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Biomedical subjects

G Mann

Publications and source records attributed to G Mann.

At least 91 records · Page 5Linked to original sources

Successful treatment strategy for Ki-1 anaplastic large-cell lymphoma of childhood: a prospective analysis of 62 patients enrolled in three consecutive Berlin-Frankfurt-Munster group studies.

PURPOSE: To prove prospectively the efficacy of a short-pulse chemotherapy for treatment of Ki-1 anaplastic large-cell lymphoma (ALCL) of childhood. PATIENTS AND METHODS: From October 1983 to December 1992, 62 patients (median age, 9.7 years) with newly diagnosed Ki-1 ALCL were enrolled onto Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Munster (NHL-BFM) studies 83, 86, and 90. The most frequent immunophenotype was T cell. Ki-1 ALCL differed from other subsets of NHL of childhood by the more frequent involvement of bone, soft tissue, and skin, and by the lack of bone marrow (BM) disease. A 5-day prephase course (prednisone/cyclophosphamide) was followed by two different 5-day courses of chemotherapy: course A consisted of dexamethasone, methotrexate (MTX) 0.5 g/m2 (24-hour infusion), intrathecal chemotherapy, ifosfamide, cytarabine (Ara-C), and etoposide (VP-16); course B consisted of cyclophosphamide and doxorubicin instead of ifosfamide, and Ara-C/VP-16, respectively. Treatment was stratified into three branches. Branch 1 (stage I and stage II resected) received three courses; branch 2 (stage II not resected, stage III), six courses; and branch 3 (stage IV), six intensified courses containing MTX 5 g/m2, and Ara-C 2 g/m2. Local radiotherapy was not performed. RESULTS: Four patients failed to enter remission, and one died of infection. Seven patients relapsed within 9 months after diagnosis; two patients had isolated local relapses, but BM and CNS were never involved. Fifty patients have been in first continuous complete remission (CR) for 0.6 to 9.7 years (median, 2.5), and 56 are alive. The probabilities for survival and event-free survival (EFS) at 9 years are 83% +/- 7% (SE) and 81% +/- 5%. Skin involvement was the only negative prognostic parameter. CONCLUSION: Short-pulse chemotherapy over 2 to 5 months without local therapy modalities is effective in the treatment of Ki-1 ALCL.

Adolescent↗

Rapid discrimination of early CD34+ myeloid progenitors using CD45-RA analysis.

Mononuclear cells (MNC) isolated by density centrifugation of cord blood and healthy bone marrow, and of peripheral blood (PB) from patients treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF after chemotherapy, were double-stained with anti CD34 monoclonal antibody (MoAb) (8G12) versus anti CD45, CD45-RB, CD45-RO, and CD45-RA, respectively, and analyzed by flow cytometry. In all specimens, CD34+ MNC co-expressed CD45 at a low level and the expression of CD45-RB was similar or slightly higher. Most CD34+ MNC were negative for CD45-RO, a weak coexpression was only seen in some bone marrow (BM) and blood samples. In contrast, CD45-RA could subdivide the CD34+ population into fractions negative, dim (+), and normal positive (++) for these subgroups, and typical staining patterns were observed for the different sources of hematopoietic cells: in BM, most CD34+ MNC were RA++. In PB, their majority was RA++ after G-CSF but RA+ or RA- after GM-CSF. In cord blood, the hematopoietic progenitors were mainly RA-/RO-. Semisolid culture of sorted CD34+ MNC showed that clusters and dispersed (late) colony-forming unit-GM (CFU-GM) originated from 34+/RA++ cells, while the 34+/RA- MNC formed compact and multicentric, both white and red colonies derived from early progenitors. Addition of 20 ng stem cell factor per milliliter of medium containing 34+/RA- cord blood MNC led to a change of many burst-forming unit-erythrocyte (BFU-E) to CFU-mix which was not, at least to this extent, seen in blood and BM. We conclude that early myeloid CD34+ cells are 45+/RA-. Because this population excludes 34+/19+ B cells and 33+ myeloid cells, both of which are RA++, two-color flow cytometric analysis using CD34 and CD45-RA facilitates the characterization and quantification of early myeloid progenitor cells.

Antibodies, Monoclonal↗

Detection of Ip36 deletions in paraffin sections of neuroblastoma tissues.

Nonradioactive in situ hybridization (NISH) on sections of paraffin-embedded neuroblastoma tissue was performed to evaluate numerical and structural aberrations of chromosome 1. Two biotinylated probes specific for the heterochromatic (D1Z1) and subtelomeric regions of chromosome 1 (D1S32) were used to study normal tissue and 4 neuroblastoma samples with and without Ip36 deletions. The NISH findings in 3 of the 4 neuroblastomas correlated well with the results obtained by cytogenetic banding analysis. In 1 tumor sample, however, a deletion at Ip36 was observed by NISH, both on metaphase spreads and interphase nuclei, but not by cytogenetics. The NISH method is therefore advantageous when only paraffin-embedded material is available and can be even more sensitive than conventional cytogenetic analyses under certain conditions. Moreover, the technique provides morphological information that cannot be obtained by methods relying on tissue extracts or cell suspensions.

Aneuploidy↗

Peripheral and central components of alerting: habituation of acoustic startle, orienting responses, and elicited waveforms.

Behavioral orienting (OR), the acoustic startle reflex (ASR), pontogeniculooccipital (PGO) waves in the lateral geniculate body, and midlatency auditory evoked responses (MLR) represent components of alerting. The habituation rate for each was examined to test the hypothesis that OR, ASR, and PGO waves have related underlying neural mechanisms and determine the similarity in responsiveness between elicited PGO waves (PGOE) and elicited waves in the thalamic central lateral nucleus (CLE), a site that yields MLR. PGOE and CLE waves did not habituate in amplitude after 120 tones; however, the pattern of responses for each waveform was different. OR and ASR significantly decreased amplitude across trials with OR exhibiting a faster, more pronounced decrement. Some separation exists between the peripheral (OR and ASR) and central (PGOE and CLE) components of alerting. PGO and CL waves may have common underlying neural mechanisms.

Animals↗

Treatment of infant leukemia with busulfan, cyclophosphamide +/- etoposide and bone marrow transplantation.

Infants with acute leukemia have a poor chance of being cured by conventional chemotherapy. We therefore treated cases of infant leukemia with high dose chemotherapy followed by bone marrow transplantation (BMT). Six suffered from acute leukemia and one from refractory anemia with excess of blasts (RAEB-t). The conditioning regimen consisted of busulfan (BU) and cyclophosphamide (CY), and was intensified by adding etoposide (VP) in four cases. At the time of BMT the children were 4, 5, 12, 13, 13, 14, and 20 months old. Three children were autografted, three received HLA-identical marrow from a sibling donor, and one child received matched unrelated donor marrow. All five children who were grafted in complete (CR) or partial remission (PR) are alive and well in CR 7, 13, 24, 37, and 46 months after allogeneic (two patients) or autologous (three patients) BMT, and 13, 17, 29, 42, and 53 months after initial diagnosis. The child with RAEB-t and the one transplanted in second chemotherapy-resistant relapse of acute non-lymphoblastic leukemia relapsed at 7 and 17 months respectively. The chemotherapy regimen was well tolerated. BU-CY-VP is a promising alternative treatment to regimens including total body irradiation for very young children suffering from acute leukemia.

Bone Marrow Transplantation↗

[Viper envenomation by Echis coloratus].

Clinical and therapeutic experience with 24 cases of envenomation by Echis coloratus, the Mideast saw-scaled viper, is reported. These cases were seen between 1979-1989 at this hospital (Mt. Scopus). A clinical classification is proposed, based on severity of the bleeding diathesis and platelet count at presentation. It is suggested as a predictor of clinical outcome and as a guide to whether antiserum should be administered.

Antivenins↗

[Pitfalls in the diagnosis of tuberculous arthritis].

Jewish immigrants from Russia, and Arabs added to the population register since 1967, have a relatively high incidence of bone and joint tuberculosis. These patients now account for most of this disease in Israel. Skeletal tuberculosis imitates various joint conditions, most commonly, rheumatoid arthritis, and therefore presents a diagnostic problem. Injections of corticosteroids and/or immunosuppressive therapy can reactivate quiescent tuberculous lesions. During a 12-year period 14 patients with tuberculous arthritis involving 16 joints were seen in this hospital. They included 9 males and 5 females, 14-70 years old, 4 of whom were known to have had previous skeletal tuberculosis: 3 had spinal and 1 had hip involvement. None of the other 10 had a clinical history of tuberculosis, nor X-ray evidence of active pulmonary disease. 7 patients were diagnosed postoperatively as having joint tuberculosis on histopathological and bacteriological examination; 3 had positive cultures from joint aspirations. Most commonly involved were the spine and knee--4 cases of each. The wrist and acromioclavicular joint were affected in 2 cases each, and the hip, sacroiliac joint, ankle and elbow joints in 1 case each. The youngest patient, 14 years old, had triple-joint involvement of the wrist and the acromioclavicular and sacroiliac joints; the others had single-joint disease. In 1 patient the disease was reactivated after 36 years by surgical conversion of a fused hip to a mobile artificial joint. 3, whose joints were injected with corticosteroids, developed active, destructive tuberculous arthritis. A patient with rheumatoid arthritis who underwent total knee replacement was found to have active tuberculous arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Not Available].

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Germany↗

Reflex sympathetic dystrophy of the patellofemoral joint.

Eighteen patients with a diagnosis of reflex sympathetic dystrophy (RSD) affecting the knee were reviewed. Minor isolated injuries and operations about the knee triggered the original episode. The symptoms, regardless of location and mechanism of injury, occurred in the patellofemoral joint. Roentgenographic features of patchy demineralization and abnormal uptake on a 99mTc scan were typically located in the patella and corresponding femoral articular surface. At the initial stage of the syndrome, pain, hypersensitivity to touch, and inhibition of the quadriceps muscle were the most prominent features. In the later stages of the syndrome, functional instability due to quadriceps weakness created dependence on a knee brace or crutch support. Six patients whose RSD was initially misdiagnosed underwent numerous unsuccessful surgical procedures. In three of these patients, the knee was ultimately fused. All patients had an initial isolated knee injury (usually after minor trauma), and prolonged periods of immobilization and a cast, and 12 of the 18 patients were involved with workers' compensation. Early diagnosis and prompt treatment with an epidural block, followed by intensive physiotherapy, are recommended. A personal doctor/patient relationship that offers guidance and encouragement is key to successful management of this syndrome.

Accidents, Occupational↗

Persistence of hepatitis A virus in fulminant hepatitis and after liver transplantation.

A peroxidase-labelled, specific mouse monoclonal antibody to hepatitis A virus (HAV) and an in situ hybridization technique (streptavidin-biotin-horseradish peroxidase reaction) with an HAV-specific cDNA probe (recombinant plasmid pAWHA comprising 1.8 kb of the HAV-specific cDNA, located toward the 3' end of the genome) were used to detect HAV in liver tissues in two patients with fulminant viral hepatitis type A treated by liver transplantation after a protracted (day 40: case 1) and relapsing (day 60: case 2) clinical course. HAV antigens and HAV-specific genomic sequences were detected in the hepatectomy tissues and in serial biopsies of the liver grafts through to final follow-up at 2 months (case 2) or death at 7 months after re-grafting for chronic rejection (case 1). In the fulminant liver parenchyma, numerous degenerating and some surviving hepatocytes were positive and randomly scattered. The immunoperoxidase staining was predominantly cytoplasmic and often granular. The localization of the cDNA probe was predominantly nuclear/perinuclear but was occasionally cytoplasmic. High-titre IgM-anti-HAV antibodies persisted until death (case 1) or resolution (5 months) of an acute hepatitis (case 2), which occurred at 2 months, accompanied by HAV antigen (ELISA), in stool. Intact replicating virus particles must have been present in one or more sites in each case, including extrahepatic locations, with a viraemia as the most likely explanation for subsequent reinfection of the grafts.

Adult↗

Paracetamol inhibits replicative DNA synthesis and induces sister chromatid exchange and chromosomal aberrations by inhibition of ribonucleotide reductase.

Effects of paracetamol have been studied in a hydroxyurea (HU)-resistant mouse mammary tumour cell line TA3H2, shown to overproduce the small subunit of ribonucleotide reductase. These TA3H2 cells were much more resistant than the TA3H (wild-type) cells towards the inhibitory effect of paracetamol on cell growth, IC50 0.55 mM paracetamol for the wild-type compared to 2.7 mM for the HU-resistant cells. The reduced cell growth was due to an inhibition of replicative DNA synthesis, judged from an increased percentage of cells in S-phase measured by flow cytometry. Furthermore, in the wild-type cells, the increase in the number of cells in S phase was already observed at 0.1 mM while in the HU-resistant cell line this effect was first seen at 3.0 mM paracetamol. HU inhibits ribonucleotide reductase by destroying a tyrosyl free radical located on the small subunit of the enzyme. By electron paramagnetic resonance we demonstrate that paracetamol added to crude cell extracts of HU-resistant cells also immediately destroys this radical. These results show that paracetamol reduces DNA synthesis by a specific inhibition of ribonucleotide reductase. A concentration-dependent induction of sister chromatid exchanges was found both with paracetamol (1.0-10 mM) and HU (0.3-3 mM) in wild-type cells whereas no such increase was observed in HU-resistant cells. Paracetamol (1 mM for 2 h) also increased the number of chromosomal aberrations CAs in wild-type cells (i.e. chromatid breaks and chromatid exchanges). The frequency of CAs was not increased in HU-resistant cells at paracetamol concentrations up to 10 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗

Field evaluation of measles vaccine efficacy in Mozambique.

Monitoring measles vaccine efficacy is an important form of quality control in immunization programs. Retrospective cohort studies of vaccine efficacy were conducted in Mozambique with the aim of adopting this method for regular use. The authors studied 1,215 and 790 children aged 12-35 months in the cities of Nampula and Beira, respectively. In Nampula (1985), vaccine efficacy was estimated to be 40%, and in Beira (1986), it was estimated to be 59%. To investigate the possibility of falsely low results due to poor specificity of maternal reporting of measles cases, a seroepidemiologic study of 600 children aged 12-47 months was conducted in Nampula in 1986. The specificity and sensitivity of a maternal history of measles in an unvaccinated child were estimated as 83% and 56%, respectively. These results were used to obtain an adjusted vaccine efficacy estimate of 66%, almost double the estimate of 37% obtained using data on history of vaccination and illness alone. The large bias introduced into the vaccine efficacy estimation by low specificity of disease diagnosis is a serious limitation to the use of retrospective cohort methods to assess efficacy.

Child, Preschool↗