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Biomedical subjects

M Gonzalez

Publications and source records attributed to M Gonzalez.

At least 217 records · Page 12Linked to original sources

Sympatho-adrenal and cardiovascular responses during hand-grip in human hypertension.

Circulating norepinephrine and epinephrine levels were correlated with echocardiographic indices of cardiovascular function during isometric exercise (hand-grip at 30% of maximum force for 3 minutes) in 19 patients with mild essential hypertension and 9 normotensive subjects. At the end of the third minute of exercise, plasma norepinephrine and epinephrine, blood pressure and heart rate, increased significantly and similarly in both groups of patients. In contrast, peripheral resistance tended to increase in hypertensives but tended to decrease in normotensives. Moreover, indices of ventricular function increased in normotensives but decreased in hypertensives. At the end of the exercise, systolic and diastolic blood pressures were directly correlated with epinephrine levels in normotensives but were correlated only with norepinephrine levels in hypertensives. On the other hand, norepinephrine and epinephrine levels were inversely correlated with changes in indices of left ventricular performance in hypertensive patients only. These results demonstrate that during isometric exercise, the increase in blood pressure in normotensives is associated with a sympatho-adrenal activation of cardiac performance and contractility, while in hypertensives the increase in blood pressure results mainly from an increase in peripheral resistance associated with a reduction in cardiac performance and contractility, despite a similar sympatho-adrenal activation in both groups. These differences in the hemodynamic responses may be compatible with the hypothesis of beta-adrenoceptor desensitization or structural alterations of the cardiovascular system in hypertensive patients.

Adrenal Glands↗

Prognostic value of immunological markers in acute myeloblastic leukemia.

In order to investigate the prognostic value of immunologic markers together with the most relevant clinical and hematological disease characteristics in acute myeloblastic leukemia (AML), the reactivity of blast cells from 102 patients with AML was analyzed with a panel of twenty monoclonal antibodies. The univariate analysis showed that five parameters had an adverse effect on both complete remission (CR) and survival: advanced age (greater than 60 years), anemia (hemoglobin concentration (Hb) less than 10g/dl), the expression of the antigens detected by the anti-megakaryocytic antibodies (CDw41/CDw42), the monocytic antibodies (CD14), and the CD9 (FMC56, FMC8) antigen. In addition, the failure to obtain CR had a significant adverse effect on survival (p less than 0.0001). Multivariate analysis showed that only age and Hb had a significant influence on CR while for predicting survival the most important independent prognostic factors were: CR, age, number of platelets and reactivity with the CD9 antibody. These results show that immunological markers could represent a valuable tool in the assignment of risk categories in AML patients.

Age Factors↗

Bone marrow histopathologic patterns and immunologic phenotype in B-cell chronic lymphocytic leukaemia.

The present work analyzes the clinicobiological and immunological characteristics - the latter hitherto unexplored - of the different bone marrow histopathological patterns of the B-cell chronic lymphocytic leukaemia (B-CLL). In addition, we studied whether any or some of these parameters were able to predict the probability of a particular pattern of bone marrow involvement appearing. Of the 100 B-CLL cases studied 41 had a diffuse pattern and 59 were non-diffuse - interstitial 27, nodular 11 and mixed 21 -. Neither clinical nor immunological differences were observed among the distinct non-diffuse patterns. The patients in the diffuse group displayed an increased incidence of mu+ isotype and a higher proportion of HLA-DR and HAN-PC 1 positive cells while, conversely, reactivity with the FMC 8 McAb was lower. In addition, patients with a diffuse pattern of BM involvement displayed features of a more extensive disease: a higher incidence of adenopathies (p less than 0.05), hepatomegaly (p less than 0.01), splenomegaly (p less than 0.01), anaemia (p less than 0.01) and thrombopenia (p less than 0.01) as well as higher levels of peripheral blood lymphocytosis (p less than 0.05) and a higher percentage of BM lymphocytic infiltration (p less than 0.001). Multiple regression analysis showed that thrombopenia and splenomegaly were the two most important features in predicting the probability of a diffuse pattern.

Aged↗

Clinical and immunological findings in large B-cell chronic lymphocytic leukemia.

In order to define the characteristics of B-CLL cases in which the predominant cell population is composed of large lymphocytes, we studied 97 patients with B-CLL, comparing the cell morphological features with the clinical and biological findings and the immunological phenotype of the proliferating cells. Multivariant analysis showed that there were three significantly different morphological groups: Typical CLL, large lymphocyte CLL (LLL), and CLL with prolymphocytes (CLL/PL). The LLL group showed a greater incidence of lymphadenopathies (P less than 0.05) and higher percentages of both mu + delta + cells (P less than 0.01) and Fmc/7+ cells (P less than 0.001) than in typical CLL. The main differences between LLL and CLL/PL were the peripheral blood lymphocyte count and the percentage of Fmc/7+ cells (P less than 0.002)--both higher in the CLL/PL group--and the percentage of mouse rosette-forming cells (P less than 0.01)--lower in CLL/PL. Further studies including functional assays and survival analyses could contribute to elucidating whether these groups are different entities or a single disease with marked heterogeneity.

Antibodies, Monoclonal↗

Efficacy of enoximone in the management of refractory low-output states following cardiac surgery.

Fifteen consecutive patients with post-cardiac surgery low-output states refractory to catecholamine inotropic support and intra-aortic balloon counter-pulsation (seven patients), were given enoximone (MDL 17,043, a phosphodiesterase inhibitor), 1 to 2 mg/kg, as a slow intravenous bolus injection, followed by a continuous infusion of 3 to 10 microg/kg/min. Enoximone resulted in a marked improvement in clinical and hemodynamic conditions. Despite the severity of their initial status, all the patients survived their acute circulatory failure and all but two were discharged from the hospital. Hemodynamic improvement was observed as early as 15 minutes after the drug administration and reflected the previously reported inotropic and vasodilatory properties of enoximone. No serious adverse effects were observed. Enoximone thus appears safe and effective in the management of post-cardiac surgery low-output states. Its effects are additive to those of high-dose catecholamines.

Aged↗

Distribution of the CD45R antigen in the maturation of lymphoid and myeloid series: the CD45R negative phenotype is a constant finding in T CD4 positive lymphoproliferative disorders.

We have compared the expression of the common leucocyte antigen (CD45) and the restricted leucocyte antigen (CD45R) on normal haematopoietic cells, cell lines, and a total number of 136 cases of myeloid and lymphoid proliferative syndromes. CD45, the conventional leucocyte antigen, presents a generalized distribution along the lymphoid and myeloid maturation pathway with the exception of some myelomas and pre-B leukaemias. In contrast, the expression of the CD45R determinant is more limited. Although it is found in the majority of the differentiation stages of B cells and monocytes, it is present only in the early stages of myeloid differentiation. On T cells it is expressed on mature thymocytes and in the majority of CD8+ lymphocytes and a subset of CD4+ cells on peripheral blood. Finally, our results also indicated that CD4+ T lymphoproliferative syndromes are derived from the CD4+ CD45R- subset (20/20 cases).

Animals↗

Leukemias with megakaryoblastic involvement: clinical, hematologic, and immunologic characteristics.

The clinical, hematologic, and phenotypic features of 28 patients with acute leukemia with megakaryocytic involvement (AMKL) were analyzed. The prevalence of this type of leukemia in the entire series was 11.6%, with a higher incidence among patients with acute transformation of a previous myeloproliferative disorder (MPD) (24%) than among the transformed myelodysplastic syndrome (13%) patients. The incidence in the "de novo" ANLL was 8% and 16% among secondary leukemias. The presence of bone marrow fibrosis together with low WBC and normal or increased platelet counts despite a severe anemia are the most relevant features in these patients who otherwise displayed an apparently poor prognosis. Megakaryoblasts were morphologically recognized more frequently in the acute transformations of MPD than in de novo ANLL. Only two cases were considered pure AMKL, and in the remaining 26 patients, megakaryoblasts coexisted with other granulomonocytic and/or erythroid populations. Antiglycoprotein IIIa (anti-GPIIIa) (C17) and anti-GPIIb/IIIa (CDw41-, J15-) antibodies are probably the best markers for AMKL, although the monoclonal antibody against GPIX (FMC25) was also positive in a majority of cases but in a lower percentage of cells. On the other hand, megakaryoblasts were generally negative for granulocytic or monocytic markers (CD13, CD14, CD15); the expression of HLA-DR antigens in these cells was variable. Our present results indicate that megakaryoblastic involvement is more common than previously recognized. This is true not only in acute transformed leukemias but also in de novo ANLL. Although the diagnosis of these cases should be based on megakaryocytic markers, it is often possible to suspect a diagnosis according to certain clinical and hematologic features.

Adult↗

Immunological markers in a coexisting chronic lymphocytic leukemia and Hodgkin's disease.

A 57 year old patient in whom Hodgkin's disease (HD) and Chronic Lymphocytic Leukemia (CLL) was simultaneously diagnosed is described. The infiltration of peripheral blood and bone marrow by mature lymphocytes, with special immunological phenotype (SIg negative, mouse rosette positive and monoclonal antibodies B1+, B4+) consistent with B-CLL and histological findings of lymphnode and axillary mass biopsies were typical of HD. The immunological study of the cell suspension from the axillary mass displayed a phenotype similar to that of the peripheral blood lymphocytes. Whether HD and CLL are two processes of fortuitous association, or a single clinical entity remains to be elucidated. The immunological findings in our patient suggest a common origin for both disorders and that HD could sometimes be the result of a B cell proliferation.

Biomarkers, Tumor↗

Comparative effects on hemodynamics of enoximone (MDL 17,043), dobutamine and nitroprusside in severe congestive heart failure.

To assess their comparative effects on hemodynamics, nitroprusside, dobutamine and enoximone were sequentially administered to 10 patients with severe congestive heart failure. Nitroprusside, dobutamine (at 10 micrograms/kg/min) and enoximone (at 2 mg/kg) increased stroke volume index to a similar extent (31%, 34% and 36%, respectively). Enoximone produced less tachycardia than dobutamine and, consequently, a smaller improvement in cardiac index. Mean arterial pressure was not altered by dobutamine but was reduced 9% by enoximone, 2 mg/kg. This finding accounts for the larger (although not significant) increase in left ventricular stroke work index observed with dobutamine compared with enoximone. Ventricular filling pressures and vascular resistances were significantly decreased by all 3 drugs (p = 0.001). All 3 drugs improved cardiac pump function when assessed by the increase in stroke index to a similar extent; however, enoximone (2 mg/kg) resulted in less hypotension than nitroprusside (mean arterial pressure -9% vs -22%, p = 0.0001) and in less tachycardia than dobutamine 10 micrograms/kg/min. Those differences in mode of action account for the variations observed in the heart rate-blood pressure product (dobutamine 10 micrograms/kg/min, +18%, enoximone 2 mg/kg, -5%, p = 0.003). Enoximone thus appears to be of great value in the management of severe congestive heart failure by its combination of vasodilatory and inotropic properties. Enoximone (2 mg/kg) provides a clinically significant increase in cardiac index, a clear reduction of ventricular filling pressures, a moderate reduction of mean arterial pressure and only minor changes of heart rate and of rate pressure product.

Aged↗

Protection against severe rotavirus diarrhoea by rhesus rotavirus vaccine in Venezuelan infants.

The efficacy of the rhesus rotavirus vaccine candidate MMU-18006 was evaluated in a longitudinal double-blind field trial in Caracas, Venezuela. 247 infants aged 1-10 months were studied and followed for up to 1 year (201 completed the 1-year surveillance): 123 received a dose of 10(4) plaque-forming units of the vaccine orally and 124 received placebo. 21 episodes of rotavirus diarrhoea were detected, 16 in the controls and 5 in the vaccines: vaccine efficacy against any rotavirus diarrhoea was thus 68%. In the 1-5-month-old group the vaccine efficacy was 93%; only 1 episode of rotavirus diarrhoea was detected in 68 vaccinees and 15 such illnesses were observed in 65 controls (p less than 0.0001). For the entire study group vaccine efficacy was 100% against the most severe rotavirus diarrhoeal episodes.

Antibodies, Viral↗

Study of the morphological, electrophysiological and behavioral effects of unilateral kainic acid injection into the cat's substantia nigra.

Morphological, electrophysiological and behavioral studies were carried out in cats after unilateral kainic acid injection in the substantia nigra. A forced contralateral head turning and compulsive circling was observed after surgery. Fifteen days after, when asymmetry disappeared, apomorphine induced an ipsilateral head and body turning, that was blocked by haloperidol. The percentage of turning, after electrical stimulation in the superior colliculus or pulvinar-lateralis posterior complex, was affected by substantia nigra lesion. This work demonstrates that the nigro-pulvinar-lateral posterior and the nigrotectal projection modulate the capability of electrical stimulation of the target structures to elicit turning, and after unilateral substantia nigra lesion, two opposite directions of asymmetry appear, which are time-dependent and modulated by different neurotransmitters.

Animals↗

Discrepancies between morphologic, cytochemical, and immunologic characteristics in acute myeloblastic leukemia.

This study was designed to compare the cytochemical pattern with the immunologic phenotype in 108 cases of acute myeloblastic leukemia (AML) classified according to the French-American-British (FAB) criteria. Special attention was paid to the cases where discrepancy existed between these approaches and to a group of 11 patients considered as unclassifiable mainly because a second cell population--megakaryoblastic--was detected. Three types of discrepancies were observed: cases with typical morphologic characteristics and cytochemistry but devoid of lineage-specific antigens; these mainly include poorly differentiated leukemias (eight M1, four M2, and eight M5a), suggesting that the cytochemical enzymes are earlier myeloid markers than the currently available monoclonal antibodies; cases in which immunologic characteristics were discordant with morphologic characteristics and cytochemistry; these include two M2 cases positive for monocytic monoclonal antibodies (CD14); six M5b cases positive for granulocytic monoclonal antibodies (CD15); and seven M4 cases lacking in CD14 or CD15 antigens; cases with discrepancies between morphologic characteristics and cytochemistry and in which the immunologic markers permitted the correct assessment of cell lineage (six cases). These results show that the classification of these patients is better achieved by a combined morphologic, cytochemical, and immunologic approach.

Antibodies, Monoclonal↗