Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In chronic granulomatous disease (CGD) enzyme-deficient neutrophils and mononuclear cells lack the respiratory burst required for biocidal activity. Recurrent infections lead to granulomas in various organs but brain lesions are rare. In the present case, a 23-year-old male with numerous infections since early childhood died of overwhelming pulmonary aspergillosis. He first began to experience neurological deficits at the age of 17. Computerized tomography and magnetic resonance imaging revealed fleeting white matter lesions that were interpreted as multiple sclerosis (MS). At post mortem, three types of brain lesions were found: (1) Pigmented macrophages in perivascular spaces and the leptomeninges similar to those reported previously. They contained fine, golden-brown, lipofuscin-like material whose chemical composition included a sulfur peak by X-ray analysis. (2) Focal, well-demarcated, "burnt out" white matter lesions with loss of both myelin and axons and intense sclerosis. (3) Diffuse areas of mild pallor in the centrum ovale which spared the U fibers. The pigmented macrophages are characteristic of those seen in the periphery in CGD. The origin of the discrete, destructive white matter lesions is unclear. They may have resulted from: (i) earlier activity by CGD macrophages; (ii) previous infections due to sepsis or embolism; or (iii) possibly post-infectious encephalomyelitis. The more diffuse, mild, white matter lesions are attributed to edema. Evidence for MS, progressive multifocal leukoencephalopathy, or human immunodeficiency virus encephalitis was lacking. This case is presented to alert us to look more carefully for brain lesions in CGD, characterize them and to help determine their cause.
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PMID:Brain lesions in chronic granulomatous disease. 202 50

In fifty newborn babies, gastric aspirate fluids obtained during the one-hour post partum period were examined from the stand point of PML and cultures. A susceptibility to infections (especially lung infections and sepsis) were established in 8 (30.8%) out of 26 cases with EMR more than twelve hours. PML counts of these cases were 13 and more than 13 per high power field. Significant differences were found between the babies with and without EMR, from the point-of-view of PML count in gastric aspirate fluid and the increased incidence of infections (p less than 0.05).
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PMID:[Relationship of gastric aspirate fluid examination to infections in the newborn infant in cases of premature rupture of the membranes]. 377 98

The authors describe the case of a 66-year-old female patient after transplantation of the kidney where a rare complication of immunosuppressive treatment was diagnosed--progressive multifocal leukoencephalopathy. The disease was manifested by gradually developing hemiparesis of the lower extremity five months after transplantation. Examination of the brain by computed tomography and examination of cerebrospinal fluid were normal. Subsequently the neurological finding developed into quadruparesis. Imaging of the brain by magnetic resonance revealed multiple demyelinization foci. In brain biopsy there were typical structures of progressive multifocal leukoencephalopathy and positive hybridization in situ for JC-virus in cell nuclei. Immunosuppressive treatment was restricted and ganciclovirus administration was started. Further progression of the clinical symptomatology ceased, the function of the transplanted kidney remained satisfactory. The patient died 14 months after the transplantation from sepsis. Examination of the post-mortem material revealed positivity of the JC-virus only in the cytoplasm of the affected cells. As effective treatment of infection with JC-virus is not known so far, the possible action of ganciclovirus is only speculative.
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PMID:[Progressive multifocal leukoencephalopathy in a female patient after kidney transplantation]. 982 86

All-trans-retinoic acid (ATRA) has been incorporated in front-line therapy for newly diagnosed acute promyelocytic leukemia (APL). We conducted a multicenter study of differentiation therapy with ATRA alone or in combination with chemotherapy followed by intensive postremission chemotherapy in patients with APL (the JALSG APL92 study), and analyzed prognostic factors to increase the cure rate in our subsequent trial. From 1992 to 1997, adult patients with newly diagnosed APL received oral ATRA 45 mg/m2 daily alone until complete remission (CR) if initial leukocyte counts were < 3.0x10(9)/l, and ATRA daily plus daunorubicin (DNR) 40 mg/m2x3 days plus enocitabine (BHAC) 200 mg/m2x5 days if leukocyte counts were > or =3.0 x 10(9)/l. If peripheral blasts exceeded 1.0x10(9)/l during therapy, DNRx3 days plus BHACx5 days was added. After CR was achieved, three courses of consolidation and six courses of maintenance/intensification chemotherapy were administered. Of 376 patients enrolled, 369 were evaluable (median age 46 years, range 15-86 years; median leukocyte counts 2.0x10(9)/l), and 333 (90%) achieved CR (94% of patients treated with ATRA alone, 88% with ATRA plus later chemotherapy, 89% with ATRA plus initial chemotherapy, and 86% with ATRA plus initial and later chemotherapy). At a median follow-up of 45 months, the predicted 6-year overall and event-free survival (EFS) rates for all patients were 65% and 52%, respectively. Favorable prognostic factors for CR were younger age, no or mild purpura, high serum total protein level, low lactate dehydrogenase level, and no or mild disseminated intravascular coagulation (DIC). Favorable prognostic factors for EFS were leukocyte counts < 10.0x10(9)/l, mild DIC, and no sepsis during induction therapy. In the JALSG APL97 study, we intensified chemotherapy for patients with leukocyte counts > or =3.0x10(9)/l, and are randomly testing whether further chemotherapy is required for APL patients with negative PCR for PML/retinoic acid receptor alpha in the maintenance phase.
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PMID:Analysis of prognostic factors in newly diagnosed patients with acute promyelocytic leukemia: the APL92 study of the Japan Adult Leukemia Study Group (JALSG). 1158 70

We report the case of a 24-year-old woman with a history of radiotherapy for a cerebellar medulloblastoma 2 years prior to detection of a lymph node metastasis of the former disease and a pancytopenia in the peripheral blood. On bone marrow (BM) examination promyelocyte leukemia vs. a reactive 'promyelocyte arrest' were discussed. The translocation t(15;17) was found in some nuclei and there was a PML-RARalpha gene rearrangement detectable by RT-PCR. Furthermore, there was BM infiltration by the primary cancer. All these results led to the diagnosis of a relapse of the medulloblastoma and of a beginning promyelocyte leukemia. As the patient was pregnant, she had to be parted with the baby to facilitate intensive chemotherapy. She did not respond to a therapeutic regimen specific for promyelocytic leukemia but achieved complete remission of the medulloblastoma as well as the leukemia after the administration of polychemotherapy specific for medulloblastoma. One year later, she suffered from a relapse of her leukemia. Now nearly all cells showed a t(15;17) aberration. Immunophenotype analyses showed a shift to a more undifferentiated blast phenotype that was, however, still HLA-DR negative. The patient again received chemotherapy for leukemia but developed a sepsis 3 months later and died of pancytopenia ensuing her leukemia. There was no clinical evidence for recurrence of the medulloblastoma.
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PMID:Genetic analyses permit the differentiation between reactive malfunctions ('promyelocyte arrest') and arising promyelocyte leukemia in a pregnant patient with a history of a medulloblastoma. 1522 53

Progressive multifocal leukoencephalopathy (PML) is a demyelinating brain disease caused by Jamestown Canyon virus (JCV). This disease is an important cause of morbidity and mortality in acquired immunodeficiency syndrome (AIDS) patients. We report a 34-year-old man infected with HIV-1 who presented with frequent general tonic clonic seizure and left side weakness for 2 months. Clinical features and magnetic resonance imaging (MRI) findings with hyperintensity on T2-weighted imaging and low density on T2 fluid attenuated inversion recovery involving multiple white matter were compatible with PML. He died of sepsis 2 months after diagnosis. Autopsy demonstrated progressive multifocal leukoencephalopathy according to characteristic histopathologic picture with multifocal demyelination, bizarre astrocytes formation and basophilic intranuclear inclusion bodies in the oligodendrocytes. JCV genome was demonstrated in the nucleus of oligodendrocytes using in situ hybridization. In conclusion, in AIDS patients with neurologic signs and typical MRI findings who present with multifocal demyelination lesions, PML should be diagnosed clinically.
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PMID:Progressive multifocal leukoencephalopathy in an AIDS patient. 1749 5

Progressive Multifocal Leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system (CNS) caused by the human virus JC (JCV), a small DNA virus which belongs to the subfamily of polyomaviruses. JVC infection is widely extended in the human population in asymptomatic patients; however, in severely immunocompromised patients the virus is able to replicate itself and reach the brain causing PML. It is an extremely rare disease in patients with a competent immune system and few cases have been described in medical literature. We report the case of an elderly immunocompetent man, with no pathological antecedents, who died of sepsis 50 days after suffering extensive and severe flame burns. In the forensic autopsy, a PML was discovered as an incidental finding in the neuropathological examination that was not detected during his time in hospital. Diagnosis was confirmed by the detection of JCV in the brain by in situ hybridization. Possible pathophysiological mechanisms for the reactivation of the JCV and the rapid evolution to the fatal brain demyelinating lesions are discussed. One of the main clinical implications of this case is that immunocompetence should not be considered as an exclusion criterion for the diagnosis of PML.
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PMID:Progressive multifocal leukoencephalopathy--incidental finding in the forensic neuropathological examination. 1921 17

A 74-year-old man, who had mantle cell lymphoma treated with several anticancer drugs including rituximab, was admitted to our hospital because of gait disturbance and progressive paralysis of the right lower limb. T2-weighted MR image showed multiple high intensity lesions in the left parietal lobe. Suspected of being cerebral invasion of lymphoma, high-dose methotrexate was begun, but the patient died of sepsis without neurological improvement. At autopsy, it was proven that neurological symptoms had been caused by progressive multifocal leukoencephalopathy (PML). PML should be considered as a possible complication of heavily treated lymphoma.
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PMID:[Progressive multifocal leukoencephalopathy after rituximab therapy in a patient with mantle cell lymphoma]. 2125 90

A 41-year-old man diagnosed with malignant lymphoma (MLy) in November 2007 developed paralysis that worsened rapidly in January 2008. Magnetic resonance imaging (MRI) showed multifocal T2 high-intensity lesions without edema or gadolinium enhancement in the white matter. The lesions were characterized by a central core with low signal intensity, surrounded by a rim of high signal intensity on diffusion-weighted images (DWIs). At first, we suspected brain metastasis of MLy and used anti-cancer drugs, but the patient's condition worsened. A brain biopsy was then taken to determine whether the patient had MLy metastasis or progressive multifocal leukoencephalopathy (PML) so that an appropriate course of treatment could be determined. The biopsy contained no characteristic nuclear inclusions of PML, but we were able to rule out MLy; therefore, the patient was treated with cytarabine in February 2008, but he died because of sepsis in March. Upon autopsy, many characteristic nuclear inclusions of PML were found in the periphery of the lesions, and in the central core, there was severe demyelinating and tissue softening without typical nuclear inclusions of oligodendroglias. This structure is similar to the structure observed on DWIs, in which a low signal intensity core is surrounded by a rim of high signal intensity. The presence of inclusion bodies in the rim would correspond to the high signal intensity area on DWIs. The peripheral area may have given high signal intensity on DWIs because of the active findings of many swelling oligodendroglias with typical nuclear inclusions. Conversely, the central lesions would give low signals on DWIs because of demyelination and softening. Hence, the region with high signal intensity adjacent to the central low signal area on DWIs would be an appropriate biopsy point for PML diagnosis. ).
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PMID:[An autopsy case of progressive multifocal leukoencephalopathy: comparison of magnetic resonance imaging findings with the pathological findings]. 2187 3

A considerable minority of patients with ANCA-associated small-vessel vasculitis are refractory to conventional therapy or experience dose-limiting side effects. Novel therapeutic approaches include rituximab, a genetically engineered chimeric murine-human monoclonal antibody that binds to CD20, which is expressed on human B cells. It was approved in 1997 for the treatment of CD20-positive B-cell non-Hodgkin lymphoma and in 2006 for the treatment of rheumatoid arthritis. The multiple mechanisms proposed for rituximab-mediated B-cell depletion are discussed in this paper. Cumulative data from several open studies on the treatment of microscopic ANCA-associated polyangiitis suggest that in the vast majority of cases rituximab has a beneficial effect. Two randomized controlled trials confirmed these promising results, suggesting that rituximab might be considered as an option for first-line therapy of induction of remission of ANCA-associated vasculitis, and providing an additional tool for treating patients with disease relapse after previous therapy. While rituximab is very effective in the depletion of B cells, current research suggests it could also influence other immune system cells and reestablish immune homeostasis and tolerance. The safety profile of rituximab reveals that most reactions are infusion-related and that the incidence of serious side effects is low. Systemic infection remains a major concern and may result in death. A small number of cases of progressive multifocal leukoencephalopathy reported in patients receiving rituximab in off-label use (albeit none with ANCA-associated vasculitis) highlights the importance of pharmacovigilance.
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PMID:[The role of rituximab in the treatment of ANCA-associated systemic vasculitis]. 2202 61


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