The effect of carbon tetrachloride on the detection of hemoglobin H using various commercially available electrophoresis products.
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Biomedical subjects
Publications and source records attributed to K Carstairs.
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The results of studies from a regional cancer cytogenetics diagnostic service are reported. In a 10-year period, 1,143 marrow samples from patients with newly diagnosed leukemia and myelodysplastic syndrome were referred. Successful studies were completed on 992 cases (87%). Among all referred cases, the rates of detection of cytogenetically abnormal clones were 95% for chronic myelogenous leukemia (CML), 54% for acute lymphoblastic leukemia (ALL), 51% for acute myeloid leukemia (ANLL), and 43% for myelodysplastic syndrome (MDS). Of 169 cases of CML studied, 90.5% bore the standard Philadelphia chromosome (Ph), 3.55% had an unusual Ph, and 5.33% were Ph-negative. Among the 59 cases of cytogenetically abnormal MDS, common abnormalities observed were trisomy 8 and changes resulting in loss of material from the long arm of chromosomes 5 and 7, and 20q-. Of the 168 abnormal ANLL, there was a strikingly non-random pattern of aneuploidy, with monosomy 7 and trisomy 8 predominating. Common structural changes observed were changes resulting in loss of material from the long arm of chromosomes 5 and 7, trisomy 8, rearrangements of 11q23, t(15;17), t(8;21), rearrangements of 12q13 and 3q, inversion 16, trisomy 11, Ph, trisomy 21, t(6;9) and t(1;22). The differences between adult and pediatric findings were minor, with the exception of chromosome 5 abnormalities, which were common among adults with ANLL but rare in the pediatric cases. There were 273 ALLs with abnormal cytogenetic findings. There was preferential gain of chromosomes 21, X, 14, 6, 4, 18, 17, and 10 (in decreasing order of frequency) in leukemic clones. Of the 193 ALLs with structural changes, many fell into-well-defined categories with established correlations to FAB subtypes. Common changes in ALL were rearrangements of 9p, 12p, 6q, TCR loci, 11q23, Ig loci, and 8q24, and duplication of 1q, Ph, i(17q), t(1;19), i(9q) and dic(9;12). The detailed documentation of the cytogenetic findings in this relatively large, single-institution study will likely facilitate the further characterization of rare, primary cytogenetic changes associated with leukemias and MDS. From a managed health care perspective, regional cancer cytogenetic services may be cost-effective alternatives to single-institution laboratories.
The Laboratory Proficiency Testing Program has been in effect for 20 years. During the past 6 years, samples were distributed for screening, investigation, and identification of hemoglobinopathies to test laboratory proficiency. Six samples for hemoglobin (Hb) S screening were distributed to from 37 to 163 laboratories that perform screening tests for sickle cell disease, and 10 samples were distributed to from 52 to 71 laboratories that perform Hb electrophoresis. Assessment of unacceptable results was based on clinical significance of the errors; educational follow-up was implemented to address these results. Most participants demonstrated acceptable performance. The error rates for sickle cell screening were 2.7% to 19.7%; the poorest performance was noted for Hb SC disease. The error rates for Hb electrophoresis were 1.4% to 36.8%; the poorest performance was noted in the investigation of Hb H disease and alpha-thalassemia trait. Improved survey performance was observed in the screening for Hb S trait and in the investigation of Hb H disease, which illustrates the benefits of proficiency testing and its positive effect on laboratory services.
Patients with intermediate grade non-Hodgkin's lymphoma (NHL) who relapse or fail to achieve a complete remission after anthracycline-containing induction regimens have a poor outcome with conventional-dose salvage treatment. This outcome may be improved with intensive therapy and autologous transplantation (ABMT) but even in patients with proven chemotherapy-sensitive disease, relapse rates of up to 60% are observed. Reliable and powerful prognostic indicators are needed to identify appropriate patients for this expensive procedure and those subjects to whom alternative or additional treatment should be offered. We were interested in testing the hypothesis that tumour burden, and hence remission status immediately prior to transplant, is an important prognostic indicator of survival. We aggressively treated patients with conventional-dose salvage chemotherapy to maximum tumour response, and tested, by multivariate regression analysis, predictors of outcome post-transplant. We studied 81 consecutive patients with intermediate grade and immunoblastic NHL who achieved either a partial (PR) or complete remission (CR) following repetitive cycles of conventional-dose salvage therapy. Intensive therapy consisted of etoposide (60 mg/kg) and intravenous melphalan (160-180 mg/m2) with or without total body irradiation (TBI) followed by infusion of autologous unpurged bone marrow and/or blood cells. The predicted 4-year survival and progression-free survival (PFS) with a median follow-up of 37 months was 58% and 48% (95% confidence interval (CI) 37-55%), respectively. The only factor predictive of outcome was remission status at transplant (P=0.0001). The PFS at 4 years for the CR group was 61% (95% CI 53-75%). In contrast, only 25% (95% CI 11-40%) of patients undergoing autotransplant in PR were progression free at 4 years. We conclude that remission status at transplant after maximum tumour reduction is a powerful prognostic indicator.
BACKGROUND: Patients with Hodgkin's disease (HD) and intermediate or high-grade non-Hodgkin's lymphoma (NHL) who fail to achieve a complete remission (CR) with standard induction therapy have a poor prognosis with conventional-dose salvage therapy alone. We examined the role of subsequent intensive therapy and autologous bone marrow transplantation (ABMT) in patients who demonstrated a response to conventional-dose therapy. PATIENTS AND METHODS: Sixty-six patients with either HD (n = 30) or NHL (n = 36) underwent intensive therapy with etoposide (60 mg/kg), intravenous melphalan (160-180 mg/m2) followed by infusion of unpurged autologous bone marrow and/or blood cells. All patients had advanced stage or bulky disease at diagnosis and failed to achieve a CR after an anthracycline-containing front-line chemotherapy regimen (NHL) or ABVD or equivalent regimen (HD). Patients who achieved a CR after involved-field radiotherapy were excluded. All patients demonstrated sensitivity to conventional-dose salvage treatment before advancing to intensive therapy and ABMT. RESULTS: The CR, partial response (PR) and overall response rate (RR) following ABMT for HD patients was 48%, 17% and 65%, respectively. At a median follow-up of 35 months, the predicted three-year overall survival (OS) is 51% (95% CI: 44%-60%) and event-free survival (EFS) is 34% (95% CI: 26%-54%). For patients with NHL, the CR, PR and RR were 68%, 9% and 77%, respectively. At a median follow-up of 28 months, the predicted three-year OS is 51% (95% CI: 35%-66%) and EFS is 39% (95% CI: 21%-57%). CONCLUSIONS: Intensive therapy with etoposide and melphalan followed by ABMT results in prolonged survival in selected patients with lymphoma who fail to achieve a complete remission to front-line chemotherapy. Based on our previous studies of outcome to conventional-dose salvage chemotherapy, we estimate that of all patients failing induction therapy, 28% with HD and 15% with NHL will be event-free at three years after ABMT.
This critique of Mahler's derivation of a developmental stage of normal symbiosis from her work with psychotic children reveals some clear parallels with Klein's description of the paranoid-schizoid position. The defence mechanisms of splitting, and of projective and introjective identification are already operative in the symbiotic stage and imply some distinction between self and other in the unconscious. Both theorists described the same confusion between self and other, but they attributed different explanations to the phenomenon. Whereas Mahler described the experience of feeling at one with the other, Klein elucidated the unconscious psychic mechanisms which operate to create this experience. The separation-individuation process has been redefined as the developing awareness of a sense of self, as distinct from earlier unconscious processes.
Translocation (14;19)(q32;q13.1) is an acquired chromosomal rearrangement that has been associated with chronic lymphocytic leukemia of B-cell phenotype frequently progressing to lymphoma. Molecular analysis suggests that the translocation involves the immunoglobulin heavy chain gene on chromosome 14 and the BCL3 oncogene on chromosome 19. We present the first case of t(14;19) in a patient with acute leukemia. Correlation of detailed cytogenetic and molecular genetic studies, cell surface marker analysis, cytochemistry, and electron microscopy indicated that the leukemic cells were biophenotypic, with characteristics consistent with both myeloid and B-lineage lymphoid differentiation.
We present a case of large cell lymphoma in a 20-year-old Oriental male who presented with massive splenomegaly and mild anemia. Surface marker and molecular genetic analyses of lymphomatous cells obtained from the spleen indicated a T-cell origin. Chromosomal analysis identified an isochromosome 7q as the sole abnormality. This is the first report of isochromosome 7q as the sole cytogenetic abnormality in a T-lineage malignant clonal expansion.
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