and spleen weights were determined. In the remaining rats with portal hypertension TNF-α, IL-1β, and IL-10 were quantified in liver and ileum by enzyme-linked immunosorbent assay. NO synthase activity was studied in liver and ileum. CO and NO were measured in portal and systemic blood by spectrophotometry and Griess reaction, respectively. Portal hypertensive rats with mayor spleen weight show hepatomegaly and mayor development of collateral circulation. Ileum release of IL-10 (0.30 ± 0.12 versus 0.14 ± 0.02 pmol/mg protein; P < .01) is associated with a liver production of both proinflammatory mediators (TNF-α: 2 ± 0.21 versus 1.32 ± 0.60 pmol/mg protein; P < .05, IL-1β: 19.17 ± 2.87 versus 5.96 ± 1.84 pmol/mg protein; P = .005, and NO: 132.10 ± 34.72 versus 61.05 ± 8.30 nmol/mL; P = .005) and an antiinflammatory mediator (CO: 6.49 ± 2.99 versus 3.03 ± 1.59 pmol/mL; P = .005). In short-term prehepatic portal hypertension a gut-liver inflammatory loop, which could be fundamental in the regulation both of the portal pressure and of its complications, could be proposed. PMID:16030393

  2. Clinicopathological correlates in HIV seropositive tuberculosis cases presenting with jaundice after initiating antiretroviral therapy with a structured review of the literature

    PubMed Central

    2012-01-01

    Background The development of jaundice after initiation of HAART in HIV-TB co-infected patients is a challenging presentation in resource constrained settings, and is often attributed to drug induced liver injury (DILI).Some investigators have described hepatic tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) as a cause of liver disease in patients initiating HAART, which could also cause jaundice. Case presentations We report the clinical and histopathological features of five HIV-TB co-infected patients presenting with a syndrome of jaundice, tender hepatomegaly, bile canalicular enzyme rise and return of constitutional symptoms within 8 weeks of initiation of highly active antiretroviral therapy (HAART) for advanced HIV infection at a rural clinic in KwaZulu Natal, South Africa. All five patients had been diagnosed with tuberculosis infection prior to HAART initiation and were on antituberculous medication at time of developing jaundice. There was evidence of multiple aetiologies of liver injury in all patients. However, based on clinical course and pathological findings, predominant hepatic injury was thought to be drug induced in one case and hepatic tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS) in the other four. In these later 4 patients, liver biopsy findings included necrotising and non-necrotising granulomatous inflammation in the lobules and portal tracts. The granulomas demonstrated – in addition to epithelioid histiocytes and Langhans giant cells – neutrophils, plasma cells and large numbers of lymphocytes, which are not features of a conventional untreated tuberculous response. Conclusion In this high TB prevalent, low resource setting, TB-IRIS may be an important cause of jaundice post-HAART initiation. Clinicopathological correlation is essential for optimal diagnosis. Further multi-organ based histopathological studies in the context of immune reconstitution would be useful to clinicians in low

  3. Natural history of untreated primary hepatocellular carcinoma: a retrospective study of 157 patients.

    PubMed

    Pawarode, A; Voravud, N; Sriuranpong, V; Kullavanijaya, P; Patt, Y Z

    1998-08-01

    Primary hepatocellular carcinoma (HCC) is a common malignancy with a dismal prognosis; new modalities of treatment as alternatives to surgery have been developed for unresectable patients. The authors obtain baseline data for the natural history of HCC so that the efficacy of new treatments may be evaluated. A retrospective study of 157 untreated patients with tissue-proven or serodiagnosed HCC was conducted. Clinical characteristics including laboratory investigation, treatment received, survival from the time of diagnosis, and prognostic factors were evaluated. There were 129 men and 28 women (ratio, 4.6:1). Median age was 50.9 years (range, 14.1-85.3 years). The most common symptoms and signs were weight loss (68.2%), abdominal fullness (62.5%), abdominal pain (51.6%), hepatomegaly (73.7%), ascites (45.2%), and jaundice (40.6%). Eighteen percent had extrahepatic metastases of which the lungs were the most common site. Seventy percent were hepatitis B virus related. Overall median survival was 8.7 weeks after the time of diagnosis. Survivals by stages were: TNM II, 16.6 weeks; TNM III, 7.3 weeks; TNM IVA, 9.7 weeks; TNM IVB, 7.6 weeks; Okuda II, 10.7 weeks; and Okuda III, 7.3 weeks. Multivariate analysis revealed serum total bilirubin and albumin as independent prognostic factors of survival. Common causes of death were upper gastrointestinal hemorrhage (34.1%), cancer-related causes (cachexia, HCC rupture, metastatic disease, 31.8%), and hepatic failure (25.0%). Patients with HCC were diagnosed at late stages of their disease and the advanced nature of the tumor precluded effective therapy. Earlier tumor detection at a time when patients are better candidates for treatment may be aided by an active surveillance program of high risk groups.

  4. The effect of recombinant human lactoferrin from the milk of transgenic cows on Salmonella enterica serovar typhimurium infection in mice.

    PubMed

    Wu, Jinghuan; Hu, Yujie; Du, Chunming; Piao, Jianhua; Yang, Lichen; Yang, Xiaoguang

    2016-01-01

    Lactoferrin (LF) is a multifunctional protein with antibacterial and immunomodulatory activities. Given this beneficial effect, transgenic approaches have been used to produce lactoferrin. The aim of the current study was to investigate the in vivo effect of recombinant human lactoferrin (rhLF) from the milk of transgenic cows on Salmonella enterica serovar typhimurium (ST) infection in mice. Two hours before the infection with 0.3 ml at 2 × 10(5) CFU ml(-1) of ST, each animal in the ST + rhLF group received 0.3 ml of rhLF with 20 mg ml(-1) concentration while the ST group received PBS as placebos with the same volume through oral gavage. The mice were infected with ST once only on the first day. After the infection, the mice received 0.3 ml of rhLF with 20 mg ml(-1) (6 mg d(-1)) concentration or PBS, respectively, for 7 days. Mortality and weight were monitored daily. Bacterial enumeration in the blood, liver, and spleen and histopathological analysis of the liver, spleen, kidney and intestine were conducted. The results showed that rhLF decreased the bacterial load in the liver and spleen of mice, reduced the degree of mice hepatomegaly and splenomegaly, and attenuated infectious inflammation with less histopathological abnormalities in the liver, spleen and kidney of mice in the ST infection. This study showed that rhLF with 6 mg per day had antibacterial activity of alleviating the infection caused by ST bacteria, which indicated that rhLF could be used as a supplement in special products.

  5. Dietary krill oil supplementation reduces hepatic steatosis, glycemia, and hypercholesterolemia in high-fat-fed mice.

    PubMed

    Tandy, Sally; Chung, Rosanna W S; Wat, Elaine; Kamili, Alvin; Berge, Kjetil; Griinari, Mikko; Cohn, Jeffrey S

    2009-10-14

    Krill oil (KO) is rich in n-3 fatty acids that are present in phospholipids rather than in triglycerides. In the present study, we investigated the effects of dietary KO on cardiometabolic risk factors in male C57BL/6 mice fed a high-fat diet. Mice (n = 6-10 per group) were fed for 8 weeks either: (1) a nonpurified chow diet (N); (2) a high-fat semipurified diet containing 21 wt % buttermilk + 0.15 wt % cholesterol (HF); (3) HF supplemented with 1.25 wt % KO (HFKO1.25); (4) HF with 2.5 wt % KO (HFKO2.5); or (5) HF with 5 wt % KO (HFKO5.0). Dietary KO supplementation caused a significant reduction in liver wt (i.e., hepatomegaly) and total liver fat (i.e., hepatic steatosis), due to a dose-dependent reduction in hepatic triglyceride (mean +/- SEM: 35 +/- 6, 47 +/- 4, and 51 +/- 5% for HFKO1.25, -2.5, and -5.0 vs HF, respectively, P < 0.001) and cholesterol (55 +/- 5, 66 +/- 3, and 71 +/- 3%, P < 0.001). Serum cholesterol levels were reduced by 20 +/- 3, 29 +/- 4, and 29 +/- 5%, and blood glucose was reduced by 36 +/- 5, 34 +/- 6, and 42 +/- 6%, respectively. Serum adiponectin was increased in KO-fed animals (HF vs HFKO5.0: 5.0 +/- 0.2 vs 7.5 +/- 0.6 microg/mL, P < 0.01). These results demonstrate that dietary KO is effective in improving metabolic parameters in mice fed a high-fat diet, suggesting that KO may be of therapeutic value in patients with the metabolic syndrome and/or nonalcoholic fatty liver disease.

  6. Facilitated physiological adaptation to prolonged circadian disruption through dietary supplementation with essence of chicken.

    PubMed

    Wu, Tao; Yao, Cencen; Tsang, Fai; Huang, Liangfeng; Zhang, Wanjing; Jiang, Jianguo; Mao, Youxiang; Shao, Yujian; Kong, Boda; Singh, Paramjeet; Fu, Zhengwei

    2015-01-01

    Synchrony between circadian and metabolic processes is critical to the maintenance of energy homeostasis. Studies on essence of chicken (EC), a chicken meat extract rich in proteins, amino acids and peptides, showed its effectiveness in alleviating fatigue and promoting metabolism. A recent study revealed that it facilitated the re-entrainment of clock genes (Bmal1, Cry1, Dec1, Per1 and Per2) in the pineal gland and liver in a rat model of circadian disruption. Here, we investigated the role of EC-facilitated circadian synchrony in the maintenance of the energy homeostasis using a mouse model of prolonged circadian disruption. Prolonged circadian disruption (12 weeks) resulted in hepatic maladaptation, manifested by a mild but significant (p < 0.05) hepatomegaly, accompanied by disturbed hepatic lipid metabolism and liver injury (indicated by increased circulating hepatic enzymes). Evidently, there was marked elevations of hepatic inflammatory mediators (interleukin-1beta and interleukin-6), suggesting an underlying inflammation leading to the hepatic injury and functional impairment. Importantly, the disruption paradigm caused the decoupling between key metabolic regulators (e.g. mTOR and AMPK) and hepatic clock genes (Per1, Cry1, Dec1, Bmal1). Further, we showed that the loss of circadian synchrony between the master and hepatic clock genes (Per1, Cry1, Dec1, Bmal1) could be the underlying cause of the maladaptation. When supplemented with EC, the functional impairment and inflammation were abolished. The protective effects could be linked to its effectiveness in maintaining the synchrony between the master and hepatic clocks, and the resultant improved coupling of the circadian oscillators (Per1, Cry1, Dec1, Bmal1) and metabolic regulators (mTOR, AMPK). Overall, EC supplementation promoted the physiological adaptation to the prolonged circadian disruption through facilitation of endogenous circadian synchrony and the coupling of circadian oscillators and

  7. Budd-Chiari Syndrome in a Patient with JAK-2 V617F and Factor V G1691A Mutations

    PubMed Central

    Velarde-Félix, JS; Sanchez-Zazueta, J; Gonzalez-Ibarra, FP; González-Valdez, JA; Salcido-Gómez, B; Gallardo-Angulo, E; Murillo-Llanes, J

    2014-01-01

    ABSTRACT Myeloproliferative neoplasms (MPN) are considered a risk factor for Budd-Chiari syndrome (BCS). The current classification of MPN by the World Health Organization is based on the presence of JAK-2 V617F somatic mutation, which is present in 40 to 60% of patients with BCS. Factor V Leiden mutation is found in around 53% of patients with BCS, representing the most common prothrombotic disease associated with the disorder. We describe a 48-year old woman with a past medical history of deep venous thrombosis in the left upper extremity and one episode in both lower extremities, one episode of transient ischaemic attack and essential thrombocythemia, who presented with jaundice, ascites and hepatomegaly. Budd-Chiari syndrome was diagnosed based on findings on Doppler ultrasound and liver biopsy. Doppler ultrasound showed narrowness of hepatic veins and inferior vena cava in its hepatic portion, diffuse echotexture and portal hypertension. Liver biopsy showed congestion of sinusoids and portal fibrosis. The patient was found to be a heterozygous carrier of Factor V and homozygous wild type G20210A prothrombin mutations. The JAK-2 V617F mutation was detected by allele-specific polymerase chain reaction (AS-PCR). The association of these mutations is rare, with only a few cases reported in the literature. The patient was treated with oral anticoagulation and antiplatelets with good results and proper follow-up. In conclusion, due to the possible coexistence of multiple prothrombotic factors in patients with Budd-Chiari syndrome, the approach to these patients must be focussed on searching for multiple factors and should include the JAK-2 V617F mutation PMID:25781296

  8. Enzyme induction and histopathology elucidate aryl hydrocarbon receptor-mediated versus non-aryl hydrocarbon receptor-mediated effects of Aroclor 1268 in American mink (Neovison vison).

    PubMed

    Folland, William R; Newsted, John L; Fitzgerald, Scott D; Fuchsman, Phyllis C; Bradley, Patrick W; Kern, John; Kannan, Kurunthachalam; Zwiernik, Matthew J

    2016-03-01

    Polychlorinated biphenyl (PCB) concentrations reported in preferred prey and blubber of bottlenose dolphins from the Turtle-Brunswick River estuary (Georgia, USA) suggest the potential for adverse effects. However, PCBs in Turtle-Brunswick River estuary dolphins are primarily derived from Aroclor 1268, and predicting toxic effects of Aroclor 1268 is uncertain because of the mixture's unique composition and associated physiochemical characteristics. These differences suggest that toxicity benchmarks for other PCB mixtures may not be relevant to dolphins exposed to Aroclor 1268. American mink (Neovison vison) were used as a surrogate model for cetaceans to characterize mechanisms of action associated with Aroclor 1268 exposure. Mink share similarities in phylogeny and life history with cetaceans and are characteristically sensitive to PCBs, making them an attractive surrogate species for marine mammals in ecotoxicity studies. Adult female mink and a subsequent F1 generation were exposed to Aroclor 1268 through diet, and effects on enzyme induction, histopathology, thyroid hormone regulation, hematology, organ weights, and body condition index were compared to a negative control and a 3,3',4,4',5-pentachlorobiphenyl (PCB 126)-positive control. Aroclor 1268 dietary exposure concentrations ranged from 1.8 µg/g wet weight to 29 µg/g wet weight. Anemia, hypothyroidism, and hepatomegaly were observed in mink exposed to Aroclor 1268 beyond various dietary thresholds. Cytochrome P450 induction and squamous epithelial proliferation jaw lesions were low in Aroclor 1268 treatments relative to the positive control. Differences in enzyme induction and the development of squamous epithelial proliferation jaw lesions between Aroclor 1268 treatments and the positive control, coupled with effects observed in Aroclor 1268 treatments not observed in the positive control, indicate that mechanisms additional to the aryl hydrocarbon receptor-mediated pathway are associated with

  9. Crimean-Congo hemorrhagic fever: aid of abdominal ultrasonography in prediction of severity.

    PubMed

    Ziraman, Ipek; Celikbas, Aysel; Ergonul, Onder; Degirmenci, Tulin; Uyanik, Sadik Ahmet; Koparal, Suha; Dokuzoguz, Basak

    2014-11-01

    Crimean-Congo hemorrhagic fever (CCHF) is a fatal viral infection that involves multiple organs, and endothelium. We described abdominal sonographic findings of the patients infected with the Crimean-Congo hemorrhagic fever virus (CCHFV) in relation to the severity of the disease. This is a prospective study performed among hospitalized patients infected with CCHF between 2005 and 2011. A total of 210 hospitalized patients with confirmed CCHF infection were included in the study. The mean age was 47 and 49.5% of the patients were female. Patients were classified as mild, moderate, or severe disease according to their clinical and laboratory findings. The relationship between the clinical severity of CCHF and the abdominal sonographic findings was analyzed. Sonographic findings of abdomen included gallbladder wall thickening (GBWT) in 44 (21%), splenomegaly in 39 (19%), hepatomegaly in 52 (25%), decrease in echo of liver parenchyma in nine (4%), increase in echo liver parenchyma in 13 (6%), intra-abdominal fluid collection/ascites in 23 (11%), and enlarged periportal lymph nodes in seven (3%) cases. GBWT was detected in 3% of mild patients, 23% of moderate patients, and 61% of severe patients (p<0.001). In multivariate analysis to predict the severity, GBWT (odds ratio [OR] 5.4, confidence interval [CI] 1.76-16.49, p=0.003) and intra-abdominal fluid collection/ascites (OR 3.5, CI 1.07-12.61, p=0.049) were found to be significantly associated with disease severity. In conclusion, ultrasonography is a reliable, useful, and noninvasive diagnostic tool for evaluation of the abdominal findings of the patients with CCHFV infection. GBWT and intra-abdominal fluid collection/ascites were found to be predictors of severity.

  10. Tetralogy of Fallot and pheochromocytoma in a situs inversus totalis: An unusual association

    PubMed Central

    Tapia-Orihuela, Rubén Kevin Arnold; Huaringa-Marcelo, Jorge; Loja-Oropeza, David

    2016-01-01

    Introduction: Situs inversus totalis is an uncommon anomaly which exist a complete transposition of organs and it’s occasionally associated with congenital heart diseases, such as tetralogy of fallot. Pheochromocytoma is a rare neuroendocrine tumor with an annual incidence of 2-8 cases per million people and for years has been studied its relationship with the hypoxic pathway. Case Report: A 29 year old male with a history of tetralogy of fallot corrected at 10 years and situs inversus totalis. He was admitted to hospital with a progressive story of four months of constipation, palpitations, headache, dyspnea and sweating. Physical examination revealed a thinned man with peripheral cyanosis, clubbing and signs of decompensated congestive heart failure as hepatomegaly, legs edema, multifocal systodiastolic murmurs, abdominal distension and jugular venous distention. The echocardiogram shows severe right ventricular dysfunction and severe pulmonary hypertension. Furthermore, abdominal computed tomography shows right adrenal mass. Elevated metanephrines and catecholamines confirmed the diagnosis of pheochromocytoma. Surgical removal is decided and preoperative management begins with alpha-adrenergic blockade, however the patient had a hemodynamic decompensation with an unfavorable evolution. Discussion: In conclusion, there are few reports of cyanotic congenital heart disease with pheochromocytoma. Several studies show a significant association between both of them due to chronic hypoxia leads sustained hyperresponsiveness in adrenal medulla and it would cause the tumor. Special preoperative management of pheochromocytoma is recommended when there underlying heart disease and congestive heart failure. We present the first international report of tetralogy of fallot and pheochromocytoma in a patient with situs inversus totalis. PMID:27777699

  11. Sinusoidal obstruction syndrome (hepatic veno-occlusive disease).

    PubMed

    Fan, Cathy Q; Crawford, James M

    2014-12-01

    Hepatic sinusoidal obstruction syndrome (SOS) is an obliterative venulitis of the terminal hepatic venules, which in its more severe forms imparts a high risk of mortality. SOS, also known as veno-occlusive disease (VOD), occurs as a result of cytoreductive therapy prior to hematopoietic stem cell transplantation (HSCT), following oxaliplatin-containing adjuvant or neoadjuvant chemotherapy for colorectal carcinoma metastatic to the liver and treated by partial hepatectomy, in patients taking pyrrolizidine alkaloid-containing herbal remedies, and in other particular settings such as the autosomal recessive condition of veno-occlusive disease with immunodeficiency (VODI). A central pathogenic event is toxic destruction of hepatic sinusoidal endothelial cells (SEC), with sloughing and downstream occlusion of terminal hepatic venules. Contributing factors are SEC glutathione depletion, nitric oxide depletion, increased intrahepatic expression of matrix metalloproteinases and vascular endothelial growth factor (VEGF), and activation of clotting factors. The clinical presentation of SOS includes jaundice, development of right upper-quadrant pain and tender hepatomegaly, ascites, and unexplained weight gain. Owing to the potentially critical condition of these patients, transjugular biopsy may be the preferred route for liver biopsy to exclude other potential causes of liver dysfunction and to establish a diagnosis of SOS. Treatment includes rigorous fluid management so as to avoid excessive fluid overload while avoiding too rapid diuresis or pericentesis, potential use of pharmaceutics such as defibrotide, coagulolytic agents, or methylprednisolone, and liver transplantation. Proposed strategies for prevention and prophylaxis include reduced-intensity conditioning radiation for HSCT, treatment with ursodeoxycholic acid, and inclusion of bevacizumab with oxaliplatin-based chemotherapeutic regimes. While significant progress has been made in understanding the pathogenesis

  12. Choline supplementation protects against liver damage by normalizing cholesterol metabolism in Pemt/Ldlr knockout mice fed a high-fat diet.

    PubMed

    Al Rajabi, Ala; Castro, Gabriela S F; da Silva, Robin P; Nelson, Randy C; Thiesen, Aducio; Vannucchi, Helio; Vine, Donna F; Proctor, Spencer D; Field, Catherine J; Curtis, Jonathan M; Jacobs, René L

    2014-03-01

    Dietary choline is required for proper structure and dynamics of cell membranes, lipoprotein synthesis, and methyl-group metabolism. In mammals, choline is synthesized via phosphatidylethanolamine N-methyltransferase (Pemt), which converts phosphatidylethanolamine to phosphatidylcholine. Pemt(-/-) mice have impaired VLDL secretion and developed fatty liver when fed a high-fat (HF) diet. Because of the reduction in plasma lipids, Pemt(-/-)/low-density lipoprotein receptor knockout (Ldlr(-/-)) mice are protected from atherosclerosis. The goal of this study was to investigate the importance of dietary choline in the metabolic phenotype of Pemt(-/-)/Ldlr(-/-) male mice. At 10-12 wk of age, Pemt(+/+)/Ldlr(-/-) (HF(+/+)) and half of the Pemt(-/-)/Ldlr(-/-) (HF(-/-)) mice were fed an HF diet with normal (1.3 g/kg) choline. The remaining Pemt(-/-)/Ldlr(-/-) mice were fed an HF diet supplemented (5 g/kg) with choline (HFCS(-/-) mice). The HF diet contained 60% of calories from fat and 1% cholesterol, and the mice were fed for 16 d. HF(-/-) mice lost weight and developed hepatomegaly, steatohepatitis, and liver damage. Hepatic concentrations of free cholesterol, cholesterol-esters, and triglyceride (TG) were elevated by 30%, 1.1-fold and 3.1-fold, respectively, in HF(-/-) compared with HF(+/+) mice. Choline supplementation normalized hepatic cholesterol, but not TG, and dramatically improved liver function. The expression of genes involved in cholesterol transport and esterification increased by 50% to 5.6-fold in HF(-/-) mice when compared with HF(+/+) mice. Markers of macrophages, oxidative stress, and fibrosis were elevated in the HF(-/-) mice. Choline supplementation normalized the expression of these genes. In conclusion, HF(-/-) mice develop liver failure associated with altered cholesterol metabolism when fed an HF/normal choline diet. Choline supplementation normalized cholesterol metabolism, which was sufficient to prevent nonalcoholic steatohepatitis development

  13. Chronic myelogenous leukemia: a multivariate analysis of the associations of patient characteristics and therapy with survival.

    PubMed

    Kantarjian, H M; Smith, T L; McCredie, K B; Keating, M J; Walters, R S; Talpaz, M; Hester, J P; Bligham, G; Gehan, E; Freireich, E J

    1985-12-01

    The prognostic importance of patient pretreatment clinical and laboratory features was investigated in a group of 303 patients with Philadelphia chromosome-positive benign-phase chronic myelogenous leukemia. Intensive chemotherapy was given to 97 patients, and 78 underwent an early elective splenectomy. The overall median survival time, dated from hospital admission, was 39 months. Patient characteristics associated with shortened survival were age 60 years or older, black race, the presence of hepatomegaly, splenomegaly, symptoms, weight loss, and poor performance status. Adverse blood and bone marrow parameters were anemia, thrombocytosis or thrombocytopenia, a high proportion of peripheral blasts plus promyelocytes or of basophils, a high proportion of marrow blasts or basophils, decreased marrow megakaryocytes, and cytogenetic abnormalities in addition to the Philadelphia chromosome. Several of these factors were interrelated. A multivariate regression analysis demonstrated that the combination blood basophilia, race, additional cytogenetic abnormalities, age and marrow basophilia had the strongest predictive relationship to survival time. This resulted in a model segregating patients into low-, intermediate-, and high-risk groups, with median survivals of 53, 39, and 25 months, respectively. Another model was derived that did not include the marrow features and identified splenomegaly and platelet counts as adding to the prognosis prediction by blood basophilia, race, and age. Evaluation of the effect of therapy, after adjusting for differences in prognostic characteristics, showed that intensive chemotherapy was associated with survival prolongation among patients at intermediate and high risk of death. We conclude that a combination of pretreatment factors identifies different risk subcategories in patients with chronic myelogenous leukemia and is helpful in assessing overall prognosis and treatment effect.

  14. The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue

    PubMed Central

    Thein, Tun-Linn; Leo, Yee-Sin; Lye, David C.

    2016-01-01

    Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. A total of 2843 polymerase-chain reaction (PCR) confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. Sixty-nine percent of them were male with a median age of 34 years. Prolonged fever (fever > 7 days duration) was present in 572 (20.1%) of patients. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT) and aspartate transaminase (AST), higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT) were significantly associated with prolonged fever but not platelet count or prothrombin time (PT). Saddleback fever was present in 165 (5.8%). Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF), while saddleback fever showed associations with DHF and SD but not DSS. The presence of prolonged or saddleback fever in dengue patients should therefore prompt

  15. Safety and efficacy of packed red blood cell transfusions at different doses in very low birth weight infants

    PubMed Central

    Govande, Vinayak P.; Shetty, Ashita; Beeram, Madhava R.

    2016-01-01

    This double-blinded, randomized, crossover study evaluated the safety and effectiveness of 20 mL/kg aliquots of packed red blood cell (PRBC) transfusions versus 15 mL/kg aliquot transfusions in very low birth weight (VLBW) infants with anemia. The study enrolled 22 hemodynamically stable VLBW infants requiring PRBC transfusions, with a mean gestational age of 25.7 ± 2.2 weeks and birth weight of 804 ± 261 g. Each infant was randomized to receive one of two treatment sequences: 15 mL/kg followed by 20 mL/kg or 20 mL/kg followed by 15 mL/kg. The infants were monitored during and after transfusions, and the efficacy and safety of the treatments were evaluated. Infants had higher posttransfusion hemoglobin (13.2 g/dL vs 11.8 g/dL, P < 0.01) and hematocrit levels (38.6 g/dL vs 34.4 g/dL, P < 0.01) following 20 mL/kg PRBC transfusions when compared to 15 mL/kg transfusions. There were no differences in the incidence of tachypnea, hepatomegaly, edema, hypoxia, necrotizing enterocolitis, or vital sign instability between groups. In conclusion, high-volume PRBC transfusions (20 mL/kg) were associated with higher posttransfusion hemoglobin and hematocrit levels but no adverse effects. Higher-volume transfusions may reduce the need for multiple transfusions and therefore the number of donors the infant is exposed to. PMID:27034542

  16. Hepatic sarcoidosis: a case series

    PubMed Central

    Ennaifer, Rym; Ayadi, Shema; Romdhane, Hayfa; Cheikh, Myriam; Nejma, Houda Ben; Bougassas, Wassila; Hadj, Najet Bel

    2016-01-01

    Sarcoidosis is a systemic non caseous granulomas disease. Liver is a common location but usually asymptomatic. Evidence based guidelines for this location treatment is lacking and the effect of corticosteroids may be inadequate. The aim of our study was to describe the clinical, biochemical, radiological and therapeutic features of seven patients with systemic sarcoidosis and liver involvement. A retrospective and descriptive monocentric study, over 3 years, including seven patients with systemic sarcoidosis and liver involvement. We included 5 women and 2 men with an average age of 43 years. Hepatic localization revealed sarcoidosis in 5 cases. Hepatomegaly was observed in all patients as well as abnormal serum liver function test reflected by anicteric cholestasis. Liver biopsy, showed in all granulomatous lesions consistent with sarcoidosis and severe fibrosis in 2 cases. Extra-hepatic manifestations were present in all patients represented mainly by pulmonary location. All patients were treated, five by corticosteroid and two with ursodeoxycholic acid (UDCA). Complete response was observed in one case, partial response in another case and corticosteroid refractoriness in one case. In two cases, corticosteroid therapy was introduced for less than 1 month, not allowing assessment of response. Antimalarials in combination with UDCA were used successfully in a patient with steroid-resistant liver disease. Liver involvement can reveal systemic sarcoidois. Given the risk of progression to severe liver disease, it must be screened in all patients with systemic sarcoidosis. Treatment is not systematic, and still based on corticosteroid therapy. In the absence of prospective randomized controlled trials, the efficacy of UDCA need to be proven. PMID:27795804

  17. A Case Report of Primary Nasal Natural Killer (NK)/T-Cell Lymphoma in an African American Patient Presenting with Hemophagocytic Syndrome

    PubMed Central

    Tan, Bowei; Abdelmalek, Cherif; O’Donnell, James E.; Toltaku, Thomas; Chaudhry, Rashid; Wang, Jen C.; Gotlieb, Vladimir

    2017-01-01

    Patient: Male, 55 Final Diagnosis: Primary NK-T cell lymphoma • nasal type Symptoms: Fever • nasal bleeding • nasal mass • weight loss Medication: — Clinical Procedure: Chemotherapy×2 cycles • radiation therap Specialty: Oncology Objective: Rare disease Background: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTCL) is generally an aggressive and rare non-Hodgkin lymphoma. It is most common in East Asians, Native Americans, and South Americans, but is rarely reported in blacks. Case Report: A 55-year-old African American male born in Grenada presented with a left nostril mass with facial swelling and biopsy subsequently confirmed a diagnosis of extranodal NK/T-cell lymphoma, nasal type (ENKTCL). Immunochemistry was positive for CD2, cytoplasmic CD3, CD7, CD 43, CD 56, granzyme B, and TIA-1. In situ hybridization was positive for Epstein-Barr virus encoded ribonucleic acid (EBERs). Bone marrow aspiration did not show lymphoma involvement. The patient had progressive neutropenia upon presentation, with further investigations showing hepatomegaly, hyperferritinemia, and hemophagocytosis in the bone marrow. We reached a diagnosis of hemophagocytic syndrome. He was treated with a high-dose combination chemotherapy and radiation therapy; the neutropenia improved significantly with steroids as treatment for immune activation in the setting of hemophagocytic syndrome. Conclusions: To the best of our knowledge, this is the only second report of extranodal NK/T-cell lymphoma, nasal type in a black patient, and it raises the awareness of early recognition of rare manifestations of NK/T-cell lymphoma such as hemophagocytic syndrome. PMID:28193996

  18. Fatal hepatitis E viral infection in pregnant women in Ghana: a case series

    PubMed Central

    2012-01-01

    Background Viral infections during pregnancy can pose serious threats to mother and fetus from the time of conception to the time of delivery. These lead to congenital defects, spontaneous abortion and even death. The definitive diagnosis and management of pregnancy-related viral infections may be challenging especially in less resourced countries. Case presentation We present clinical and laboratory responses to the diagnosis and management of three cases of fulminant hepatitis secondary to Hepatitis E viral infection in pregnancy. Case 1 was a 31-year-old Ghanaian woman who presented with a week’s history of passing dark urine as well as yellowish discoloration of the eyes. She subsequently developed fulminant hepatitis secondary to Hepatitis E viral infection, spontaneously aborted at 24 weeks of gestation and later died. Case 2 was also a 31-year-old Ghanaian woman who was admitted with a four-day history of jaundice. She had low grade fever, but no history of abdominal pain, haematuria, pale stool or pruritus. She next developed fulminant hepatitis secondary to Hepatitis E viral infection. However, she did not miscarry but died at 28 weeks of gestation. Case 3 was a 17-year-old Ghanaian woman who was referred to the tertiary health facility on account of jaundice and anaemia. She had delivered a live male infant at maturity of 32 weeks but noticed she was jaundiced and had a presentation of active disease 3 days prior to delivery. The baby was icteric at birth and on evaluation, had elevated bilirubin (mixed type) with normal liver enzymes. Hepatitis E virus infection was confirmed in both mother and baby. However, the jaundice and the hepatomegaly resolved in mother and baby after 5 and 12 days respectively. Conclusion To the best of our knowledge, these are the first documented cases of fatal fulminant hepatic failures resulting from HEV infection in Ghana. PMID:22937872

  19. Identification and characterization of avian hepatitis E virus in 2013 outbreaks of hepatitis-splenomegaly syndrome in two US layer operations.

    PubMed

    Gerber, Priscilla F; Trampel, Darrell W; Opriessnig, Tanja

    2014-01-01

    Two commercial Midwestern egg-type chicken flocks experienced significant increases in mortality rates in April 2013 with clinical signs appearing in 17-week-old pullets on Farm A and in 46-week-old hens on Farm B. Average weekly mortality was 0.44% over a 4-week period on Farm A and 0.17% over an 8-week period on Farm B. On Farm A, flocks in the affected house had a 45% decrease in daily egg production from weeks 19 to 27 when compared with standard egg production curves (P < 0.01) while no decrease in egg production was noticed on Farm B. Post-mortem examination revealed changes consistent with hepatitis-splenomegaly syndrome, including hepatomegaly with serosanguineous fluid in the coelomic cavity and hepatic subcapsular haemorrhages. Microscopic lesions were characterized by multifocal necrotizing hepatitis and intrahepatic haemorrhage. No significant bacteria were recovered from liver samples, but 72 to 100% of the liver samples from affected chickens on Farm A (8/11) and Farm B (7/7) contained detectable amounts of avian hepatitis E virus (aHEV) RNA as determined by polymerase chain reaction. Sequencing and phylogenetic analysis of a 361-base-pair fragment of the helicase gene demonstrated 98.6 to 100% nucleotide identity between the aHEV genomes from Farm A and Farm B, whereas identities ranged from 74.6 to 90.5% when compared with other representative sequences. Sequences from this study clustered within aHEV genotype 2 previously recognized in the USA. In contrast to other reported aHEV outbreaks that occurred in 30-week-old to 80-week-old chickens, in the present investigation clinical aHEV was identified in 17-week-old chickens on one of the farms.

  20. Natural Infection with Avian Hepatitis E Virus and Marek's Disease Virus in Brown Layer Chickens in China.

    PubMed

    Yang, Shuqing; Wang, Liyuan; Sun, Shuhong

    2016-09-01

    In the present study, avian hepatitis E virus (HEV) and serotype-1 strains of Marek's disease virus (MDV-1) were detected from a flock of 27-wk-old brown layer hens in China, accompanied by an average daily mortality of 0.44%. Postmortem examination of 25 sick hens and five apparently healthy hens selected randomly from the flock showed significant pathologic changes consistent with hepatitis-splenomegaly syndrome (HSS), including hepatomegaly, peritoneal fluid, and hepatic subcapsular hemorrhages. Microscopic examination of these livers showed multifocal necrotizing hepatitis and mild lymphocytic infiltration. These liver samples were investigated for HEV by reverse-transcription PCR. The overall detection rate of HEV RNA in samples of sick chickens was about 56% (14/25), while in samples from apparently healthy hens, it was 80% (4/5). Sequencing analysis of three 242-base-pair fragments of the helicase gene revealed 95.5% to 97.9% nucleotide identity compared with published avian HEV genotype 3, whereas identities demonstrated only 77.3% to 86.0% similarity when compared with genotypes 1, 2, and 4. Unexpectedly, the MDV meq gene was detected in livers from both apparently healthy chickens (2/5) and sick chickens (12/25) by PCR analysis. The meq gene (396 base pairs) was determined to belong to MDV-1 by further sequencing. The co-infection rate of avian HEV and MDV in this flock was 30% (9/30). This is the first report of dual infection of a nonenvelope RNA virus (HEV) with a herpesvirus (MDV) in chickens in China.

  1. VAV1-Cre mediated hematopoietic deletion of CBL and CBL-B leads to JMML-like aggressive early-neonatal myeloproliferative disease.

    PubMed

    An, Wei; Mohapatra, Bhopal C; Zutshi, Neha; Bielecki, Timothy A; Goez, Benjamin T; Luan, Haitao; Iseka, Fany; Mushtaq, Insha; Storck, Matthew D; Band, Vimla; Band, Hamid

    2016-09-13

    CBL and CBL-B ubiquitin ligases play key roles in hematopoietic stem cell homeostasis and their aberrations are linked to leukemogenesis. Mutations of CBL, often genetically-inherited, are particularly common in Juvenile Myelomonocytic Leukemia (JMML), a disease that manifests early in children. JMML is fatal unless corrected by bone marrow transplant, which is effective in only half of the recipients, stressing the need for animal models that recapitulate the key clinical features of this disease. However, mouse models established so far only develop hematological malignancy in adult animals. Here, using VAV1-Cre-induced conditional CBL/CBL-B double knockout (DKO) in mice, we established an animal model that exhibits a neonatal myeloproliferative disease (MPD). VAV1-Cre induced DKO mice developed a strong hematological phenotype at postnatal day 10, including severe leukocytosis and hepatomegaly, bone marrow cell hypersensitivity to cytokines including GM-CSF, and rapidly-progressive disease and invariable lethality. Interestingly, leukemic stem cells were most highly enriched in neonatal liver rather than bone marrow, which, along with the spleen and thymus, were hypo-cellular. Nonetheless, transplantation assays showed that both DKO bone marrow and liver cells can initiate leukemic disease in the recipient mice with seeding of both spleen and bone marrow. Together, our results support the usefulness of the new hematopoietic-specific CBL/CBL-B double KO animal model to study JMML-related pathogenesis and to further understand the function of CBL family proteins in regulating fetal and neonatal hematopoiesis. To our knowledge, this is the first mouse model that exhibits neonatal MPD in infancy, by day 10 of postnatal life.

  2. VAV1-Cre mediated hematopoietic deletion of CBL and CBL-B leads to JMML-like aggressive early-neonatal myeloproliferative disease

    PubMed Central

    An, Wei; Mohapatra, Bhopal C.; Zutshi, Neha; Bielecki, Timothy A.; Goez, Benjamin T.; Luan, Haitao; Iseka, Fany; Mushtaq, Insha; Storck, Matthew D.; Band, Vimla; Band, Hamid

    2016-01-01

    CBL and CBL-B ubiquitin ligases play key roles in hematopoietic stem cell homeostasis and their aberrations are linked to leukemogenesis. Mutations of CBL, often genetically-inherited, are particularly common in Juvenile Myelomonocytic Leukemia (JMML), a disease that manifests early in children. JMML is fatal unless corrected by bone marrow transplant, which is effective in only half of the recipients, stressing the need for animal models that recapitulate the key clinical features of this disease. However, mouse models established so far only develop hematological malignancy in adult animals. Here, using VAV1-Cre-induced conditional CBL/CBL-B double knockout (DKO) in mice, we established an animal model that exhibits a neonatal myeloproliferative disease (MPD). VAV1-Cre induced DKO mice developed a strong hematological phenotype at postnatal day 10, including severe leukocytosis and hepatomegaly, bone marrow cell hypersensitivity to cytokines including GM-CSF, and rapidly-progressive disease and invariable lethality. Interestingly, leukemic stem cells were most highly enriched in neonatal liver rather than bone marrow, which, along with the spleen and thymus, were hypo-cellular. Nonetheless, transplantation assays showed that both DKO bone marrow and liver cells can initiate leukemic disease in the recipient mice with seeding of both spleen and bone marrow. Together, our results support the usefulness of the new hematopoietic-specific CBL/CBL-B double KO animal model to study JMML-related pathogenesis and to further understand the function of CBL family proteins in regulating fetal and neonatal hematopoiesis. To our knowledge, this is the first mouse model that exhibits neonatal MPD in infancy, by day 10 of postnatal life. PMID:27449297

  3. Mycobacterium genavense infections: a retrospective multicenter study in France, 1996-2007.

    PubMed

    Charles, Pierre; Lortholary, Olivier; Dechartres, Agnès; Doustdar, Fahranoosh; Viard, Jean Paul; Lecuit, Marc; Gutierrez, Maria Cristina

    2011-07-01

    Mycobacterium genavense, a nontuberculous mycobacterium, led to devastating infections in patients with acquired immunodeficiency syndrome (AIDS) before highly active antiretroviral therapy (HAART) was available, as well as in other immunocompromised patients. We conducted the current study to describe the features of this infection in patients infected with human immunodeficiency virus (HIV) in the HAART era and in non HIV-infected patients.We conducted a retrospective cohort survey in France. All patients with M. genavense infection diagnosed from 1996 to 2007 at the National Reference Center, Institut Pasteur, Paris, were identified and their clinical, laboratory, and microbiologic data were centralized in a single database. Twenty-five cases of M. genavense infection originating from 19 centers were identified. Twenty patients had AIDS, 3 had solid organ transplantation, and 2 had sarcoidosis. Sixty-four percent (n = 16) were male, mean age was 42 years, and median CD4 count was 13/mm (range, 0-148/mm) in patients with AIDS. Twenty-four patients had disseminated infection with fever (75%, n = 18), weight loss (79%, n = 19), abdominal pain (71%, n = 17), diarrhea (62.5%, n = 15), splenomegaly (71%, n = 17), hepatomegaly (62.5%, n = 15), or abdominal adenopathy (62.5%, n = 15). M. genavense was isolated from the lymph node (n = 13), intestinal biopsy (n = 9), blood (n = 6), sputum (n = 3), stool (n = 3), and bone marrow (n = 5). Eleven patients (44%) died, 8 (32%) were considered cured with no residual symptoms, and 6 (24%) had chronic symptoms. The 1-year survival rate was 72%.The prognosis of M. genavense infection in HIV-infected patients has dramatically improved with HAART. Clinical presentations in HIV and non-HIV immunocompromised patients were similar.

  4. Partial trisomy 5q resulting from chromosome 7 insertion: An expansion of the phenotype

    SciTech Connect

    Fries, M.H.; Reilly, P.A.; Williams, T.C.

    1994-09-01

    Partial trisomy 5q has been categorized into three separate phenotypes; however, a distinctive phenotype has not been described for duplications spanning 5q23-q35. We report a case of partial trisomy 5q for this region as a result of a ins(7,5)(q31.3;q23.2q35.1)mat. The liveborn male infant was delivered by emergency cesarean section at 37 weeks after a pregnancy notable for oligohydramnios, with birth weight 1792 g (<3%). Postnatal course was marked by psychomotor delay, failure to thrive, and biopsy demonstrated neonatal giant cell hepatitis with a paucity of intrahepatic bile ducts. His appearance was remarkable for lack of subcutaneous fat, midline displaced hair whorl, bitemporal narrowing with frontal bossing, wide anterior fontanel, widow`s peak, protuberant eyes with periorbital and lid edema, short flat nasal bridge with broad flattened nasal tip, long smooth philtrum, wide mouth with thin lips, wide gingival ridges, micrognathia, posteriorly rotated low-set ears, hepatomegaly, flexion contractions of elbows, and generalized hypertonicity. Urine organic acids, oligosaccharide/mucopolysaccharide screen, and plasma amino acids were negative. GTG-banding on prometaphase chromosomes showed an unbalanced translocation involving chr. 7. This was identified as an insertion of chr. 5 (q23.2q35.1) into distal 7q after FISH using chr. 5 and chr. 7 painting probes. The infant`s mother carries the balanced insertional rearrangement: 46,XX,dir ins(7,5)(q31.3;q23.2q35.1). This phenotype overlaps that of previously described duplications with the addition of giant cell hepatitis, coarsened facial features, gingival thickening, and flexion contractures, suggestive of a yet undiagnosed storage disorder.

  5. 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.

  6. Higher plasma bilirubin predicts veno-occlusive disease in early childhood undergoing hematopoietic stem cell transplantation with cyclosporine

    PubMed Central

    Kim, Kwi Suk; Moon, Aree; Kang, Hyoung Jin; Shin, Hee Young; Choi, Young Hee; Kim, Hyang Sook; Kim, Sang Geon

    2016-01-01

    AIM: To analyze the association between plasma bilirubin levels and veno-occlusive disease (VOD) in non-adult patients undergoing hematopoietic stem cell transplantation (HSCT) during cyclosporine therapy. METHODS: A total of 123 patients taking cyclosporine were evaluated using an electronic medical system at the Seoul National University Children’s Hospital from the years 2004 through 2011. Patients were grouped by age and analyzed for incidence and type of adverse drug reactions (ADRs) including VOD. RESULTS: The HSCT patients were divided into three age groups: G#1 ≥ 18; 9 ≤ G#2 ≤ 17; and G#3 ≤ 8 years of age). The majority of transplant donor types were cord blood transplantations. Most prevalent ADRs represented acute graft-vs-host disease (aGVHD) and VOD. Although the incidences of aGVHD did not vary among the groups, the higher frequency ratios of VOD in G#3 suggested that an age of 8 or younger is a risk factor for developing VOD in HSCT patients. After cyclosporine therapy, the trough plasma concentrations of cyclosporine were lower in G#3 than in G#1, indicative of its increased clearance. Moreover, in G#3 only, a maximal total bilirubin level (BILmax) of ≥ 1.4 mg/dL correlated with VOD incidence after cyclosporine therapy. CONCLUSION: HSCT patients 8 years of age or younger are more at risk for developing VOD, diagnosed as hyperbilirubinemia, tender hepatomegaly, and ascites/weight gain after cyclosporine therapy, which may be represented by a criterion of plasma BILmax being ≥ 1.4 mg/dL, suggestive of more sensitive VOD indication in this age group. PMID:27358786

  7. Veno-occlusive disease of the liver in the absence of elevation in bilirubin in pediatric patients after hematopoietic stem cell transplantation.

    PubMed

    Myers, Kasiani C; Dandoy, Christopher; El-Bietar, Javier; Davies, Stella M; Jodele, Sonata

    2015-02-01

    Veno-occlusive disease (VOD) of the liver is a well-described and significant complication of hematopoietic stem cell transplantation (HSCT), with limited successful therapeutic options in severe cases. Prompt diagnosis and initiation of treatment is crucial to restrict the extent of disease. However, a subset of patients may not meet all current diagnostic criteria at presentation, and waiting for these to be met may delay therapy. We retrospectively reviewed 794 HSCT patients treated at our institution between 2003 and 2013, identifying 17 (2.1%) who developed VOD. Of these, 5 (29%) were noted to have an absence of elevated bilirubin at the time of VOD diagnosis and reversal of portal venous flow on ultrasound. Median total and conjugated bilirubin at VOD diagnosis were 1.0 and 0.2 mg/dL, respectively. All 5 patients were subsequently diagnosed with multiorgan failure associated with VOD, including 1 with encephalopathy. Four were treated with intravenous high-dose methylprednisolone (500 mg/m(2) per dose every 12 hours for 6 doses). One patient received defibrotide therapy in addition to steroids and another supportive care alone. VOD resolved in 4 of 5 patients, with median time to resolution of VOD, defined as recovery of all organ function and normalization of bilirubin and portal venous flow, of 8 days. Two patients died later from progressive primary disease and chronic graft-versus-host disease, respectively. We conclude that a high index of suspicion for VOD should be maintained in patients despite lack of bilirubin elevation in the presence of other diagnostic criteria such as hepatomegaly, abdominal pain, ascites, or weight gain. Early ultrasound evaluation in these patients may lead to more timely diagnosis and therapeutic interventions.

  8. PRD125, a potent and selective inhibitor of sterol O-acyltransferase 2 markedly reduces hepatic cholesteryl ester accumulation and improves liver function in lysosomal acid lipase-deficient mice.

    PubMed

    Lopez, Adam M; Chuang, Jen-Chieh; Posey, Kenneth S; Ohshiro, Taichi; Tomoda, Hiroshi; Rudel, Lawrence L; Turley, Stephen D

    2015-11-01

    In most organs, the bulk of cholesterol is unesterified, although nearly all possess a varying capability of esterifying cholesterol through the action of either sterol O-acyltransferase (SOAT) 1 or, in the case of hepatocytes and enterocytes, SOAT2. Esterified cholesterol (EC) carried in plasma lipoproteins is hydrolyzed by lysosomal acid lipase (LAL) when they are cleared from the circulation. Loss-of-function mutations in LIPA, the gene that encodes LAL, result in Wolman disease or cholesteryl ester storage disease (CESD). Hepatomegaly and a massive increase in tissue EC levels are hallmark features of both disorders. While these conditions can be corrected with enzyme replacement therapy, the question arose as to whether pharmacological inhibition of SOAT2 might reduce tissue EC accretion in CESD. When weaned at 21 days, Lal(-/-) mice, of either gender, had a whole liver cholesterol content that was 12- to 13-fold more than that of matching Lal(+/+) littermates (23 versus 1.8 mg, respectively). In Lal(-/-) males given the selective SOAT2 inhibitor PRD125 1,11-O-o-methylbenzylidene-7-O-p-cyanobenzoyl-1,7,11-trideacetylpyripyropene A in their diet (∼10 mg/day per kg body weight) from 21 to 53 days, whole liver cholesterol content was 48.6 versus 153.7 mg in untreated 53-day-old Lal(-/-) mice. This difference reflected a 59% reduction in hepatic EC concentration (mg/g), combined with a 28% fall in liver mass. The treated mice also showed a 63% reduction in plasma alanine aminotransferase activity, in parallel with decisive falls in hepatic mRNA expression levels for multiple proteins that reflect macrophage presence and inflammation. These data implicate SOAT2 as a potential target in CESD management.

  9. Hepatic entrapment of esterified cholesterol drives continual expansion of whole body sterol pool in lysosomal acid lipase-deficient mice.

    PubMed

    Aqul, Amal; Lopez, Adam M; Posey, Kenneth S; Taylor, Anna M; Repa, Joyce J; Burns, Dennis K; Turley, Stephen D

    2014-10-15

    Cholesteryl ester storage disease (CESD) results from loss-of-function mutations in LIPA, the gene that encodes lysosomal acid lipase (LAL). Hepatomegaly and deposition of esterified cholesterol (EC) in multiple organs ensue. The present studies quantitated rates of synthesis, absorption, and disposition of cholesterol, and whole body cholesterol pool size in a mouse model of CESD. In 50-day-old lal(-/-) and matching lal(+/+) mice fed a low-cholesterol diet, whole animal cholesterol content equalled 210 and 50 mg, respectively, indicating that since birth the lal(-/-) mice sequestered cholesterol at an average rate of 3.2 mg·day(-1)·animal(-1). The proportion of the body sterol pool contained in the liver of the lal(-/-) mice was 64 vs. 6.3% in their lal(+/+) controls. EC concentrations in the liver, spleen, small intestine, and lungs of the lal(-/-) mice were elevated 100-, 35-, 15-, and 6-fold, respectively. In the lal(-/-) mice, whole liver cholesterol synthesis increased 10.2-fold, resulting in a 3.2-fold greater rate of whole animal sterol synthesis compared with their lal(+/+) controls. The rate of cholesterol synthesis in the lal(-/-) mice exceeded that in the lal(+/+) controls by 3.7 mg·day(-1)·animal(-1). Fractional cholesterol absorption and fecal bile acid excretion were unchanged in the lal(-/-) mice, but their rate of neutral sterol excretion was 59% higher than in their lal(+/+) controls. Thus, in this model, the continual expansion of the body sterol pool is driven by the synthesis of excess cholesterol, primarily in the liver. Despite the severity of their disease, the median life span of the lal(-/-) mice was 355 days.

  10. PRD125, a Potent and Selective Inhibitor of Sterol O-Acyltransferase 2 Markedly Reduces Hepatic Cholesteryl Ester Accumulation and Improves Liver Function in Lysosomal Acid Lipase-Deficient Mice

    PubMed Central

    Lopez, Adam M.; Chuang, Jen-Chieh; Posey, Kenneth S.; Ohshiro, Taichi; Tomoda, Hiroshi; Rudel, Lawrence L.

    2015-01-01

    In most organs, the bulk of cholesterol is unesterified, although nearly all possess a varying capability of esterifying cholesterol through the action of either sterol O-acyltransferase (SOAT) 1 or, in the case of hepatocytes and enterocytes, SOAT2. Esterified cholesterol (EC) carried in plasma lipoproteins is hydrolyzed by lysosomal acid lipase (LAL) when they are cleared from the circulation. Loss-of-function mutations in LIPA, the gene that encodes LAL, result in Wolman disease or cholesteryl ester storage disease (CESD). Hepatomegaly and a massive increase in tissue EC levels are hallmark features of both disorders. While these conditions can be corrected with enzyme replacement therapy, the question arose as to whether pharmacological inhibition of SOAT2 might reduce tissue EC accretion in CESD. When weaned at 21 days, Lal−/− mice, of either gender, had a whole liver cholesterol content that was 12- to 13-fold more than that of matching Lal+/+ littermates (23 versus 1.8 mg, respectively). In Lal−/− males given the selective SOAT2 inhibitor PRD125 1,11-O-o-methylbenzylidene-7-O-p-cyanobenzoyl-1,7,11-trideacetylpyripyropene A in their diet (∼10 mg/day per kg body weight) from 21 to 53 days, whole liver cholesterol content was 48.6 versus 153.7 mg in untreated 53-day-old Lal−/− mice. This difference reflected a 59% reduction in hepatic EC concentration (mg/g), combined with a 28% fall in liver mass. The treated mice also showed a 63% reduction in plasma alanine aminotransferase activity, in parallel with decisive falls in hepatic mRNA expression levels for multiple proteins that reflect macrophage presence and inflammation. These data implicate SOAT2 as a potential target in CESD management. PMID:26283692

  11. Deletion of sterol O-acyltransferase 2 (SOAT2) function in mice deficient in lysosomal acid lipase (LAL) dramatically reduces esterified cholesterol sequestration in the small intestine and liver.

    PubMed

    Lopez, Adam M; Posey, Kenneth S; Turley, Stephen D

    2014-11-07

    Sterol O-acyltransferase 2 (SOAT2), also known as ACAT2, is the major cholesterol esterifying enzyme in the liver and small intestine (SI). Esterified cholesterol (EC) carried in certain classes of plasma lipoproteins is hydrolyzed by lysosomal acid lipase (LAL) when they are cleared from the circulation. Loss-of-function mutations in LIPA, the gene that encodes LAL, result in Wolman disease (WD) or cholesteryl ester storage disease (CESD). Hepatomegaly and a massive increase in tissue EC levels are hallmark features of both disorders. While these conditions can be corrected with enzyme replacement therapy, the question arose as to what effect the loss of SOAT2 function might have on tissue EC sequestration in LAL-deficient mice. When weaned at 21 days, Lal(-)(/)(-):Soat2(+)(/)(+) mice had a whole liver cholesterol content (mg/organ) of 24.7 mg vs 1.9mg in Lal(+/+):Soat2(+/+) littermates, with almost all the excess sterol being esterified. Over the next 31 days, liver cholesterol content in the Lal(-)(/)(-):Soat2(+)(/)(+) mice increased to 145 ± 2 mg but to only 29 ± 2 mg in their Lal(-)(/)(-):Soat2(-)(/)(-) littermates. The level of EC accumulation in the SI of the Lal(-)(/)(-):Soat2(-)(/)(-) mice was also much less than in their Lal(-)(/)(-):Soat2(+)(/)(+) littermates. In addition, there was a >70% reduction in plasma transaminase activities in the Lal(-)(/)(-):Soat2(-)(/)(-) mice. These studies illustrate how the severity of disease in a mouse model for CESD can be substantially ameliorated by elimination of SOAT2 function.

  12. TRIM37 defective in mulibrey nanism is a novel RING finger ubiquitin E3 ligase

    SciTech Connect

    Kallijaervi, Jukka; Lahtinen, Ulla; Haemaelaeinen, Riikka; Lipsanen-Nyman, Marita; Palvimo, Jorma J.; Lehesjoki, Anna-Elina . E-mail: anna-elina.lehesjoki@helsinki.fi

    2005-08-01

    Mulibrey nanism is an autosomal recessive prenatal-onset growth disorder characterized by dysmorphic features, cardiomyopathy, and hepatomegaly. Mutations in TRIM37 encoding a tripartite motif (TRIM, RING-B-box-coiled-coil)-family protein underlie mulibrey nanism. We investigated the ubiquitin ligase activity predicted for the RING domain of TRIM37 by analyzing its autoubiquitination. Full-length TRIM37 and its TRIM domain were highly polyubiquitinated when co-expressed with ubiquitin. Polyubiquitination was decreased in a mutant protein with disrupted RING domain (Cys35Ser;Cys36Ser) and in the Leu76Pro mutant protein, a disease-associated missense mutation affecting the TRIM domain of TRIM37. Bacterially produced GST-TRIM domain fusion protein, but not its Cys35Ser;Cys36Ser or Leu76Pro mutants, were polyubiquitinated in cell-free conditions, implying RING-dependent modification. Ubiquitin was also identified as an interaction partner for TRIM37 in a yeast two-hybrid screen. Ectopically expressed TRIM37 rapidly formed aggregates that were ubiquitin-, proteasome subunit-, and chaperone-positive in immunofluorescence analysis, defining them as aggresomes. The Cys35Ser;Cys36Ser mutant and the Leu76Pro and Gly322Val patient mutant proteins were markedly less prone to aggregation, implying that aggresomal targeting reflects a physiological function of TRIM37. These findings suggest that TRIM37 acts as a TRIM domain-dependent E3 ubiquitin ligase and imply defective ubiquitin-dependent degradation of an as-yet-unidentified target protein in the pathogenesis of mulibrey nanism.

  13. Cystic fibrosis-related liver disease: a single-center experience.

    PubMed

    Costa, Paula Catarino; Barreto, Celeste Canha; Pereira, Luisa; Lobo, Maria Luisa; Costa, Maria Adília; Lopes, Ana Isabel Gouveia

    2011-06-30

    Prospective studies concerning liver disease in pediatric cystic fibrosis patients are scarce. The present study aimed to describe the prevalence and clinical expression of cystic fibrosis - related liver disease, in a cohort of 62 pediatric patients. Descriptive study, resulting from the prospective evaluation, between 1994 and 2009, of 62 pediatric patients (age <18 years) with cystic fibrosis. The follow-up protocol included a clinical assessment every 2 months, liver function tests every 6 months and annual liver ultrasonography. The cumulative prevalence of liver disease was 11.2% (7/62 cases). All patients had ΔF508 mutation and pancreatic insufficiency, none had meconium ileus. The liver involvement became clinically evident at a mean age of 8 years (3-15 years), revealed by hepatomegaly or hepatosplenomegaly (3 cases) and/ or abnormalities of liver function tests (3 cases) changes of liver ultrasound (7 cases) with evidence of portal hypertension (2 cases). Four patients were submitted to liver biopsy; biliary fibrosis was documented in one case, focal biliary cirrhosis in 2 cases and multilobular cirrhosis in another case. Within a median 11.6 years follow-up period (all patients under UDCA therapy after liver disease diagnosis), progression of liver disease was observed in 2 patients; one patient developed refractory variceal bleeding and progressive hepatic failure, requiring liver transplant. The results of the present study agree with those of previous pediatric studies, further documenting clinical expression of liver disease in CF patients, which is usually detected in the first decade of life and emphasize the contribution of ultrasound to early diagnosis of liver involvement. Moreover, although advanced liver disease is a relatively rare event, early isolated liver transplantation may have to be considered at this age group.

  14. PGC-1{beta} regulates mouse carnitine-acylcarnitine translocase through estrogen-related receptor {alpha}

    SciTech Connect

    Gacias, Mar; Perez-Marti, Albert; Pujol-Vidal, Magdalena; Marrero, Pedro F.; Haro, Diego; Relat, Joana

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer The Cact gene is induced in mouse skeletal muscle after 24 h of fasting. Black-Right-Pointing-Pointer The Cact gene contains a functional consensus sequence for ERR. Black-Right-Pointing-Pointer This sequence binds ERR{alpha} both in vivo and in vitro. Black-Right-Pointing-Pointer This ERRE is required for the activation of Cact expression by the PGC-1/ERR axis. Black-Right-Pointing-Pointer Our results add Cact as a genuine gene target of these transcriptional regulators. -- Abstract: Carnitine/acylcarnitine translocase (CACT) is a mitochondrial-membrane carrier proteins that mediates the transport of acylcarnitines into the mitochondrial matrix for their oxidation by the mitochondrial fatty acid-oxidation pathway. CACT deficiency causes a variety of pathological conditions, such as hypoketotic hypoglycemia, cardiac arrest, hepatomegaly, hepatic dysfunction and muscle weakness, and it can be fatal in newborns and infants. Here we report that expression of the Cact gene is induced in mouse skeletal muscle after 24 h of fasting. To gain insight into the control of Cact gene expression, we examine the transcriptional regulation of the mouse Cact gene. We show that the 5 Prime -flanking region of this gene is transcriptionally active and contains a consensus sequence for the estrogen-related receptor (ERR), a member of the nuclear receptor family of transcription factors. This sequence binds ERR{alpha}in vivo and in vitro and is required for the activation of Cact expression by the peroxisome proliferator-activated receptor gamma coactivator (PGC)-1/ERR axis. We also demonstrate that XTC790, the inverse agonist of ERR{alpha}, specifically blocks Cact activation by PGC-1{beta} in C2C12 cells.

  15. Early onset of Chanarin-Dorfman syndrome with severe liver involvement in a patient with a complex rearrangement of ABHD5 promoter

    PubMed Central

    2014-01-01

    Background α/β-hydrolase domain-containing protein 5 (ABHD5) plays an important role in the triacylglycerols (TAG) hydrolysis. Indeed, ABHD5 is the co-activator of adipose triglyceride lipase (ATGL), that catalyses the initial step of TAG hydrolysis. Mutations in ABHD5 gene are associated with the onset of Chanarin-Dorfman syndrome (CDS), a rare autosomal recessive lipid storage disorder, characterized by non-bullous congenital ichthyosiform erythroderma (NCIE), hepatomegaly and liver steatosis. Case presentation We describe here a 5-years-old Brazilian child who presented with NCIE at birth and diffuse micro and macro-vesicular steatosis on liver biopsy since she was 2 years old. Molecular analysis of coding sequence and putative 5′ regulatory region of ABHD5 gene was performed. A homozygous novel deletion, affecting the promoter region and the exon 1, was identified, confirming the suspected diagnosis of CDS for this patient. RT-PCR analysis showed that the genomic rearrangement completely abolished the ABHD5 gene expression in the patient, while only a partial loss of expression was detected in her parents. This is the first report describing the identification of a large deletion encompassing the promoter region of ABHD5 gene. The total loss of ABHD5 expression may explain the early onset of CDS and the severe liver involvement. After molecular diagnosis, the patient started a special diet, poor in fatty acids with medium chain triglycerides (MCT), and showed hepatic and dermatologic improvement in spite of severe molecular defect. Conclusions This case report extends the spectrum of disease-causing ABHD5 mutations in CDS providing evidence for a novel pathogenic mechanism for this rare disorder. Moreover, our preliminary data show that early diagnosis and prompt treatment of neutral lipid accumulation might be useful for CD patients. PMID:24628803

  16. Effects of Boswellia serrata in mouse models of chemically induced colitis.

    PubMed

    Kiela, Pawel R; Midura, Anna J; Kuscuoglu, Nesrin; Jolad, Shivanand D; Sólyom, Anikó M; Besselsen, David G; Timmermann, Barbara N; Ghishan, Fayez K

    2005-04-01

    Extracts from Boswellia serrata have been reported to have anti-inflammatory activity, primarily via boswellic acid-mediated inhibition of leukotriene synthesis. In three small clinical trials, boswellia was shown to improve symptoms of ulcerative colitis and Crohn's disease, and because of its alleged safety, boswellia was considered superior over mesalazine in terms of a benefit-risk evaluation. The goal of this study was to evaluate the effectiveness of boswellia extracts in controlled settings of dextran sulfate- or trinitrobenzene sulfonic acid-induced colitis in mice. Our results suggest that boswellia is ineffective in ameliorating colitis in these models. Moreover, individual boswellic acids were demonstrated to increase the basal and IL-1beta-stimulated NF-kappaB activity in intestinal epithelial cells in vitro as well as reverse proliferative effects of IL-1beta. We also observed hepatotoxic effect of boswellia with pronounced hepatomegaly and steatosis. Hepatotoxity and increased lipid accumulation in response to boswellia were further confirmed in vitro in HepG2 cells with fluorescent Nile red binding/resazurin reduction assay and by confocal microscopy. Microarray analyses of hepatic gene expression demonstrated dysregulation of a number of genes, including a large group of lipid metabolism-related genes, and detoxifying enzymes, a response consistent with that to hepatotoxic xenobiotics. In summary, boswellia does not ameliorate symptoms of colitis in chemically induced murine models and, in higher doses, may become hepatotoxic. Potential implications of prolonged and uncontrolled intake of boswellia as an herbal supplement in inflammatory bowel disease and other inflammatory conditions should be considered in future clinical trials with this botanical.

  17. Visceral leishmaniasis in Malta—an 18 year paediatric, population based study

    PubMed Central

    Grech, V.; Mizzi, J.; Mangion, M.; Vella, C.

    2000-01-01

    BACKGROUND—Visceral leishmaniasis (VL) is a chronic parasitic infection that infects approximately 400 000 individuals annually, with a predilection towards early childhood.
AIMS—To study the epidemiology of VL in childhood.
METHODS—VL is endemic in Malta, a small archipelago of islands in the centre of the Mediterranean with a total population approaching half a million. Notification of human cases of leishmaniasis is compulsory. Case records of all 81 paediatric patients with VL between 1980 and 1998 were analysed.
RESULTS—The annual incidence of VL declined for all cases of VL, and declined significantly for paediatric cases (p = 0.01). For 1994to 1998, the overall incidence of VL was 0.9 per 100 000 total population and the paediatric incidence was 2.5 per 100 000 population. Median age at presentation was 34 months. Common features at presentation were splenomegaly, hepatomegaly, fever, and pancytopenia with high lymphocyte and monocyte counts. The diagnostic sensitivity of isolated immunofluorescent antibody testing was equivalent to bone marrow aspiration (95%). Blood transfusions for anaemia were required in 93% of patients. Eleven per cent had intercurrent infections. All patients were cured, and were initially treated with intravenous sodium stibogluconate. Defervescence occurred after a median of six days of treatment, and patients continued to be treated on a day case basis. Nine relapsers were retreated with sodium stibogluconate, achieving a cure rate of 94%, but five patients required additional drug therapy. There were no permanent sequelae associated with VL or its treatment.
CONCLUSIONS—The decreased incidence is attributed to the eradication of stray dogs which are the disease reservoir.

 PMID:10799428

  18. Secondary disorders of glycosylation in inborn errors of fructose metabolism.

    PubMed

    Quintana, E; Sturiale, L; Montero, R; Andrade, F; Fernandez, C; Couce, M L; Barone, R; Aldamiz-Echevarria, L; Ribes, A; Artuch, R; Briones, P

    2009-12-01

    Adamowicz and colleagues raised the alert in 2007 about patients with atypical hereditary fructose intolerance (HFI) primarily misdiagnosed as CDG Ix. We describe a girl with neonatal hypertonia, facial trismus, absent swallowing and coughing reflexes, gastro-oesophageal reflux and sporadically elevated Krebs cycle metabolites and lactate. At 14 months microcephaly and hepatomegaly were noted, with hypertransaminasaemia but normal blood coagulation, glucose, phosphate, and absent urinary reducing substances. Neurological impairment persisted. Because of hepatic and neurological abnormalities with developmental delay, Tf IEF was performed and showed a severe type 1 pattern, resulting in a wrong diagnosis of CDG. Subsequently, an aversion to fruits suggested HFI, confirmed by the finding of ALDOB mutations (p.A150P/p.N335K). The girl improved with fructose-free diet, but liver cirrhosis led to hepatic transplantation. She is now 7 years old with good evolution; facial trismus and hypertonia reversed, but microcephaly persists. Transferrin MALDI-TOF MS characterization revealed underoccupation of glycosylation sites and glycan abnormalities, which reversed with dietary treatment. High maternal fructose concentrations might have caused neonatal abnormalities. Although in our patient's mother there is no fructose accumulation at present, it is possible that increased ingestion of fruits and vegetables during pregnancy, together with her heterozygosity, caused an accumulation of fructose that finally affected the fetus. We also describe slightly abnormal transferrin isoelectric focusing and MALDI-TOF MS patterns of intact transferrin and N-glycans in a fructose-1,6-bisphosphatase (FBP1)-deficient patient. While HFI is a well-known cause of secondary CDG, we found no reports of abnormal transferrin isoelectric focusing patterns in FBP1 deficiency and we introduce this condition as a possible secondary cause for altered transferrin isoelectric focusing.

  19. Doctor, my son is so tired... about a case of hereditary fructose intolerance.

    PubMed

    Guery, M J; Douillard, C; Marcelli-Tourvieille, S; Dobbelaere, D; Wemeau, J L; Vantyghem, M C

    2007-12-01

    We present the case of a 17-year-old male who was diagnosed at birth with hereditary fructose intolerance (HFI). The patient complained of morning-time asthenia and post-prandial drowsiness despite a correct sleep pattern. The physical examination and biological check-up only showed severe vitamin C deficiency (<10 mol/l; normal range: 26-84). The patient's tiredness was attributed to this vitamin C deficiency, which is a frequent side-affect of the fructose-free diet. A change in diet associated with a supplementation in vitamin C was advised, with an increase in vegetable intake, principally avoiding carrots, onions, leaks and tinned sweet-corn. This case offers the opportunity for a review of this rare disease. Two kinds of fructose metabolism disorders (both autosomal recessive) are recognized: 1) essential fructosuria caused by a deficiency of fructokinase, which has no clinical consequence and requires no dietary treatment; 2) HFI, linked to three main mutations identified in aldolase B gene that may be confirmed by fructose breath test, intravenous fructose tolerance test, and genetic testing. In HFI, fructose ingestion generally induces gastro-intestinal (nausea and vomiting, abdominal pain, meteorism) and hypoglycemic symptoms. Fasting is well tolerated. If the condition remains undiagnosed, it leads to liver disease with hepatomegaly, proximal tubular dysfunction, and slow growth and weight gain. In conclusion, endocrinologists should be aware of this rare metabolic disease in order to provide careful follow-up, particularly important when the patient reaches adulthood. Moreover, hypoglycemia induced by fructose absorption, unexplained liver disease, irritable bowel syndrome or familial gout in an adult is suggestive of the diagnosis.

  20. Clinical and Molecular Characterization of Patients with Mucopolysaccharidosis Type I in an Algerian Series

    PubMed Central

    Tebani, Abdellah; Zanoutene-Cheriet, Lahouaria; Adjtoutah, Zoubir; Abily-Donval, Lenaig; Brasse-Lagnel, Carole; Laquerrière, Annie; Marret, Stephane; Chalabi Benabdellah, Abla; Bekri, Soumeya

    2016-01-01

    Mucopolysaccharidoses (MPS’s) represent a subgroup of lysosomal storage diseases related to a deficiency of enzymes that catalyze glycosaminoglycans degradation. Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disorder caused by a deficiency of α-l-iduronidase encoded by the IDUA gene. Partially degraded heparan sulfate and dermatan sulfate accumulate progressively and lead to multiorgan dysfunction and damage. The aim of this study is to describe the clinical, biochemical, and molecular characteristics of 13 Algerian patients from 11 distinct families. MPS I diagnosis was confirmed by molecular study of the patients’ IDUA gene. Clinical features at the diagnosis and during the follow-up are reported. Eighty-four percent of the studied patients presented with a mild clinical phenotype. Molecular study of the IDUA gene allowed the characterization of four pathological variations at the homozygous or compound heterozygote status: IDUA NM_00203.4:c.1598C>G-p.(Pro533Arg) in 21/26 alleles, IDUA NM_00203.4:c.532G>A-p.(Glu178Lys) in 2/26 alleles, IDUA NM_00203.4:c.501C>G-p.(Tyr167*) in 2/26 alleles, and IDUA NM_00203. 4: c.1743C>G-p.(Tyr581*) in 1/26 alleles. This molecular study unveils the predominance of p.(Pro533Arg) variation in our MPS I patients. In this series, the occurrence of some clinical features linked to the Scheie syndrome is consistent with the literature, such as systematic valvulopathies, corneal opacity, and umbilical hernia; however, storage signs, facial dysmorphic features, and hepatomegaly were more frequent in our series. Screening measures for these debilitating diseases in highly consanguineous at-risk populations must be considered a priority health problem. PMID:27196898

  1. Fatty Liver and Insulin Resistance in the Liver-Specific Knockout Mice of Mitogen Inducible Gene-6

    PubMed Central

    Park, Byung Kil; Kim, Hee-Youn; Lee, Jun Choul; Kim, Koon Soon; Jeong, Won Hoon; Kim, Ki Young

    2016-01-01

    Mitogen inducible gene-6 (Mig-6) is a feedback inhibitor of epidermal growth factor receptor (EGFR) signaling pathway. The liver-specific knockout mice of the Mig-6 gene (Mig-6d/d) showed hepatomegaly and increased hypercholesterolemia. In this study, the biomarkers of insulin resistance and the effects of high-fat diets in the wild (Mig-6f/f) and Mig-6d/d mice were analyzed. The fasting plasma concentrations of glucose, triglyceride, cholesterols, free fatty acids, and HOMA-IR were measured and the glucose tolerance and insulin resistance tests were performed in the 25-week-old Mig-6f/f and the Mig-6d/d mice. The protein levels of active insulin receptor, glucose 6-phosphatase, and phosphoenolpyruvate carboxykinase were analyzed in the liver and fat. The fasting plasma cholesterol and glucose concentration were higher in the Mig-6d/d mice than the Mig-6f/f mice with increased fat deposition in the liver. But the Mig-6d/d mice had the improved glucose intolerance and insulin resistance without increased amount of phosphoinsulin receptor after insulin infusion in the liver. The hepatic concentration of phosphoenolpyruvate carboxykinase was increased in fasting Mig-6d/d mice. The feeding of high-fat diet accelerated the plasma lipids profiles and HOMA-IR in the Mig-6d/d mice but had no differential effects in oral glucose tolerance test and insulin tolerance test in both genotypes. These results suggest that the activated EGFR signaling might increase the fasting plasma glucose concentration through inducing the hepatic steatosis and the improved whole-body insulin resistance in the KO mice be caused by decreased adipogenesis in fat tissues. PMID:28053990

  2. Unusual Presentation of Diffuse Large B-Cell Lymphoma With Splenic Infarcts

    PubMed Central

    Kumar, Vivek; Soni, Parita; Dave, Vishangi; Harris, Jonathan

    2017-01-01

    A 67-year-old man presented with a 3-day history of abdominal pain, fever, and significant weight loss over 2 months. Physical examination revealed left upper quadrant tenderness, hepatomegaly, splenomegaly, and bilateral pitting edema but peripheral lymphadenopathy was absent. Laboratory tests showed anemia, thrombocytopenia, elevated prothrombin time (PT), partial thromboplastin time (PTT), and increased lactate dehydrogenase (LDH). PTT was corrected completely in mixing study. Further workup for the cause of coagulopathy revealed decreased levels of all clotting factors except factor VIII and increase fibrinogen levels, which ruled out disseminated intravascular coagulation (DIC). Flow cytometry of peripheral blood was normal. Contrast-enhanced computed tomography (CECT) revealed splenomegaly with multiple splenic infarcts without any mediastinal or intraabdominal lymphadenopathy. Further investigations for infective endocarditis (blood cultures and transthoracic echocardiography) and autoimmune disorders (ANA, dsDNA, RA factors) were negative. The patient received treatment for sepsis empirically without any significant clinical improvement. The diagnosis remained unclear despite extensive workup and liver biopsy was conducted due to high suspicion of granulomatous diseases. However, the liver biopsy revealed high-grade diffuse large B-cell lymphoma (DLBCL). Unfortunately, patient died shortly after the diagnosis. Here we report a case of high-grade DLBCL with hepatosplenomegaly and splenic infarcts in the absence of any lymphadenopathy or focal lesions. This case highlights the fact that unusually lymphoma can present in the absence of lymphadenopathy or mass lesion mimicking autoimmune and granulomatous disorders. The diagnosis in these cases can only be made on histology, and hence the threshold for biopsy should be low in patients with unclear presentations and multiorgan involvement. PMID:28203580

  3. Attenuation of 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity by resveratrol: a comparative study with different routes of administration.

    PubMed

    Ishida, Takumi; Takeda, Tomoki; Koga, Takayuki; Yahata, Masahiro; Ike, Ayako; Kuramoto, Chihiro; Taketoh, Junko; Hashiguchi, Isamu; Akamine, Akifumi; Ishii, Yuji; Yamada, Hideyuki

    2009-05-01

    The activation of aryl hydrocarbon receptor with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to be antagonized by co-treatment with resveratrol. However, such a protective effect has been suggested from studies using subcutaneous injection of this polyphenol. To evaluate the practical usefulness of resveratrol, this study examined the protective effect of oral resveratrol on the sub-acute toxic effects of TCDD in C57BL/6J mice. A TCDD-induced wasting syndrome was not alleviated by treating mice for 28 d with oral resveratrol. However, subcutaneous injection of resveratrol for 5 d significantly improved the symptoms. Neither oral nor subcutaneous administration of resveratrol alleviated TCDD-induced hepatomegaly and thymic atrophy. Steatosis produced by TCDD was markedly counteracted by co-treatment with oral resveratrol, whereas resveratrol injected subcutaneously had no effect. The reason for the lack of protective effect via the latter dosing route was assumed to be due to the minor accumulation of hepatic lipids 5 d after TCDD treatment. To clarify the mechanisms, the activity of ethoxyresorufin O-deethylase and the content of thiobarbituric acid-reactive substances in the liver were measured. Both indices increased by TCDD treatment were significantly suppressed by subcutaneous injection of resveratrol. In contrast, oral resveratrol failed to rescue them. In agreement with the greater protective effects of subcutaneously-injected resveratrol, pharmacokinetic studies indicated that the area under the curve extrapolated to infinity (AUC(infinity)) was 8.2-times greater following subcutaneous injection compared with oral administration. These data suggest that 1) oral resveratrol is attractive candidate as an agent capable of combating dioxin toxicity and 2) increasing the bioavailability of this polyphenol enhances its protective effect.

  4. Polybrominated diphenyl ether (PBDE)-induced alterations in vitamin A and thyroid hormone concentrations in the rat during lactation and early postnatal development

    SciTech Connect

    Ellis-Hutchings, Robert G.; Cherr, Gary N.; Hanna, Lynn A.; Keen, Carl L. . E-mail: clkeen@ucdavis.edu

    2006-09-01

    In experimental animals fed standard laboratory diets, penta-BDE mixtures can decrease circulating thyroid hormone and liver vitamin A concentrations. A substantial number of pregnant women and their children have marginal vitamin A status, potentially increasing their risk of adverse effects to penta-BDE exposure. The current study investigated the effects of maternal gestational and lactational penta-BDE exposure on thyroid hormone and vitamin A homeostasis in rats of sufficient vitamin A (VAS) or marginal vitamin A (VAM) status and their offspring. Dams were administered daily oral doses of 18 mg/kg DE-71 (a penta-BDE mixture) or a corn oil vehicle from gestation day 6 through lactation day (LD) 18. Thyroid hormone and vitamin A homeostasis were assessed in plasma and tissues of LD 19 dams and postnatal day (PND) 12, 18, and 31 pups. DE-71 exposure induced hepatomegaly in VAS and VAM pups at all timepoints and increased testes weights at PND 31. While liver vitamin A concentrations were low in DE-71 treated dams and pups, plasma retinol concentrations and plasma retinol binding protein levels were only low in VAM animals exposed to DE-71. DE-71 exposure lowered plasma thyroxine concentrations in VAS and VAM dams and pups. Plasma thyroid stimulating hormone concentrations were high in VAM dams exposed to DE-71, suggesting that marginal vitamin A status enhances the susceptibility to thyroid hormone axis disruption by DE-71. These results support the concept that marginal vitamin A status in pregnant women may increase the risk for PBDE-induced disruptions in vitamin A and thyroid hormone homeostasis.

  5. Rescuing effects of RXR agonist bexarotene on aging-related synapse loss depend on neuronal LRP1.

    PubMed

    Tachibana, Masaya; Shinohara, Mitsuru; Yamazaki, Yu; Liu, Chia-Chen; Rogers, Justin; Bu, Guojun; Kanekiyo, Takahisa

    2016-03-01

    Apolipoprotein E (apoE) plays a critical role in maintaining synaptic integrity by transporting cholesterol to neurons through the low-density lipoprotein receptor related protein-1 (LRP1). Bexarotene, a retinoid X receptor (RXR) agonist, has been reported to have potential beneficial effects on cognition by increasing brain apoE levels and lipidation. To investigate the effects of bexarotene on aging-related synapse loss and the contribution of neuronal LRP1 to the pathway, forebrain neuron-specific LRP1 knockout (nLrp1(-/-)) and littermate control mice were administered with bexarotene-formulated diet (100mg/kg/day) or control diet at the age of 20-24 months for 8 weeks. Upon bexarotene treatment, levels of brain apoE and ATP-binding cassette sub-family A member 1 (ABCA1) were significantly increased in both mice. While levels of PSD95, glutamate receptor 1 (GluR1), and N-methyl-d-aspartate receptor NR1 subunit (NR1), which are key postsynaptic proteins that regulate synaptic plasticity, were decreased with aging, they were restored by bexarotene treatment in the brains of control but not nLrp1(-/-) mice. These results indicate that the beneficial effects of bexarotene on synaptic integrity depend on the presence of neuronal LRP1. However, we also found that bexarotene treatment led to the activation of glial cells, weight loss and hepatomegaly, which are likely due to hepatic failure. Taken together, our results demonstrate that apoE-targeted treatment through the RXR pathway has a potential beneficial effect on synapses during aging; however, the therapeutic application of bexarotene requires extreme caution due to its toxic side effects.

  6. Can non-human primates serve as models for investigating dengue disease pathogenesis?

    PubMed Central

    Clark, Kristina B.; Onlamoon, Nattawat; Hsiao, Hui-Mien; Perng, Guey C.; Villinger, Francois

    2013-01-01

    Dengue Virus (DV) infects between 50 and 100 million people globally, with public health costs totaling in the billions. It is the causative agent of dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), vector-borne diseases that initially predominated in the tropics. Due to the expansion of its mosquito vector, Aedes spp., DV is increasingly becoming a global problem. Infected individuals may present with a wide spectrum of symptoms, spanning from a mild febrile to a life-threatening illness, which may include thrombocytopenia, leucopenia, hepatomegaly, hemorrhaging, plasma leakage and shock. Deciphering the underlining mechanisms responsible for these symptoms has been hindered by the limited availability of animal models that can induce classic human pathology. Currently, several permissive non-human primate (NHP) species and mouse breeds susceptible to adapted DV strains are available. Though virus replication occurs in these animals, none of them recapitulate the cardinal features of human symptomatology, with disease only occasionally observed in NHPs. Recently our group established a DV serotype 2 intravenous infection model with the Indian rhesus macaque, which reliably produced cutaneous hemorrhages after primary virus exposure. Further manipulation of experimental parameters (virus strain, immune cell expansion, depletion, etc.) can refine this model and expand its relevance to human DF. Future goals include applying this model to elucidate the role of pre-existing immunity upon secondary infection and immunopathogenesis. Of note, virus titers in primates in vivo and in vitro, even with our model, have been consistently 1000-fold lower than those found in humans. We submit that an improved model, capable of demonstrating severe pathogenesis may only be achieved with higher virus loads. Nonetheless, our DV coagulopathy disease model is valuable for the study of select pathomechanisms and testing DV drug and vaccine candidates

  7. Multiple genes exhibit phenobarbital-induced constitutive active/androstane receptor-mediated DNA methylation changes during liver tumorigenesis and in liver tumors.

    PubMed

    Phillips, Jennifer M; Goodman, Jay I

    2009-04-01

    The constitutive active/androstane receptor (CAR) mediates responses to the nongenotoxic rodent liver tumor promoter phenobarbital (PB), including certain gene expression changes, hepatomegaly, and tumor formation. Aberrant DNA methylation represents epigenetic events that can play multiple roles in tumorigenesis. Previously, 146 unique PB-induced regions of altered DNA methylation (RAMs) were observed in liver tumor-susceptible CAR wild-type (WT) mice (in 23 weeks, precancerous tissue, and 32 weeks, tumor tissue), as compared to the resistant knockout (KO). We believe that at least some of these might be key for tumorigenesis. In the current study, cloning and annotation of a subset (82%) of the unique RAMs revealed 47 genes exhibiting altered methylation; 17 are already implicated in cancer or related processes and, thus, we have identified 30 "new" candidate genes that might be involved in carcinogenesis due to an epigenetic alteration. These may contribute to tumor development through their involvement in angiogenesis, apoptosis, epithelial-mesenchymal cell transition, growth/survival, and invasion/migration/metastasis. We have also, previously, discerned unique PB-elicited RAMs in liver tumor-prone B6C3F1 mice, as compared to the relatively resistant C57BL/6 strain, at 2 or 4 weeks, and identified 51 genes exhibiting altered methylation. Importantly, 11 of these genes were identified from identical, unique RAMs discerned in both the sensitive B6C3F1 and CAR WT mice, thus representing an initial, potential candidate "fingerprint" which might serve as a biomarker for PB-induced tumorigenesis. These two studies reveal "new" genes whose epigenetic statuses changed uniquely in liver tumor-susceptible mice (B6C3F1 and CAR WT), as compared to their resistant counterparts (C57BL/6 and CAR KO, respectively), within a continuum of PB-induced tumorigenesis.

  8. Hepatic Alveolar Hydatid Cyst: A Brief Review of Published Cases from Iran in the Last 20 Years

    PubMed Central

    Geramizadeh, Bita; Baghernezhad, Mohammad

    2016-01-01

    Context Echinococcus multilocularis is the cause of alveolar hydatid disease, which most commonly involves the liver in more than 90% of cases. This disease is endemic in northern Iran. However, there are very few published cases from Iran. In this article, we will review all of the published cases of hepatic alveolar echinococcosis from Iran regarding all aspects, including clinical, paraclinical, and treatment protocols. Evidence Acquisition In this brief review, the published cases of hepatic Alveolar Echinococcosis (AE) from Iran were retrieved for review via a search in PubMed, Scopus, Google Scholar, IranMedex, scientific information database (SID), Magiran, and Irandoc (1995 - 2015) using the keywords Echinococcus multilocularis and Iran, Alveolar hydatid cyst and Iran, liver and Alveolar hydatid cyst and Iran, and Hepatic alveolar hydatid cyst and Iran. The following inclusion criteria were employed: 1, articles must be written in English or Farsi; 2, articles must have been published between 1995 and 2015; 3) cases must have been confirmed by pathological diagnosis. Results There were 24 published cases of liver-involved alveolar hydatid cyst from Iran. The disease was more common in young- to middle-aged women in northeast Iran. The most common presenting signs and symptoms were abdominal pain with hepatomegaly and liver mass. Most of the patients were treated by surgery and albendazole. The few unresectable liver masses were treated by medical therapy. No liver transplantation for this disease was reported from Iran. Conclusions Hepatic alveolar hydatid cyst should be considered one of the important differential diagnoses of liver masses, especially in endemic areas of the world. PMID:27882065

  9. Validation of an Excretory/Secretory Antigen Based-Elisa for the Diagnosis of Opisthorchis felineus Infection in Humans from Low Trematode Endemic Areas

    PubMed Central

    Gómez-Morales, Maria Angeles; Ludovisi, Alessandra; Amati, Marco; Pozio, Edoardo

    2013-01-01

    Since opisthorchiasis does not show pathognomonic signs or symptoms, physicians can have serious problems to make a differential diagnosis of this infection in non endemic areas, in particular when there is a simultaneous occurrence with other seasonal infections. Moreover, symptomatic infections due to O. felineus can last a few weeks and then the signs and symptoms disappear, but the worms survive in the bile ducts for years causing hepatobiliary diseases including hepatomegaly, cholangitis, fibrosis of the periportal system, cholecystitis, and gallstones. Consequently, an early diagnosis prevents chronicity and loss of working days. The detection of specific antibodies has been considered as a complementary tool to the fecal examination to establish the definitive diagnosis of this infection and for the follow up. Therefore the aim of this work was the development and validation of an enzyme-linked immunosorbent assay (ELISA) using excretory/secretory antigens (ESA) from O. felineus adult worms to detect anti-Opisthorchis IgG in human sera. A total of 370 human sera were tested: 144 sera from persons with a confirmed diagnosis of opisthorchiasis, 110 sera from healthy Italian people, and 116 sera from people with other parasitic or non-parasitic infections. Results were analyzed by receiver-operator characteristic (ROC) curve analysis. The accuracy of the test, calculated by the area under curve (AUC), yielded a 0.999 value, indicating the high performance of the test. The sensitivity was 100% (95% CI: 97.40% to 100%) and no false-negative sera were detected; the specificity was 99.09% (95% CI: 95.02% to 99.83%). The validated ELISA shows a good performance in terms of sensitivity, repeatability and reproducibility, and it is suitable to detect anti-Opisthorchis IgG in human sera for diagnostic purposes and for the follow up to assess the efficacy of drug treatment. PMID:23671589

  10. [Tumorous actinomycosis of the pelvis with in situ intrauterine device].

    PubMed

    Bilek, K; Horn, L C; Schinagl, A

    1993-11-01

    The case is described of a 53-year old woman who had given birth three times and had undergone one abortion. After she was treated as an outpatient because of back pain in the lower waist area suppuration occurred from a fistula laterally right to the sacral bone in the area of the buttocks triangle, which persisted even after several outpatient surgical interventions. In addition, she had experienced a weight loss of 24 kg. At admission she had a temperature of 39 degrees Celsius, anemia, and leukocytosis. Sonography indicated slight hepatomegaly, hydroureter, right-sided hydronephrosis, and an right ovarian cyst of 4 cm size. Computer tomography showed a blurry structure that extended from the right kidney pole along the M. iliopsoas caudally up to the small pelvis, pressing against the organs caudally-ventrally, which also broke through dorsally between the lumbar region vertebrae and pelvis in the gluteal region percutaneously. The process was categorized as a frank paranephritis prolapsus abscess. Cessation of urine was determined. Laparotomy was carried out because of the suspicion of an inflammatory adnexal disease with parametritis. The uterus, including both adnexa as well as the conglomeration tumor, were removed. In the uterine cavity a Dana Cor IUD was found that had been inserted 13 years before and forgotten by the patient. At the site of the right adnexum there was a tumor (9 x 6 x 5 cu. cm) as well as a tube changed by inflammation (7 x 1.5 sq. cm). On the right side there was unspecific, suppurative salpingitis and in the ovary an abscess formation on the grounds of actinomycosis. On the left side there was only a suppurative inflammation of the tube without actinomycosis sediment. Immediately a high-dose antibiotic therapy (Penicillin G, 10 million IU) was started, lasting for 1 year. The kidney cessation with the back complaints rapidly disappeared. The cutaneous fistulae healed with scarring, however, a fully normal right-sided kidney function

  11. Postoperative complications necessitating right lower lobectomy in a heart-lung transplant recipient with previous sternotomy.

    PubMed

    Diethrich, E B; Bahadir, I; Gordon, M; Maki, P; Warner, M G; Clark, R; Siever, J; Silverthorn, A

    1987-09-01

    Heart-lung transplantation for treatment of end-stage cardiopulmonary disease continues to be plagued by many problems. Three primary ones are the technical difficulties that can be encountered, particularly in those patients who have undergone previous cardiac operations, the additional restriction on donor availability imposed by the lack of satisfactory preservation techniques, and the need for lung size compatibility. Two of these difficulties and others surfaced postoperatively in a heart-lung transplant recipient who presented a series of unique operative and therapeutic challenges. A 42-year-old woman with chronic pulmonary hypertension and previous atrial septal defect repair underwent a heart-lung transplantation in August 1985. The operative procedure was expectedly complicated by bleeding from extensive mediastinal adhesions from the previous sternotomy and bronchial collateralization. Excessive chest tube drainage postoperatively necessitated reoperation to control bleeding from a right bronchial artery tributary. Phrenic nerve paresis, hepatomegaly, and marked abdominal distention caused persistent atelectasis and eventual right lower lobe collapse. Arteriovenous shunting and low oxygen saturation necessitated right lower lobectomy 15 days after transplantation, believed to be the first use of this procedure in a heart-lung graft recipient. Although oxygenation improved dramatically, continued ventilatory support led to tracheostomy. An intensive, psychologically oriented physical therapy program was initiated to access and retrain intercostal and accessory muscles. The tracheostomy cannula was removed after 43 days and gradual weaning from supplemental oxygen was accomplished. During this protracted recovery period, an episode of rejection was also encountered and successfully managed with steroid therapy. The patient continued to progress satisfactorily and was discharged 83 days after transplantation. She is well and active 20 months after discharge.

  12. Waldenström's macroglobulinemia: clinical course and prognostic factors in 60 patients. Experience from a single hematology unit.

    PubMed

    Kyrtsonis, M C; Vassilakopoulos, T P; Angelopoulou, M K; Siakantaris, P; Kontopidou, F N; Dimopoulou, M N; Boussiotis, V; Gribabis, A; Konstantopoulos, K; Vaiopoulos, G A; Fessas, P; Kittas, C; Pangalis, G A

    2001-12-01

    Waldenström's macroglobulinemia (WM) is a lymphoplasmacytic lymphoma characterized by the presence in patients' serum of an IgM monoclonal component. We report on our experience with 60 WM patients, focusing on their clinical findings, response to treatment, and the possible identification of prognostic factors. Of these patients, 70% presented with fatigue, and lymphadenopathy was observed in 22%, splenomegaly in 18%, hepatomegaly in 13%, and extranodal site of involvement in 6%. Bleeding tendency was seen in 17%, infections in 17%, hyperviscosity syndrome in 12%, and cardiac failure in 25% of the patients. The median of IgM levels was 30 g/l with hypoalbuminemia in 20% of cases, hypogammaglobulinemia in 27%, polyclonal hypergammaglobulinemia in 15%, kappa light-chain restriction in 78%, and Bence-Jones proteinuria in 54%. Anemia was frequent (85%), followed by leukocytosis (18%), lymphocytosis (12%), leukopenia (10%), and thrombocytopenia (10%). Cryoglobulinemia and autoimmune hemolytic anemia were encountered in 5%. In all cases but two, bone marrow was involved. Of 50 patients initially treated with intermittent oral chlorambucil, 46 (92%) responded. Median overall survival was 108 months. Factors associated with adverse prognosis were age > or =65 years (p=0.06), presence of lymphadenopathy (p=0.06), bone marrow infiltration > or =50% (p=0.007), international prognostic index (IPI) > or =3 (p=0.0001), and Morel's scoring system (p=0.04). Concluding, we found in this series of WM patients that chlorambucil is an effective treatment and that the parameters of age, lymphadenopathy, percentage of bone marrow infiltration, IPI, and Morel's scoring system carry prognostic significance.

  13. Beneficial effects of rosuvastatin on insulin resistance, adiposity, inflammatory markers and non-alcoholic fatty liver disease in mice fed on a high-fat diet.

    PubMed

    Fraulob, Julio Cesar; Souza-Mello, Vanessa; Aguila, Marcia Barbosa; Mandarim-de-Lacerda, Carlos Alberto

    2012-08-01

    The aim of the present study was to evaluate the effects of ST (rosuvastatin) and GZ (rosiglitazone) on IR (insulin resistance) and on liver as well as adipose tissue in mice fed on an HF (high-fat) diet. Our data show that treatment with ST resulted in a marked improvement in insulin sensitivity characterized by enhanced glucose clearance during the insulin tolerance test and a 70% decrease in the HOMA-IR (homoeostasis model assessment of insulin resistance) index level (P=0.0008). The ST-treated mice exhibited lower gains in BM (body mass; -8%; P<0.01) and visceral fat pad thickness (-60%; P<0.01) compared with the untreated HF group. In comparison with HF-diet-fed mice, HF+ST-treated mice showed a significant reduction in hepatomegaly and liver steatosis (-6%, P<0.05; and -21%, P<0.01 respectively). In HF+ST-treated mice, the hepatic TAG (triacylglycerol) levels were reduced by 58% compared with the HF group (P<0.01). In addition, the expression of SREBP-1c (sterol-regulatory-element-binding protein-1c) was decreased by 50% in the livers of HF+ST-treated mice (P<0.01) relative to the HF-diet-fed mice. The levels of resistin were lower in the HF+ST-treated group compared with the HF group (44% less, P< 0.01). In conclusion, we demonstrated that ST treatment improved insulin sensitivity and decreased liver steatosis in mice fed on an HF diet. Furthermore, ST reduced BM gains, improved the circulating levels of plasma cholesterol and TAG, and reduced hepatic TAG, which was concomitant with lower resistin levels.

  14. Triglyceride-induced diabetes mellitus in congenital generalized lipodystrophy.

    PubMed

    Montenegro, Renan Magalhães; Montenegro, Ana Paula Dias Rangel; Fernandes, Maria Inez Machado; de Moraes, Renata Ribeiro; Elias, Jorge; Gouveia, Leonor Maria Ferreira Braz; Muglia, Valdair Francisco; Foss, Milton Cesar; Moreira, Ayrton Custódio; Martinelli, Carlos Eduardo

    2002-04-01

    High levels of triglycerides and free fatty acids have been implicated in the pathogenesis of type 2 diabetes mellitus (DM). Congenital generalized lipodystrophy (CGL) is an autosomal recessive syndrome characterized by intense whole body reduction of subcutaneous fat. Its clinical manifestations appear during the first years of life. However, DM is usually a late event. We report a patient with CGL, diagnosed at 4 months of age, who has severe hypertriglyceridemia (serum triglyceride 12.34 mmol/l and cholesterol 3.90 mmol/l), muscular hypertrophy, hepatomegaly and DM (fasting glycemia 25.9 mmol/l). Hepatic biopsy revealed steatosis and fibrosis. A modified normolipidic (composed of medium chain triglycerides) normocaloric normoproteic milky diet and insulin therapy were instituted. After 1 month treatment a reduction of serum glucose and triglyceride levels (4.13 mmol/I and 7.7 mmol/l, respectively) was noted, with later normalization, which led to the discontinuation of insulin therapy. The patient has been maintaining good control with diet alone, presenting normal serum lipid levels (triglycerides 1.07 mmol/l, total cholesterol 2.71 mmol/l) and the following glycemic profile at OGTT: 0' 4.4 mmol/l; 30' 7.0 mmol/l; 60' 3.8 mmol/l; 90' 5.3 mmol/l, and 120' 5.2 mmol/l. The disappearance of hepatic steatosis was evidenced by a biopsy obtained 1 year after the beginning of treatment. In conolusion, this report suggests that the DM occurring in CGL can be precipitated by high triglyceride levels.

  15. Bone marrow microvessel density and plasma angiogenic factors in myeloproliferative neoplasms: clinicopathological and molecular correlations.

    PubMed

    Lekovic, Danijela; Gotic, Mirjana; Skoda, Radek; Beleslin-Cokic, Bojana; Milic, Natasa; Mitrovic-Ajtic, Olivera; Nienhold, Ronny; Sefer, Dijana; Suboticki, Tijana; Buac, Marijana; Markovic, Dragana; Diklic, Milos; Cokic, Vladan P

    2017-03-01

    Increased angiogenesis in BCR-ABL1 negative myeloproliferative neoplasms (MPNs) has been recognized, but its connection with clinical and molecular markers needs to be defined. The aims of study were to (1) assess bone marrow (BM) angiogenesis measured by microvessel density (MVD) using CD34 and CD105 antibodies; (2) analyze correlation of MVD with plasma angiogenic factors including vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8; (3) examine the association of MVD with clinicopathological and molecular markers. We examined 90 de novo MPN patients (30 polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET)) and 10 age-matched controls. MVD was analyzed by immunohistochemistry "hot spot" method, angiogenic factors by immunoassay and JAK2V617F, and CALR mutations by DNA sequencing and allelic PCR. MVD was significantly increased in MPNs compared to controls (PMF > PV > ET). Correlation between MVD and plasma angiogenic factors was found in MPNs. MVD was significantly increased in patients with JAK2V617F mutation and correlated with JAK2 mutant allele burden (CD34-MVD: ρ = 0.491, p < 0.001; CD105-MVD: ρ = 0.276, p = 0.02) but not with CALR mutation. MVD correlated with leukocyte count, serum lactate dehydrogenase, hepatomegaly, and splenomegaly. BM fibrosis was significantly associated with CD34-MVD, CD105-MVD, interleukin-8, and JAK2 mutant allele burden. JAK2 homozygote status had positive predictive value (100%) for BM fibrosis. Patients with prefibrotic PMF had significantly higher MVD than patients with ET, and we could recommend MVD to be additional histopathological marker to distinguish these two entities. This study also highlights the strong correlation of MVD with plasma angiogenic factors, JAK2 mutant allele burden, and BM fibrosis in MPNs.

  16. Can Radiology Play a Role in Early Diagnosis of Dengue Fever?

    PubMed Central

    Chandak, Shruti; Kumar, Ashutosh

    2016-01-01

    Background: Dengue fever (DF) is a viral hemorrhagic fever causing severe morbidity and mortality in affected patients. Aims: The purpose of our study was to evaluate the changing trends in radiological findings in DF, to find if ultrasound is useful in the diagnosis of DF during an epidemic in absence of serological tests, and also to investigate the effects of DF in pregnancy. Materials and Methods: A prospective study was conducted in 2013 comprising of 400 patients who were serologically positive for dengue. Out of these, radiological investigations were conducted for 107 patients who were analyzed. Results: Out of the 107 patients, 85 patients underwent ultrasound, 12 computed tomography (CT) scans of brain or paranasal sinuses, and 21 chest radiography. The maximum numbers of patients (79%) were in the age group of 20-50 years. The most common ultrasound finding was hepatomegaly that was seen in 62% of the patients. Other findings were splenomegaly (45%), gallbladder (GB) wall edema (45%), right-sided pleural effusion (37%), bilateral pleural effusion (22%), and ascites (36%). Out of 10 pregnant patients, 5 had oligohydramnios, 2 had intrauterine growth restriction, 2 had intrauterine fetal demise, and 5 had a normal antenatal ultrasound. Conclusion: Ultrasound findings of hepatosplenomegaly, GB wall edema, right-sided or bilateral pleural effusion, and ascites in patients presenting with signs and symptoms of DF during an epidemic are virtually diagnostic of DF. There have been recent changing trends with hepatosplenomegaly being the more common manifestation, in comparison to ascites and GB wall edema. DF also has catastrophic effects in pregnancy such as oligohydramnios and intrauterine fetal demise. PMID:27042608

  17. Hepatocellular autophagy modulates the unfolded protein response and fasting-induced steatosis in mice.

    PubMed

    Kwanten, Wilhelmus J; Vandewynckel, Yves-Paul; Martinet, Wim; De Winter, Benedicte Y; Michielsen, Peter P; Van Hoof, Viviane O; Driessen, Ann; Timmermans, Jean-Pierre; Bedossa, Pierre; Van Vlierberghe, Hans; Francque, Sven M

    2016-10-01

    Autophagy and the unfolded protein response (UPR) are key cellular homeostatic mechanisms and are both involved in liver diseases, including nonalcoholic fatty liver disease (NAFLD). Although increasing but conflicting results link these mechanisms to lipid metabolism, their role and potential cross talk herein have been poorly investigated. Therefore, we assessed the effects of hepatocyte-specific autophagy deficiency on liver parenchyma, the UPR, and lipid metabolism. Adult hepatocellular-specific autophagy-deficient mice (Atg7(F/F)Alb-Cre(+)) were compared with their autophagy-competent littermates (Atg7(+/+)Alb-Cre(+)). Livers were analyzed by electron microscopy, histology, real-time qPCR, and Western blotting. Atg7(F/F)Alb-Cre(+) mice developed hepatomegaly with significant parenchymal injury, as shown by inflammatory infiltrates, hepatocellular apoptosis, pericellular fibrosis, and a pronounced ductular reaction. Surprisingly, the UPR exhibited a pathway-selective pattern upon autophagy deficiency. The activity of the adaptive activating transcription factor 6 (ATF6) pathway was abolished, whereas the proapoptotic protein kinase RNA-like ER kinase pathway was increased compared with Atg7(+/+)Alb-Cre(+) mice. The inositol-requiring enzyme-1α signal was unaltered. Fasting-induced steatosis was absent in Atg7(F/F)Alb-Cre(+) mice. Remarkably, some isolated islands of fat-containing and autophagy-competent cells were observed in these livers. Hepatocellular autophagy is essential for parenchymal integrity in mice. Moreover, in the case of autophagy deficiency, the three different UPR branches are pathway selectively modulated. Attenuation of the ATF6 pathway might explain the observed impairment of fasting-induced steatosis. Finally, autophagy and lipid droplets are directly linked to each other.

  18. Assessment of the Mitigative Capacity of Dietary Zinc on PCB126 Hepatotoxicity and the Contribution of Zinc to Toxicity.

    PubMed

    Klaren, William D; Gibson-Corley, Katherine N; Wels, Brian; Simmons, Donald L; McCormick, Michael L; Spitz, Douglas R; Robertson, Larry W

    2016-05-16

    Hepatic levels of the essential micronutrient, zinc, are diminished by several hepatotoxicants, and the dietary supplementation of zinc has proven protective in those cases. 3,3',4,4',5-Pentachlorobiphenyl (PCB126), a liver toxicant, alters hepatic nutrient homeostasis and lowers hepatic zinc levels. The current study was designed to determine the mitigative potential of dietary zinc in the toxicity associated with PCB126 and the role of zinc in that toxicity. Male Sprague-Dawley rats were divided into three dietary groups and fed diets deficient in zinc (7 ppm Zn), adequate in zinc (30 ppm Zn), and supplemented in zinc (300 ppm). The animals were maintained for 3 weeks on these diets, then given a single IP injection of vehicle or 1 or 5 μmol/kg PCB126. After 2 weeks, the animals were euthanized. Dietary zinc increased the level of ROS, the activity of CuZnSOD, and the expression of metallothionein but decreased the levels of hepatic manganese. PCB126 exposed rats exhibited classic signs of exposure, including hepatomegaly, increased hepatic lipids, increased ROS and CYP induction. Liver histology suggests some mild ameliorative properties of both zinc deficiency and zinc supplementation. Other metrics of toxicity (relative liver and thymus weights, hepatic lipids, and hepatic ROS) did not support this trend. Interestingly, the zinc supplemented high dose PCB126 group had mildly improved histology and less efficacious induction of investigated genes than did the low dose PCB126 group. Overall, decreases in zinc caused by PCB126 likely contribute little to the ongoing toxicity, and the mitigative/preventive capacity of zinc against PCB126 exposure seems limited.

  19. Clinicohematological profiles of hospitalized patients with dengue in kolkata in 2012 epidemic, west bengal.

    PubMed

    Saha, Ashis Kumar; Chatterjee, Gautam; Hazra, Subhas Chandra

    2014-09-01

    Dengue usually presents itself with subclinical or mild infection to full blown dengue fever (DF) to dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). In Kolkata, dengue started in 1824 followed by five epidemics that occurred in 1836, 1906, 1911, 1923 and 2005. The aim of this investigation is to study the clinicohematological correlation of all patients with respect to their gender that were admitted to "Kali Pada Chowdhury Medical College and Hospital" during 2012 epidemic. Amongst a total of 1237 dengue patients (either dengue Nonstructural protein1 antigen or dengue Immunoglobulin M positive) that were admitted to the hospital, 11 patients died within 48 hours of admission; hence they have been excluded from the study. DHF patients were divided into males and females. During admission, proper history, physical examinations with necessary hematological investigations were performed and repeated again after 24-48 hours. After collection of all the reports, correlations of the collected data were carried out. 170 and 1056 patients were diagnosed with DF and DHF respectively; significant symptoms and signs were headache, backache/myalgia, nausea/vomiting, loose motion and anorexia hepatomegaly. Hemoglobin level was low in females, leucopenia observed in 79.52% patients and thrombocytopenia seen in 57.58% and 86.13% patients during and 24-48 hours after admission respectively. 96 and 97 DHF patients showed evidences of ascites and plural effusion respectively. In 2012 epidemic, 86.13% patients suffered from DHF, headache, backache, nausea/vomiting, loose motion and anorexia were predominant symptoms. Significant number of patients had leucopenia; only few showed evidence of plasma leakage.

  20. Progression of micronutrient alteration and hepatotoxicity following acute PCB126 exposure.

    PubMed

    Klaren, W D; Gadupudi, G S; Wels, B; Simmons, D L; Olivier, A K; Robertson, L W

    2015-12-02

    Polychlorinated Biphenyls (PCBs) are industrial chemicals that have become a persistent threat to human health due to ongoing exposure. A subset of PCBs, known as dioxin-like PCBs, pose a special threat given their potent hepatic effects. Micronutrients, especially Cu, Zn and Se, homeostatic dysfunction is commonly seen after exposure to dioxin-like PCBs. This study investigates whether micronutrient alteration is the byproduct of the ongoing hepatotoxicity, marked by lipid accumulation, or a concurrent, yet independent event of hepatic damage. A time course study was carried out using male Sprague-Dawley rats with treatments of PCB126, the prototypical dioxin-like PCB, resulting in 6 different time points. Animals were fed a purified diet, based on AIN-93G, for three weeks to ensure micronutrient equilibration. A single IP injection of either tocopherol-stripped soy oil vehicle (5 mL/kg) or 5 μmol/kg PCB126 dose in vehicle was given at various time points resulting in exposures of 9h, 18 h, 36 h, 3 days, 6 days, and 12 days. Mild hepatic vacuolar change was seen as early as 36 h with drastic changes at the later time points, 6 and 12 days. Micronutrient alterations, specifically Cu, Zn, and Se, were not seen until after day 3 and only observed in the liver. No alterations were seen in the duodenum, suggesting that absorption and excretion may not be involved. Micronutrient alterations occur with ROS formation, lipid accumulation, and hepatomegaly. To probe the mechanistic underpinnings, alteration of gene expression of several copper chaperones was investigated; only metallothionein appeared elevated. These data suggest that the disruption in micronutrient status is a result of the hepatic injury elicited by PCB126 and is mediated in part by metallothionein.

  1. Hamsters predisposed to sucrose-induced cholesterol gallstones (LPN strain) are more resistant to excess dietary cholesterol than hamsters that are not sensitive to cholelithiasis induction.

    PubMed

    Souidi, M; Combettes-Souverain, M; Milliat, F; Eckhardt, E R; Audas, O; Dubrac, S; Parquet, M; Férézou, J; Lutton, C

    2001-06-01

    We compared the effects of cholesterol feeding in male hamsters from two strains with different propensities to sucrose-induced cholelithiasis; Laboratoire de Physiologie de la Nutrition (LPN) hamsters are predisposed to developing biliary cholesterol gallstones, whereas Janvier (JAN) hamsters are not. When fed a basal control diet, LPN hamsters had a lower cholesterolemia (-21%, P = 0.01) than JAN hamsters, and a higher activity of 3-hydroxy-3-methyl glutaryl coenzyme A reductase in liver (+148%, P = 0.018) and intestine (+281%, P < 0.0001). After feeding the same diet enriched with 0.3% cholesterol for 5 wk, cholesterolemia increased more dramatically in JAN hamsters (+235%, P < 0.001) than in LPN hamsters (+108%, P < 0.001), as did the liver concentration of cholesterol, which reached 152.30 +/- 13.00 and 44.41 +/- 9.06 micromol/g, respectively. Only JAN hamsters displayed hepatomegaly, with an increased cholesterol saturation index of the gallbladder bile (+100%, P < 0.01), due to the cholesterol challenge. In liver, cholesterol feeding reduced cholesterol 7alpha-hydroxylase activity and mRNA level, and stimulated sterol 27-hydroxylase and oxysterol 7alpha-hydroxylase activities. Hepatic levels of LDL receptor decreased by approximately 60% in both strains, whereas HDL receptor scavenger class B type 1 (SR-BI) levels were unaffected by dietary cholesterol. The greater resistance of LPN hamsters to the hypercholesterolemic diet can be explained by a lower capacity to store cholesterol in the liver and greater efficiency in reducing the activity of 3-hydroxy-3-methyl glutaryl coenzyme A reductase in response to cholesterol feeding [from 11263 to 261 pmol/(min x organ) in LPN hamsters and from 4530 to 694 pmol/(min x organ) in JAN hamsters]. These results highlight the usefulness of this two-strain model, which offers some analogy with the inverse association between the predisposition to cholelithiasis and the risk of atherosclerosis in humans.

  2. The common marmoset as a model for the study of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

    PubMed

    Kramer, J A; Grindley, J; Crowell, A M; Makaron, L; Kohli, R; Kirby, M; Mansfield, K G; Wachtman, L M

    2015-03-01

    Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. The more clinically concerning form of the disease, nonalcoholic steatohepatitis (NASH), is characterized by steatosis, lobular inflammation, and ballooning degeneration. Here we describe a naturally occurring syndrome in the common marmoset that recapitulates the pathologic findings associated with NAFLD/NASH in humans. Hepatomegaly determined to result from NAFLD was observed in 33 of 183 marmosets. A comprehensive histopathologic assessment performed in 31 marmosets demonstrated that NAFLD was characterized by variably sized, Oil Red O staining cytoplasmic vacuoles and observed primarily in animals with evidence of obesity and insulin resistance. A subset of marmosets (16 of 31) also demonstrated evidence of NASH characterized by multifocal inflammation combined with ballooning hepatocellular degeneration. Marmosets with NASH demonstrated an increase in immunostaining with an antibody targeted against the human leukocyte antigens (HLA)-DP, HLA-DQ, and HLA-DR compared with marmosets without NASH (38.89 cells/10× field vs 12.05 cells/10× field, P = .05). In addition, marmosets with NASH demonstrated increased Ki-67 immunopositive cellular proliferation compared with those without (5.95 cells/10× field vs 1.53 cells/10× field, P = .0002). Finally, animals with NASH demonstrated significantly increased mean circulating serum iron levels (160.47 μg/dl, P = .008) and an increase in numbers of Prussian blue-positive Kupffer cells (9.28 cells/40× field, P = .005) relative to marmosets without NASH (97.75 μg/dl and 1.87 cells/40×, respectively). This study further characterizes the histopathology of NAFLD/NASH and suggests that the marmoset may be a valuable animal model with which to investigate the host and environmental factors contributing to the progression of NAFLD/ NASH.

  3. Effect of bezafibrate treatment on late-onset mitochondrial myopathy in mice.

    PubMed

    Yatsuga, Shuichi; Suomalainen, Anu

    2012-02-01

    Mitochondrial dysfunction is an important cause of metabolic disorders of children and adults, with no effective therapy options. Recently, induction of mitochondrial biogenesis, by transgenic overexpression of PGC1-alpha [peroxisome proliferator-activated receptor (PPAR)-gamma coactivator 1-alpha], was reported to delay progression of early-onset cytochrome-c-oxidase (COX) deficiency in skeletal muscle of two mouse models: a muscle-specific knock-out of COX10 (COX10-mKO) and a constitutive knock-out of Surf1 (Surf1-KO). A pan-PPAR agonist, bezafibrate, could similarly delay myopathy progression in COX10-mKOs, but not in SURF1-KOs. We asked whether bezafibrate affected disease progression in late-onset adult-type mitochondrial myopathy mice. These 'Deletor mice' express a dominant patient mutation in Twinkle-helicase, leading to accumulation of multiple mtDNA deletions and subsequent progressive respiratory chain (RC) deficiency with COX-negative muscle fibers at 12 months of age. The primary and secondary molecular findings in Deletor mice mimic closely those in patients with Twinkle myopathy. We applied 0.5% bezafibrate diet to Deletors for 22 weeks, starting at disease manifestation, mimicking patient treatment after diagnosis. Bezafibrate delayed significantly the accumulation of COX-negative fibers and multiple mtDNA deletions. However, mitochondrial biogenesis was not induced: mitochondrial DNA copy number, transcript and RC protein amounts decreased in both Deletors and wild-type mice. Furthermore, bezafibrate induced severe lipid oxidation effects, with hepatomegaly and loss of adipose tissue, the mechanism involving lipid mobilization by high hepatic expression of FGF21 cytokine. However, as bezafibrate has been tolerated well by humans, the beneficial muscle findings in Deletor mice support consideration of bezafibrate trials on adult patients with mitochondrial myopathy.

  4. Control of liver size by RNAi-mediated multiplex knockdown and its application for discovery of regulatory mechanisms

    PubMed Central

    Yin, Hao; Bogorad, Roman L.; Barnes, Carmen; Walsha, Stephen; Zhuang, Iris; Nonaka, Hidenori; Ruda, Vera; Kuchimanchi, Satya; Nechev, Lubomir; Akinc, Akin; Xue, Wen; Zerial, Marino; Langer, Robert; Anderson, Daniel G.; Koteliansky, Victor

    2017-01-01

    Background and aims The Hippo pathway controls organ size through a negative regulation of the transcription co-activator Yap1. The overexpression of hyperactive mutant Yap1 or deletion of key components in the Hippo pathway leads to increased organ size in different species. Analysis of interactions of this pathway with other cellular signals corroborating organ size control is limited in part due to the difficulties associated with development of rodent models. Methods Here, we develop a new model of reversible induction of the liver size in mice using siRNA-nanoparticles targeting two kinases of Hippo pathway, namely, mammalian Ste20 family kinases 1 and 2 (Mst1 and Mst2), and an upstream regulator, neurofibromatosis type II (NF2). Results The triple siRNAs nanoparticle-induced hepatomegaly in mice phenocopies one observed with Mst1-/- Mst2-/- liver-specific depletion, as shown by extensive proliferation of hepatocytes and activation of Yap1. The simultaneous co-treatment with a fourth siRNA nanoparticle against Yap1 fully blocked the liver growth. Hippo pathway-induced liver enlargement is associated with p53 activation, evidenced by its accumulation in the nuclei and upregulation of its target genes. Moreover, injections of the triple siRNAs nanoparticle in p53LSL/LSL mice shows that livers lacking p53 expression grow faster and exceed the size of livers in p53 wild type animals, indicating a role of p53 in controlling Yap1-induced liver growth. Conclusion Our data show that siRNA-nanoparticulate manipulation of gene expression can provide the reversible control of organ size in adult animals, which presents a new avenue for the investigation of complex regulatory networks in liver. PMID:26658687

  5. GLUT2, glucose sensing and glucose homeostasis.

    PubMed

    Thorens, Bernard

    2015-02-01

    The glucose transporter isoform GLUT2 is expressed in liver, intestine, kidney and pancreatic islet beta cells, as well as in the central nervous system, in neurons, astrocytes and tanycytes. Physiological studies of genetically modified mice have revealed a role for GLUT2 in several regulatory mechanisms. In pancreatic beta cells, GLUT2 is required for glucose-stimulated insulin secretion. In hepatocytes, suppression of GLUT2 expression revealed the existence of an unsuspected glucose output pathway that may depend on a membrane traffic-dependent mechanism. GLUT2 expression is nevertheless required for the physiological control of glucose-sensitive genes, and its inactivation in the liver leads to impaired glucose-stimulated insulin secretion, revealing a liver-beta cell axis, which is likely to be dependent on bile acids controlling beta cell secretion capacity. In the nervous system, GLUT2-dependent glucose sensing controls feeding, thermoregulation and pancreatic islet cell mass and function, as well as sympathetic and parasympathetic activities. Electrophysiological and optogenetic techniques established that Glut2 (also known as Slc2a2)-expressing neurons of the nucleus tractus solitarius can be activated by hypoglycaemia to stimulate glucagon secretion. In humans, inactivating mutations in GLUT2 cause Fanconi-Bickel syndrome, which is characterised by hepatomegaly and kidney disease; defects in insulin secretion are rare in adult patients, but GLUT2 mutations cause transient neonatal diabetes. Genome-wide association studies have reported that GLUT2 variants increase the risks of fasting hyperglycaemia, transition to type 2 diabetes, hypercholesterolaemia and cardiovascular diseases. Individuals with a missense mutation in GLUT2 show preference for sugar-containing foods. We will discuss how studies in mice help interpret the role of GLUT2 in human physiology.

  6. Trim37-deficient mice recapitulate several features of the multi-organ disorder Mulibrey nanism

    PubMed Central

    Kettunen, Kaisa M.; Karikoski, Riitta; Hämäläinen, Riikka H.; Toivonen, Teija T.; Antonenkov, Vasily D.; Kulesskaya, Natalia; Voikar, Vootele; Hölttä-Vuori, Maarit; Ikonen, Elina; Sainio, Kirsi; Jalanko, Anu; Karlberg, Susann; Karlberg, Niklas; Lipsanen-Nyman, Marita; Toppari, Jorma; Jauhiainen, Matti; Hiltunen, J. Kalervo; Jalanko, Hannu; Lehesjoki, Anna-Elina

    2016-01-01

    ABSTRACT Mulibrey nanism (MUL) is a rare autosomal recessive multi-organ disorder characterized by severe prenatal-onset growth failure, infertility, cardiopathy, risk for tumors, fatty liver, and type 2 diabetes. MUL is caused by loss-of-function mutations in TRIM37, which encodes an E3 ubiquitin ligase belonging to the tripartite motif (TRIM) protein family and having both peroxisomal and nuclear localization. We describe a congenic Trim37 knock-out mouse (Trim37−/−) model for MUL. Trim37−/− mice were viable and had normal weight development until approximately 12 months of age, after which they started to manifest increasing problems in wellbeing and weight loss. Assessment of skeletal parameters with computer tomography revealed significantly smaller skull size, but no difference in the lengths of long bones in Trim37−/− mice as compared with wild-type. Both male and female Trim37−/− mice were infertile, the gonads showing germ cell aplasia, hilus and Leydig cell hyperplasia and accumulation of lipids in and around Leydig cells. Male Trim37−/− mice had elevated levels of follicle-stimulating and luteinizing hormones, but maintained normal levels of testosterone. Six-month-old Trim37−/− mice had elevated fasting blood glucose and low fasting serum insulin levels. At 1.5 years Trim37−/− mice showed non-compaction cardiomyopathy, hepatomegaly, fatty liver and various tumors. The amount and morphology of liver peroxisomes seemed normal in Trim37−/− mice. The most consistently seen phenotypes in Trim37−/− mice were infertility and the associated hormonal findings, whereas there was more variability in the other phenotypes observed. Trim37−/− mice recapitulate several features of the human MUL disease and thus provide a good model to study disease pathogenesis related to TRIM37 deficiency, including infertility, non-alcoholic fatty liver disease, cardiomyopathy and tumorigenesis. PMID:27044324

  7. [Non-alcoholic fatty liver disease--new view].

    PubMed

    Raszeja-Wyszomirska, Joanna; Lawniczak, Małgorzata; Marlicz, Wojciech; Miezyńska-Kurtycz, Joanna; Milkiewicz, Piotr

    2008-06-01

    Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology--from steatosis alone, through the necroinflammatory disorder of non-alcoholic steatohepatitis (NASH) to cirrhosis and liver cancer. NAFLD/NASH is mostly related with visceral adiposity, obesity, type 2 diabetes melitus (DM t.2) and metabolic syndrome. Pathogenetic concepts of NAFLD include overnutrition and underactivity, insulin resistance (IR) and genetic factor. The prevalence of NAFLD has been estimated to be 17-33% in some countries, NASH may be present in about 1/3 of such cases, while 20-25% of NASH cases could progress to cirrhosis. NAFLD is now recognized as one of the most frequent reason of liver tests elevation without clinical symptoms. Insulin resistance is considering as having a central role in NAFLD pathogenesis. In hepatocytes, IR is related to hyperglycaemia and hyperinsulinaemia, formation of advanced glycation end-products, increased free fatty acids and their metabolites, oxidative stress and altered profiles of adipocytokines. Early stages of fatty liver are clinically silent and include elevation of ALT and GGTP, hyperechogenic liver in USG and/or hepatomegaly. Among clinical symptoms, abdominal discomfort is relatively common as well as chronic fatigue. NAFLD/NASH is not a benign disease, progressive liver biopsy have shown histological progression of fibrosis in 32%, the estimated rate of cirrhosis development is 20% and a liver--related death is 12% over 10 years. No treatment has scientifically proved to ameliorate NAFLD or to avoid its progression. The various therapeutic alternatives are aimed at interfering with the risk factors involved in the pathogenesis of the disorder in order to prevent the progression to end-stage liver disease. The most important therapeutic measure is increasing insulin sensitivity by an attempt to change a lifestyle mostly by dieting and physical activity in order to loose weight. The most used agent is metformin, the others

  8. Dichlorodiphenyltrichloroethane technical mixture regulates cell cycle and apoptosis genes through the activation of CAR and ERα in mouse livers

    SciTech Connect

    Kazantseva, Yuliya A.; Yarushkin, Andrei A.; Pustylnyak, Vladimir O.

    2013-09-01

    Dichlorodiphenyltrichloroethane (DDT) is a widely used organochlorine pesticide and a xenoestrogen that promotes rodent hepatomegaly and tumours. A recent study has shown significant correlation between DDT serum concentration and liver cancer incidence in humans, but the underlying mechanisms remain elusive. We hypothesised that a mixture of DDT isomers could exert effects on the liver through pathways instead of classical ERs. The acute effects of a DDT mixture containing the two major isomers p,p′-DDT (85%) and o,p′-DDT (15%) on CAR and ERα receptors and their cell cycle and apoptosis target genes were studied in mouse livers. ChIP results demonstrated increased CAR and ERα recruitment to their specific target gene binding sites in response to the DDT mixture. The results of real-time RT-PCR were consistent with the ChIP data and demonstrated that the DDT was able to activate both CAR and ERα in mouse livers, leading to target gene transcriptional increases including Cyp2b10, Gadd45β, cMyc, Mdm2, Ccnd1, cFos and E2f1. Western blot analysis demonstrated increases in cell cycle progression proteins cMyc, Cyclin D1, CDK4 and E2f1 and anti-apoptosis proteins Mdm2 and Gadd45β. In addition, DDT exposure led to Rb phosphorylation. Increases in cell cycle progression and anti-apoptosis proteins were accompanied by a decrease in p53 content and its transcriptional activity. However, the DDT was unable to stimulate the β-catenin signalling pathway, which can play an important role in hepatocyte proliferation. Thus, our results indicate that DDT treatment may result in cell cycle progression and apoptosis inhibition through CAR- and ERα-mediated gene activation in mouse livers. These findings suggest that the proliferative and anti-apoptotic conditions induced by CAR and ERα activation may be important contributors to the early stages of hepatocarcinogenesis as produced by DDT in rodent livers. - Highlights: • DDT activated both CAR and ERα and their cell

  9. Comorbidities in Children and Adolescents with AIDS Acquired by HIV Vertical Transmission in Vitória, Brazil

    PubMed Central

    Moreira-Silva, Sandra F.; Zandonade, Eliana; Frauches, Diana O.; Machado, Elisa A.; Lopes, Lays Ignacia A.; Duque, Lívia L.; Querido, Polyana P.; Miranda, Angélica E.

    2013-01-01

    Background Studying diseases associated with AIDS is essential for establishing intervention strategies because comorbidities can lead to death. The objectives were to describe the frequency of comorbidities and verify their distribution according to demographic, epidemiological and clinical data as well as to classify diseases in children and adolescents with AIDS in Vitória, Brazil. Methods A retrospective cohort study was conducted among children with AIDS, as defined according to the criteria established by the Ministry of Health, who acquired HIV via vertical transmission, were aged 0 to 18 years, and were monitored at a referral hospital from January 2001 to December 2011. Results A total of 177 patients were included, of whom 97 were female (55%). There were 60 patients (34%) <1 year old, 67 patients (38%) between the ages of 1 and 5, and 50 patients (28%) ≥6 years of age included at the time of admission to the Infectious Diseases Ward. Regarding clinical-immunological classification, 146 patients (82.5%) showed moderate/severe forms of the disease at the time of admission into the Ward, and 26 patients (14.7%) died during the study. The most common clinical signs were hepatomegaly (81.62%), splenomegaly (63.8%), lymphadenopathy (68.4%) and persistent fever (32.8%). The most common comorbidities were anaemia (67.2%), pneumonia/septicaemia/acute bacterial meningitis (ABM) (64.2%), acute otitis media (AOM)/recurrent sinusitis (55.4%), recurrent severe bacterial infections (47.4%) and dermatitis (43.1%). An association between severe clinical-immunological classification and admission to the Ward for children aged less than one year old was found for several comorbidities (p<0.001). Conclusion Delayed diagnosis was observed because the majority of patients were admitted to the Infectious Diseases Ward at ≥1 year of age and were already presenting with serious diseases. The general paediatrician should be alert to this possibility to make an early

  10. Visceral Leishmaniasis and HIV Coinfection in Latin America

    PubMed Central

    Lindoso, José Angelo; Cota, Gláucia Fernandes; da Cruz, Alda Maria; Goto, Hiro; Maia-Elkhoury, Ana Nilce Silveira; Romero, Gustavo Adolfo Sierra; de Sousa-Gomes, Márcia Leite; Santos-Oliveira, Joanna Reis; Rabello, Ana

    2014-01-01

    Visceral leishmaniasis (VL) is an endemic zoonotic disease in Latin America caused by Leishmania (Leishmania) infantum, which is transmitted by sand flies from the genus Lutzomyia. VL occurs in 12 countries of Latin America, with 96% of cases reported in Brazil. Recently, an increase in VL, primarily affecting children and young adults, has been observed in urban areas of Latin America. The area in which this spread of VL is occurring overlaps regions with individuals living with HIV, the number of whom is estimated to be 1.4 million people by the World Health Organization. This overlap is suggested to be a leading cause of the increased number of reported VL-HIV coinfections. The clinical progression of HIV and L. infantum infections are both highly dependent on the specific immune response of an individual. Furthermore, the impact on the immune system caused by either pathogen and by VL-HIV coinfection can contribute to an accelerated progression of the diseases. Clinical presentation of VL in HIV positive patients is similar to patients without HIV, with symptoms characterized by fever, splenomegaly, and hepatomegaly, but diarrhea appears to be more common in coinfected patients. In addition, VL relapses are higher in coinfected patients, affecting 10% to 56.5% of cases and with a lethality ranging from 8.7% to 23.5% in Latin America, depending on the study. With regards to the diagnosis of VL, parasitological tests of bone marrow aspirates have proven to be the most sensitive test in HIV-infected patients. Serologic tests have demonstrated a variable sensitivity according to the method and antigens used, with the standard tests used for diagnosing VL in Latin America displaying lower sensitivity. For this review, few articles were identified that related to VL-HIV coinfections and originated from Latin America, highlighting the need for improving research within the regions most greatly affected. We strongly support the formation of a Latin American network for

  11. [Detection of psittacid herpesvirus 1 in Amazon parrots with cloacal papilloma (internal papillomatosis of parrots, IPP) in an aviary of different psittacine species].

    PubMed

    Legler, Marko; Kothe, Ruth; Rautenschlein, Silke; Kummerfeld, Norbert

    2008-12-01

    Amazon parrots (Amazona aestiva aestiva;Amazona ochrocephala, n=6) from an aviary with different psittacine species (n=100) were submitted to the Clinic for Pet Animals, Reptiles, Pet- and Wild birds with the clinical picture ofa cloacal prolaps. The cloacal mucosa showed papillomas, and internal papillomatosis of parrots (IPP) was suspected. Hepatomegaly was detected in the radiographs of the clinically diseased amazon parrots, indicating the involvement of the liver in the disease process. The cloacal area was enlarged and showed higher densities in the radiographic picture. One of the amazons had an increased level of bile acids in the plasma supporting the suspicion of the involvement of the liver. Macroscopical and histological investigation of amazons with cloacal prolaps revealed a papillomic adenoma of the cloacal mucosa accompanied by varying degrees of bile duct carcinomas in the liver and adenocarcinomas of the pancreas. Herpesvirus genome was detected by nested PCR in cloacal swabs, liver, and cloacal tissue samples. Sequencing of part of the herpesvirus DNA-polymerase gene indicated 95% homology of the detected herpesviruses with the Psittacid Herpesvirus (PsHV) 1. No cytopathic herpesvirus was recovered from cloacal swabs and liver samples after up to four passages in chicken embryofibroblast cultures. Cloacal and choanal swabs, which were taken from the remaining 47 healthy amazon parrots and 5 Green-winged Macaws (Ara chloroptera) of the aviary, were negative for herpesvirus in the nested PCR. Only birds with cloacal papillomas and the Green-winged Macaws were tested positive for herpesvirus DNA in the nested PCR. We may speculate that there is correlation between the infection with PsHV-1 and the development of cloacal adenomas, adenocarcinomas in the pancreas and carcinomas of the bile ducts. Our results indicate that there may be a higher susceptibility in certain amazon species, while other species may not get infected even if housed in close

  12. [An imported Chikungunya fever case from New Delhi, India to Ankara, Turkey: the first imported case of Turkey and review of the literature].

    PubMed

    Yağcı Çağlayık, Dilek; Uyar, Yavuz; Korukluoğlu, Gülay; Ertek, Mustafa; Unal, Serhat

    2012-01-01

    Chikungunya virus (CHIKV) is an arthropod-borne alphavirus that causes an acute febrile illness, chikungunya fever. CHIKV virus is geographically distributed in Africa, India, and South-East Asia. Chikungunya fever outbreaks have been reported from India since 2006. The incubation period is 3-7 days, and the disease is characterized by sudden onset of high fever and severe arthralgia. Other symptoms can be rash, headache, fatigue, nausea-vomiting, and myalgias. Here, we report the first Chikungunya case imported from India, New-Delhi to Ankara, Turkey. In December 2010, a 55-year-old female Turkish government employee living in urban area of New Delhi for the last 3 years had sudden onset fever up to 38.4°C for 2 days. Itching rash and arthralgia also developed. Symptomatic treatment was given to patient in New Delhi. She returned to Turkey and was admitted to Hacettepe University Medical Faculty, Department of Internal Medicine, Infectious Diseases Unit, since arthralgia has continued on the 26th day of her complaints. Hepatomegaly and tenosynovitis were detected in her physical examination. Serum sample sent to Refik Saydam National Public Health Agency, Virology Reference and Research Laboratory, yielded negative results for specific IgM and IgG antibodies against Hantavirus and Dengue virus types 1-4; however, the results were positive for CHIKV specific IgM and IgG antibodies by commercial immunofluorescence method (Euroimmun, Germany). CHIKV RNA which was searched by in-house real-time RT-PCR was negative. The second serum sample obtained three weeks later also found positive for CHIKV specific IgM and IgG antibodies. This was the first laboratory confirmed imported Chikungunya case in Turkey. There are predictions regarding the presence of Aedes species mosquitos that can transmit this virus in Turkey. This case report will be an alarming signal for the clinicians in our country to consider Chikungunya fever in the differential diagnosis of patients

  13. GRP78 as a regulator of liver steatosis and cancer progression mediated by loss of the tumor suppressor PTEN.

    PubMed

    Chen, W-T; Zhu, G; Pfaffenbach, K; Kanel, G; Stiles, B; Lee, A S

    2014-10-16

    Glucose-regulated protein 78 (GRP78), a molecular chaperone widely elevated in human cancers, is critical for endoplasmic reticulum (ER) protein folding, stress signaling and PI3K/AKT activation. Genetic knockout models of GRP78 revealed that GRP78 maintains homeostasis of metabolic organs, including liver, pancreas and adipose tissues. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the most common liver cancers. There is a lack of effective therapeutics for HCC and CC, highlighting the need to further understand liver tumorigenic mechanisms. PTEN (phosphatase and tenson homolog deleted on chromosome 10), a tumor suppressor that antagonizes the PI3K/AKT pathway, is inactivated in a wide range of tumors, including 40-50% of human liver cancers. To elucidate the role of GRP78 in liver cancer, we created a mouse model with biallelic liver-specific deletion of Pten and Grp78 mediated by Albumin-Cre-recombinase (cP(f/f)78(f/f)). Interestingly, in contrast to PTEN, deletion of GRP78 was progressive but incomplete. At 3 months, cP(f/f)78(f/f) livers showed hepatomegaly, activation of lipogenic genes, exacerbated steatosis and liver injury, implying that GRP78 protects the liver against PTEN-null-mediated pathogenesis. Furthermore, in response to liver injury, we observed increased proliferation and expansion of bile duct and liver progenitor cells in cP(f/f)78(f/f) livers. Strikingly, bile duct cells in cP(f/f)78(f/f) livers maintained wild-type (WT) GRP78 level, whereas adjacent areas showed GRP78 reduction. Analysis of signaling pathways revealed selective JNK activation, β-catenin downregulation, along with PDGFRα upregulation, which was unique to cP(f/f)78(f/f) livers at 6 months. Development of both HCC and CC was accelerated and was evident in cP(f/f)78(f/f) livers at 8-9 months, coinciding with intense GRP78 expression in the cancer lesions, and GRP78 expression in adjacent normal areas reverted back to the WT level. In contrast, c78(f/f) livers

  14. Morbidity, beta S haplotype and alpha-globin gene patterns among sickle cell anemia patients in Kuwait.

    PubMed

    Adekile, A D; Haider, M Z

    1996-01-01

    Admission records of children with sickle cell anemia (SS), in the two main teaching hospitals in Kuwait, were reviewed for a 1-year period. The haplotypes of 92 beta s chromosomes (from 39 SS, 11 AS, 2 S beta-thalassemia [S beta-thal] and 1 SD individuals) were determined using an allele-specific oligonucleotide (ASO) hybridization technique, while the alpha-globin gene status of 27 SS and 33 AS individuals, i.e. 120 chromosomes, was determined with a combination of polymerase chain reaction and AS techniques. A vasooclusive crisis was the most common (60.0%) cause of hospitalization, followed by infections (20%). Hospital admissions were most common during the hottest month of the year (July). Few complications of the disease were seen among patients on follow-up; however, splenomegaly was present in 24.0%, hepatomegaly in 15.2%, gallstones in 15.2% and aseptic necrosis of the femoral head in 6.1%. Haplotype 31 (Saudi Arabia/India) is the most frequent in this community, being present in 80.4% of the chromosomes tested; Benin haplotype 19 was found in 12.0% and Bantu haplotype 20 in 6.5%. Hb F in the haplotype 31 homozygotes and heterozygotes ranged from 11.4 to 35.1% (mean 22.5 +/- 5.2%). The frequency of alpha-thal determinants in the study was 40.0%, the commonest being the -alpha 3.7-kb deletion (27.5%), the alpha 2 polyadenylation signal (AATAAA-> AATAAG) mutation (10.2%) and the IVS-I 5' end GAGGT-GAGG->GAGG pentanucleotide (5 nt) deletion (3.3%). SS patients with coexistent alpha-thal trait did not have severe recurrent infections and none had gallstones. The high frequencies of the Saudi Arabia/India beta s haplotype and alpha-thalassemia trait contribute to the mild nature of SS disease among Kuwaiti Arabs comparable to that in eastern Saudi Arabia.

  15. Effect of feeding solanidine, solasodine and tomatidine to non-pregnant and pregnant mice.

    PubMed

    Friedman, Mendel; Henika, P R; Mackey, B E

    2003-01-01

    The aglycone forms of three steroidal glycoalkaloids-solanidine (derived by hydrolytic removal of the carbohydrate side chain from the potato glycoalkaloids alpha-chaconine and alpha-solanine), solasodine (derived from solasonine in eggplants) and tomatidine (derived from alpha-tomatine in tomatoes)-were evaluated for their effects on liver weight increase (hepatomegaly) in non-pregnant and pregnant mice and on fecundity in pregnant mice fed for 14 days on a diet containing 2.4 mmol/kg of aglycone. In non-pregnant mice, observed ratios of % liver weights to body weights (%LW/BWs) were significantly greater than those of the control values as follows (all values in % vs matched controls+/-S.D.): solanidine, 25.5+/-13.2; solasodine 16.8+/-12.0; and tomatidine, 6.0+/-7.1. The corresponding increases in pregnant mice were: solanidine, 5.3+/-10.7; solasodine, 33.1+/-15.1; tomatidine, 8.4+/-9.1. For pregnant mice (a) body weight gains were less with the algycones than with controls: solanidine, -36.1+/-14.5; solasodine, -17.9+/-14.3; tomatidine, -11.9+/-18.1; (b) litter weights were less than controls: solanidine, -27.0+/-17.1; solasodine, -15.5+/-16.8; tomatidine, no difference; (c) the %LTW/BW ratio was less than that of the controls and was significant only for solasodine, -8.7+/-13.7; and (d) the average weight of the fetuses was less than the controls: solanidine, -11.2+/-15.2; solasodine, -11.4+/-9.4; tomatidine, no difference. Abortion of fetuses occurred in five of 24 pregnant mice on the solanidine and none on the other diets. To obtain evidence for possible mechanisms of the observed in vivo effects, the four glycoalkaloids (alpha-chaconine, alpha-solanine, solasonine and alpha-tomatine) mentioned above and the aglycones solanidine and tomatidine were also evaluated in in vitro assays for estrogenic activity. Only solanidine at 10 microM concentration exhibited an increase in the MCF-7 human breast cancer cell proliferation assay. Generally, the biological

  16. Biopsy-driven diagnosis in infants with cholestatic jaundice in Iran

    PubMed Central

    Talachian, Elham; Bidari, Ali; Mehrazma, Mitra; Nick-khah, Nahid

    2014-01-01

    AIM: To determine the frequencies of diagnoses confirmed by liver biopsy in infants with cholestasis in an Iranian pediatric hospital. METHODS: This was a retrospective study conducted in a tertiary referral children’s hospital in Iran. We retrieved all pathology reports of liver biopsies from children less than two years of age who had presented for evaluation of cholestatic jaundice from March 2001 to March 2011. Additional specimen samples obtained from archived pathology blocks were reviewed by a pathologist blinded to the final diagnosis. These results were compared with the pathology reports from chart records to ensure consensus and eliminate any inconsistencies in final diagnoses. A structured checklist was used to gather information on multiple variables including age, sex, gestational age at birth, birth weight, age at which hyperbilirubinemia manifested, presence and identification of associated anomalies, clinical manifestations, and histological findings from liver biopsies. The baseline data are reported using descriptive statistics, and differences between groups were assessed by Fisher’s exact test and Student’s t test when indicated. RESULTS: Fifty-five cases (28 females; 27 males) of infantile cholestasis (IC) were included in this study. The mean serum total bilirubin and direct bilirubin at presentation were 13.6 ± 5.9 and 7.3 ± 3.4, respectively. Forty cases (72.7%) were the product of term pregnancies. Common associated clinical findings were acholic stool in 33 cases (60.0%), hepatomegaly in 30 cases (54.5%), and dark-colored urine in 21 cases (38.2%). Biliary atresia (BA) was the most frequent diagnosis, found in 32 cases (58.2%), followed by intrahepatic bile duct paucity found in 6 cases (10.9%), metabolic disease in 6 cases (10.9%), idiopathic neonatal hepatitis in 5 cases (9.1%), choledochal cyst in 2 cases (3.6%), liver cirrhosis in 2 cases (3.6%), and progressive familial intrahepatic cholestasis and portal fibrosis each in 1

  17. Selective surgical management of progressive familial intrahepatic cholestasis (Byler's disease).

    PubMed

    Emond, J C; Whitington, P F

    1995-12-01

    Progressive familial intrahepatic cholestasis (PFIC) presents in early childhood with pruritus, jaundice, hepatomegaly, and growth failure. Medical therapy is unsuccessful, with progression from cholestasis to hepatic fibrosis, cirrhosis, and ultimately death before the age of 10 years. Because of evidence that biliary diversion can arrest or reverse progression to hepatic fibrosis, we have used partial biliary diversion (PBD) as primary therapy in PFIC, reserving orthotopic liver transplantation (OLT) for children who have progressive disease or established cirrhosis. Seventeen children with PFIC (aged 2 months to 19 years) have been treated. PBD was performed in eight cases. In these procedures, a 10-cm properistaltic jejunal segment was anastomosed to the side of the gallbladder, terminating as an end stoma for the collection and discard of bile. Eleven patients with hepatic insufficiency (or end-stage cirrhosis) received OLT using standard techniques, at the average age of 4 years. Six of the eight children treated with PBD had complete resolution of clinical symptoms and remain well 1 to 13 years postoperatively. These six patients have conjugated bilirubin values of less than 0.3 mg/dL, normal transaminases, and a serum bile salt concentration of less than 10 nmol/mL. All have had either reversal or no progression of the hepatic fibrosis. Postoperative bleeding complications occurred in two (25%), which required reoperation. One patient had an adhesive intestinal obstruction that was managed surgically 9 months postoperatively. Two patients had no benefit from PBD, and all of them had severe bridging fibrosis (1) or cirrhosis (3). These and nine others with cirrhosis at the time of presentation received orthotopic liver transplantation; of these, eight are alive (1 to 5 years postoperatively). These results show the importance of establishing a correct diagnosis in children with cholestasis. Clinical symptoms often are severe in children with PFIC before the

  18. Pediatric visceral leishmaniasis in northwest of Iran.

    PubMed

    Abdinia, Babak; Oliaei-Motlagh, Mohammad; Teimouri-Dereshki, Amir

    2016-11-01

    Leishmaniasis is one of the major health problems in Iran. Although the incidence of visceral leishmaniasis (VL) is reported almost everywhere, the northwestern Iran is one of the major endemic regions.To do this study, clinical, laboratory as well as disease characteristics of children admitted to Children Cure and Health Hospital, Tabriz University of Medical Sciences, were examined as the reference hospital for the treatment of VL in northwestern Iran.In this study, 156 children hospitalized in a pediatric hospital from 2000 to 2015 for VL were included. Gender, age, anemia, thrombocytopenia, increase in the erythrocyte sedimentation rate (ESR), alanine transaminase (SGPT), and aspartate transaminase (SGOT), major clinical manifestations such as fever, splenomegaly, hepatomegaly, treatment type, and the disease were studied.Among 156 patients examined in this study, 88 (56.41%) and 68 (43.59%) participants were male and female, respectively. The minimum and maximum ages of the infection were 4.5 months and 6 years, respectively. The mean age of the infected children was 17.94 months. Fever (94.24%) and splenomegaly (86.53%) were the most common symptoms of this disease among children. In addition, 49 (31.41%), 64 (41.02%), 18 (11.53%), 33 (21.15%), and 40 (25.64%) participants had leukopenia, hemoglobin count below 8, ESR above 100, ESR above 60, and platelets below 100,000, respectively. Moreover, 39 (25%) and 17 (10.89%) patients had high aspartate transaminase (AST) and alanine transaminase (ALT). Also, 96.2% of the participants responded to the treatment with glucantime. The rate of mortality in this study was 3.2%.Clinically, almost all children had fever and splenomegaly at the onset of the disease. In addition, hepatic involvement was observed in all cases of mortality, cases with a lack of initial response, and those in need of auxiliary medication. Hepatic involvement appears to be related to the prognosis of the disease. In our study, bone marrow

  19. The liver in acquired immune deficiency syndrome: emphasis on patients with intravenous drug abuse.

    PubMed

    Dworkin, B M; Stahl, R E; Giardina, M A; Wormser, G P; Weiss, L; Jankowski, R; Rosenthal, W S

    1987-03-01

    To assess the spectrum of hepatic abnormalities in acquired immune deficiency syndrome (AIDS), we reviewed clinical, biochemical, and pathological material in 32 patients with AIDS. Eight-four percent of AIDS cases had a history of intravenous drug abuse. Ninety percent of AIDS patients has some liver biochemical abnormality at the first presentation of illness. During the course of AIDS, significant (p less than 0.05, paired Student's t test) rises in alkaline phosphatase and bilirubin occurred, without rises in aminotransferases. Mean abnormalities were mild, reflecting approximately 2-fold increases over baseline. Liver failure was not believed to contribute to the death of any AIDS patient. Pathological findings in AIDS included specific infectious diagnosis in 26%, granulomas in 16%, hemosiderosis in 26%, nonspecific abnormalities in 39%, cirrhosis in 23%, and chronic active hepatitis in 3%. AIDS cases were also compared to 10 selected age, sex, and epidemiologically similar non-AIDS patients. Although granulomas or infections were not seen in our comparison group, only the incidence of chronic active hepatitis was significantly different between the groups. If only those with intravenous drug abuse were studied, then none of 24 AIDS patients versus four of eight non-AIDS cases (p less than 0.005) had chronic active hepatitis. AIDS patients with specific hepatic infections tended to have a higher alkaline phosphatase and aspartate aminotransferase (p less than 0.05) than noninfected cases. However, substantial overlap existed, and no difference in hepatomegaly was noted. Ninety percent of AIDS patients were ingesting at least one potentially hepatotoxic drug. We conclude that AIDS patients have a high incidence of underlying hepatic abnormalities. However, clinical and biochemical abnormalities are similar in our selected liver biopsy patients with intravenous drug abuse with or without AIDS. As expected, AIDS patients have a higher incidence of hepatic

  20. Systematic review of the global epidemiology, clinical and laboratory profile of enteric fever

    PubMed Central

    Azmatullah, Asma; Qamar, Farah Naz; Thaver, Durrane; Zaidi, Anita KM; Bhutta, Zulfiqar A

    2015-01-01

    Background Children suffer the highest burden of enteric fever among populations in South Asian countries. The clinical features are non–specific, vary in populations, and are often difficult to distinguish clinically from other febrile illnesses, leading to delayed or inappropriate diagnosis and treatment. We undertook a systematic review to assess the clinical profile and laboratory features of enteric fever across age groups, economic regions, level of care and antibiotic susceptibility patterns. Methods We searched PubMed (January 1964–December 2013) for studies describing clinical features in defined cohorts of patients over varying time periods. Studies with all culture–confirmed cases or those with at least 50% culture–confirmed cases were included. 242 reports were screened out of 4398 relevant articles and 180 reports were included for final review. Results 96% of studies were from an urban location, 96% were hospital–based studies, with 41% of studies were from South Asia. Common clinical features in hospitalized children include high–grade fever, coated tongue, anaemia, nausea/vomiting, diarrhea, constipation, hepatomegaly, splenomegaly neutrophilia, abdominal distension and GI bleeding. In adults’ nausea/vomiting, thrombocytopenia and GI perforation predominate. The case–fatality rate in children under 5 years is higher than school aged children and adolescents, and is highest in Sub Saharan Africa and North Africa/Middle East regions. Multi–drug resistant enteric fever has higher rates of complications than drug sensitive enteric fever, but case fatality rates were comparable in both. Conclusions Our findings indicate variability in disease presentation in adults compared to children, in different regions and in resistant vs sensitive cases. Majority of studies are from hospitalized cases, and are not disaggregated by age. Despite higher complications in MDR enteric fever, case fatality rate is comparable to sensitive cases, with an

  1. Incidence and Risk Factors for Developing Dengue-Associated Hemophagocytic Lymphohistiocytosis in Puerto Rico, 2008 - 2013

    PubMed Central

    Ellis, Esther M.; Pérez-Padilla, Janice; González, Liza; Poole-Smith, B. Katherine; Lebo, Emmaculate; Baker, Charlotte; Delorey, Mark J.; Torres-Velasquez, Brenda; Ochoa, Eduardo; Rivera-Garcia, Brenda; Díaz-Pinto, Hector; Clavell, Luis; Puig-Ramos, Anabel; Janka, Gritta E.; Tomashek, Kay M.

    2016-01-01

    Background Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal disorder characterized by fever, pancytopenia, hepatosplenomegaly, and increased serum ferritin. HLH is being increasingly reported as a complication of dengue, a common tropical acute febrile illness. Methodology/Principal Findings After a cluster of pediatric dengue-associated HLH patients was identified during the 2012–2013 dengue epidemic in Puerto Rico, active surveillance and a case-control investigation was conducted at four referral hospitals to determine the incidence of HLH in children and identify risk factors for HLH following dengue. Patients with dengue-associated HLH (cases) were matched by month of illness onset and admission hospital to dengue patients that did not develop HLH (controls). During 2008–2013, a total of 33 HLH patients were identified, of which 22 (67%) were associated with dengue and 1 died (dengue-associated HLH case-fatality rate: 4.5%). Two patients with dengue-associated HLH had illness onset in 2009, none had illness onset during the 2010 dengue epidemic, and 20 had illness onset during the 2012–2013 epidemic. Frequency of infection with either dengue virus (DENV)-1 or DENV-4 did not differ between cases and controls. Cases were younger than controls (median age: 1 vs. 13 years, p < 0.01), were hospitalized longer (18 vs. 5 days, p < 0.01), and were admitted more frequently to pediatric intensive care units (100% vs. 16%, p < 0.01). Cases had co-infection (18.2% vs. 4.5%, p = 0.04), recent influenza-like illness (54.5% vs. 25.0%, p = 0.01), and longer duration of fever (7 vs. 5 days; p < 0.01). Cases were more likely to have lymphadenopathy, hepatomegaly, splenomegaly, anemia, and elevated liver transaminases (p ≤ 0.02). Conclusions/Significance During this cluster of dengue-associated HLH cases that was temporally associated with the 2012–2013 epidemic, most patients with dengue-associated HLH were infants and had higher morbidity than

  2. Fire disaster following LPG tanker explosion at Chala in Kannur (Kerala, India): August 27, 2012.

    PubMed

    Kumar, Pramod

    2013-11-01

    A fire disaster following LPG tanker explosion occurred at Chala bypass, Kannur, Kerala, India on August 27, 2012. The three chambered tanker with total 16tonnes (162.57 quintal) LPG collided with a road divider and exploded thrice. A total of 41 people became victims during first blast; out of which 20 died in various hospitals. Five people remained inside the house after first blast and escaped unhurt from the zone of accident before second blast. All the victims were transferred to various hospitals; of these, six were transferred to the burns unit of the Kasturba Hospital, Manipal (320km from Chala). Five (5/6) were transferred within 1-5 days at our burns unit suffered 31-72% total body surface area (TBSA) burn, none had external injuries. One (1/6) was transferred on 20th day as a follow up case of 15% TBSA burn with 4% residual raw area and diabetes mellitus. Except one, all were managed conservatively using Limited access dressings (LAD; Negative Pressure Wound Therapy). One of the patient wound bed prepared under LAD and on 41 post burn day underwent split skin grafting under LAD. Out of the six patients admitted at the burns unit, two (2/6) admitted patients expired (one due to inhalation injury and another due to sepsis with multiple organ failure). One survivor (1/4) developed sepsis related liver dysfunction with hepatomegaly but recovered well. The total hospital stay of survivors at the burns unit varied from 8 to 60 days (mean hospital stay 36.5 days). All the victims who developed psychological symptoms were treated by psychiatrists and counselled before discharge. Three of survivors developed psychological symptoms. Two of them (2/3) developed mixed anxiety-depression disorder (ICD 10 code F41.8) and one of these two showed grief reaction too (ICD 10 code F43.23). One victim (1/3) developed non-organic insomnia (ICD 10 code F51.0) and responded to counselling. The article describes the incident, mechanism of the incident, injuries sustained

  3. Teratology of 2,3,7,8-tetrachlorodibenzo-p-dioxin in a complex environmental mixture from the Love Canal

    SciTech Connect

    Silkworth, J.B.; Cutler, D.S.; Antrim, L.; Houston, D.; Tumasonis, C.; Kaminsky, L.S. )

    1989-07-01

    The organic phase of a leachate (OPL) from the Love Canal chemical dump site contains more than 100 organic compounds including 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). The teratogenic potential of OPL was determined in two inbred and one hybrid mouse strain which differ in their sensitivity to aromatic hydrocarbon (Ah) receptor-mediated toxicity. OPL was orally administered in corn oil on Days 6-15 of gestation to C57BL/6J mice (Ahb/Ahb) at doses of 0, 0.1, 0.3, 0.5, and 0.7 g kg-1 day-1 and to DBA/2J (Ahd/Ahd) females, which were mated with either DBA/2J or C57BL/6J males, at 0, 0.5, 1, and 2.0 g kg-1 day-1. In C57BL/6J mice, which express a high-affinity Ah receptor that avidly binds TCDD, the ED50's of OPL for cleft palate and hydronephrosis were 0.44 and 0.11 g OPL kg-1 day-1, respectively. Maternal mortality was 5% at the highest dose. In DBA/2J fetuses, which express a low-affinity receptor, neither treatment-related cleft palate nor hydronephrosis was induced by dose levels that caused 36% maternal mortality. In hybrid D2B6F1 fetuses, the incidence of cleft palate reached only 8% at 2 g OPL kg-1 day-1 but the ED50 for hydronephrosis was 0.76 g OPL kg-1 day-1. TCDD was similarly administered to pregnant C57BL/6J mice at 0, 0.5, 1, 2, and 4 micrograms kg-1 day-1 and to DBA/2J mice at 0, 0.5, 2, 4, and 8 micrograms kg-1 day-1. In C57BL/6J fetuses, the ED50's for cleft palate and hydronephrosis were 4.6 and 0.73 microgram TCDD kg-1 day-1, respectively. In DBA/2J fetuses the ED50's for cleft palate and hydronephrosis were 15.0 and 6.4 micrograms TCDD kg-1 day-1, respectively. Both the OPL and TCDD caused maternal hepatomegaly and thymic atrophy in all strains, but increased only C57BL/6J fetal weights. OPL decreased the number of fetuses per C57BL/6J dam at the two highest doses but there were no other reproductive effects in any of the groups.

  4. Potentiation and antagonism of 2,3,7,8-tetrachlorodibenzo-p-dioxin effects in a complex environmental mixture.

    PubMed

    Silkworth, J B; Cutler, D S; O'Keefe, P W; Lipinskas, T

    1993-04-01

    There is increasing need to understand the toxicity of complex environmental mixtures. The organic phase of a leachate (OPL) from the Love Canal chemical dump site is a complex mixture that contains over 100 organic compounds, including 0.74 ppm 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mice congenic at the Ah locus were used to evaluate several toxic effects of the OPL, including immune function and hepatic enzyme induction. OPL toxicity was compared with that of pure TCDD in both C57BL/6J Ahb/b and congenic C57BL/6 Ahd/d (B6.D2) mice. Mice were given single oral doses of up to 2 g OPL/kg or 100 micrograms TCDD/kg, immunized, and evaluated after 7 days. The TCDD equivalent of the OPL was determined to be 3.9 and 5.0 ppm in C57BL/6J and B6.D2 mice, respectively. This is six times the TCDD content. The Ah phenotype-dependent response ratio was calculated by dividing the dose required to cause an effect in the B6.D2 strain by the dose causing the same effect in the C57BL/6J strain. Ratios based on both ED50s and the lowest observed adverse effect levels were used to determine whether each adverse effect was Ah phenotype-dependent, the extent to which TCDD contributed to the effect, whether there were interactive effects between the AhR ligands and nonligands and if they were additive, antagonistic, or synergistic, and whether the response was predictable based on the known chemical composition of the mixture. It was concluded that the non-TCDD component potentiated TCDD immune suppression, and possibly thymic atrophy, through AhR mechanisms. In contrast, this analysis indicated that the non-TCDD component of the OPL antagonized the ability of the TCDD component to induce hepatic AHH activity whereas OPL hepatomegaly was caused primarily by the non-TCDD component of the OPL. This study demonstrates that the toxicity of mixtures containing TCDD may not be accurately predicted based on the TCDD content alone and that this approach could be useful in the toxicologic

  5. Visceral leishmaniasis and HIV coinfection in Latin America.

    PubMed

    Lindoso, José Angelo; Cota, Gláucia Fernandes; da Cruz, Alda Maria; Goto, Hiro; Maia-Elkhoury, Ana Nilce Silveira; Romero, Gustavo Adolfo Sierra; de Sousa-Gomes, Márcia Leite; Santos-Oliveira, Joanna Reis; Rabello, Ana

    2014-09-01

    Visceral leishmaniasis (VL) is an endemic zoonotic disease in Latin America caused by Leishmania (Leishmania) infantum, which is transmitted by sand flies from the genus Lutzomyia. VL occurs in 12 countries of Latin America, with 96% of cases reported in Brazil. Recently, an increase in VL, primarily affecting children and young adults, has been observed in urban areas of Latin America. The area in which this spread of VL is occurring overlaps regions with individuals living with HIV, the number of whom is estimated to be 1.4 million people by the World Health Organization. This overlap is suggested to be a leading cause of the increased number of reported VL-HIV coinfections. The clinical progression of HIV and L. infantum infections are both highly dependent on the specific immune response of an individual. Furthermore, the impact on the immune system caused by either pathogen and by VL-HIV coinfection can contribute to an accelerated progression of the diseases. Clinical presentation of VL in HIV positive patients is similar to patients without HIV, with symptoms characterized by fever, splenomegaly, and hepatomegaly, but diarrhea appears to be more common in coinfected patients. In addition, VL relapses are higher in coinfected patients, affecting 10% to 56.5% of cases and with a lethality ranging from 8.7% to 23.5% in Latin America, depending on the study. With regards to the diagnosis of VL, parasitological tests of bone marrow aspirates have proven to be the most sensitive test in HIV-infected patients. Serologic tests have demonstrated a variable sensitivity according to the method and antigens used, with the standard tests used for diagnosing VL in Latin America displaying lower sensitivity. For this review, few articles were identified that related to VL-HIV coinfections and originated from Latin America, highlighting the need for improving research within the regions most greatly affected. We strongly support the formation of a Latin American network for

  6. Undiagnosed diabetes and impaired fasting glucose in HFE C282Y homozygotes and HFE wild-type controls in the HEIRS Study

    PubMed Central

    Barton, James C; Barton, J Clayborn; Adams, Paul C; Acton, Ronald T

    2016-01-01

    Objective To determine prevalences and predictors of undiagnosed diabetes mellitus (UDM) and impaired fasting glucose (IFG) in non-Hispanic whites with HFE p.C282Y homozygosity and controls without common HFE mutations identified in population screening. Research design and methods We analyzed these observations in a postscreening examination: age; sex; body mass index; systolic/diastolic blood pressure; metacarpophalangeal joint hypertrophy; hepatomegaly; blood neutrophils; alanine and aspartate aminotransferase; elevated C reactive protein; transferrin saturation; serum ferritin; and Field Center. Results There were 223 p.C282Y homozygotes and 449 controls without diagnosed diabetes (43.9% men). Mean age of p.C282Y homozygotes was 52±13 years (controls 57±14 years; p<0.0001). Mean transferrin saturation in p.C282Y homozygotes was 67±26% (controls 34±14%; p<0.0001). Mean serum ferritin in p.C282Y homozygotes was 607 pmol/L (95% CI 497 to 517; controls 274 pmol/L (247 to 301); p<0.0001). Overall prevalences of UDM (4.0% vs 4.2%) and IFG (23.8% vs 25.6%) did not differ significantly between p.C282Y homozygotes and wt/wt controls, respectively. In logistic regressions, male sex, body mass index, and alanine aminotransferase were significantly associated with UDM. ORs were 2.7 (1.2 to 2.8); 1.0 (1.0 to 1.1); and 1.0 (1.0 to 1.0), respectively. Age, male sex, and body mass index were significantly associated with IFG. ORs were 1.0 (1.0 to 1.1); 2.8 (1.9 to 4.2); and 1.0 (1.0 to 1.1), respectively. Conclusions Prevalences of UDM and IFG were similar in p.C282Y homozygotes and controls in a postpopulation screening examination. Male sex was the strongest predictor of UDM and IFG. PMID:28074138

  7. Immunoblot for the detection of Ascaris suum-specific antibodies in patients with visceral larva migrans (VLM) syndrome.

    PubMed

    Schneider, Renate; Obwaller, Andreas; Auer, Herbert

    2015-01-01

    Visceral larva migrans (VLM) syndrome caused by Toxocara canis larvae was first described in the 1950s. The role of other nematode larvae, i.e. the pig roundworm Ascaris suum as a causative agent of visceral larva migrans-associated symptoms like general malaise, cough, liver dysfunction, hypereosinophilia with hepatomegaly and/or pneumonia, was discussed controversially during the last decades. Recent serological screening studies for specific A. suum antibodies carried out in the Netherlands and Sweden yielded remarkable high seroprevalences, while a number of case reports from Japan report pulmonal, hepatic and cerebral symptoms caused by A. suum larvae after ingestion of infected raw meat (liver) or contaminated vegetables. We present here a sensitive and specific larval excretory-secretory (E/S) antigen-based immunoblot (As-IB) for the serodiagnosis of A. suum-infected patients suffering from symptoms associated to the VLM syndrome. In total, 34 sera from patients with hypereosinophilia and other clinical symptoms associated to the VLM syndrome tested negative for Toxocara sp. antibodies but positive in our newly established As-IB, 30 sera from healthy volunteers, 53 sera from patients with clinically and serologically confirmed toxocarosis and other helminthoses as well as 3 sera from patients with intestinal ascariosis due to Ascaris lumbricoides were included in the study. When evaluated with 30 sera from healthy volunteers and 53 sera from patients suffering from different helminthoses, the calculated specificity of our new As-IB is 95%. Problems hampering the establishment of simple serological screening tests for specific A. suum antibodies, like extensive antigenic similarities between the nematodes Ascaris and Toxocara or the absence of suitable experimental animals, are discussed. We assume that specific serological testing for antibodies of A. suum is very important for the treatment of individual patients on one hand and seroepidemiological

  8. Uveitis in autoimmune hepatitis: A case report

    PubMed Central

    Romanelli, Roberto Giulio; Villa, Giorgio La; Almerigogna, Fabio; Vizzutti, Francesco; Pietro, Elena Di; Fedi, Valentina; Gentilini, Paolo; Laffi, Giacomo

    2006-01-01

    In this case report we describe for the first time an association between autoimmune hepatitis (AIH) and uveitis, without any doubts about other possible etiologies, such as HCV, since all the old reports describe the association of AIH with iridocyclitis before tests for HCV-related hepatitis could be available. A 38-year-old businessman with abnormal liver function tests and hyperemia of the bulbar conjunctiva was admitted to the hospital. Six years before admission, the patient presented with persistent fever, arthralgias, conjunctival hyperemia, leukocytosis and increased ESR, referred to acute rheumatic fever. The presence of systemic diseases, most commonly associated with uveitis, was investigated without results and the patient was then treated with topical corticosteroids. His symptoms resolved. A test for anti-nuclear antibodies was positive, at a titre of 1:320, with a speckled and nucleolar staining pattern. Liver ultrasound showed mild hepatomegaly with an increased echostructure of the liver. Percutaneous liver biopsy was performed under ultrasound assistance. Histological examination showed necroinflammation over the portal, periportal and lobular areas, fibrotic portal tracts, with periportal fibrosis and occasional portal-to-portal bridgings, but intact hepatic architecture. Some hepatocytes showed barely discernible granules of hemosiderin in the lobular area. Bile ductules had not any significant morphological alterations. METAVIR score was A2-F3, according to the modified HAI grading/fibrosis staging. The patient was diagnosed to have AIH with mild activity and fibrosis and was discharged on 25 mg prednisone, entering clinical and biochemical remission, further confirming diagnosis. After discharge the patient continued to have treatment with corticosteroids as an outpatient at a dose of 5 mg. On January 2002 the patient was readmitted to the hospital. A test for anti-nuclear antibodies was positive, at a titre of 1:320, with a speckled and

  9. Risk factors and outcomes stratified by severity of acute kidney injury in malaria.

    PubMed

    Saravu, Kavitha; Rishikesh, Kumar; Parikh, Chirag R

    2014-01-01

    Severe acute kidney injury (AKI) is known to have prognostic value for in-hospital outcomes in malaria. However, little is known about the association of AKI of lesser severity with malarial risk factors and outcomes--and such a gap is becoming increasingly relevant with the upsurge in the incidence of AKI due to Plasmodium falciparum malaria and Plasmodium vivax malaria over the last decade. We aimed to identify risk factors of AKI in malaria and assessed in-hospital outcomes stratified by severity of AKI. We performed an observational study of 1,191 hospitalized malaria patients enrolled between 2007 and 2011 in a tertiary care academic center in India. Patients were categorized based on peak serum creatinine into one of three groups: no AKI (<1.6 mg/dL), mild AKI (1.6-3.0 mg/dL), and severe AKI (>3 mg/dL). Plasmodium vivax was the predominant species (61.41%), followed by Plasmodium falciparum (36.41%) and mixed infections with both the species (2.18%). Mild and severe AKI were detected in 12% and 5.6% of patients, respectively. Mild AKI due to Plasmodium vivax (49%) and Plasmodium falciparum (48.5%) was distributed relatively equally within the sample population; however, cases of severe AKI due to Plasmodium falciparum (80%) and Plasmodium vivax (13%) was significantly different (P<0.001). On history and physical examination, risk factors for AKI were age, absence of fever, higher heart rate, lower diastolic blood pressure, icterus, and hepatomegaly. The only laboratory parameter associated with risk of AKI on multivariate analysis was direct bilirubin. Patients with mild and severe AKI had greater organ complications, supportive requirements, longer duration of hospital stay and in-hospital mortality in a dose-dependent relationship, than patients with no AKI. Mild AKI is associated with significant (P<0.05) morbidity compared to no AKI, and future studies should assess strategies for early diagnosis of AKI and prevent AKI progression.

  10. Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival

    PubMed Central

    Lustosa de Sousa, Daniel Willian; de Almeida Ferreira, Francisco Valdeci; Cavalcante Félix, Francisco Helder; de Oliveira Lopes, Marcos Vinicios

    2015-01-01

    Objective To describe the clinical and laboratory features of children and adolescents with acute lymphoblastic leukemia treated at three referral centers in Ceará and evaluate prognostic factors for survival, including age, gender, presenting white blood cell count, immunophenotype, DNA index and early response to treatment. Methods Seventy-six under 19-year-old patients with newly diagnosed acute lymphoblastic leukemia treated with the Grupo Brasileiro de Tratamento de Leucemia da Infância – acute lymphoblastic leukemia-93 and -99 protocols between September 2007 and December 2009 were analyzed. The diagnosis was based on cytological, immunophenotypic and cytogenetic criteria. Associations between variables, prognostic factors and response to treatment were analyzed using the chi-square test and Fisher's exact test. Overall and event-free survival were estimated by Kaplan–Meier analysis and compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors. Results The average age at diagnosis was 6.3 ± 0.5 years and males were predominant (65%). The most frequently observed clinical features were hepatomegaly, splenomegaly and lymphadenopathy. Central nervous system involvement and mediastinal enlargement occurred in 6.6% and 11.8%, respectively. B-acute lymphoblastic leukemia was more common (89.5%) than T-acute lymphoblastic leukemia. A DNA index >1.16 was found in 19% of patients and was associated with favorable prognosis. On Day 8 of induction therapy, 95% of the patients had lymphoblast counts <1000/μL and white blood cell counts <5.0 × 109/L. The remission induction rate was 95%, the induction mortality rate was 2.6% and overall survival was 72%. Conclusion The prognostic factors identified are compatible with the literature. The 5-year overall and event-free survival rates were lower than those reported for developed countries. As shown by the multivariate analysis, age and baseline white

  11. Miliary tuberculosis

    PubMed Central

    Mert, Ali; Arslan, Ferhat; Kuyucu, Tülin; Koç, Emine Nur; Yılmaz, Mesut; Turan, Demet; Altın, Sedat; Pehlivanoglu, Filiz; Sengoz, Gonul; Yıldız, Dilek; Dokmetas, Ilyas; Komur, Suheyla; Kurtaran, Behice; Demirdal, Tuna; Erdem, Hüseyin A.; Sipahi, Oguz Resat; Batirel, Ayse; Parlak, Emine; Tekin, Recep; Tunçcan, Özlem Güzel; Balkan, Ilker Inanc; Hayran, Osman; Ceylan, Bahadır

    2017-01-01

    Abstract The aim of this study was to determine the clinical features, and outcome of the patients with miliary tuberculosis (TB). We retrospectively evaluated 263 patients (142 male, 121 female, mean age: 44 years, range: 16–89 years) with miliary TB. Criteria for the diagnosis of miliary TB were at least one of the followings in the presence of clinical presentation suggestive of miliary TB such as prolonged fever, night sweats, anorexia, weight loss: radiologic criterion and pathological criterion and/or microbiological criterion; pathological criterion and/or microbiological criterion. The miliary pattern was seen in 88% of the patients. Predisposing factors were found in 41% of the patients. Most frequent clinical features and laboratory findings were fever (100%), fatigue (91%), anorexia (85%), weight loss (66%), hepatomegaly (20%), splenomegaly (19%), choroid tubercules (8%), anemia (86%), pancytopenia (12%), and accelerated erythrocyte sedimentation rate (89%). Tuberculin skin test was positive in 29% of cases. Fifty percent of the patients met the criteria for fever of unknown origin. Acid-fast bacilli were demonstrated in 41% of patients (81/195), and cultures for Mycobacterium tuberculosis were positive in 51% (148/292) of tested specimens (predominantly sputum, CSF, and bronchial lavage). Blood cultures were positive in 20% (19/97). Granulomas in tissue samples of liver, lung, and bone marrow were present in 100% (21/21), 95% (18/19), and 82% (23/28), respectively. A total of 223 patients (85%) were given a quadruple anti-TB treatment. Forty-four (17%) patients died within 1 year after diagnosis established. Age, serum albumin, presence of military pattern, presence of mental changes, and hemoglobin concentration were found as independent predictors of mortality. Fever resolved within first 21 days in the majority (90%) of the cases. Miliary infiltrates on chest X-ray should raise the possibility of miliary TB especially in countries where TB is

  12. Miliary tuberculosis: Epidemiologicaland clinical analysis of large-case series from moderate to low tuberculosis endemic Country.

    PubMed

    Mert, Ali; Arslan, Ferhat; Kuyucu, Tülin; Koç, Emine Nur; Ylmaz, Mesut; Turan, Demet; Altn, Sedat; Pehlivanoglu, Filiz; Sengoz, Gonul; Yldz, Dilek; Dokmetas, Ilyas; Komur, Suheyla; Kurtaran, Behice; Demirdal, Tuna; Erdem, Hüseyin A; Sipahi, Oguz Resat; Batirel, Ayse; Parlak, Emine; Tekin, Recep; Tunçcan, Özlem Güzel; Balkan, Ilker Inanc; Hayran, Osman; Ceylan, Bahadr

    2017-02-01

    The aim of this study was to determine the clinical features, and outcome of the patients with miliary tuberculosis (TB).We retrospectively evaluated 263 patients (142 male, 121 female, mean age: 44 years, range: 16-89 years) with miliary TB. Criteria for the diagnosis of miliary TB were at least one of the followings in the presence of clinical presentation suggestive of miliary TB such as prolonged fever, night sweats, anorexia, weight loss: radiologic criterion and pathological criterion and/or microbiological criterion; pathological criterion and/or microbiological criterion.The miliary pattern was seen in 88% of the patients. Predisposing factors were found in 41% of the patients. Most frequent clinical features and laboratory findings were fever (100%), fatigue (91%), anorexia (85%), weight loss (66%), hepatomegaly (20%), splenomegaly (19%), choroid tubercules (8%), anemia (86%), pancytopenia (12%), and accelerated erythrocyte sedimentation rate (89%). Tuberculin skin test was positive in 29% of cases. Fifty percent of the patients met the criteria for fever of unknown origin. Acid-fast bacilli were demonstrated in 41% of patients (81/195), and cultures for Mycobacterium tuberculosis were positive in 51% (148/292) of tested specimens (predominantly sputum, CSF, and bronchial lavage). Blood cultures were positive in 20% (19/97). Granulomas in tissue samples of liver, lung, and bone marrow were present in 100% (21/21), 95% (18/19), and 82% (23/28), respectively. A total of 223 patients (85%) were given a quadruple anti-TB treatment. Forty-four (17%) patients died within 1 year after diagnosis established. Age, serum albumin, presence of military pattern, presence of mental changes, and hemoglobin concentration were found as independent predictors of mortality. Fever resolved within first 21 days in the majority (90%) of the cases.Miliary infiltrates on chest X-ray should raise the possibility of miliary TB especially in countries where TB is endemic. Although

  13. Clinical Manifestations in 82 Neurobrucellosis Patients from Kosovo

    PubMed Central

    Dreshaj, Shemsedin; Shala, Nexhmedin; Dreshaj, Gresa; Ramadani, Naser; Ponosheci, Albina

    2016-01-01

    Background: Central nervous system involvement is a serious complication of brucellosis with various incidence and various clinical presentations. Patients and Methods: Hospitalized patients in University Clinical Centre, Clinic for Infectious diseases in Prishtina, with laboratory-confirmed brucellosis, were analyzed, a brucellosis-endemic region. Among the 648 confirmed cases with brucellosis during the period 1991- 2013, 82 patients (12.65%) were diagnosed with neurobrucellosis. The clinical manifestations in patients with neurobrucellosis were evaluated and compared with brucellosis patients. Results: The major presentations among the brucellosis patients were headache, fever, sweating, nausea, weight loss and arthralgia, while from CNS predominant complains were: headache, vomiting, tremor, low back pain, hearing loss and visual disturbance. The mean age of 82 neurobrucellosis patients was 31.46 years with age distribution 12-71 years, from them 5 (6.1%), younger than 16 years, with a non-significant predominance of women (53.65%). The most common neurological findings were radiculopathies of legs (41.46%) neck rigidity (46.34%), agitation (25,6%), behavioral disorders (18.3%), disorientation (19.5%) and stroke (1.22%). Cranial nerves were involved in 20 of 82 patients (24.4%). Neurological consequences were evidenced in 5 (6.1%) patients. Three patients leave hospital with consequences of peripheral facial paresis, two with sensorineural hearing loss and one with left hemiparesis. Headache, nausea and vomiting and weight loss are significantly (p<0.001) more frequent complains in neurobrucellosis patients compare to patients with brucellosis. On the other hand, as regard to the physical findings and complications, meningeal signs and splenomegaly are significantly more frequent in neurobrucellosis (p<0.01) whereas the hepatomegaly and lymphadenopathy were more frequent (p<0.01) in brucellosis patients. Different significant correlations were observed among

  14. [A difficult and complicated case study: neonatal intrahepatic cholestasis caused by citrin deficiency].

    PubMed

    Song, Yuan-Zong; Hao, Hu; Ushikai, Miharu; Liu, Guo-Sheng; Xiao, Xin; Saheki, Takeyori; Kobayashi, Keiko; Wang, Zi-Neng

    2006-04-01

    Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a kind of inborn errors of metabolism, with the main clinic manifestations of jaundice, hepatomegaly, and abnormal liver function indices. As a mitochondrial solute carrier protein, citrin plays important roles in aerobic glycolysis, gluconeogenesis, urea cycle, and protein and nucleotide syntheses. Therefore citrin deficiency causes various and complicated metabolic disturbances, such as hypoglycemia, hyperlactic acidemia, hyperammonemia, hypoproteinemia, hyperlipidemia, and galactosemia. This paper reported a case of NICCD confirmed by mutation analysis of SLC25A13, the gene encoding citrin. The baby (male, 6 months old) was referred to the First Affiliated Hospital with the complaint of jaundice of the skin and sclera, which it had suffered from for nearly 6 months. Physical examination showed obvious jaundice and a palpable liver 5 cm below the right subcostal margin. Liver function tests revealed elevated enzymatic activities, like GGT, ALP, AST, and ALT, together with increased levels of TBA, bilirubin (especially conjugated bilirubin), and decreased levels of total protein/albumin and fibrinogen. Blood levels of ammonia, lactate, cholesterol, and triglyceride were also increased, and in particular, the serum AFP level reached 319,225.70 microg/L, a extremely elevated value that has rarely been found in practice before. Tandem mass analysis of a dried blood sample revealed increased levels of free fatty acids and tyrosine, methionine, citrulline, and threonine as well. UP-GC-MS analysis of the urine sample showed elevated galactose and galactitol. The baby was thus diagnosed with suspected NICCD based on the findings. It was then treated with oral arginine and multiple vitamins (including fat-soluble vitamins A, D, E, and K), and was fed with lactose-free and medium-chain fatty acids enriched formula instead of breast feeding. After half a month of treatment, the jaundice disappeared

  15. Effect of dietary supplementation with clay-based binders on biochemical and histopathological changes in organs of turkey fed with aflatoxin-contaminated diets.

    PubMed

    Lala, A O; Ajayi, O L; Oso, A O; Ajao, M O; Oni, O O; Okwelum, N; Idowu, O M O

    2016-12-01

    This study was carried out to investigate the effect of dietary supplementation with molecular or nano-clay binders on biochemical and histopathological examination of organs of turkeys fed diets contaminated with aflatoxin B1. Two hundred and sixteen unsexed 1-day-old British United Turkeys were randomly allotted to nine diets in a 3 × 3 factorial arrangement of diets supplemented with no toxin binder, molecular toxin binder (MTB) and nano-clay toxin binder, each contaminated with 0, 60 and 110 ppb aflatoxin B1 respectively. There were three replicates per treatment with eight turkeys per replicate. Biochemical analyses, organ weights and histopathological changes of some organs were examined at the end of the study which lasted for 84 days. Turkeys fed diets supplemented with molecular and nano-binders showed higher (p < 0.001) total serum protein, reduced (p < 0.001) serum uric acid and GGT concentration values when compared with those fed aflatoxin-contaminated diets supplemented with no binder. Turkeys fed aflatoxin-contaminated diets supplemented with no binder had increased (p < 0.001) AST and ALT concentration when compared with other treatments. The heaviest (p < 0.001) liver and intestinal weight was noticed with turkeys fed diets supplemented with no binder and contaminated with 110 ppb aflatoxin B1 . Pathologically, there was no visible morphological alteration noticed in all turkeys fed uncontaminated diets and nano-clay-supplemented group. Hepatic paleness, hepatomegaly and yellowish discolouration of the liver were observed with turkeys fed diets containing no binder but contaminated with 60 and 110 ppb aflatoxin B1. Intestinal histopathological changes such as goblet cell hyperplasia, villous atrophy and diffuse lymphocytic enteritis were more prominent in turkeys fed diets containing no toxin binder and MTB. In conclusion, there were improved biochemical parameters and reduced deleterious effects of aflatoxin B1 in turkeys fed diet

  16. Assessment of gallstone predictor: comparative analysis of ultrasonographic and biochemical parameters

    PubMed Central

    2013-01-01

    Background Gallstones represent a significant burden for health care systems worldwide and are one of the most common disorders presenting to emergency room. Ultrasonography, complete blood picture test and liver function tests are procedures of choice in suspected gallstones or biliary diseases. They are the most sensitive, specific, non-invasive and inexpensive tests for the detection of gallstones. Our main objective was to evaluate the relationship of ultrasonographic findings, hemolytic indices and liver function tests with gallstones. Methodology It was a prospective study carried out in Civil Hospital Karachi (DUHS) and Liaquat National Hospital, two largest tertiary care hospitals of Karachi, Pakistan. Duration of the study was from July 2011 to October 2012. The study was carried out on diagnosed, pre-operative and symptomatic patients of cholelithiases. Exclusion criteria were patients of gallbladder and pancreatic carcinoma, emergency operations, patients having age <12 years and non-cooperative patients, who refused to give written consent for participation in the study. Total two tests were performed on each patient after diagnosis by ultrasonography. These were complete blood count and liver function tests. All the demographic data, laboratory findings and ultrasonographic features were noted in a pre-structured Performa. Sample size was calculated by using open-epidemiological sample size calculator prevalence (p) = 35%, d = 5%, and confidence interval (CI) 95% = 350. All the data was entered and analyzed through SPSS 19. Result There were 454 diagnosed and pre-operative cases of gallstones present in the study. There were 120(26.4%) males and 334(73.6%) females, with a mean age of 42.80 ± 12.26 years. Most of the suspects had multiple stones 384 (84.5%) while few had single stones 70(15.4%). Fatty liver was found to be present in 144(31.7%) patients and 92(20.2%) had hepatomegaly. Splenomegaly was present in 16(3.5%) patients

  17. The role of per oral cholangiopancreatoscopy (POCPS) in complicated pancreaticobiliary disease.

    PubMed

    Syam, Ari F; Wafa, Syahidatul; Makmun, Dadang

    2015-04-01

    A fifty-five year old female patient presented with jaundice, subfebrile fever and dark yellow urine since one month before admission. She lost weight 10 kilograms during one month. One day before admission to Ciptomangunkusumo General Hospital, she complained of worsened abdominal pain at right upper quadrant urging her to come to the emergency room. An abdominal examination revealed Murphy sign, mild hepatomegaly and deeply icteric sclera. Serum bilirubin was 21.8 mg/dl, alkaline phosphatase and gamma-glutamyltransferase levels were significantly elevated (1090 IU/L and 560 IU/L consecutively) while the transaminases were moderately high (ALT 80 U/L). The C-reactive protein was 555 mg/L. An abdominal ultrasound examination revealed dilatation of right and left intrahepatic bile duct and presence of common hepatic duct stone. Subsequent magnetic resonance imaging/magnetic cholangiopancreatography (MRI/MRCP) revealed intrahepatic bile duct dilatation, multiple CBD stone and benign stricture at common hepatic duct causing right and left intrahepatic bile duct obstruction.We assessed the patient as acute cholangitis and obstructive jaundice suspected to be caused by biliary duct stone then we performed endoscopic retrograde cholangiopancreatography (ERCP), we revealing stenosis at distal CBD, multiple CBD stone, giant stone in CHD and dilatation of bilateral IHBD. We performed CBD stone extraction then inserted biliary stent for drainage. Then we planned to do second ERCP with SpyGlassTM for giant stone extraction. After the first ERCP, the clinical condition of the patient improved and the bilirubin decreased to 10 mg/dL. In the next two weeks we performed a second ERCP to extract the giant stone with SpyGlass TM. However, after we inserted SpyGlassTM into the biliary duct, what we found were not as we expected before. We revealed that there was a mass in biliary duct and there was no CBD stone. We did the biopsy and inserted a new plastic stent (after removed the

  18. Type I glycogen storage diseases: disorders of the glucose-6-phosphatase complex.

    PubMed

    Chou, Janice Yang; Matern, Dietrich; Mansfield, Brian C; Chen, Yuan-Tsong

    2002-03-01

    Glycogen storage disease type I (GSD-I) is a group of autosomal recessive disorders with an incidence of 1 in 100,000. The two major subtypes are GSD-Ia (MIM232200), caused by a deficiency of glucose-6-phosphatase (G6Pase), and GSD-Ib (MIM232220), caused by a deficiency in the glucose-6-phosphate transporter (G6PT). Both G6Pase and G6PT are associated with the endoplasmic reticulum (ER) membrane. G6PT translocates glucose-6-phosphate (G6P) from the cytoplasm into the lumen of the ER, where G6Pase hydrolyses the G6P into glucose and phosphate. Together G6Pase and G6PT maintain glucose homeostasis. G6Pase is expressed in gluconeogenic tissues, the liver, kidney, and intestine. However G6PT, which transports G6P efficiently only in the presence of G6Pase, is expressed ubiquitously. This suggests that G6PT may play other roles in tissues lacking G6Pase. Both GSD-Ia and GSD-Ib patients manifest phenotypic G6Pase deficiency, characterized by growth retardation, hypoglycemia, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic academia and the current treatment is a dietary therapy. GSD-Ib patients also suffer from chronic neutropenia and functional deficiencies of neutrophils and monocytes, which is treated with granulocyte colony stimulating factor to restore myeloid function. The GSD-Ia and GSD-Ib genes have been cloned. To date, 76 G6Pase and 69 G6PT mutations have been identified in GSD-I patients. A database of the residual enzymatic activity retained by the G6Pase missense mutants is facilitating the correlation of the disease phenotype with the patients' genotype. While the molecular basis for the GSD-I disorders are now known and symptomatic therapies are available, many aspects of the diseases are still poorly understood, and there are no cures. Recently developed animal models of the disorders are now being exploited to delineate the disease more precisely and develop new, more causative therapies.

  19. Di-n-octyl phthalate (DOP), a relatively ineffective peroxisome inducing straight chain isomer of the environmental contaminant di(2-ethylhexyl)phthalate (DEHP), enhances the development of putative preneoplastic lesions in rat liver.

    PubMed

    DeAngelo, A B; Garrett, C T; Manolukas, L A; Yario, T

    1986-11-01

    Di-n-octyl phthalate (DOP) is the straight chain isomer of di(2-ethylhexyl) phthalate (DEHP) which is a widely used plasticizer and an environmental contaminant. DEHP is a strong inducer of peroxisome proliferation in rat liver. This is significant since other compounds which are strong inducers of peroxisome proliferation have been reported to be weak carcinogens (Reddy, J.K. and Lalwani, N.D., CRC Crit. Rev. Toxicol., 12 (1983) 1). In contrast to DEHP, DOP causes little or no induction of liver peroxisomes (Mann, A.H. et al., Toxicol. Appl. Pharmacol., 77 (1985) 116, and Gray, T.J.B. et al., Toxicology, 28 (1983) 167). In the current study the ability of 1% DOP to promote the development of putative preneoplastic lesions was evaluated. The effect of feeding 0.5% DEHP as well as equimolar amounts of its 2 major metabolites, mono(2-ethylhexyl)phthalate (MEHP) and 2-ethylhexanol (2-EH) were also investigated. GGT+ foci were initiated in the livers of Sprague--Dawley male rats with a single dose of diethylnitrosamine (DEN) following partial hepatectomy. The control group of rats was fed a semipurified diet (Co) for 10 weeks while the experimental groups received the semipurified diet containing the respective compounds. Induction of peroxisome proliferation was monitored by carnitine acetyltransferase (CAT) levels. DOP treatment resulted in a 6-fold increase in the number of GGT+ foci (20.8 +/- 4.0 vs. 3.5 +/- 1.3; P less than 0.05). This was accompanied by no change in liver weight and only a slight increase in CAT activity when compared with control animals. In contrast to DOP, 2-EH produced essentially no effect with regard to number of foci, peroxisome proliferation or liver weight. DEHP and MEHP induced significant peroxisome proliferation and hepatomegaly but the number of foci were significantly lower than in 2-EH-treated rats. The mechanism for the promoting ability of DOP is not clear but would not appear to be related to peroxisome proliferation. Because of

  20. Effect of Oral Eliglustat vs Placebo on Spleen Volume in Patients with Splenomegaly and Gaucher Disease Type 1: The ENGAGE Randomized Clinical Trial

    PubMed Central

    Mistry, Pramod K.; Lukina, Elena; Turkia, Hadhami Ben; Amato, Dominick; Baris, Hagit; Dasouki, Majed; Ghosn, Marwan; Mehta, Atul; Packman, Seymour; Pastores, Gregory; Petakov, Milan; Assouline, Sarit; Balwani, Manisha; Danda, Sumita; Hadjiev, Evgueniy; Ortega, Andres; Shankar, Suma; Solano, Maria Helena; Ross, Leorah; Angell, Jennifer; Peterschmitt, M. Judith

    2016-01-01

    Importance In Gaucher disease type 1, inherited deficiency of acid-β-glucosidase underlies accumulation of glucosylceramide in lysosomes of macrophages and resultant hepatosplenomegaly, anemia, thrombocytopenia, and skeletal disease. The standard of care is lifelong intravenous enzyme replacement therapy. A safe, effective oral therapy appropriate for a broad spectrum of patients is an important unmet need. Objective To determine whether eliglustat, a novel oral substrate-reduction therapy, safely reverses clinical manifestations in previously untreated adults with Gaucher disease type 1. Design, Setting, and Participants Phase-3, randomized, double-blind, placebo-controlled, multinational trial conducted from November 2009 to July 2012 in eligible untreated patients with Gaucher disease type 1 who had splenomegaly plus thrombocytopenia and/or anemia. Interventions Patients were stratified by spleen volume and randomized 1:1 to receive eliglustat (50 or 100 mg twice daily) or placebo for 9 months. Main Outcome and Measures The primary efficacy endpoint was percent change in spleen volume from baseline to 9 months; secondary efficacy endpoints were change in hemoglobin and percent changes in liver volume and platelet count. Results Of 72 patients screened, 40 patients from 12 countries and 18 sites were enrolled. All had baseline splenomegaly and thrombocytopenia (mostly moderate or severe), most had mild to moderate hepatomegaly and moderate to severe bone marrow infiltration, and 20% had mild anemia. Least square mean spleen volume decreased by 27.8% (95% CI: −32.57, −22.97) in the eliglustat group (13.89 MN to 10.17 MN) compared to an increase of 2.3% (95% CI: −2.54, 7.06) in the placebo group (12.50 MN to 12.84 MN), for an overall treatment difference of −30% (95% CI: −36.82, −23.24, P<0.001). For the secondary endpoints, the least squares mean difference between groups all favored eliglustat over placebo with a 1.2 g/dL increase in hemoglobin level

  1. Socio-economic, health and nutritional status of the villagers in the Nong Wai irrigation area, Khon Kaen, Northeast Thailand.

    PubMed

    Harinasuta, C; Sornamani, S; Migasena, P; Vivatanasesth, P; Pongpaew, P; Intarakao, C; Vudhivai, N

    1976-12-01

    Studies were carried out from June 1974 to May 1975 on the socio-economic status, health and nutritional status of the people in 4 villages, in the irrigation area of the Nong Wai Pioneer Agricultural Project of Khon Kaen Province, Northeast Thailand. The result obtained were compared with those in 2 non-irrigated villages in the same province, in order to identify the health and nutritional problems which might arise during the water resource development in the irrigation area. It was found that in the irrigated villages 90% of the peoples were farmers, while in the non-irrigated villages all were farmers. The socio-economic status of the people in the irrigated villages was much better than those in the non-irrigated ones. The income per family in the former was about three times greater than that in the latter. In the study of the health conditions of the villagers, the vulnerable age group including pre-school children under 7 years of age and school children in the elementary school class 1 and class 2, aged 7-9 years old, served as subjects for investigation. Haematological and physical examinations revealed many children with mild to moderate anaemia, vitamin B2 deficiency and a few cases of hepatomegaly. Anaemic children were found to be more prevalent in the non-irrigated villages than in the irrigated area. The overall parasitic infection rates in children in the irrigated and non-irrigated villages were similar with respect to severity of the infection. Hookworm infection, opisthorchiasis, strongyloidiasis and giardiasis were the leading parasitic infections, while amoebiasis was rare. Ascariasis and trichuriasis were not found. However, the first two helminthic infections had a low grade of intensity. The nutritional status of pre-school children, showed that there were more children with good growth in the irrigated villages than in the non-irrigated one. Serum proteins, albumin and globulin, and urinary urea nitrogen-creatinine ratio revealed normal

  2. Teratology of 2,3,7,8-tetrachlorodibenzo-p-dioxin in a complex environmental mixture from the love canal.

    PubMed

    Silkworth, J B; Cutler, D S; Antrim, L; Houston, D; Tumasonis, C; Kaminsky, L S

    1989-07-01

    The organic phase of a leachate (OPL) from the Love Canal chemical dump site contains more than 100 organic compounds including 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). The teratogenic potential of OPL was determined in two inbred and one hybrid mouse strain which differ in their sensitivity to aromatic hydrocarbon (Ah) receptor-mediated toxicity. OPL was orally administered in corn oil on Days 6-15 of gestation to C57BL/6J mice (Ahb/Ahb) at doses of 0, 0.1, 0.3, 0.5, and 0.7 g kg-1 day-1 and to DBA/2J (Ahd/Ahd) females, which were mated with either DBA/2J or C57BL/6J males, at 0, 0.5, 1, and 2.0 g kg-1 day-1. In C57BL/6J mice, which express a high-affinity Ah receptor that avidly binds TCDD, the ED50's of OPL for cleft palate and hydronephrosis were 0.44 and 0.11 g OPL kg-1 day-1, respectively. Maternal mortality was 5% at the highest dose. In DBA/2J fetuses, which express a low-affinity receptor, neither treatment-related cleft palate nor hydronephrosis was induced by dose levels that caused 36% maternal mortality. In hybrid D2B6F1 fetuses, the incidence of cleft palate reached only 8% at 2 g OPL kg-1 day-1 but the ED50 for hydronephrosis was 0.76 g OPL kg-1 day-1. TCDD was similarly administered to pregnant C57BL/6J mice at 0, 0.5, 1, 2, and 4 micrograms kg-1 day-1 and to DBA/2J mice at 0, 0.5, 2, 4, and 8 micrograms kg-1 day-1. In C57BL/6J fetuses, the ED50's for cleft palate and hydronephrosis were 4.6 and 0.73 microgram TCDD kg-1 day-1, respectively. In DBA/2J fetuses the ED50's for cleft palate and hydronephrosis were 15.0 and 6.4 micrograms TCDD kg-1 day-1, respectively. Both the OPL and TCDD caused maternal hepatomegaly and thymic atrophy in all strains, but increased only C57BL/6J fetal weights. OPL decreased the number of fetuses per C57BL/6J dam at the two highest doses but there were no other reproductive effects in any of the groups. It was concluded that the OPL is teratogenic and that hydronephrosis is a sensitive measure of TCDD toxicity in a

  3. Concomitant malaria among visceral leishmaniasis in-patients from Gedarif and Sennar States, Sudan: a retrospective case-control study

    PubMed Central

    2013-01-01

    Background In areas where visceral leishmaniasis (VL) and malaria are co-endemic, co-infections are common. Clinical implications range from potential diagnostic delay to increased disease-related morbidity, as compared to VL patients. Nevertheless, public awareness of the disease remains limited. In VL-endemic areas with unstable and seasonal malaria, vulnerability to the disease persists through all age-groups, suggesting that in these populations, malaria may easily co-occur with VL, with potentially severe clinical effects. Methods A retrospective case-control study was performed using medical records of VL patients admitted to Tabarakallah and Gedarif Teaching Hospitals (Gedarif State) and Al`Azaza kala-azar Clinic (Sennar State), Sudan (2005-2010). Patients positively diagnosed with VL and malaria were identified as cases, and VL patients without microscopy-detectable malaria as controls. Associations between patient characteristics and the occurrence of the co-infection were investigated using logistic regression analysis. Confirmation of epidemiological outcomes was obtained with an independently collected dataset, composed by Médecins Sans Frontières (MSF) at Um-el-Kher and Kassab Hospitals, Gedarif State (1998). Results The prevalence of malaria co-infection among VL surveyed patients ranged from 3.8 to 60.8%, with a median of 26.2%. Co-infected patients presented at hospital with deteriorated clinical pictures. Emaciation (Odds Ratio (OR): 2.46; 95% Confidence Interval (95% CI): 1.72-3.50), jaundice (OR: 2.52; 95% CI: 1.04-6.09) and moderate anemia (OR: 1.58; 95% CI: 1.10-2.28) were found to be positively associated with the co-infection, while severity of splenomegaly (OR: 0.53; 95% CI: 0.35-0.81) and, to a less extent, hepatomegaly (OR: 0.52; 95% CI: 0.27-1.01) appeared to be reduced by concomitant VL and malaria. The in-hospital case-fatality rates did not significantly differ between co- and mono-infected patients (OR: 1.13; 95% CI: 0

  4. Insulin resistance and clinical aspects of non-alcoholic steatohepatitis (NASH).

    PubMed

    Agarwal, Naresh; Sharma, Barjesh Chander

    2005-10-01

    Non-alcoholic steatohepatitis (NASH) is one of the most common liver disorders. This is highly prevalent in obese and diabetic subjects. Persons with central obesity are at particular risk. Other clinical predictors are age more than 40-50 years and hyperlipidemias, but none of these factors is invariable for causation of NASH. Other reported associations are, celiac disease, Wilson's Disease and few other metabolic diseases. Drugs, particularly amiodarone, tamoxifen, nucleoside analogues and methotrxate have also been linked to NASH. The disease is evenly distributed in both sexes but advanced disease is more common in women. Ethnic variation exists and African Americans are less affected than Hispanic Americans. Specific clinical features of NASH are infrequent. Patients usually come to clinical attention by elevated liver enzymes found on routine evaluation but on history, about two third of patients will admit to have mild fatigue and about half will report right upper quadrant pain. Rarely, patient may present with a complication of cirrhosis. Physical examination may reveal hepatomegaly and splenomegaly. Research in last few years has stressed that development of steatosis, stetohepatitis, fibrosis with subsequent cirrhosis are most probably the result of insulin resistance. Therefore, clinical features may reflect existence of insulin resistance. Obesity, particularly central obesity is most important of these. Patients may have sleep apnea syndrome. Hypertension and manifestations of diabetes mellitus like polyuria, polydypsia, and neurological deficits may occur. Patients may have varying combination of obesity, diabetes, hyperlipidemia, hypertension and impaired fibrinolysis (syndrome X). Children with insulin resistance may show acanthosis nigricance. Patients with polycystic ovary syndrome, which consists of insulin resistance, diabetes, obesity, hirsutism, oligo or polymenorrha and hyperlipidemia may have NASH. Other rare manifestations of insulin

  5. Human Cytomegalovirus: detection of congenital and perinatal infection in Argentina

    PubMed Central

    Distéfano, Angélica Lidia; Alonso, Alicia; Martin, Fabián; Pardon, Fabián

    2004-01-01

    Background Human cytomegalovirus (CMV) is one of the most commonly found agents of congenital infections. Primary maternal infection is associated with risk of symptomatic congenital diseases, and high morbidity is frequently associated with very low birth weight. Neonates with asymptomatic infection develop various sequelae during infancy. This is the first Argentine study performed in neonates with congenital and postnatal HCMV infection. The purpose of this study was to evaluate the performance of the polymerase chain reaction (PCR) technique with different pairs of primers, to detect cytomegalovirus isolated in tissue cultures and directly in urine and dried blood spot (DBS) specimens. Results were compared with IgM detection. Methods The study was performed between 1999 and 2001 on routine samples in the Laboratory. A total of 61 urine and 56 serum samples were selected from 61 newborns/infants, 33 patients whose samples were analyzed during the first two to three weeks of life were considered congenital infections; the remaining 28 patients whose samples were taken later than the third week were grouped as perinatal infections, although only in 4 the perinatal transmission of infection was determined unequivocally Cytomegalovirus diagnosis was made by isolating the virus from urine samples in human foreskin fibroblast cells. Three different primer pairs directed to IE, LA and gB genes were used for the HCMV PCR assay in viral isolates. Subsequently, PCR and nested PCR (nPCR) assays with gB primers were performed directly in urine and in 11 samples of dried blood spot (DBS) on Guthrie Card, these results were then compared with serology. Results The main clinical manifestations of the 33 patients with congenital infection were purpura, jaundice, hepatomegaly and anaemia. Three patients presented low birth weight as single symptom, 10, intracranial calcifications, and 2, kidney failure. In the 28 patients grouped as with perinatal infection, anaemia

  6. Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy

    PubMed Central

    Kristiansen, Maria Nicoline Baandrup; Veidal, Sanne Skovgård; Rigbolt, Kristoffer Tobias Gustav; Tølbøl, Kirstine Sloth; Roth, Jonathan David; Jelsing, Jacob; Vrang, Niels; Feigh, Michael

    2016-01-01

    AIM: To characterize development of diet-induced nonalcoholic steatohepatitis (NASH) by performing liver biopsy in wild-type and genetically obese mice. METHODS: Male wild-type C57BL/6J (C57) mice (DIO-NASH) and male Lepob/Lepob (ob/ob) mice (ob/ob-NASH) were maintained on a diet high in trans-fat (40%), fructose (22%) and cholesterol (2%) for 26 and 12 wk, respectively. A normal chow diet served as control in C57 mice (lean chow) and ob/ob mice (ob/ob chow). After the diet-induction period, mice were liver biopsied and a blinded histological assessment of steatosis and fibrosis was conducted. Mice were then stratified into groups counterbalanced for steatosis score and fibrosis stage and continued on diet and to receive daily PO dosing of vehicle for 8 wk. Global gene expression in liver tissue was assessed by RNA sequencing and bioinformatics. Metabolic parameters, plasma liver enzymes and lipids (total cholesterol, triglycerides) as well as hepatic lipids and collagen content were measured by biochemical analysis. Non-alcoholic fatty liver disease activity score (NAS) (steatosis/inflammation/ballooning degeneration) and fibrosis were scored. Steatosis and fibrosis were also quantified using percent fractional area. RESULTS: Diet-induction for 26 and 12 wk in DIO-NASH and ob/ob-NASH mice, respectively, elicited progressive metabolic perturbations characterized by increased adiposity, total cholesterol and elevated plasma liver enzymes. The diet also induced clear histological features of NASH including hepatosteatosis and fibrosis. Overall, the metabolic NASH phenotype was more pronounced in ob/ob-NASH vs DIO-NASH mice. During the eight week repeated vehicle dosing period, the metabolic phenotype was sustained in DIO-NASH and ob/ob-NASH mice in conjunction with hepatomegaly and increased hepatic lipids and collagen accumulation. Histopathological scoring demonstrated significantly increased NAS of DIO-NASH mice (0 vs 4.7 ± 0.4, P < 0.001 compared to lean chow

  7. [Contraception and hepatogastroenterology].

    PubMed

    Grimaud, J C; Bourliere, M

    1989-05-01

    Complications of oral contraceptives (OCs) affecting the gastrointestinal tract, liver and pancreas are rare but potentially serious. Hepatobiliary complications are by far the most frequent and varied. Hepatic lesions will probably decline in frequency as low-dose OCs replace higher dosed pills. Intrahepatic cholestasis induced by OCs resembles that of pregnancy. There may be a genetic predisposition to both conditions involving a dose-dependent estrogen effect of decreasing bile secretion. Intrahepatic cholestasis appears within 6 cycles of OC use. Symptoms include pruritus with anorexia, asthenia, vomiting, and weight loss without fever, rash or abdominal pain. Termination of OCs clears the condition without sequelae within 1-3 months, sometimes after a temporary aggravation. A moderate and asymptomatic cytolysis may appear when OC treatment is begun. Sinusoidal dilatation has been conclusively linked to OCs although few cases have been published. Clinical manifestations other than hepatomegaly are variable. Abdominal pain and fever are the most common. The condition is not related to duration of use and disappears 5-15 days after OC use is terminated. The relative risk of Budd-Chiari syndrome in OC users is estimated at 2.37. OCs increase the prevalence of hepatic adenomas as a function of duration of treatment. They are usually discovered fortuitously but may be revealed by vague abdominal pains. Hemorrhagic complications are more likely in OC users. It may be difficult to distinguish between adenomas, hepatocellular carcinoma, and focal nodular hyperplasia. A puncture biopsy guided by sonography may aid diagnosis. The natural history of adenomas is poorly understood and treatment remains controversial. OCs do not appear to increase the risk of focal nodular hyperplasia but they increase the size of the tumor and the risk of hemorrhage. OCs should be terminated because of risk of hemorrhage. Surgical resection is not indicated unless there are complication or

  8. NTP Toxicology and Carcinogenesis Studies of Polybrominated Biphenyls (CAS No. 67774-32-7)(Firemaster FF-1(R)) in F344/N Rats and B6C3F1 Mice (Feed Studies).

    PubMed

    1993-08-01

    F0 F1 exposure combinations selected for the 2-year study are shown in the following table (see page 6 of full technical report). Adult-Only Exposure The major organ affected by toxicity of polybrominated biphenyls was the liver. Rats evaluated at 9 months had decreased body weights, hepatomegaly, nonneoplastic histopathologic changes in the liver, mild anemia, increases in serum cholesterol concentrations, and decreases in serum triglyceride concentrations (males only). In rats receiving adult only exposure (F0 F1 concentrations of 0:10 or 0:30 ppm), there were no significant effects on survival. Mean body weights were significantly reduced in 0:10 and 0:30 ppm male rats and in 0:30 ppm female rats. Males and females exposed to 0:10 or 0:30 ppm had increased incidences of hepatocellular neoplasms (males: 0:0 ppm, 1/50; 0:10 ppm, 12/49; 0:30 ppm, 41/50; females: 0/50,12/50, 39/50). Increased incidences of the following nonneoplastic lesions were associated with the administration of polybrominated biphenyls: eosinophilic foci, cytoplasmic vacuolization, oval cell hyperplasia, and hypertrophy in the liver of males and females; acanthosis, inflammation, and ulceration of the forestomach in exposed males; and cystic endometrial hyperplasia of the uterus in 0:30 ppm females. Perinatal-Only Exposure For rats receiving only perinatal exposure (10:0 ppm), there were no changes in survival or body weights compared to the 0:0 ppm control groups. In female rats, there were no effects on neoplasm incidences, but perinatal exposure was associated with a marginally increased incidence of hepatocellular adenoma in male rats (0:0 ppm, 1/50; 10:0 ppm, 5/50). The incidences of nonneoplastic lesions in the liver were increased in exposed males (eosinophilic foci and cytoplasmic vacuolization) and females (eosinophilic foci). Combined Perinatal and Adult Exposure Combined perinatal and adult exposure resulted in marginally reduced survival compared to the 0:0 ppm control group for

  9. NTP Toxicology and Carcinogenesis Studies of 2-Mercaptobenzothiazole (CAS No. 149-30-4) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    PubMed

    1988-05-01

    Toxicology and carcinogenesis studies of technical-grade 2-mercaptobenzothiazole (96%-97% pure), a rubber accelerant and preservative, were conducted by administering the chemical by gavage in a corn oil vehicle to groups of F344/N rats and B6C3F1 mice of each sex for 16 days, 13 weeks, or 2 years. 2-Mercaptobenzothiazole was nominated for study by the National Institute of Environmental Health Sciences and the National Institute for Occupational Safety and Health. Sixteen-Day and Thirteen-Week Studies: In 16-day studies, mean body weight gains of rats receiving 2,500 mg/kg were 6-7 g lower than those of vehicle controls; 4/5 male and 5/5 female mice dosed with 3,000 mg/kg and 4/5 female mice dosed with 1,500 mg/kg died; lethargy and prostration occurred in most of these animals after gavage. Based on these results, doses were selected for both species in the 13-week studies were 0, 94 (mice only), 188, 375, 750, and 1,500 mg/kg. In the 13-week studies, no chemical-related deaths occurred in rats, but body weight gains in males dosed with 1,500 mg/kg and in females dosed with 750 or 1,500 mg/kg were lower than those in the vehicle control groups. Hepatomegaly occurred at the two highest doses in males and at all doses in females; however, no microscopic pathologic changes were noted in any tissue. More than half the mice dosed with 1,500 mg/kg died, but no compound-related body weight changes occurred. Clinical signs in mice were dose related and included lethargy in animals dosed with 375 mg/kg and lacrimation, salivation, and clonic seizure in some dosed with 750 or 1,500 mg/kg. No association between these clinical signs of toxicity and gross or microscopic pathologic effects were observed. Doses selected for the 2-year studies were 0, 375, and 750 mg/kg for male rats and for mice of each sex and 0, 188, or 375 mg/kg for female rats. Body weight and Survival in the Two-Year Studies: Fifty animals of each species and sex were administered 2-mercaptobenzothiazole