[The management of the acute postinfarct myocardium].
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Angioplasty, Balloon, Coronary↗
Biomedical subjects
R Bassan
Publications and source records attributed to R Bassan.
Treatment of adult acute lymphoblastic leukaemia (ALL) over a 16 year period.
Between 1972 and 1988 269 newly diagnosed adolescents and adults (age range 14-78 years) with ALL were managed with three protocols of increasing intensity (OPAL, HEAV'D, OPAL-HDAraC). The complete remission (CR) rate in 212 patients treated with OPAL and HEAV'D was 151/212 (71%), the median CR duration was 1.9 years. With a median follow-up of 9 years, 49 patients remain free of disease. On multivariate analysis age, blast cell count, and immunophenotype were found to correlate significantly with CR rate, remission duration and survival. CR was achieved in 38/57 (67%) patients subsequently treated with OPAL-HDAraC; however, although remission duration was longer in 'high risk' patients (T, B and Null phenotype irrespective of blast cout, cALLA+ve with blast count greater than 10 x 10(9)/l) as compared to the results achieved in similar patients with OPAL/HEAV'D, overall, the results were no better than those achieved previously. Indeed, patients in the 'standard risk' category (cALLA+ve, blast count less than 10 x 10(9)/l) fared better previously. Subsequently, neither treatment according to prognostic variables, or the addition of different pairs of drugs in rotation, to HEAV'D, have improved outcome in 63 other patients. Currently, further intensification of the early treatment is being evaluated.
Adolescent↗
Short term therapy (STT) for acute myelogenous leukaemia (AML).
Between 1978 and 1988 (median follow up 5 1/2 years), 396 newly diagnosed adults with AML (age range 14-59 years, median 44) received STT comprising daily Adriamycin: 25mg/m2 for 3 days, Cytosine arabinoside (ara-C): 100mg/m2 bd and 6-thioguanine: 100mg/m2 bd, each for 7 days. A maximum of 6 cycles was administered with as short an intercycle time as possible. No further treatment was given. Complete remission (CR) was achieved in 243/396 patients (62%), 71 patients (18%) having resistant leukaemia and 82 (21%) dying within 6 weeks. Antecedent myelodysplasia and advanced age correlated unfavourably with achievement of CR (p = less than 0.001 and 0.005 respectively). Sixty nine patients continue in first remission between 2 1/2 and 12 years; the median duration of remission was 1 year. M3 morphology (p = 0.005) and absence of hepatosplenomegaly (p = 0.001) correlated favourably with duration of remission. Ninety one patients remain alive with an actuarial survival of 22% at 5 years. More recently, additional consolidation comprising high-dose ara-C and total body irradiation (TBI) with autologous bone marrow transplantation (ABMT) has been evaluated in an open study. CR has been achieved in 41/66 patients under the age of 50 but only 19/41 have proceeded to ara-C + TBI + ABMT. Twenty two have not (early recurrence 10, allogeneic BMT 4, debility 6, refusal 2). 11/19 who proceeded to ablative therapy continue in remission (4 treatment related deaths, 4 recurrences) as compared to 9/22 who did not. Currently the overall median duration of remission for the 41 patients intended to proceed is identical to that of age-matched historical controls illustrating the difficulties inherent in demonstrating benefit for the use of myeloablative therapy and ABMT in patients with AML in first remission.
Adolescent↗
Long-term results of the HEAVD protocol for adult acute lymphoblastic leukaemia.
Between 1979 and 1987, 82 adults (age 14-71 years) with acute lymphoblastic leukaemia (ALL) were treated with a 6-course protocol called HEAVD, the main feature of which was the early postremission administration of escalating doses of doxorubicin (total 405 mg/m2) and cyclophosphamide (total 2.5 g/m2). A complete remission (CR) was attained in 66 patients (80%, 95% confidence intervals, [CI] 71%-89%). Factors affecting favourable CR achievement were age less than 60 years and absence of lymphadenopathy-hepatosplenomegaly at presentation (P less than 0.05). Median duration of CR was 27 months. 26 patients remain in first continuous and unmaintained CR, 18 of whom between 5.9 and 11.1 years, for an estimated 39% prolonged disease-free survival (95% CI 27%-51%). CR duration correlated significantly with absolute blast cell count (15 x 10(9)/l or less compared to more) and age (30 years or under compared to over). Overall, 29 patients are alive with a median follow-up of 6.7 years, the projected long term survival being 35% at 11 years (95% CI 24%-46%). Treatment-related toxicity included 1 lethal case of L-asparaginase-related thromboembolism and 3 toxic deaths among 66 CR patients. Late-onset toxicity was not observed in long-term survivors. The relatively late occurrence of endpoint events (relapse and death) in adult ALL confirms that long-term updating is necessary to determine the curative potential of modern chemotherapy programs for the disease.
Adolescent↗
Long-term outcome of adults with acute myelogenous leukaemia: results of a prospective, randomized study of chemotherapy with a minimal follow-up of 7 years.
In a prospective study running between 1981 and 1983, a group of 156 adult (under 60 years of age) patients with de-novo acute myelogenous leukaemia were randomly assigned to receive a daunorubicin, cytosine arabinoside and thioguanine combination or a regimen containing lower dosages of these drugs but also containing etoposide and vindesine. Patients who entered complete remission received maintenance therapy for 2 years. The survival and remission duration curves of the two groups were exactly superimposable and for this long-term analysis all patients have been considered together. The follow-up times range between 84 and 104 months. Actual survival at 7 years is 15% (95% confidence intervals 9-20%), with a stable curve thereafter. Actual probability of continuous complete remission at 7 years is 22% (95% C.I. 13-31%) with a stable curve beyond that point. These findings, similar to those of the few other studies of chemotherapy with comparable follow-up times, suggest that only a small fraction of adult patients become long-term survivors, irrespective of the precise type or amount of antineoplastic agents administered.
Adolescent↗
Monoclonal lymphocytosis with villous lymphocytes: a chronic lymphoproliferative disease of CD11c+ B-cells.
Most of the circulating lymphocytes from three asymptomatic adults (one male, two female, age range 61-67 years) with isolated persistent lymphocytosis of between 7.1 and 10 x 10(9)/l possessed characteristic villous projections of the cell membrane. Morphological, histochemical, ultrastructural, immunological, and genotypic studies confirmed a clonal proliferation of tartrate-resistant acid phosphatase (TRAP)-negative CD5-CD10-CD25- and CD11c+ B-cells. In addition to CD11c, these cells expressed other adhesion receptors (LFA-1/CD11a, VLA-4/CD29/49d, ICAM-1/CD54, and LAM-1) and produced detectable amounts of interleukin-1 beta, interleukin-6, and in one case tumour necrosis factor-alpha mRNA. This monoclonal villous lymphocytosis (MVL) could be differentiated from B-cell chronic lymphocytic, prolymphocytic, and hairy cell leukaemias, and from previously recognized CD11c+ chronic B-cell leukaemia. A rare splenomegalic non-Hodgkin's lymphoma variant with circulating villous B-lymphocytes (SLVL), usually CD10+ and sometimes CD11c- and TRAP+, appears to be a closely related disorder. In all three patients the lymphocyte count increased very slowly, at a rate less than 5 x 10(9)/l per year, over 3-7.5 years of follow up, and a moderate splenomegaly eventually developed in one of the patients. Chemotherapy was never required. MVL may be a relatively benign clinical entity akin to SLVL within the group of CD11c+ B-cell lymphoproliferative disorders.
Aged↗
[Is coronary cineangiography more accurate than early bicycle ergometry test in the identification of high-risk acute myocardial infarction survivors?].
PURPOSE: To determine if attenuated early treadmill stress testing is more or less accurate than cinecoronary arteriography in the identification of high-risk acute myocardial infarction (AMI) survivors. PATIENTS AND METHODS: In a prospective study 96 non-selected and consecutive AMI survivors underwent cinecoronary arteriography in the 4th week of hospitalization and were followed up for a period of 3 to 39 (21.7 +/- 11.0) months. One-half of the patients were randomly submitted to an attenuated heart rate-limited treadmill stress testing in the 3rd week. Seven patients were lost in the follow-up. Of the remaining 89 patients 5 died of cardiac causes. Cardiac events (death, reinfarction, angina and heart failure) occurred in 26 patients. Multivessel coronary artery disease was found in 67 patients (75%) and mean left ventricular ejection fraction was 49.1 +/- 15.6%. Positive treadmill stress testing for myocardial ischemia occurred in 20 of 43 patients (46%). RESULTS: All patients who died of cardiac causes or who had a cardiac event had multivessel coronary artery disease, the mean left ventricular ejection fraction was 38.6 +/- 16.6% and 45.2 +/- 16.4%, respectively, and two-thirds of patients had positive stress testing. For cardiac death, multivessel coronary artery disease had better sensitivity than positive stress testing and left ventricular ejection fraction less than 0.3 (100% vs 67% vs 20%, respectively) while ejection fraction had better specificity than stress testing and multivessel coronary artery disease (87% vs 55% vs 21%, respectively). Stress testing had a better positive predictive value than multivessel coronary artery disease and ejection fraction (53% vs 38% vs 36%, respectively while multivessel coronary artery disease had better negative predictive value than stress testing and ejection fraction (100% vs 77% vs and 70%, respectively). The association of data obtained from cinecoronarography study between themselves and with positive treadmill stress testing did not significantly improve the sensitivities, specificities and predictive values in relation to the results obtained by isolated data. CONCLUSION: In survivors of acute myocardial infarction cinecoronary arteriography is not more accurate than, treadmill stress testing and both have limited value in the identification of patients who are candidates for cardiac death or events in the first few years after AMI. A negative stress testing and coronary arteriography (one-vessel disease) is more informative than a positive one.
Chi-Square Distribution↗
[Torsades de Pointes: analysis of 105 episodes].
PURPOSE: To analyze episodes of Torsades de Pointes (TP), in search of its electrocardiographic characteristics. PATIENTS AND METHODS: We analyzed 105 episodes of TP, in 4 patients using quinidine and diuretics, recorded by 24-hour Holter monitoring. The following parameters were studied; ventricular repolarization out of TP, rhythm disturbances before TP; EKG characteristics of the onset, the bouts and the end of the TP. RESULTS: Ventricular repolarization, out of the TP, was abnormal, with the presence of U-waves at the end of the T-waves, resulting in prolongation of the QT (QU) interval. The U-wave voltage was noted to be cycle-length dependent. Ventricular bigeminy preceded TP in 100 episodes (95%) and the mean interval between both parameters was 18 +/- 16 min. The onset of the TP episodes showed the "short/long/short cycle rule", hereby called "pre-pause cycle", "preparing cycle" and "trigger cycle" respectively. The rotatory QRS-T morphology around the baseline, was seen in 75% of episodes, at the beginning or throughout the bout. Monomorphic ventricular tachycardia pattern was seen in the other 25% of episodes. Termination of bouts was sudden in all cases, and persistent ventricular bigeminy led to another bout in 90 episodes (85%). CONCLUSION: In TP patients, there is enlargement of QT intervals mostly due to U-waves appearance. The U-waves seen in these cases, probably have an important role in the genesis of TP and are probably related to ventricular after-potentials (triggered activity). Ventricular bigeminy is a premonitory sign of TP in patients using class 1A antiarrhythmic drugs. Persistent ventricular bigeminy post-TP episodes is a strong indicator of another bout of TP. The onset of TP is more important than its morphology for the correct diagnosis of this arrhythmia.
Aged↗
[Arrhythmogenic right ventricular dysplasia].
PURPOSE: To evaluate the clinical findings and complementary investigation to support the diagnosis of arrhythmogenic right ventricular dysplasia. METHODS: Six males with a mean age of 40 years old with episodes of sustained ventricular tachycardia with left bundle branch block pattern. All patients were submitted to a clinical investigation, EKG X rays and echocardiograms. In five patients an electrophysiologic study was performed. All patients were treated with anti-arrhythmic drugs. RESULTS: Palpitation was the most common complaint. T-wave inversion in leads V1-V3 was present in 4 patients. An epsilon wave was noted in 2 patients. The chest X ray was abnormal in only 1 patient. All patients had an abnormal echocardiogram, with consisted in the dilatation of the outflow tract of the RV and hypocontractility. In 2 patients aneurysm of the basal RV free wall below tricuspid valve were detected. Ventricular post-excitation waves were present in 4 patients. After a mean follow-up of 37 months, 5 patients were asymptomatic with anti-arrhythmic drugs and one in therapeutic adjustment. CONCLUSION: In patients with ventricular tachycardia with left bundle branch block pattern, the diagnosis of arrhythmogenic right ventricular dysplasia was substantiated by echocardiographic data and electrocardiographic findings such a T-wave inversion during sinus rhythm and ventricular post-excitation waves. The results obtained with anti-arrhythmic drugs in our study group, suggest that drug therapy should be the first and best approach to treat patients with this type of pathology.
Adult↗
[The elderly patient with coronary disease: is it worth to remove obstructions?].
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Aged↗
Prognostic value of junctional recovery times and long-time follow-up of complete atrioventricular nodal block at a young age.
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Adult↗
Expression of leukocyte alkaline phosphatase gene in normal and leukemic cells: regulation of the transcript by granulocyte colony-stimulating factor.
The levels of leukocyte alkaline phosphatase (LAP) messenger RNA (mRNA) are evaluated in B and T lymphocytes, monocytes, and polymorphonuclear cells (PMNs), and this transcript is found to be present only in PMNs. Precursors of the myelomonocytic pathway, represented by leukemic cells isolated from several cases of chronic myelogenous leukemia (CML) in its stable and blastic phase and acute myelogenous leukemia (AML), are devoid of LAP transcript. These data support the notion that LAP is a marker of the granulocyte terminal differentiation. Despite the absence of LAP mRNA in both the myeloid and the lymphoid precursors, nuclear run-on experiments show constitutive transcription of the LAP gene in leukemic cells obtained from AML, CML, as well as acute lymphoblastic leukemia (ALL) and B-cell chronic lymphocytic leukemia (B-CLL). In CML and in chronic myelo-monocytic leukemia (CMML) PMNs, granulocyte colony-stimulating factor (G-CSF) specifically accumulates LAP mRNA without showing a substantial increase in the rate of transcription of the LAP gene. Once increased by G-CSF, LAP mRNA is very stable, showing a half-life of more than 4 hours in the presence of actinomycin-D. G-CSF is suggested to play a pivotal role in the modulation of LAP transcript in PMNs.
Alkaline Phosphatase↗
Cancer procoagulant in acute non lymphoid leukemia: relationship of enzyme detection to disease activity.
Blast cell extracts from patients with acute non lymphoid leukemia (ANLL) express cancer procoagulant (CP). This factor X (FX) activator is distinct from tissue factor (TF) in that it does not require factor VII (FVII) to trigger blood coagulation, it acts as a cysteine proteinase and is not present in normal mononuclear cells. To assess whether there is any relationship between the presence of CP and the status of the disease, ANLL patients have been studied at diagnosis, during remission, at relapse. The procoagulant activity in either the presence or absence of F VII and sensitivity to cysteine proteinase inhibitors were tested on cell extracts. Immunoreactivity was explored with an anti-CP polyclonal antibody. Data obtained in 91 newly-diagnosed ANLL patients (subtypes M1 to M5, FAB classification) confirmed the presence of CP in M1 to M4 groups (mean +/- SE FVII-independent activity: M1 = 2.1 +/- 0.7 unit/mg; M2 = 5.7 +/- 1.7 unit/mg; M3 = 31.5 +/- 8 unit/mg; M4 = 1.6 +/- 1.2 unit/mg); CP was absent in the M5 type. In eight patients analyzed in a subsequent phase of partial remission, specific activity had dropped from 26.9 +/- 7.8 to 10.5 +/- 4.0 unit/mg. Activity was virtually absent (0-0.05 unit/mg) in the bone marrow of 37 patients studied at complete remission. Bone marrow samples from six subjects tested at different intervals after complete remission were repeatedly negative for CP but became positive 2 to 5 months before relapse. Upon relapse, the FVII independent activity rose to 24.2 +/- 8.2 unit/mg.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Intensive chemotherapy for acute lymphoblastic leukaemia in adults.
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Adolescent↗
High dose cytosine arabinoside in the initial treatment of adults with acute lymphoblastic leukaemia.
In a study conducted at St Bartholomew's Hospital between 1972 and 1982, using moderately intensive therapy (OPAL/HEAV'D), a low blast count at presentation (less than 10 x 10(9) 1(-1)) and common ALL (C-ALL) phenotype correlated favourably with duration of remission. Fifty-four patients (age range 15-57, median 32) subsequently received a modification of the previous treatment programme which included high-dose ara-C 2 g m-2 b.d. for 6 days as cycle 3 (OPAL + HD ARA-C). CR was achieved in 36/54 (67%) patients, response correlating favourably with younger age (15-30 years vs 31-57 years, P = 0.02). Three patients died in CR. Overall, there was no difference in survival or remission duration between patients who received high dose ara-C and those in the control group. However, in contrast to the early results, there was a reversal in the relevance of the prognostic factors with a trend in favour of high blast count (greater than 10 x 10(9) 1(-1)) and T-cell phenotype in terms of remission duration. Moreover, comparison of duration of remission for the previously defined prognostic groups according to therapy suggests that the prognosis of patients with 'high risk' disease (T, B, null ALL or high blast count) is improved with more intensive therapy. In contrast, those with 'low risk' disease (C-ALL and low blast count) have a better prognosis with less intensive therapy. These observations confirm those of others and allow for individualization of therapy on the basis of pre-treatment variables.
Adolescent↗
Association of NK-cell lymphoproliferative disease and nephrotic syndrome.
A 56-year-old white man with a seven-year history of lymphocytosis of large granular lymphocytes (LGL) developed mild renal insufficiency (serum creatinine 150 mumol/L (1.7 mg/dL) with proteinuria (3.4 g/day). Laboratory investigations confirmed a proliferative disease of non-T lineage cytotoxic LGL/natural killer (NK) cells, and the renal biopsy documented focal and segmental glomerulosclerosis associated with interstitial inflammation and tubular atrophy. These findings could be explained by production and release of humoral mediators by pathologic LGL/NK cells. The renal function must be carefully monitored in patients with LGL/NK proliferative disorders, and the role of the NK cell system in renal diseases should be investigated.
Biopsy↗
Cancer procoagulant in acute lymphoblastic leukemia.
In a previous study we characterized cancer procoagulant (CP), a 68 kd cysteine proteinase which directly activates coagulation factor X in various subtypes (from M1 to M5) of acute non-lymphoblastic leukemia (ANLL). The aim of this study was to determine whether CP is also expressed by acute lymphoblastic leukemia (ALL) cells. Blasts from 25 ALL patients were extracted and tested for their procoagulant properties. 16 samples (64%) shortened the recalcification time of normal human plasma, and 9 (36%) did not. 8 of the 16 active samples showed properties compatible with CP, i.e. independence from factor VII in triggering blood coagulation and sensitivity to cysteine proteinase inhibitors. Selected samples also cross-reacted with a polyclonal antibody raised against purified CP. The specific activity of CP in ALL extracts was significantly lower than in most ANLL types previously studied (all but M4). These finding indicate that CP can be a property of the lymphoid phenotype although its expression may be lower than in the myeloid phenotype.
Adolescent↗
T cell receptor delta gene organization and expression in normal and leukemic natural killer cells.
In peripheral blood most NK activity is mediated by CD3- cells with large granular lymphocyte morphology which cannot be assigned to a specific hemopoietic lineage. In accordance with previous studies we have analyzed the organization of the TCR delta gene, which rearranges early in thymic ontogeny, in normal NK cells, and in granular lymphocytes proliferative disorders (GLPD), in an effort to further define their relationship to the T cell differentiation pathway and to identify a possible marker of clonality for CD3- GLPD. The alpha/delta locus was rearranged in five cases of CD3+ GLPD with a biallelic deletion of the C delta region, suggesting V-J alpha rearrangement, whereas CD3- GLPD and normal CD3- NK cells had the delta gene in germ-line configuration, but surprisingly expressed high levels of TCR delta-related mRNA. On the basis of this finding and of the presence of truncated TCR-beta and CD3-epsilon mRNA, we are led to speculate on a possible ontogenic relationship of NK cells to the T cell differentiation pathway at stages preceding TCR gene rearrangement.
Antigens, Differentiation, T-Lymphocyte↗