Biomedical subjects

G Sanz

Publications and source records attributed to G Sanz.

At least 91 records · Page 5Linked to original sources

PubMed1996

The role of endogenous nitric oxide in the response of coronary blood flow to tachycardia.

BACKGROUND: The role of endogenous nitric oxide as mediator of flow-dependent dilation is well established. However, its role in the adaptation of coronary blood flow to tachycardia is less well defined. This study was designed to determine whether nitric oxide is a mediator in pacing-induced hyperaemia. METHODS: Twenty pigs were instrumented for coronary blood flow, aortic pressure and atrial pacing measurements. Their heart rate was increased by 20 beats every 5 min. Coronary blood flow was measured basally and at each pacing interval before and after each of the following interventions: intracoronary saline infusion (n = 6), N omega-nitro-L-arginine methyl ester infusion (L-NAME, 20 micrograms/kg per min intracoronarily, n = 9) and infusion of L-NAME plus L-arginine (0.3 mg/kg per min intracoronarily, n = 5). RESULTS: The coronary peak flow increased with atrial pacing. The maximum increase in coronary blood flow with pacing was significantly reduced after infusion of L-NAME (159 +/- 33 versus 143 +/- 30%), whereas no change was observed in the saline group (163 +/- 28 versus 172 +/- 29%). However, it increased significantly in the group receiving L-NAME plus L-arginine (147 +/- 29 versus 182 +/- 40%). CONCLUSIONS: In the pig, the increase in coronary blood flow and therefore the vasodilation of the microvasculature that accompanies tachycardia depend, partly, on the release of endogenous nitric oxide.

Animals↗

PubMed1996

Improvement of exercise-induced ischaemia and myocardial perfusion after aminophylline.

BACKGROUND: Previous studies have suggested that aminophylline improves exercise-induced ischaemia by preventing the redistribution of the coronary flow from ischaemic to non-ischaemic myocardium. The purpose of the study was to assess whether aminophylline improves myocardial perfusion in zones supplied by collateral circulation. METHODS: Twenty-three patients with an occluded coronary artery and collateral circulation from a non-diseased vessel underwent two symptom-limited exercise 99mTc-MIBI, single-photon emission computed tomography (SPECT) myocardial scintigraphy experiments, which were preceded by an intravenous infusion of either aminophylline (5 mg/kg over 20 min) or saline solution in a randomized double-blind control procedure. The MIBI SPECT images were analysed by two experienced observers who were blinded to each other's data. RESULTS: All patients underwent cardiac catheterization. For 16 patients this was because of stable angina and the remaining eight were post-myocardial infarction patients with a positive exercise test. Aminophylline significantly increased the time to the onset of ischaemia in the 15 patients with a positive exercise test (mean +/- SD, 6.5 +/- 1.9 compared with 5.3 +/- 1.8 min, P < 0.005); and ischaemia occurred at higher rate-pressure product (230 +/- 68 compared with 195 +/- 68 HB x mmHg, P < 0.03). After aminophylline, exercise ST-segment depression was 1.1 +/- 0.5 mV, compared with 1.5 +/- 0.8 mV after placebo (P < 0.01). All patients had perfusion defects that resolved partially or completely in the rest images. The imaging score was significantly lower after aminophylline infusion than after placebo (9.7 +/- 9 compared with 12.1 +/- 10, P < 0.01). CONCLUSIONS: Aminophylline significantly delayed the time to onset of exercise-induced ischaemia and improved perfusion in zones supplied by collateral circulation. Aminophylline-like drugs may be useful in the treatment of selected patients with ischaemic heart disease.

Aminophylline↗

PubMed1996

Allogeneic peripheral blood progenitor cell transplantation: analysis of short-term engraftment and acute GVHD incidence in 33 cases. allo-PBPCT Spanish Group.

The results of 33 allogeneic peripheral blood progenitor cells transplants (allo-PBPCT) in adult patients with hematologic malignancies were analyzed in a retrospective and multicenter study. In 21 of 33 cases (63%) the disease was refractory or in advanced stage and eight of the 33 cases (24%) were second transplants after relapse. Donors were treated with a median of 10 (4-16) micrograms/kg/day of rhG-CSF subcutaneously for 5-7 days. Three required a central venous line for harvesting. Peripheral blood leukapheresis product contained a median of 5.9 (1.8-13) 10(6)/kg CD34+ cells and a median of 309.5 (153-690) 10(6)/kg CD3+ cells. After a myeloablative regimen, all patients received PBPC from HLA-identical donors as the sole source of progenitor cells. Cyclosporin A (CsA) alone (n = 2), CsA and steroids (n = 9), and CsA and methotrexate (MTX) (n = 22) were used for GVHD prophylaxis. Growth factors post-transplant were given to 11 patients (33%). The median follow-up of the patients was 3 months. Actuarial median day for hemopoietic recovery was: neutrophils to >0.5 (>1) x 10(9)/l, day 14 (15); platelets to >20 (>50) x 10(9)/l, day 14 (21). The quantity of CD34+ cells infused did not significantly affect the engraftment kinetics, from a starting cutoff of 2.5 x 10(6)/kg. The speed of neutrophil recovery seemed to be influenced strongly by using rhG-CSF post-transplant and marginally by the type of GVHD prophylaxis. Actuarial probability for grade II-IV acute GVHD of the whole group was 37% (95% Cl, 20-54%).

Actuarial Analysis↗

PubMed1995

[Immunohematologic study in 112 patients with myelodysplastic syndromes: 10-year analysis].

PURPOSE: To describe the immunohematological response after multiple red blood cells transfusions in 112 patients with myelodysplastic syndromes (MDS). PATIENTS AND METHODS: From 1982 to 1992 every patient with MDS entered the study. Immunohematological studies consisted of an antibody screening test (AST) and a direct antiglobulin test (DAT) at diagnosis and after every four transfused units of red blood cell concentrates. RESULTS: Twenty-three out of 112 patients (20.5%) presented a positive AST and/or DAT during the study period. Eleven out of the 23 patients (9.8%) developed a positive DAT, six of them with red cell alloantibodies associated. In the remaining 12 patients (10.7%) the immune response observed was the development of red cell alloantibodies without a positive DAT. No patient presented with positive AST or DAT at diagnosis and no differences were observed in the pattern of immunohematological response and the FAB subtype. CONCLUSION: Patients with MDS have disordered immune systems with a high prevalence of autoantibodies against red cells. However, the incidence of red cell alloimmunization is similar to that observed in other multitransfused populations. Finally, despite the high immunization rate, the absence of any hemolytical reaction make the AST and DAT a safe and effective method of pretransfusion testing in this heavily transfused population.

Adolescent↗

PubMed1993

Predictors of early saphenous vein aortocoronary bypass graft occlusion. The GESIC Study Group.

To identify factors determining early saphenous vein aortocoronary bypass occlusion, we analyzed the data base of the GESIC study, a trial comparing antiplatelet drug regimens that included 927 patients with 1,854 saphenous vein grafts. The univariate analysis showed female sex (p < 0.0097), obesity (p < 0.001), rest angina (p < 0.0026), history of congestive heart failure (p < 0.037), the revascularized artery (p < 0.0001), the quality of distal bed (p < 0.00001), the diameter of the grafted vessel (p < 0.00001), the lack of antiaggregant treatment (p < 0.017), and a nonsequential technique (p < 0.0002) as predictors of early (28 days) graft occlusion. In the multivariate analysis the last five variables were independent predictors. Using the two preoperative variables, it was possible to identify groups at different risk; the occlusion rate ranged between 8.79% (left anterior descending coronary artery and good distal vessel) and 27.58% (right coronary artery or left circumflex coronary artery and poor distal vessel). The combination of three variables (grafted vessel, artery diameter, and antiaggregant treatment) also allowed identification of different risk groups; the occlusion rate ranged between 3.5% and 63.1%. Thus, it is possible to anticipate the risk of graft occlusion in patients undergoing coronary artery bypass grafting, which may help in the selection of both patients and antithrombotic treatment.

Aged↗

PubMed1993

Feasibility of early discharge after acute Q wave myocardial infarction in patients not receiving thrombolytic treatment.

OBJECTIVES: The purpose of this study was to analyze the feasibility of early discharge (4 days) after acute myocardial infarction in patients not receiving thrombolytic therapy by first identifying predictors of short-term prognosis and then testing the derived risk profile in an independent cohort of patients. BACKGROUND: Previous studies have shown that early discharge after acute myocardial infarction is possible. However, physicians are reluctant to shorten the standard 7- to 10-day hospital stay, presumably because of difficulty in selecting low risk patients. METHODS: From January 1985 to November 1986, 358 patients with acute myocardial infarction who did not receive thrombolytic therapy were screened. Those with a Q-wave infarction showing no complications on day 4 were considered candidates for early discharge and were transferred to the ward for a mean of 12 days. During this period, we looked for any event (cardiac or noncardiac) that would have prompted readmission if the patient had been previously discharged. Univariate and multiple regression analysis were performed to identify predictors of these events among 25 baseline variables. The derived risk profile was tested in an independent validation cohort. RESULTS: One hundred five (29.3%) of the 358 patients were free of symptoms on day 4, and 29 (27.6%) had at least one cardiac event, including four deaths and one reinfarction. Multivariate analysis selected diabetes, ejection fraction < 40% and age as independent predictors of events. Using the risk profile, 18 (13.2%) of the 136 validation cohort patients were categorized as low risk, and only 1 of them had a major event (progressive angina). Sensitivity for the risk profile was high (91%), but specificity was low (34%). CONCLUSIONS: The use of simple clinical variables may allow the safe reduction of hospital stay after infarction in selected patients. However because the proportion of candidates for early discharge is small (12.6%), it seems unlikely that the current policies on length of hospital stay will change in the near future.

Cohort Studies↗

PubMed1993

Prognostic value of exercise radionuclide angiography in low risk acute myocardial infarction survivors.

Patients with an uneventful course during hospital stay, which represent from 30 to 50% of all myocardial infarction survivors, still have an incidence of new coronary events up to 7% during the first year of follow-up. To assess the value of radionuclide angiography in predicting new coronary events in this low risk population, 93 patients without evidence of left ventricular failure or recurrent postinfarction angina underwent rest and exercise radionuclide angiography and treadmill exercise testing before hospital discharge. During follow-up (16 +/- 5 months, range 12 to 32) 14 patients developed new coronary events: two patients died, four had a new myocardial infarction and the remaining eight had unstable angina. There were no differences regarding clinical variables, the results of the exercise test and the resting ejection fraction, between patients with or without new coronary events; however, patients without events during follow-up exercised longer during both exercise treadmill test and exercise radionuclide angiography. Resting end-diastolic and end-systolic volume indexes were higher in patients presenting coronary events (122 +/- 50 vs 92 +/- 32 ml.m-2, P < 0.05, 69 +/- 47 vs 47 +/- 26 ml.m-2, P < 0.05). These patients also had a higher incidence of wall motion abnormalities in more than one area (64 vs 28%, P < 0.02). During exercise, ejection fraction increased significantly in patients with an uneventful outcome (49 +/- 13 to 56 +/- 14%, P < 0.01), while it did not change in their counterparts (46 +/- 14 to 45 +/- 14%, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1992

Arginine vasopressin infusion increases plasma levels of atrial natriuretic factor in humans.

Seven normal subjects underwent sequential 20-min infusion of arginine vasopressin (AVP) at 0.5 and 2 ng/(kg.min) and a complete right-side heart hemodynamic evaluation during the study to analyze the effect of this hormone on atrial natriuretic factor (ANF) secretion in humans and to elucidate whether this effect was primary or secondary to the hemodynamic or hormonal changes induced by AVP. Plasma ANF levels increased at the end of the first (P less than 0.05) and second (P less than 0.01) infusion periods. No significant changes in mean arterial, pulmonary artery, right and left atrial pressures were recorded during the study. Cardiac output (P less than 0.05) and heart rate (P less than 0.05) decreased, while total vascular resistances (P less than 0.05) increased with respect to basal values in both infusion periods. Plasma renin activity decreased (P less than 0.01) at the end of the infusion, while plasma aldosterone, epinephrine and norepinephrine showed no significant changes. We conclude that arginine vasopressin increases plasma ANF levels in humans and that this effect cannot be ascribed to hemodynamic or hormonal changes induced by this hormone, suggesting a direct effect of vasopressin on the atrial myocyte.

Adult↗

PubMed1992

Pulmonary complications after long term amiodarone treatment.

BACKGROUND: Amiodarone hydrochloride is an antiarrhythmic agent useful in arrhythmias refractory to standard therapy. Although interstitial pneumonitis is known to be its most serious side effect, several aspects of amiodarone lung toxicity are still controversial. METHODS: Pulmonary side effects were examined in a sample of 61 symptomless patients (mean (SD) age 55 (7) years) who had had long term treatment with amiodarone (daily maintenance dose 400 mg), selected from 482 men attending the University of Barcelona myocardial infarction project. To allow for the confounding effects of coronary artery disease and tobacco history on lung function, 46 patients who had taken amiodarone for more than one year were matched with a control group from the same population. Subjects underwent measurement of lung volumes, arterial blood gas analysis and an incremental bicycle exercise test. RESULTS: Most lung function values were close to predicted values, though there was a small increase in resting alveolar-arterial oxygen tension difference (A-aDO2) at rest (4.8 (1.4) kPa in both groups). There were no differences in the results of forced spirometry or static lung volumes between the two groups, or in the fall in A-aDO2 from rest to exercise. There was a small difference between the amiodarone and the control group in transfer factor for carbon monoxide corrected for lung volume (KCO 1.67 (0.3) and 1.83 (0.3) mmol min-1 kPa-1 l-1 respectively) and in exercise capacity (140 (25) and 120 (30)w). Only three patients showed lung function impairment consistent with pneumonitis. No relation between lung function measures and cumulative doses of amiodarone or desethylamiodarone was found. CONCLUSIONS: The prevalence of clinically evident pulmonary side effects was 4.9%, which is lower than that reported in studies in which higher daily maintenance doses of amiodarone were given. The slightly lower KCO values and lower work load achieved by the patients taking amiodarone suggest a small effect of amiodarone in doses of 400 mg on lung function. A role for individual susceptibility to pulmonary complications of amiodarone treatment is suggested.

Amiodarone↗

PubMed1992

[The predictive value of ventricular function during exercise after a myocardial infarct].

To assess the prognostic value of exercise left ventricular function, and if this test improves the prognostic value of clinical data and exercise test, 146 patients (mean age 56 +/- 9 years) underwent rest and exercise radionuclide angiography, 10 days after myocardial infarction. During follow-up (mean 16 +/- 5 months), 32 patients had new coronary events: 5 died, 9 had a new myocardial infarction and the remaining 18 developed unstable angina (Class III-IV of the CCS classification). Patients with new coronary events had more frequently severe left ventricular failure (Killip III-IV) (15% vs 3%; p less than 0.05) and postinfarction angina (32% vs 9%; p less than 0.01) than their counterparts. There were no differences regarding rest ejection fraction between both groups of patients. Exercise ejection fraction increased significantly (50 +/- 14% to 56 +/- 16%, p less than 0.001), while there was no change in patients with new coronary events (46 +/- 16% to 43 +/- 15%, NS). Logistic regression analysis including only clinical data identified postinfarction angina (p less than 0.01) and left ventricular failure (Killip III-IV) (p less than 0.01) as independent predictors of new coronary events. The sensitivity and specificity of the regression equation obtained with clinical data were 43% and 90%, respectively. Analyzing data from clinical variables, as well as exercise test and both, rest and exercise radionuclide angiography, logistic regression analysis identified, exercise ejection fraction (p less than 0.001), postinfarction angina (p less than 0.01) and rest ejection fraction (p less than 0.05) as independent predictors of new coronary events.(ABSTRACT TRUNCATED AT 250 WORDS)

Chi-Square Distribution↗

PubMed1992

[Prognostic predictors of left ventricular aneurysm after myocardial infarct].

We have prospectively studied the prevalence and natural history of left ventricular aneurysm in a series of 386 consecutive male patients with an acute myocardial infarction. Definition of aneurysm was angiographic and based on a single plane left ventricular angiogram. There were 52 (13.5%) left ventricular aneurysms. Mean follow-up was 57 +/- 29 months (range 40-100). During this interval, 15 of the 52 patients died (29%). Univariate analysis showed that survivors had at admission significantly less prevalence of hypercholesterolemia, previous myocardial infarction and intraventricular conduction disturbances. In addition, their Killip class was better (p less than 0.02) and the left ventricular ejection fraction was higher (p less than 0.002). The survival rates of patients with ventricular aneurysm at 1, 3 and 5 years were 88, 82 and 75%, respectively. Left ventricular end diastolic pressure, number of diseased vessels and the presence of bifascicular block were independent predictors of survival. Stratification of patients according to the risk factors allowed identification of patients with excellent prognosis (those with left ventricular end diastolic pressure less than 20 mmHg, single vessel disease and no conduction disturbances) and others with high risk of death (left ventricular end diastolic pressure greater than or equal to 20 mmHg, three vessel disease and bifascicular block). Survival at 5 years for these two groups were 81% vs 50%, respectively (p less than 0.005).

Heart Aneurysm↗

PubMed1992

[The effect of low-dose acetylsalicylic acid on platelet aggregation parameters in vitro].

In order to elucidate whether a single dose of 150 mg acetylsalicylic acid three times a day, provokes significant changes into platelet aggregation, we analyzed a group of 50 patients who underwent coronary revascularization. During 48 hours before surgery, all patients received 100 mg dipyridamole orally every 6 hours and 1 hour after the end of the operation 100 mg dipyridamole via nasogastric tube. Patients were then randomized into three groups to receive 3 times a day a capsule containing: 50 mg acetylsalicylic acid, 50 mg acetylsalicylic acid plus 75 mg dipyridamole or placebo. Before the antiplatelet therapy was started, the day of the operation and 5 days after the onset of the treatment, blood samples were taken to determine platelet aggregation (turbidimetric technique) and the thromboxane A2 liberation. The three groups were comparable for all the studied clinical and angiographic variables. Preoperative dipyridamole did not provoke significant changes in platelet aggregation (acetylsalicylic acid group 86.5 +/- 10% vs 71 +/- 28.8%; acetylsalicylic acid + dipyridamole group 81.5 +/- 7.8% vs 75.3 +/- 22.7%; placebo group 83.7 +/- 8.9% vs 70 +/- 21.5%). After 5 days of treatment with acetylsalicylic acid, both groups under active treatment showed a significant (p less than 0.001) decrease of aggregability (acetylsalicylic acid 12.8 +/- 4.4%; acetylsalicylic acid + dipyridamole 20.5 +/- 17%; placebo 72 +/- 21.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin↗

PubMed1991

Impaired response of atrial natriuretic factor to blood volume expansion in acute right ventricular infarction.

To assess the role of atrial natriuretic factor (ANF) in right ventricular (RV) infarction, 30 patients with inferior wall acute myocardial infarction (15 with RV involvement) and normal left heart filling pressures were studied 39 +/- 12 hours after the onset of symptoms. Serial measurements of cardiac output, right atrial, pulmonary artery and pulmonary wedge pressures, as well as plasma ANF, plasma renin activity, plasma aldosterone and vasopressin were obtained before and 30 minutes after acute volume expansion to raise wedge pressure greater than or equal to 20 mm Hg. Baseline mean right atrial pressure and plasma ANF levels were greater in patients with than without RV infarction (8 +/- 3 vs 5 +/- 2 mm Hg; p less than 0.0001, and 4.6 +/- 2.9 vs 2.7 +/- 1.5 fmol/ml; p less than 0.05, respectively). There were no differences in other baseline hemodynamic or humoral parameters between both groups. After volume expansion, pulmonary wedge pressure was similar in both groups, but right atrial pressure increased to higher levels in patients with RV infarction (19 +/- 2 vs 14 +/- 2 mm Hg; p less than 0.0001). Despite this greater stimulus for ANF secretion, the increase in plasma ANF was less pronounced in patients with RV infarction (63 +/- 81 vs 455 +/- 417%; p less than 0.002), especially among those with paroxysmal supraventricular tachyarrhythmias. Thus, despite higher baseline plasma levels of ANF, response to volume loading is markedly attenuated in patients with RV infarction complicating an inferior wall acute myocardial infarction.

Adult↗

PubMed1991

Clinical and angiographic features and prognostic significance of early postinfarction angina with and without electrocardiographic signs of transient ischemia.

PURPOSE: The goal of the study was to characterize the clinical and angiographic characteristics and the prognostic significance of early postinfarction angina associated or unassociated with ST-T changes. PATIENTS AND METHODS: Four hundred forty-nine consecutive patients surviving an acute myocardial infarction and catheterized before hospital discharge were included. They were closely monitored in the coronary care unit and a 12-lead electrocardiogram (ECG) was promptly obtained before the administration of nitroglycerin whenever chest pain suggestive of ischemia occurred. Complete follow-up information was obtained for all patients a mean of 14 +/- 8 months after the qualifying infarction. RESULTS: Early postinfarction angina occurred in 164 patients. Transient ST-T changes were documented during pain in 79 patients and were absent in 85. Compared with patients without postinfarction angina, patients with angina without ST-T changes were older and had a more frequent past history of angina (42% versus 28%, p = 0.01). They also more often had a non-Q-wave myocardial infarction with lower peak creatine kinase blood level elevation. At angiography, patients with angina had more extensive coronary artery disease (1.9 +/- 0.8 diseased vessels per patient versus 1.6 +/- 0.8, p less than 0.05) and more left ventricular segments at jeopardy by a significant coronary artery stenosis (1.5 +/- 1.1 versus 1.2 +/- 1.1, p less than 0.05). The presence of ST-T changes during chest pain was associated with a further increase in the severity of coronary artery disease (2.1 +/- 0.8 diseased vessels per patient, p less than 0.05) and with a less well-developed collateral circulation (18% versus 34% of patients, p = 0.01) that was more often compromised by a coronary artery stenosis (22% versus 8% of patients, p = 0.008). In-hospital infarct extension occurred in 2% of patients without angina, 3.5% of patients with angina without ECG changes, and 28% of patients with angina and ST-T changes (p less than 0.01). The 2-year survival was similar in the first two groups (90% and 96%), and poorer (83%, p = 0.02) in patients with ST-T changes. Survival rates without myocardial infarction were respectively 80%, 78%, and 67% (p less than 0.004). CONCLUSION: A gradient in the severity of coronary artery disease and in the extent of myocardium at jeopardy exists from patients with no postinfarction angina to patients with angina and to patients with angina accompanied by ECG signs of ischemia. The presence of ST-T changes during pain indicates a much less favorable clinical outcome.

Angina Pectoris↗

PubMed1991

[Non-sedative antihistaminics and binding to central and peripheral H1 histamine receptors].

Four non-sedating antihistamines (astemizole, cetirizine, loratadine and terfenadine) were investigated for in vitro and ex vivo binding to histamine-H1 receptors in guinea-pig cerebellum and lung. In vitro, all the drugs dissociated slowly from H1 receptors (half-times greater than or equal to 100 min), Ki,app-values decreased with longer incubation times for potent lipophylic agents (astemizole and terfenadine) Ki,app-values were lower with more dilute tissue suspensions. In optimized assay conditions astemizole showed a Ki,app-value of 0.2 microM. Terfenadine, cetirizine and loratadine bound with 30-, 80- and 100-times lower affinity to H1 receptors. The occupancy of lung and cerebellar H1 receptors was investigated after oral administration of various dosages of the drugs and at several times after drug administration, using ex vivo binding techniques. Astemizole was a very potent compound showing complete differentiation between lung and cerebellar receptor occupation (with 0.63 mg/kg: 70% of lung H1 receptors were occupied, with less than 10% of cerebellar H1 receptor occupancy). A 7-times higher dose of terfenadine was required to induce the same effect. Astemizole produced a rapid and complete occupancy of lung receptors, which was maintained up to 72 h after administration. In contrast, terfenadine produced a peak effect at 1 h and was completely eliminated from lung receptors in 24 h. Loratadine and cetirizine only poorly differentiated between lung and cerebellar receptor occupancy (at 2.5 mg/kg: 70 and 60% of lung receptor occupancy, 50 and 70% of cerebellar receptor occupancy).(ABSTRACT TRUNCATED AT 250 WORDS)

Astemizole↗

PubMed1991

[Chronic lymphatic leukemia. I. Clinico-biological features and survival analysis. Study of 187 patients].

A review was carried out of 187 previously untreated cases of chronic lymphocytic leukaemia diagnosed between 1969 and 1988. The median age of the patients was 65 years (range, 36-87). There were 118 males (M/F ratio, 1.7). In accordance with Rai's staging system the patients were distributed as follows: 0.29%; I, 20%; II, 25%; III, 13%; IV, 13%, and according to Binet's staging the distribution was: A, 55%; B, 21%; C, 24%. The most frequently found physical findings were lymph node enlargement (55%), splenomegaly (32%) and hepatomegaly (28%). Anaemia was present in 20% of the cases and thrombocytopenia in 13%. The mean lymphocyte count was 62 x 10(9)/L (range, 6-475 x 10(9)/L). Bone marrow infiltration of over 80% was seen in 46% of the patients. Bone marrow biopsy was performed on 97 patients, the diffuse pattern of involvement being most commonly found (44%). Increased BUN (55%), alkaline phosphatase (42%) and LDH (38%) were the most frequent biochemical alterations. Hypogammaglobulinaemia was present in 55% of the patients, IgM being the most commonly affected immunoglobulin (66%). Monoclonal gammopathy was seen in 4% of the cases. LDT, measured in 75 patients, was less than a year in 32%. No antileukaemic drugs were needed in 34% of the patients. When concluding this study, 100 patients had died. The median survival was 57 months and death was related to chronic lymphocytic leukaemia in 53% of such patients.

Actuarial Analysis↗

PubMed1991

[Chronic lymphatic leukemia. II. Analysis of prognostic factors and development of survival predicting models. Study of 187 patients].

The univariate analysis of prognostic factors showed the value of clinical variables (age, symptoms, lymph node enlargement, splenomegaly, hepatomegaly, clinical stage), haematological variables (haemoglobin, platelet count, leucocyte count, lymphocyte count, bone marrow involvement and biopsy pattern, cleaved lymphocytes, prolymphocytes, LDT) and biochemical variables (BUN, creatinine, calcium, phosphorus, uric acid and albumin). The multivariate analysis chose the combination of Rai's stage, age, cervical lymph node involvement, phosphorus and BUN. Two predictive models capable of separating appropriately low, intermediate and high risk groups were developed and validated. The results were compared with others in the literature. The interest of predictive models arising from multivariate analysis is stressed.

Adult↗

PubMed1990

Comparative effects of the aromatase inhibitor R76713 and of its enantiomers R83839 and R83842 on steroid biosynthesis in vitro and in vivo.

R76713 (6-[(4-chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl]-1-methyl-1H- benzotriazole) is a selective, non-steroidal aromatase inhibitor containing an asymmetric carbon atom. In this paper, we compare the effects of R76713 (racemate) with its enantiomers R83839 (the levo-isomer) and R83842 (the dextro-isomer) on steroid biosynthesis in rat cells in vitro and in the rat in vivo. In rat granulosa cells, aromatase activity was inhibited by 50% at concentrations of 0.93 nM of R76713, 240 nM of R83839 and 0.44 nM of R83842, revealing a 545-fold difference in activity between both enantiomers. Up to 1 microM, none of the compounds had any effect on steroid production in primary cultures of rat testicular cells. Above this concentration all three compounds showed a similar slight inhibition of androgen synthesis with a concomitant increase in the precursor progestins, indicative for some effect on the 17-hydroxylase/17,20-lyase enzyme. In rat adrenal cells none of the compounds showed any effect on corticosterone synthesis. At concentrations above 1 microM there was an increase in the levels of 11-deoxycorticosterone pointing towards an inhibition of the 11-hydroxylase enzyme. This increase was more pronounced for R83839 than for R76713 and R83842. In vivo, in PMSG-primed rats, R83842 reduced plasma estradiol by 50%. 2 h after oral administration of 0.0034 mg/kg, whereas 0.011 mg/kg of R76713 and 0.25 mg/kg of R83839 were needed to obtain the same result. Oral administration of up to 20 mg/kg of the compounds did not significantly affect plasma levels of adrenal steroids in LHRH/ACTH-injected rats. Plasma testosterone was lowered at 10 and 20 mg/kg of R83842 and at the highest dose (20 mg/kg) of R76713 and R83839. In conclusion, the present study shows that the aromatase inhibitory activity of R76713 resides almost exclusively in its dextro-isomer R83842. R83842 exhibits a specificity for aromatase as compared to other enzymes involved in steroid biosynthesis of at least a 1000-fold in vitro as well as in vivo. This confirms the extreme selectivity previously found for the racemate.

Adrenal Cortex Hormones↗