Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The central nervous system was examined in 135 adult AIDS patients who died between August 1982 and December 1990. Twenty two brains showed non-diagnostic changes including microglial nodules, discrete myelin pallor with reactive astrocytosis, mineralization of blood vessels and granular ependymitis. In 105 brains with specific changes, toxoplasmosis was the most frequent finding (55 cases) manifested by multifocal necrotic lesions or diffuse pseudo-encephalitic process. Other opportunists included cytomegalovirus (21 case), progressive multifocal leukoencephalopathy (1 cases), cryptococcosis (6 cases), mycobacterium avium intracellulaire (2 cases), varicella-zoster virus (2 cases), aspergillosis (1 case) and multiple bacterial microabscesses (1 case). Multinucleated giant cells were found in 52 cases. In 40 cases, they were widely disseminated throughout the brain and in 39 cases, they were associated with diffuse or multifocal white matter changes. Fifteen cases had a cerebral lymphoma, 9 hepatic encephalopathy, 1 centropontine myelinolysis and 1 focal pontine leukoencephalopathy. Three cases had a cerebral haemorrhage due to disseminated intravascular coagulation, antithrombin therapy and amyloid angiopathy. Spinal changes in 13 cases included vacuolar myelopathy (7 cases), HIV myelitis (1 case) and ganglio-radiculitis (1 cases), cytomegalovirus myelo-radiculitis (1 case) secondary spread from a lymphoma (1 case) and spinal infarcts due to disseminated intravascular coagulation (1 case). These lesions were frequently atypical and various combinations of all these pathologies were encountered in the same brain, sometimes in the same area and occasionally in the same cell. Chronological variations in the incidence of some complications could be related to changes in treatment.
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PMID:[Neuropathologic study of 135 adult cases of acquired immunodeficiency syndrome (AIDS)]. 195 58

The central nervous system (CNS) has been examined at autopsy in 89 patients who died of the acquired immune deficiency syndrome (AIDS), including 14 patients who died primarily of neurologic complications of the disease. A total of 66 brains (74%) showed significant pathologic abnormalities, with opportunistic infections including cytomegalovirus (14) and cryptococcal (11) infections, progressive multifocal leukoencephalopathy (6), toxoplasmosis (6), and histoplasma microabscesses (1). Incidental Mycobacterium avium-intracellulare infection was found in 4 cases. Simultaneous CNS infection by more than one microorganism was encountered in 5 patients. Subacute (microglial nodule) encephalitis-related to cytomegalovirus infection or possibly brain infection by the causative agent of AIDS was present in 56 cases. Primary CNS lymphoma was noted in 3 patients. Secondary CNS deposits of lymphoma were found in 1 patient, and another patient had lymphomatoid granulomatosis. Vascular complications were not infrequently seen, and included infarcts secondary to vessel occlusion and disseminated intravascular coagulation in 4 patients and intracranial hemorrhage of variable severity in 13. White matter changes included vacuolar myelopathy (3 cases), central pontine myelinolysis (1 case), and foci of calcified, necrotizing leukoencephalopathy in pontocerebellar fibers of the basis pontis (2 cases). These findings highlight the variety of CNS complications in AIDS, some of which are not associated with clinical manifestations. Nevertheless, characterization of all lesions may be important in understanding the neurologic sequelae of AIDS.
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PMID:The neuropathology of AIDS. UCLA experience and review. 287 40

A 46-year-old white male presented with a two-week history of a flu-like illness and bleeding gums. A diagnosis of acute promyelocytic leukemia was made on bone marrow examination with accompanying DIC. All cytogenetically abnormal cells (28/30 at intake and 30/30 at two weeks post-induction) represented a single clone with apparent deletion of 1(p22) and 3(p25), and with a large, derivative chromosome 17. By conventional G- and C- banded analysis, the monocentric der(17) appeared to be disrupted distal to the typical (17q21) APL breakpoint, chromosome 15 did not demonstrate gross rearrangement, and the source of the additional material on the der(17) was unknown. Fluorescence in situ hybridization (FISH) with t(15;17), RAR alpha, and 17qter probes and with chromosome 1, 15, and 17 paints demonstrated that the der(17) consisted of a complex rearrangement with duplication of both RAR alpha and PML, insertion of chromosome 1 sequences, and double insertion of chromosome 15 sequences. The fusion of RAR alpha and PML consistent with APL appears to have occurred at the distal juxtaposition of these sequences in the derivative chromosome.
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PMID:Complex t(1;15;17) in acute promyelocytic leukemia with duplication of RAR alpha and PML sequences. 868 11

A 34-year-old man was admitted to our hospital for a headache in March, 1995. The patient's hemoglobin was 7.5 g/dl, platelet count was 1.8 x 10(4)/microliter and white blood cell (WBC) count was 12,400/microliters with 99% myeloblasts. Myeloblasts were agranular or hypogranular but electron microscopy revealed microgranules in cytoplasm, and a few faggots were observed. The bone marrow was hyperplastic due to myeloblasts and chromosomal abnormality was recognized: 46, XY, t(15; 17) (q22; q12). PML-RAR alpha with intron 3 breakpoint of the PML locus, and rearrangements of the T-cell receptor beta and gamma genes were detected. These cells were positive for CD2 (63%), CD8 (47%), CD13 (87%) and CD33 (99%). Microgranular variant type of acute promyelocytic leukemia (APL) was diagnosed. Disseminated intravascular coagulation (DIC) was also present. The patient was treated with enocitabine, daunorubicin, 6-mercaptopurine, dalteparin sodium, anti-thrombin III concentrates and gabexate mesilate with prophylactic frozen transfusions of fresh plasma and platelet transfusions for 5 days, but WBC count did not decrease and DIC did not improve. The patient died of cerebral hemorrhage 7 days after diagnosis of APL. APL with CD8 expression has never been reported. We suggest that therapy should be modified in this type of APL and conclusions concerning the most appropriate therapeutic strategy will depend on the results of treatment of similar cases in the future.
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PMID:[CD2 and CD8 expression in acute promyelocytic leukemia]. 899 25

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

Acute promyelocytic leukemia (APL) should be distinguished from other subtypes of acute myeloid leukemia (AML) because of the increased risk of disseminated intravascular coagulation (DIC) and its response to arsenic compounds and retinoids. Some cases of AML seem morphologically similar to the microgranular variant of APL (French-American-British [FAB] AML-M3v) but lack the t(15;17). We evaluated 8 cases of APL-like leukemias for subtle morphologic, cytochemical, immunophenotypic, and cytogenetic differences compared with 5 cases of promyelocytic leukemia/retinoic receptor alpha (PML/RARalpha)-positive APL (FAB AML-M3v). We also evaluated both groups for the presence of DIC. No differences among the groups were noted in blast size, chromatin pattern, nuclear morphologic features, intensity of myeloperoxidase staining, or presence of Auer rods. Immunophenotypes were similar; both types of cases lacked CD34 and HLA-DR and were CD13+ and CD33+. Two cases of APL-like leukemias also were CD56+. DIC was present in 2 patients with M3v. Our study shows that there are no definitive morphologic, cytochemical, or immunophenotypic findings that can distinguish these cases from PML/RARalpha-positive APL.
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PMID:Leukemias resembling acute promyelocytic leukemia, microgranular variant. 1193 42

Although gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has been shown a significant activity for recurrent non-small-cell lung cancer (NSCLC), its long-term adverse effect with its continuous usage has hitherto not been clearly elucidated. Subjects were 108 consecutive NSCLC cases who were treated with gefitinib between November 2001 and December 2004 at our single institution. A crude incidence rate ratio was calculated by ratio of crude incidence rate in our subject to population-based incident rate of all leukemia (ICD: C91-95) in the same region. The 95% confidence intervals (CIs) were calculated based upon a Poisson distribution. Three cases of acute promyelocytic leukemia (APL) occurred during gefitinib treatment, and these patients' past treatment histories are presented herein. No other malignancy was identified. All of the cases were diagnosed at the stage of mild-to-moderate cytopenia, especially thrombocytopenia, without disseminated intravascular coagulation. All presented a normal karyotype with positive PML-RARalpha in RT-PCR, indicating submicroscopic translocation. They responded well to APL treatments, including all-trans-retinoic acid. The crude incident rate ratio was 639.9 (95% confidence interval: 131.6-1,878.9, P < 0.0001) when the APL incidence in this cohort was compared to all leukemia cases in the general population in the same district in Japan. Thus we had three cases of secondary APL patients within the gefitinib-treated NSCLC cohort. Although we cannot exclude an effect of past exposure of other cytotoxic agents and radiotherapy as a cause of APL, APL inducibility of gefitinib should be clarified in the further study.
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PMID:Clustered incidence of acute promyelocytic leukemia during gefitinib treatment for non-small-cell lung cancer: experience at a single institution. 1662 31

The study was aimed to detect expression rate of survivin gene in APL cell and to explore the relationship between its expression and clinical manifestation. PML/RARalpha and survivin mRNA expression were analyzed by using reverse transcriptase polymerase chain reaction (RT-PCR) technique. The results showed: (1) the survivin gene expression was detected in NB4 cell line. By treatment with ATRA, survivin mRNA expression in NB4 cell gradually decreased along with time delay and almost could not be detected at the 72th hour. (2) the positive and negative rate of survivin mRNA expression was 67% and 33% respectively, while in all 36 cases of de novo and relapse APL patients, the PML/RAR(alpha) fusion gene expression was positive. In 22 cases at remission stage, the PML/RARalpha fusion gene expression was negative, and the positive and negative rate of survivin mRNA expression was 36% and 64% respectively. The survivin mRNA expression positive rates in the de novo group, relapse group and PML/RARalpha fusion gene L-type positive group were obviously higher than those in remission period group (P < 0.05) and were significantly lower than those in acute leukemia group (P < 0.05, < 0.001). (3) whether the survivin mRNA expression was positive or negative in 36 cases of de novo and relapse APL patients, all the 36 cases could obtain complete remission. 4 APL patients with positive expression of survivin mRNA had DIC and serious infection (one patient died). The clinical symptom showed slight skin or mucosa bleeding, fever and asthenic in the patients with negative expression of survivin mRNA. When 2 APL patients with positive expression of survivin mRNA had been treated with ATRA, induction differentiation sign in their peripheral blood and bone marrow figures was not obvious. It is concluded that the survivin gene positive expression rate is lower in acute promyelocytic leukemia than that in any other types of leukemia and is related to clinical manifestation.
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PMID:[Expression of survivin gene in NB4 cell line and cells of acute promyelocytic leukemia and its anti-apoptosis and clinical significance]. 1663 9

A review of diagnosis of acute promyelocytic leukemia (APL) is presented. There are still many patients with progressive disease with leukocytosis at presentation. These are at greater risk of early death due to bleeding (often intracranial), or, less frequently, due to thrombotic complications. In Czechia, we have, in some instances, noted an unacceptably long time from the first symptoms to diagnosis and to administration of the highly specific differentiation therapy with tretinoin (ATRA) along with anthracycline chemotherapy. This combination is highly efficient--cures are seen in some 70% of patients. Therefore, we present a diagnostic minimum for each and every internist, and even better for every general practician, to get acquainted with. All cases of pancytopenia and consumption coagulopathy should be suspected of APL and referred to a specialized hematologist without any delay. In the following more detailed review of diagnostic measures, much attention is given to APL morphology, which is the first clue leading to diagnosis. The finding of the typical hypergranular FAB M3 morphology and of cells with bundles of Auer rods ("faggot cells"), along with the HLA-DR, CD33+ immunophenotype, is highly (but not absolutely) specific for APL. In cases of the micro-/hypo-granular variant FAB M3v Form, and whenever APL cannot be ruled out with certainty, a test to prove the presence of the PML/RARalpha fusion gene is indicated, using either RT-PCR or, eventually, immunological demonstration of the specific distribution of the PML protein in the cell nucleus. Given that morphology of APL cases, as defined according to WHO criteria (95% of which carry the PML/RARalpha fusion gene), admits extremely divergent morphological pictures ofthe variant forms, we recommend these investigations to be performed in every case of de novo acute myeloid leukemia. A review of the less frequent morphological, as well as genetic variants is given, and the principles of immunophenotypic, cytogenetic and molecular diagnostics are also reviewed.
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PMID:[Urgent states in hematology: acute promyelocytic leukemia--principles of diagnosis]. 1878 May 72

There are very limited reports about childhood acute promyelocytic leukemia (APL), especially about arsenic trioxide (ATO) treatment in both induction and post-remission regimens. 35 newly diagnosed APL patients received ATO treatment in our center and the clinical course as well as the outcome of them was investigated. The dose of intravenous ATO was 0.15-0.17 mg/kg per day, only one patient got 0.33 mg/kg per day, maximum dose was 10 mg per day in induction therapy with minimal chemotherapy treatment (CT) for hyperleukocytosis. Anthracycline or anthracycline-based CT was used for consolidation therapy and followed by 0.10-0.15 mg/kg per day ATO treatment in maintenance therapy. The continuous detection for morphology of bone marrow and PML-RARa were necessary for administrating CT or not. 3 patients died during induction therapy for intracranial hemorrhage, leukocytosis and septic shock. Total of 30 patients achieved complete remission (CR) and were followed-up for 10-108 months. The overall survival (OS) for all patients was 82.7%, whereas the OS for patients obtained CR was 95.8%. The event-free survival for 5 years was 80.3%. Disseminated intravascular coagulation could be under control to reduce induction mortality with adequate supportive care, especially in the first 2 weeks. The side effects of ATO were mild and transient. This regimen of ATO treatment both in induction and post-remission therapy was effective and safe for childhood APL to get long-term survival.
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PMID:Retrospective study of arsenic trioxide for childhood acute promyelocytic leukemia in China: a single-center experience. 2046 63


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