Analysis of Incretin Hormones After Orthotopic Liver Transplantation.

BACKGROUND: Several well-known risk factors play an important role in the development of new-onset diabetes mellitus after orthotopic liver transplantation (OLT). Immunosuppressant drugs and hepatitis C virus (HCV) infection have a direct effect on pancreatic beta cells resulting insulin hyposecretion. Steroids mainly cause peripheral insulin resistance. Although in type 2 diabetes mellitus the incretin-insulin axis is impaired and incretin hormones are advantageous targets of many antidiabetic drugs, the endocrinologic background of new-onset diabetes mellitus after transplantation (NODAT) is still not completely understood. METHODS: During the first postoperative year the oral glucose tolerance test (OGTT) was performed on 21 patients after OLT. Patients' glycemic metabolic status was determined according to the results of OGTT. The level of incretin hormones, namely glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), were measured with competitive enzyme-linked immunoassay reaction. RESULTS: Six patients had normal glucose tolerance (NGT), 9 had impaired glucose tolerance (IGT, serum glucose 7.8-11.0 mmol/L), and 6 were diagnosed with NODAT (serum glucose >11.1 mmol/L). Fasting insulin and c-peptide levels were higher if IGT/NODAT was found. Insulin secretion was not further stimulated after OGTT. GIP and GLP-1 levels did not differ significantly, not even after glucose load. HCV infection had not influenced the levels of incretin hormones [GLP-1 (0 min): 1.21 ± 0.27 vs 1.38 ± 0.65; P = ns; GLP-1 (120 min): 1.46 ± 0.61 vs 1.07 ± 0.58; P = ns; GIP (0 min): 2.55 ± 0.95 vs 1.99 ± 0.63; P = ns, GIP (120 min): 2.62 ± 0.6 vs 2.33 ± 0.77; P = ns]. CONCLUSION: The stimulation of insulin secretion in NODAT is limited. Incretin hormones are present independently from the current glycemic status. The use of dipeptidyl peptidase-4 inhibitors through their positive effect on the incretin-insulin axis can be beneficial in the therapy of NODAT after liver transplantation.

New-onset diabetes mellitus and the analysis of dipeptidyl-peptidase-4 after liver transplantation.

BACKGROUND: New-onset diabetes mellitus after transplantation (NODAT) is a common complication after orthotopic liver transplantation (OLT). The diabetogenic effect of hepatitis C virus (HCV) infection is well known. The aim of this study was to analyze the glucose homeostasis before and after OLT. The oral glucose tolerance test (OGTT) was carried out, and dipeptidyl-peptidase-4 (DPP-4) activity was measured. METHODS: The study period was from 2012 to 2014. We enrolled 49 non-diabetic patients from the waiting list (group A) and 21 patients after OLT (group B). Seven patients were monitored continuously both before and after OLT. According to our preoperative OGTT results, 13 patients in group A had newly diagnosed diabetes mellitus (group A/DM) and 11 had impaired glucose tolerance (group A/IGT). In 25 cases, normal glucose tolerance was diagnosed (group A/NGT). The calculated homeostasis model assessment insulin resistance (HOMA2-IR) values were both in group A/DM and-IGT higher compared with group A/NGT (2.42 ± 0.81 vs 2 ± 0.98 vs 1.28 ± 0.67; P = .001). In the case of HCV infection (n = 14; 29%) DM and IGT were more frequent. RESULTS: Six patients in group B had NODAT. In 9 cases, IGT and in 6 cases NGT was detected. In the case of HCV infection (n = 9; 43%), DPP-4 levels were higher compared with that in patients with all other indications for OLT (15.5 ± 5.2 vs 8.7 ± 3.5; P = .008). We evaluated the same individuals before and after OLT (n = 7), and a decrease in ß-cell function was noted. CONCLUSIONS: Preoperative OGTT is an important and easy investigation to rule out glucose imbalance before OLT. The HOMA2 calculation can also be useful both in preoperative and postoperative risk assessment. In our results, DPP-4 activity is not specific for the type of glucose homeostasis imbalance, but, in HCV infection, it is higher. DPP-4 inhibitors can be effective in the therapy of NODAT, especially in HCV-infected patients.

Secondary haemochromatosis in a patient with thalassemia intermedia.

Haemochromatosis is due to excessive accumulation of iron in tissues and organs impairing their function. The most common haematologic disorders that are subject to an intensive transfusion regimen bringing excess iron in the body are: thalassemia and myelodysplastic syndrome. The value of serum ferritin in these patients (indicator of iron stores condition) reaches high values. Red cell substitution bringing additional iron intake must be accompanied by administration of chelation therapy in order to prevent haemochromatosis and related complications. We present the case of a patient with thalassemia intermedia, integumentary secondary haemochromatosis, cirrhosis with haemochromatosis, and secondary diabetes, who died at the age of 33 years because of upper gastrointestinal bleeding due to the rupture of oesophageal varices.

Deficiency Of Antithrombin III (AT III) - Case Report and Review of the Literature.

Antithrombin III (AT III) is a plasmatic α-glicoprotein formed by a single peptidic chain. AT III inhibits thrombin (first target) and free Xa, IXa ,VIIa plasmatic factors. In plasma AT III is found under two forms: α-antithrombin and ß-antithrombin. Deficiency of AT III represents a risk factor for thromboembolic disease. There are known both quantitative and qualitative AT III deficiencies. Incidence of AT III inherited deficiency is relative rare (1:10.000). Acquired deficiency of AT III is more frequent. The transmission of AT III deficiency is autosomal dominant with variable shield factor. Homozygous is incompatible with life (death immediately after birth). Thrombosis appears around the age of twenty years, and in 4-5 decades of life 2/3 of patients are symptomatics. Traumatisms, surgical interventions, estrogenic treatment, precipitated thrombotic complications. Obesity and dyslipidemic syndrome are risk factors. Thrombosis affects the venous system at these patients. Arterial thrombosis are less reported. The most frequent localisations are: the veins of the legs, mesenteric veins, cave veins, superficial periombilical veins. Treatment of AT III deficiency is: administration of AT III concentrates (with a plasmatic level by 80% from normal value) and heparinotherapy. The treatment with AT III concentrates is for patients which faced major surgical interventions, pregnant women with AT III deficiency. The women with AT III deficiency should avoid the utilisation of oral contraceptives.

Technical risk factors for hepatic artery thrombosis after orthotopic liver transplantation: the Hungarian experience.

Hepatic artery thrombosis (HAT) significantly affects graft loss and mortality after orthotopic liver transplantation (OLT). The aim of this study was to analyze the risk factors of HAT in our program, with special regard to the personal-technical factor. We retrospectively analyzed the data of 500 adult liver transplant recipients between 1995 and 2011. Operations were performed by a certain group of surgeons, with standardized technique. The incidence rate of HAT decreased since 1995 from 12% to 7.8%. In accordance with the literature, HAT associated with acute rejection, polytransfusion, and the duration of the hepatectomy, arterial variations/reconstructions, tiny arteries, and furthermore, the timing of the anastomosis in Hungary. However we did not find an association with other parameters, like cytomegalovirus infection, and hepatocellular carcinoma as indication. We created a "difficulty index" that consists of the technical parameters. The difficulty index together with surgical experience (number of OLTs performed) had an outstanding association with HAT. In conclusion, the incidence and risk factors for HAT are similar to the results published by others. However, personal factors, such as experience, timing, given anatomy, and tiredness, might also play a significant role in the occurrence of HAT.

Biliary complications after orthotopic liver transplantation: the Hungarian experience.

Biliary complications (BC) significantly affect morbidity and mortality after orthotopic liver transplantation (OLT). The aim of this study was to analyze the incidence and types of biliary complications after OLT in Hungary. We retrospectively analyzed data of 471 adult liver transplant recipients between 1995 and 2011. Biliary complications occurred in 28% of patients. The most frequent BCs were bile duct stricture, stenosis (19%), biliary leakage (12%), and necrosis (BN: 6.4%). Biliary complications were associated with the incidence of acute rejection (51% vs 31%; P = .003), hepatic artery thrombosis (43% vs 11%; P < .001), and hepatic artery stenosis (26% vs 11%; P = .002). When cold ischemic time was longer than 12 hours, leakage (10% vs 3%; P = .043), ischemic type biliary lesion (20% vs 3.4%; P = .05), and BN (12% vs 3%; P = .067) were more often diagnosed post-OLT. Most of the biliary complications were treated by radiologic interventions (70%). Bile duct necrosis was associated with lower graft and patient survival. In conclusion, acute rejection, hepatic artery thrombosis/stenosis and cold ischemic time longer than 12 hours increase the incidence of BCs. Successful management of these risk factors can reduce the incidence of biliary complications and improve mortality.

The diagnostic characteristics of a group of patients with primary gastric lymphoma: macroscopic, histopathological and immunohistochemical aspects.

UNLABELLED: Primary gastric lymphoma is defined as the malignant lymphoproliferative disease with initial symptoms located in the stomach, or tumor mass located in the stomach. This paper aims to present the macroscopic, histopathological and immunohistochemical aspects encountered in a group of patients with primary gastric lymphoma, diagnosed between 2005 and 2010 in the Hematology Clinic of Craiova and the Hematology Clinic of "Fundeni" Institute in Bucharest. MATERIALS AND METHODS: This study was performed on a group of 65 patients diagnosed with primary gastric lymphoma. The positive diagnosis in primary gastric lymphoma is established by the histopathological and immunohistochemical analysis of gastric biopsies, taken during the upper gastrointestinal endoscopy, or of gastric resection samples. We used the monoclonal antibodies CD20, CD10, CD5, k light chain, PCNA (proliferating cell nuclear antigen) and Ki67. RESULTS: The average age of the patients enrolled in the study was 52.55 years. The most common macroscopic feature encountered was the mixed ulcerative-vegetative one. We found two histological types, represented by diffuse large B-cell lymphoma (with or without MALT component), and marginal zone lymphoma (MALT type). Both the MALT type lymphoma and the diffuse large B-cell lymphoma revealed B-cell phenotype. CONCLUSIONS: A correct diagnosis is very important in terms of therapeutic approach. The characteristics of the group of patients were: a higher number of the aggressive histological type; an excessive use of gastric resection; none of the cases was a T-lymphoproliferation.

Secondary plasma cell leukemia.

Plasma cell leukemia (PCL) is a rare disease and is the least common variant of multiple myeloma accounting for 2-3% of all plasma cell dyscrasias. We report a patient who was diagnosed with multiple myeloma, 12 months earlier; he was treated with VBCMP, VCMP regime, and after 12 months he presented of high grade fever, weakness, palpitations, loss of appetite, bone pains, dyspnea. Initial evaluation revealed plasmacytosis with blood plasma cell count of 13 860/mm³. His hemoglobin (Hb) was 8.4 mg/dL, platelets were 45 000/mm³ and total leukocyte count (TLC) was 23 100/mm³ (60% plasma cells). Bone marrow examination revealed 90% plasmablastic cells. Serum LDH was high at 3117 U/L and serum calcium was also elevated at 9.1 mg/dL. A diagnosis of PCL was made and the patient was started on treatment with VAD regime along with supportive care. Patient condition deteriorated very quickly, despite treatment and he died on the third day. A detailed report of this case and a review of PCL is presented here.

Synthesis and in vitro antimicrobial evaluation of pyrazolyl-quinazolin-4(3H)-ones.

A new series of 2-[2-(2,6-dichlorophenyl)amino]phenyl methyl -3-[(1-phenyl-5-substituted phenyl)-5-hydro-1H-pyrazol-3-yl-amino]-6,8-dibromoquinazolin-4(3H)-ones C1-13 have been synthesized by the reaction of 2-[2-(2,6-dichlorophenyl)amino]phenylmethyl-3-substituted phenyl chromene amido-6,8-dibromo-quinazolin-4(3H)-ones with phenylhydrazine in the presence of glacial acetic acid. The chalcones B1-13 have been synthesized by the condensation of 2-[2-(2, 6-dichloro phenyl)amino]phenylmethyl-3-acetamido-6,8-dibromoquinazolin-4(3H)-one A with different substituted aromatic aldehydes. The structures of newly synthesized compounds have been confirmed on the basis of their elemental analysis and spectral data: IR, 'H NMR, (13)C NMR. All the compounds have been screened for antibacterial and antifungal activity.

The unexpected evolution of a case of diffuse large B-cell non-Hodgkin lymphoma.

The diffuse large B-cell lymphoma (DLBCL) represents the most common type of aggressive non-Hodgkin's lymphoma with a heterogeneous morphology, biology and clinical presentation. Gene expression profiling studies identified three distinct molecular subtypes of DLCBL arisen from B-cells at different stages of differentiation: germinal center B-cell-like (GCB) DLBCL, activated B-cell-like (ABC) DLBCL, primary mediastinal B-cell lymphoma (PMBL). The most relevant oncogenic pathways in diffuse large B-cell lymphoma are: deregulated B-cell receptor/proliferation signaling, BCL6 and NF-kB constitutive expression, defects in apoptosis and neoangiogenesis. The treatment of DLBCL has been completely modified in the last ten years by combination of anti-CD20 monoclonal antibody (rituximab) and CHOP chemotherapy, which is now the first line therapy. In the last years, there have been reported several cases of progressive multifocal leukoencephalopathy (PML) at patients with rheumatoid arthritis treated with rituximab. Progressive multifocal leukoencephalopathy is possible as an adverse reaction to rituximab at patients treated with R-CHOP for diffuse large B-cell lymphoma.

The contribution of laboratory investigations in diagnosis of congenital infections.

Congenital diseases are an important indicator of the degree of development of primary health care, because primary prevention is paramount in diagnosing and diminishing the number of those types of cases. Syphilis is a sexually transmitted chronic infectious disease and with an evolution, often unpredictable. Primary prevention aims to prevent infection of the fetus, while secondary prevention aims for a reduction in the severity of sequels already installed.

Can a cutoff value for cystatin C in the operative setting be determined to predict kidney function after liver transplantation?

Correct assessment and follow-up of kidney function is essential in liver transplant recipients. Glomerular filtration rate (GFR) represents the functional capacity of the kidney. The GFR is generally determined on the basis of creatinine clearance using several methods. It has been suggested that cystatin C be used rather than GFR. Production of cystatin C is not dependent on the same factors as creatinine. It is filtered and completely metabolized in the glomeruli, and is not secreted by the kidney tubules. The objective of this study was to determine a preoperative cutoff value for cystatin C based on kidney function estimated after liver transplantation. At prefixed times before and after orthotopic liver transplantation (OLT), serum cystatin C and creatinine concentrations were measured, and GFR was calculated using the Cockroft-Gault equation. Patients were divided into 2 groups according to GFR on postoperative days 1 to 5. Group 1 (healthy recipients) included patients with post-OLT GFR greater than 70 mL/min; and group 2 (kidney-impaired recipients), post-OLT GFR less than 70 mL/min. Group 2 demonstrated greater risk of postoperative complications, abnormal postoperative creatinine concentrations and GFR values, and worse patient and graft survival. Based on the preoperative cystatin C concentration, postoperative kidney function can be assessed. The cutoff value for preoperative cystatin was determined using receiver operating characteristics analysis. When the preoperative cystatin C concentration exceeded 1.28 mg/L, the postoperative GFR was less than 70 mL/min in the first 5 days after OLT. These findings suggest that if the cystatin C concentration exceeds the cutoff point preoperatively, there will be deterioration of kidney function after OLT. Along with other researchers, we suggest that cystatin C is a sensitive marker of post-OLT kidney function.

A case of visceral leishmaniasis in Oltenia region (Romania).

Visceral leishmaniasis is produced by a protozoan parasite that belongs to the genus Leishmania. Transmission is made through sting, the vector being represented by a species of the genus Phlebotomus. The first case of visceral leishmaniasis in Romania was reported by Manicatide (1912). In 1934, it was described a focus of visceral leishmaniasis in Oltenia region (24 cases).The symptoms of disease are unspecific: fatigue, feverishness, cephalalgia, anorexia, nausea, obnubilation status. The fever is irregular, with high oscillations. Clinical, a sallow pallor of the skin, enlarge lymph nodes, hepatomegaly, splenomegaly, weight loss have been observed. Laboratory exams showed frequently severe anemic syndromes or other cytopenias, erythrocytes sedimentation rate was increased, hypergammaglobulin-emia with monoclonal peak has been found. Immunolectrophoresis showed hyper-IgG and hyper-IgM. Bone marrow biopsy showed lympho-plasmocyte infiltration, histiocytes, Leishman-Donovan bodies intracellular or extracellular. The prognosis of the disease is unfavorable in the absence of specific treatment with antimony. In case of resistance, it is used immunotherapy, amphotericin or miltefosine.

Acquired aplastic anemia: correlation between etiology, pathophysiology, bone marrow histology and prognosis factors.

UNLABELLED: Aplastic anemia is a clonal disease of stem cell characterized by peripheral blood pancytopenia with hypocellular bone marrow. In most cases acquired aplastic anemia is an autoimmune, T-cell mediated disease (hematopoiesis is mediated by a population of CD8+ T-cells which produce inhibitory cytokines - TNF-alpha, IFN-gamma, IL-6 which suppress hematopoiesis by affecting the mitotic cycle and cell killing by inducing apoptosis). In some cases radiation, medical drugs and chemicals, viruses induce depletion of hematopoietic stem cells by direct toxicity; immune diseases induce complex immune reactions leading to bone marrow failure. Symptoms and signs are represented by fatigue, pallor induces by anemia, infections induce by neutropenia, and bleedings induce by thrombocytopenia. In peripheral blood is present pancytopenia and bone marrow are characterized by hypocellularity, fat cells hyperplasia, residual lymphocytosis, plasmocytosis and mastocytosis. The aim of this study was to establish the correlation between etiology, pathophysiology, bone marrow histology and negative prognosis factors at 16 patients with acquired aplastic anemia (seven with severe aplastic anemia and nine with moderate aplastic anemia) hospitalized in Clinic of Hematology from Craiova between 2003-2008. Eight cases presented idiopathic aplastic anemia and eight cases secondary aplastic anemia (two of them with pure red cell aplasia). CONCLUSIONS: The unfavorable evolution, correlated with etiology and pathophysiology, had been seen at the patients with severe idiopathic aplastic anemia and severe secondary aplastic anemia associated with viral infections and insecticides exposure. Pure red cell aplasia was associated in our study with B19 parvovirus infection or malignant thymoma. The negative prognosis factors in acquired aplastic anemia, correlated with laboratory findings and a low survival, were: severe neutropenia, platelets count less than 10 000/microL, corrected reticulocytes less than 1%, hypocellularity of bone marrow <10%, persistence of pancytopenia at 30 days after initiating therapy.

[IgA changes in chronic alcoholic hepatopathy]. / Modificari ale IgA în hepatopatia cronica alcoolica.

Chronic alcoholic hepatitis (CAH) has been included, in the last 10 years, among the disease accompanied by particular changes of IgA (primary glomerulonephritis with mesangial deposits of IgA, Berger; Henoch-Schonlein's purpura with IgA deposits in dermatic capillaries and herpetiform dermatitis, with deposits of IgA in dermatic papillae). The characteristics of IgA involvement in CAH are: The whole IgA system is changed, at its 3 levels: circulatory, tissular, formative. at the circulatory level, the IgA2 monomeric fraction increases characteristically; in hepatic parenchyma, perisinusoidal linear deposits of IgA are formed; they have a great significance for the alcoholic etiology, the length of time and seriousness of alcoholism.