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D C Arthur

Publications and source records attributed to D C Arthur.

103 records · Page 6Linked to original sources

Partial deletion of the long arm of chromosome 16 and bone marrow eosinophilia in acute nonlymphocytic leukemia: a new association.

Recently, several specific chromosomal abnormalities have been associated with distinctive clinical and/or morphological subtypes of acute nonlymphocytic leukemia (ANLL). To further investigate the clinical utility of karyotype analysis in ANLL, we have examined G-banded metaphase chromosomes at diagnosis in 61 consecutive patients. Of the 60 patients who had adequate mitoses, 47 (78%) had a clonal chromosome abnormality. The sole karyotypic abnormality found in 5 patients was a del(16)(q22). The unique pretreatment characteristic of these 5 patients was marrow eosinophilia ranging from 8% to 54%. No other patient had more than 4% marrow eosinophils. Among the patients with eosinophilia, all had Auer rods, serum muramidase was elevated in the 4 tested, and 4 had hepatomegaly at presentation. Both patients who survived initial treatment remain in complete remission at 23+ and 33+ mo. The data suggest that we have identified a new cytogenetic-clinical subtype of ANLL defined by the del(16)(q22).

Adolescent↗

Nonrandom chromosome abnormalities in lymphoma.

G-banded chromosomes were studied from involved lymph nodes or other tumor masses in 94 patients with malignant lymphoma. Clonal chromosome abnormalities were identified in 91 patients including all 81 B-lymphomas but only 6 of 9 T-lymphomas. Many recurring chromosome abnormalities were found. Most common numerical alterations involved gains of chromosomes 12 (19% of patients), 18 (13%), 7 (12%), and 21 (10%). Structural abnormalities, which were more frequent than numerical alterations, most commonly involved chromosome regions 14q (71% of patients), 18q (36%), 6q (31%), 1p (24%), and 8q (19%). Seven recurring translocations were identified, and all except one involved 14q32. The most frequent were t(14;18)(q32;q21) in 22 patients, t(8;14)(q24;q32) in 9 patients, and t(1;14)(q42;q32) in 3 patients. Deletions most frequently involved the long arm of chromosome 6 at band q21 (11 patients) or q23 (7 patients). The common recurring chromosome abnormalities were correlated with histology (International Working Formulation for Clinical Usage) and immunological phenotype. Four abnormalities were significantly associated with specific histologies. Eighteen (82%) patients with t(14;18)(q32;q21) were follicular. Similarly, 82% of patients with del(6)(q21) were large cell lymphomas. Lymphomas with trisomy 7 were either diffuse large cell or follicular, while patients with t(8;14)(q24;q32) were either diffuse large cell or small noncleaved cell. A significant association with immunological phenotype was seen for t(14;18) only. All patients were either B- or complement lymphomas, and the heavy chain(s) was more commonly gamma and less frequently delta mu than among the total B-lymphoma population. We conclude that essentially all lymphomas have cytogenetic abnormalities; further study is required to determine their significance. Particularly, it will be of interest to see if oncogenes are found in the regions of these chromosome abnormalities.

Adolescent↗

Successful allogeneic bone-marrow transplantation for patients in the accelerated phase of chronic granulocytic leukaemia.

Nine patients underwent allogeneic bone-marrow transplantation as treatment for chronic granulocytic leukaemia (CGL) during the accelerated phase, a point in the course of the disease when it has progressed beyond the stable chronic phase but before the onset of blast crisis. After bone-marrow transplantation, haematological and cytogenetic studies showed ablation of all evidence of leukaemia, successful engraftment, and persistence of normal haemopoiesis in all patients. In one patient severe myelofibrosis and osteosclerosis disappeared after bone-marrow transplantation. Two patients have died of complications related to graft-versus-host disease (GvHD) but with no evidence of CGL. In one patient haematological and cytogenetic evidence of recurrent disease developed after bone-marrow transplantation, and she survives in chronic phase. Six patients are free of disability, do not require transfusions, possess normal marrow chromosomes, and have persistent clinical and haematological evidence of complete remission from CGL. Intervention with allogeneic bone-marrow transplantation during the accelerated phase of CGL can eradicate the disease and can provide normal haemopoiesis with acceptably low early morbidity and mortality. The long-term efficacy of bone-marrow transplantation as treatment for CGL, and the most effective timing of the transplantation with regard to the course of disease have yet to be determined.

Adult↗

15;17 Translocation in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a relatively rare subtype of leukemia that has been reported to be associated with a specific chromosome abnormality, t(15;17). It has been suggested that this translocation may have a geographical distribution and its presence may signify a poorer prognosis. In this present series of 14 patients with APL, 9 patients (64%) had the t(15;17) and 5 did not; however, no significant differences in clinical features or outcome could be found between those who did and those who did not express the translocation. When ethnic backgrounds were explored, no differences were found. More cases of the t(15;17) were found in recent years (7 of 8 patients studied since 1978 compared to 2 of 6 before 1978). This corresponded to changes made in our cytogenetic techniques suggesting that the finding of the t(15;17) may be a function of technique, rather than a real difference in disease entities, and all patients with APL may have the t(15;17) when appropriately studied.

Adult↗

Translocation 4; 11 in acute lymphoblastic leukemia: clinical characteristics and prognostic significance.

Banded bone marrow chromosome analyses have been done on 83 unselected patients with acute lymphoblastic leukemia (ALL). Seven patients, all with non-T, non-B ALL, had a translocation involving the long arms of chromosomes 4 and 11. Five of these patients, 4 children and 1 adult, were first studied at diagnosis, and the t(4;11) (q21;q23) was the only karyotypic abnormality. All 5 presented with a marked leukocytosis (greater than 150 X 10(9)/liter). Four of these 5 patients achieved a complete remission following the same intensive treatment regimen; however, remission duration and survival were very short (medians 2.5 and 8 mo, respectively). The fifth patient is currently receiving induction chemotherapy. The remaining 2 patients, both adults, were studied in relapse only, and had other karyotypic abnormalities in addition to the t(4;11). One of these relapse patients was a female whose clinical presentation and course were similar to those above. The last patient was a male who presented with a leukocyte count of 7 X 10(9)/liter and maintained an initial complete remission for 37 mo. Our data suggest that patients who have a t(4;11) (q21;q23) at the time of diagnosis of ALL have a poor prognosis with conventional therapy and require a new therapeutic approach.

Adolescent↗

Cytogenetic studies of long-term survivors of childhood acute lymphoblastic leukemia.

Ten long-term survivors of childhood acute lymphoblastic leukemia were studied to determine if cytogenetic abnormalities were present in lymphocytes following discontinuation of therapy. The study included patients diagnosed between 1969 and 1974 who had received radiation therapy and a minimum of 3 years systemic chemotherapy. At study, the patients had been off all therapy from 1.3 to 6.5 years (median, 4 years). Peripheral blood lymphocytes were examined for spontaneous chromosome breakage and sister chromatid exchanges. In addition, G-banded metaphase and prometaphase chromosomes were analyzed. Chromosome breakage was found to be within normal limits for all patients. Likewise, there was no significant difference between patients and controls with respect to sister chromatid exchange frequency. However, seven of the ten patients were found to have one or more cells with nonclonal karyotypic abnormalities. Our results indicate that although long-term survivors of childhood acute lymphoblastic leukemia treated with intensive radiation and combination chemotherapy do not demonstrate chromosome instability or DNA damage as measured by breakage and sister chromatid exchange, a majority of these patients have a subpopulation of lymphocytes with nonclonal chromosome abnormalities years after stopping therapy.

Adolescent↗

Acute leukemia associated with the t(4;11) chromosome rearrangement: ultrastructural and immunologic characteristics.

The acute leukemia associated with the t(4;11) chromosome rearrangement is characterized by relatively consistent clinical features: occurrence primarily in young individuals, hyperleukocytosis, and poor response to therapy. This study describes the morphological, ultrastructural, and immunologic characteristics of the leukemic cells from ten patients with this type of leukemia. The morphological features of the leukemic blasts vary from lymphoid-appearing to monocytic. Ultrastructurally and cytochemically, some of the lymphoid-appearing blasts possess features of myeloid origin. The immunologic phenotype is characteristically E- SIg- CALLA- BA-1- BA-2+ HLA-DR+ and TdT+. These findings suggest that the t(4;11)-associated acute leukemia represents a proliferation of an early myeloid progenitor cell.

Acute Disease↗

The pathophysiology, presentation, and triage of altitude-related decompression sickness associated with hypobaric chamber operation.

Decompression sickness following excursions to low atmospheric pressures has recently been a topic of confusion and concern. This article provides a reference for management of decompression sickness occurring after exposure to a reduction in ambient pressure in a hypobaric chamber. The pathophysiology, recognition, classification, initial management, definitive treatment, and eventual disposition of these cases are presented in a form which is applicable to all flight surgeons and flight physiologists, especially those with responsibility for utilization of hypobaric chambers.

Aerospace Medicine↗

Evaluation of leukemic cell chromosomes as a guide to therapy.

Recent improvements in methodology permit a clonal chromosome abnormality to be identified in most cases of acute leukemia. As a consequence, leukemic cell chromosome evaluation is finding increased usefulness for diagnosis, prognosis and therapy. In this paper we review examples of the clinical utility of leukemic cell karyotype analysis drawn primarily from a recent study at the University of Minnesota for acute nonlymphoblastic leukemia and from the Third International Workshop on Chromosomes in Leukemia for acute lymphoblastic leukemia.

Acute Disease↗

Cytogenetic conversion following allogeneic bone marrow transplantation for advanced chronic myelogenous leukemia.

We performed a pilot study to test the effectiveness of allogeneic bone marrow transplantation in the treatment of chronic myelogenous leukemia. Five patients in the advanced stages of chronic myelogenous leukemia (four in blast crisis, one in accelerated phase) with abnormal chromosomes underwent matched-sibling allogeneic bone marrow transplantation after preparation with busulfan, vincristine, cyclophosphamide, and fractionated total body irradiation. Engraftment and conversion to normal chromosome patterns after transplantation occurred in all five patients. None of the patients reverted to an abnormal chromosome pattern of demonstrated clinical or hematologic evidence of recurrent disease during the course of this study; however, longest survival from transplant was 248 days. Allogeneic bone marrow transplantation can eradicate the abnormal clone even in far advanced chronic myelogenous leukemia and can provide normal hematopoiesis. We suggest that clinical complications of chemotherapeutic toxicity and infection were responsible for the short survival in this group of patients, and that these complications could be decreased by performing transplantation in the chronic phase or early accelerated phase of the disease.

Adult↗

Animal procedure laboratory surveys: use of the animal laboratory to improve physician confidence and ability.

Animal laboratories have been used for many years to teach procedures. Our department has a weekly swine laboratory devoted to training residents, interns and students in resuscitative procedures. Physicians who participated in our swine procedure laboratory over the past three years were queried as to their prelaboratory and postlaboratory comfort levels with six different resuscitative procedures, and 57 (76%) physicians responded. Statistical analysis of the data showed significant improvement in comfort levels for all six procedures. Every responder felt the swine laboratory helped or will help them perform the procedures on humans. We also surveyed all U.S. emergency medicine residency program directors from established programs regarding the status of their animal procedure laboratories, and 67 of the 68 (98%) directors responded. Of these responders, 62% offer an animal procedure laboratory. Overall, 97% of the residency directors rated the laboratory successful, and 97% of the residents rated the laboratory successful. Therefore, we conclude that an ongoing emergency medicine animal procedure laboratory is a valuable tool for improving physician-in-training ability and confidence.

Animals↗