Cerebrolysin attenuates cerebral and hepatic injury due to lipopolysaccharide in rats.

This study aimed to investigate the effect of cerebrolysin on oxidative stress in the brain and liver during systemic inflammation. Rats were intraperitoneally challenged with a single subseptic dose of lipopolysaccharide (LPS; 300 µg/kg) without or with cerebrolysin at doses of 21.5, 43 or 86 mg/kg. After 4 h, rats were euthanized and the brain and liver tissues were subjected to biochemical and histopathological analyses. Cerebrolysin revealed inhibitory effects on the elevation of lipid peroxidation and nitric oxide induced by LPS. In contrast, the decrease in reduced glutathione level and paraoxonase activity induced by LPS was attenuated by an injection of cerebrolysin in a dose-dependent manner. Moreover, cerebrolysin reduced LPS-induced activation of brain NF-κB and reversed LPS-induced decline of brain butyrylcholinesterase and acetylcholinesterase activities in a dose-dependent manner. Histopathological analyses revealed that neuronal damage and liver necrosis induced by LPS were ameliorated by cerebrolysin dose-dependently. Cerebrolysin treatment dose-dependently attenuated LPS-induced expressions in cyclooxygenase 2, inducible nitric oxide synthase, and caspase-3 in the cortex or striatum as well as the liver. These results suggest that cerebrolysin treatment might have beneficial therapeutic effects in cerebral inflammation. Cerebrolysin might also prove of value in liver disease and this possibility requires further exploration.

DNA-RNA measurements in patients with acute leukemia undergoing remission induction therapy.

Prior to therapy, 111 newly diagnosed adult patients with acute leukemia had DNA content measured (cell-cycle distributions) and 91 had RNA content measured using flow cytometry of acridine orange-stained bone marrow biopsies. The RNA index (RI) (ratio of mean RNA in G0/G1 of the sample to the median RNA in G0/G1 of normal lymphocytes) distinguished acute myelogenous leukemia (AML) from acute lymphocytic leukemia (ALL). The mean RI in AML was 2.2 and in ALL 1.5. RI did not predict for achievement of complete remission (CR). In AML the mean S-phase percent was 11.2 in patients who achieved CR and 13.1 in those who failed to respond to therapy, whereas in ALL it was 14.5 in those responding and 8.0 in those not responding (P = .02). In the 77 patients with either AML or ALL who achieved CR, a low pretreatment S-phase percent and a high RI correlated with a long duration of CR. S-phase percent and RI were also measured during remission induction and during maintenance therapy. Between days 8 and 18, the RI of responders decreased. In both AML and ALL an increase in S-phase percent between days 18 and 22, prior to morphological CR, was observed in responders but not in nonresponders. The mean S-phase percent at the time of morphological remission was 17.3. A high S-phase percent at this time correlated with a longer duration of CR. Although neither pretreatment S-phase percent nor RI was found to predict for achievement of CR in AML, both predicted for length of CR. Increases in S-phase percent during therapy indicated recovery of normal hematopoiesis.

Philadelphia chromosome-positive adult acute leukemia with monosomy of chromosome number seven: a subgroup with poor response to therapy.

Thirty-four adult patients were seen at the University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, Texas between 1969 and 1980 with acute leukemia (AL) and a deleted G-group chromosome that was shown by Giemsa banding to be a Philadelphia (Ph1) chromosome t(9;22) in 21 patients. Fourteen had the Ph1 chromosome as the sole abnormality, 12 had the Ph1 chromosome and loss of one chromosome of the C-group (identified by Giemsa banding analysis as number 7 in eight patients), while eight had the Ph1 chromosome and other changes. These three groups were similar in sex, age distribution and hematologic parameters. The median age of 40 was lower than usually seen in AL. The distribution of the morphologic subtypes was similar to that seen at this institution, with 50% being acute myeloblastic, 12% acute myelomonocytic, 20% lymphoblastic and 18% acute undifferentiated. The complete remission rate with chemotherapy was low: 25% in the Ph1 +/- 7, 50% in the Ph1 +/other group and 43% in the Ph1 +/other group. Median survival time was 8 months for the Ph1 +/- 7 group, 5.5 months for the Ph1 +/other group and 9.0 months for the Ph1 +/alone group. These patients with Ph1 + AL had higher white blood cell counts, increased extramedullary disease and poorer responses to therapy than usual for patients with AL. The deletion of chromosome 7 and the acquisition of the Ph1 chromosome identifies a group of patients with characteristics similar to all the patients with Ph1 + AL but a poor response to therapy and short remission duration.

Natural history of central nervous system acute leukemia in adults.

Central nervous system (CNS) involvement occurred in 45 of 222 (20.3%) leukemic adults achieving bone marrow (BM) complete remission (CR), including 12 of 23 (52%) acute undifferentiated leukemia (AUL), 12 of 32 (39%) lymphoma leukemia, 5 of 26 (19%) acute lymphoblastic leukemia, and 16 of 142 (11%) acute myelogenous leukemia. Risk factors for CNS disease were lactic dehydrogenase (LDH) greater than or equal to 25,000/mm3. AUL morphology, age less than 20 years, and extramedullary involvement were most significant. Pattern of CNS involvement varied with morphology. Survival after CNS relapse depended most on BM status and symptoms. Duration of CNS CR was longest for asymptomatic patients with low CSF cell counts. Also important were duration of first BM CR, ease of achievement of initial BM CR, and leukocyte count (original and at most closely antecedent BM involvement), reflecting the common origin of BM and CNS leukemic cells. Central nervous system relapse generally did not shorten BM CR or survival, although early primary CNS relapse was associated with early BM relapse.

Tumor cell phagocytosis. Its occurrence in a patient with medulloblastoma.

Phagocytosis was observed in tumor cells from a metastatic medulloblastoma to the bone marrow. Erythrocytes and leukocytes were seen in the cytoplasm of the tumor cells. Another abnormal finding was self-phagocytosis, in which tumor cells engulfed one another. The mechanism of tumor phagocytosis is not yet clearly understood. Only a few cases of erythrophagocytosis by epithelial tumor cells have been reported in the literature. To our knowledge, this is the first reported case of a medulloblastoma with hematophagocytosis.

Acute unclassified leukemia: A clinicopathologic study with diagnostic implications of electron microscopy.

By rigid cytological and cytochemical criteria, the diagnosis of acute and undifferentiated leukemia was established in 22 patients. According to defined criteria, the leukemic cells could not be classified by conventional light microscopic techniques employed in the study of hematopoietic tissue. Cytochemical studies including peroxidase, periodic acid schiff (PAS) and nonspecific esterase (alpha napthyl butyrate-reacting esterase) stains were done on fresh bone marrow samples, and the percentage of positive leukemia cells for each of these stains was determined on 200 cells. In this series of leukemias, cytochemistry at the light microscope level did not contribute to further classification. Subsequent electron microscopic examination of bone marrow samples from these patients confirmed the immaturity and nuclear/cytoplasmic asynchrony of the leukemic cells. Several in vivo neoplastic markers, such as nuclear blebs, increased nuclear bodies, and cytoplasmic fibrillar bundles could be demonstrated in these cells. Fourteen cases from this series exhibited peroxidase-positive developmental granule formation at the ultrastructural level and were reclassified as acute granulocyte leukemia (AGL). One case was reclassified as lymphoma (poor differentiated type), one case was diagnosed as acute monocytic leukemia (AmonoL), and six cases remained in the undifferentiated category (AUL). Clinical and laboratory features, response to treatment, and survival data were evaluated for these patients. This study demonstrated that electron microscopy is useful in the cytological diagnosis of human leukemia.

Acute lymphoblastic leukemia followed by acute granulocytic leukemia in a pediatric patient.

A 14-year-old white male patient had acute lymphoblastic leukemia characterized by a periodic acid-Schiff (PAS)-positive reaction, negative T and B cell markers, and negative nonspecific esterase and peroxidase reactions. Ten months after the initial diagnosis, the bone marrow appearance was compatible with acute granulocytic leukemia, with the presence of Auer rods, and with peroxidase-positive, nonspecific esterase-negative, and negative PAS reactions. Karyotyping and banding were not performed. The concurrence of both diseases in this patient is unique in pediatric oncology.

Hematologic and cytologic characterization of 8/21 translocation acute granulocytic leukemia.

Cytogenetic studies were performed in 546 patients with acute leukemia between 1968 and 1975. Two hundred thirty-four patients were aneuploid (42.9%), and 312 patients were diploid (57.1%). Among these, 32 patients were found to exhibit similar chromosomal alterations that appeared to involve specifically chromosomes 8 and 21. Banding studies in at least 15 of these patients confirmed the presence of a translocation between these two chromosomes. The cytogenetic findings were correlated with the hematologic and clinical data. It was found that each of these individuals had a typical picture of acute granulocytic leukemia with Auer rod-positive and peroxidase-positive cells. Ultrastructurally, the patients in this group also consistently demonstrated the presence of a nuclear bleb that has been positively associated with aneuploidy in acute leukemia. Clinically, they seemed to respond better to therapy than other adult patients with acute granulocytic leukemia. It is proposed that the 8/21 translocation acute leukemia represents a definite subgroup within the general category of acute granulocytic leukemia, with an incidence of approximately 7.3%.

Acute myelomonocytic leukemia following a chemotherapeutic regimen for metastatic sarcoma.

Acute myelomonocytic leukemia developed in a patient 18 months after treatment with cyclophosphamide, vincristine, adriamycin, and DTIC, a chemotherapeutic regimen used for the treatment of metastatic sarcoma. The patient had had no prior history of radiation. More than 400 patients received this treatment and none of them developed leukemia. The occurrence of leukemia in this relatively short period of time may have been caused by the combined chemotherapeutic agents. However, confirmation of this will require long-term followup studies in cancer patients receiving chemotherapy to determine the true risk of second malignancies.

Simultaneous occurrence of non-Hodgkin's lymphoma and spontaneous acute granulocytic leukemia.

The diagnosis of non-Hodgkin's lymphoma with spontaneous acute granulocytic leukemia was confirmed by examination of the patient's bone marrow and peripheral blood specimens at the light and electron microscopic level, and by autopsy findings. Only one previous case of simultaneous non-Hodgkin's lymphoma and acute myelomonocytic leukemia with no prior history of chemotherapy, radiotherapy, or both, has been reported. Although the present patient was given no mutagenic therapy, his chronic exposure to an unknown insecticide may have played a leukemogenic role.

Malignant lymphoma, small lymphocytic type: a clinicopathologic study of 84 cases with suggested criteria for intermediate lymphocytic lymphoma.

Clinical and histopathologic findings were reviewed in 84 cases of malignant lymphoma of the small (well differentiated) lymphocytic type. The slides were studied without clinical information, and the following morphologic features were evaluated: pattern of growth, number of large lymphocytes, mitotic rate, degree of capsular involvement, presence of plasma cells and/or plasmacytoid lymphocytes, and presence of residual germinal centers. Subsequently, clinical information was obtained. The minimum follow-up period on living patients was 5 years. The patients were divided into 3 clinical categories: 1) monoclonal gammopathy (MG)-11 cases, 2) chronic lymphocytic leukemia (CLL) without MG-56 cases, and 3) those without MG or CLL at the time of lymph node biopsy-17 cases. The criterion for CLL was an initial absolute lymphocyte count less than 4000/mm3. Four of the patients with MG also had CLL, and 6 of those in the third group later developed CLL, from 1 to 61 months after lymph node biopsy. Generalized lymphadenopathy was the usual presentation in all 3 groups, and bone marrow examination was positive in all but 1 of the 49 cases, representing all 3 groups, in which it was performed. Median survival for the 84 patients was 51 months. The only clinical parameters which showed a significant association with poorer survival were age above 60 and anemia (Hb. conc. less than 11.0). There was no significant relationship between morphologic characteristics and clinical categories other than the association of plasmacytoid cells with MG in 6 cases. A mitotic rate of 30 or more mitoses per 20 high power fields (HPF), found in 5 cases with at least 1 in each clinical category, showed a highly significant association with decreased survival (p = .01). Variations in mitotic rate between 0 and 29 mitoses per 20 HPF and other morphologic parameters did not show a significant relationship with prognosis. It was concluded that malignant lymphoma of the small lymphocytic type is a definite clinicopathologic entity which may or may not exhibit MG or CLL, and it is proposed that the term "intermediate lymphocytic lymphoma" be applied only to those cases showing histopathologic characteristics of small lymphocytic lymphoma and a mitotic rate of 30 or more mitoses per 20 HPF.

A computer-based reporting system for bone marrow evaluation.

A computerized system of reporting results of bone marrow examination has been implemented at The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, since 1975. All results are entered via the keyboard of cathode-ray tube (CRT) consoles and are instantly available to the attending physician in CRTs strategically located throughout the institution in patient-related areas. Differential counts are available within two to three hours after aspiration. Description of clot sections and smear, diagnosis, and differential diagnosis are completed within 24 hours. Permanent reports are also printed by the computer at regular intervals during the day. The physician can ask the computer for results on a given day or for a cumulative summary displayed in tabular or plot form. This system has proven efficient and rapid, not only for direct reporting of bone marrow examination results but also for storage and retrieval of patient information.