Imatinib mesylate (IM), a tyrosine kinase inhibitor, is the treatment of choice in patients with chronic myeloid leukemia (CML). It is considered a very safe drug, with mostly mild and reversible ...side effects. Lately, it has been suggested that adverse events may occur after a long term. We report a case of a 72-year-old woman diagnosed with blastic phase of Philadelphia chromosome positive CML treated with IM for 28 months. The patient presented first with ascites as a side effect of the drug. When the ascites re-occurred, it was caused by neuroendocrine tumor (NET) with peritoneal carcinomatosis. We believe this is the first case of a NET as a secondary malignancy (SM) after IM treatment. SM have been described in patients on IM before. It is unclear whether these tumors are caused by imatinib or found more easily because of close follow-up.
To identify changes in extracellular vesicles (EVs) secreted by the liver following drug‐induced liver injury (DILI), rats were treated with a subtoxic dose (500 mg/kg) of the analgesic drug, ...acetaminophen (APAP). EVs were collected by liver perfusion of sham and APAP‐treated rats. Changes in EVs morphology were examined by transmission electron microscopic analysis of negatively stained vesicles. Results from morphometric analysis of EVs revealed striking differences in their size and distribution. Proteome composition of EVs collected by liver perfusion was determined by mass spectrometry using methods of sample preparation that enabled better detection of both highly hydrophobic proteins and proteins with complex post‐translational modifications. The collection of EVs after liver perfusion is an approach that enables the isolation of EVs shed not only by isolated hepatocytes, but also by the entire complement of hepatic cells. EVs derived after DILI had a lower content of alpha‐1‐macroglobulin, ferritin, and members of cytochrome 450 family. Fibronectin, aminopeptidase N, metalloreductase STEAP4, integrin beta, and members of the annexin family were detected only in APAP‐treated samples of EVs. These results show that the present approach can provide valuable insights into the response of the liver following drug‐induced liver injury.
Kikuchi disease (KD) or histiocytic necrotizing lymphadenitis is a benign self-limited extremely-rare disorder of unkown etiology. It is characterized by regional cervical lymphadenopathy with ...tenderness, usually accompanied with mild fever and night sweats. The recognition of KD is crucial as it can be mistaken for or be associated with systemic lupus erythematosus (SLE).
We present a 29-year-old Croatian female admitted to the Hematology and Oncology Department, General Hospital Dr. Josip Benčević, Croatia in a life threatening condition. She was feverish (40°C) with chills and weight loss. On clinical examination the patient had bilaterally enlarged cervical, axillary and inguinal lymph nodes with sizes up to 3cm. Our differential diagnosis was SLE, lymphoma, sarcoidosis, Still’s disease, hemophagocytic syndrome and KD. An extensive workup was done to confirm one of these diagnoses. Methylprednisolone 100mg iv (1.5mg/kg) was initiated for 5days and as the patient’s condition was severe, steroids were maintained. Lymph node biopsy histopathology was compatible with KD. Antinuclear antibody and anti-double-stranded-DNA were positive. The patient fulfilled the classification criteria for SLE. A diagnosis of SLE associated with KD was held. On CT scan there was bilateral pleural effusion and ascites. Brain MRI was compatable with lupus cerebritis. On steroids plus hydroxychloroquine the patient remarkably improved and remained in remission after 3months.
Prompt diagnosis and treatment with steroids may save the life of SLE patients with KD and leads to a favorable outcome. Raising the awareness towards this possibly serious association is important.
We examined proteomic profiles of rat liver extracellular vesicles (EVs) shed following treatment with a sub-toxic dose (500 mg/kg) of the pain reliever drug, acetaminophen (APAP). EVs representing ...the entire complement of hepatic cells were isolated after perfusion of the intact liver and analyzed with LC-MS/MS. The investigation was focused on revealing the function and cellular origin of identified EVs proteins shed by different parenchymal and non-parenchymal liver cells and their possible role in an early response of this organ to a toxic environment. Comparison of EV proteomic profiles from control and APAP-treated animals revealed significant differences. Alpha-1-macroglobulin and members of the cytochrome P450 superfamily were highly abundant proteins in EVs shed by the normal liver. In contrast, proteins like aminopeptidase N, metalloreductase STEAP4, different surface antigens like CD14 and CD45, and most members of the annexin family were detected only in EVs that were shed by livers of APAP-treated animals. In EVs from treated livers, there was almost a complete disappearance of members of the cytochrome P450 superfamily and a major decrease in other enzymes involved in the detoxification of xenobiotics. Additionally, there were proteins that predominated in non-parenchymal liver cells and in the extracellular matrix, like fibronectin, receptor-type tyrosine-protein phosphatase C, and endothelial type gp91. These differences indicate that even treatment with a sub-toxic concentration of APAP initiates dramatic perturbation in the function of this vital organ.
Background: Endemic nephropathy (EN) and associated urothelial cell cancers (UUC) are an environmental form of aristolochic acid nephropathy where the most probable rout of ingestion of aristolochic ...acid (AA) was made by bread contaminated with AA, leading to chronic dietary intoxication. Clinical courses of three members of the same family, similarly exposed to toxin, who exhibited different clinical courses of the disease are presented. Methods: Questionnaires on AA exposure were taken. Tissue samples were obtained during therapeutic nephrouretectomies. Histopathology, immunohistochemical detection of p53, p53 mutation screening in tumor DNA and analysis on the presence of aristolactam (AL)-DNA adducts were performed. Results: Case 1 had UUC with typical EN histopathological signs, whereas Case 2 had bilateral UUCs with typical EN histopathological signs. In contrast, the patient in Case 3 initially showed renal insufficiency, complicated afterwards by right UUC, and later on by left UUC with histopathological end-stage chronic changes but without typical EN changes. AA-DNA adducts and specific p53 mutational spectra (A:T→ T:A transversion) were found in tissues of cases 1 and 2. Conclusion: Diverse clinical courses seem to be related not to differences in exposure but to differences in metabolic activation or detoxification of AA and/or DNA repair resulting from different genetic polymorphisms.
Imatinib mesylate (IM), a tyrosine kinase inhibitor, is the treatment of choice in patients with chronic myeloid leukemia (CML). It is considered a very safe drug, with mostly mild and reversible ...side effects. Lately, it has been suggested that adverse events may occur after a long term. We report a case of a 72-year-old woman diagnosed with blastic phase of Philadelphia chromosome positive CML treated with IM for 28 months. The patient presented first with ascites as a side effect of the drug. When the ascites re-occurred, it was caused by neuroendocrine tumor (NET) with peritoneal carcinomatosis. We believe this is the first case of a NET as a secondary malignancy (SM) after IM treatment. SM have been described in patients on IM before. It is unclear whether these tumors are caused by imatinib or found more easily because of close follow-up.
Background: sepsis is the common cause of death in immunocompromised patients and those suffering from malignant diseases. The mortality can be significantly reduced when early and correct diagnosis ...is given and the appropriate therapy is administered. Here we set to determine the incidence, sources and outcomes of sepsis and to resolve which bacteria, based on Gram staining, are more often the cause of sepsis.
Patients and methods: we conducted a retrospective study of medical history in a two-year period, from April 2014 to April 2016. Diagnosis was given based on patients’ blood culture findings or their clinical presentation.
Results: during a two-year period 1663 patients were treated. Sepsis was diagnosed in 35 patients (2.10%). The median age was 73 years and 22 patients (63%) were male. Sepsis was the primary cause of death in 10 patients (29%). Gram-positive bacteria were isolated in 21 patients (60%), and Gram-negative bacteria in 10 patients (31%).
Conclusion: in our retrospective study, the gastrointestinal tract had the highest frequency of identified sepsis source. The incidence of sepsis caused by Gram-positive bacteria found in blood cultures was higher than by Gram-negative bacteria. However, due to small sample size, no difference in mortality was found based on Gram status.
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