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Biomedical subjects

P Poncelet

Publications and source records attributed to P Poncelet.

At least 55 records · Page 3Linked to original sources

A double-blind, randomized, comparative study of nitrendipine and enalapril in elderly hypertensive patients.

We conducted a randomized, double-blind, double-placebo study in two groups of elderly hypertensive patients aged over 60 years to compare nitrendipine to enalapril, given once daily over 4 months, as monotherapy with 20 mg tablets. Clinic blood pressure was measured monthly and 24 h ambulatory monitoring was obtained at day 0 and day 120. Fifty-two patients entered the study (22 in the nitrendipine group, 30 in the enalapril group); 4 patients in both groups were dropped from the study because they withdrew their consent to participate. Three patients under nitrendipine and five patients under enalapril were not included in the analysis of data because of insufficient follow-up. The two groups were comparable on final analysis. The clinical blood pressure was similarly reduced in both groups at 24 h postdose (172/97 to 157/85 mm Hg on nitrendipine vs. 177/98 to 154/86 mm Hg on enalapril). Seventy percent of the patients had their blood pressure normalized at the end of the study in the two groups. With ambulatory blood pressure recording, no 24 h blood pressure significant differences were found on day 120 when we calculated the mean of systolic blood pressure (SBP) or diastolic blood pressure (DBP) (137 +/- 12/82 +/- 9 mm Hg on nitrendipine vs. 136 +/- 16/82 +/- 11 mm Hg on enalapril), or for daytime or nighttime periods. The pulse pressure or the mean of the five highest SBP values was also similar in nitrendipine and enalapril patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Predictive criteria of left ventricular hypertrophy given by ambulatory monitoring of blood pressure in hypertension of the elderly].

Eighty-nine patients over 65 years of age, with mild to moderate hypertension, underwent ambulatory blood pressure monitoring during 1988 and 45 of them also underwent echocardiography. Concentric left ventricular hypertrophy was diagnosed in 9 patients (20%) and criteria predictive of this complication were looked for in the results of the ambulatory pressure monitoring. The most predictive factors seemed to be: nocturnal systolic blood pressure (the average of the systolic values recorded between 22 h and 6 h); the percentage of excessive nocturnal values (values over 120/80 during the same nocturnal period); the loss of diurnal rythm with absence of the clearcut difference between the daytime and nocturnal blood pressure value; increased differential pressure, a sign of reduced arterial compliance. These notions, based on ambulatory blood pressure recordings, have diagnostic and prognostic implications (need for echocardiography) and important therapeutic consequences (drugs reducing LHV and improving arterial compliance).

Age Factors↗

[Ambulatory blood pressure: methods, equipment, technical problems, validations].

The measurement of ambulatory blood pressure provides a discontinuous recording which reflects the pressure load over a 24 hour period. The latest recorders allow the patient a relative autonomy due to discontinuous but programmable recording and the miniaturisation of the recorder and relative silence during inflation of the cuff. The main disadvantage of the technique is the necessity of interruption of the patient's physical activity at the moment of recording indicated by an audible "beep". The concept of "active pressure load" is therefore illusory. The traditional controversy between supporters of the auscultatory versus those for the oscillometric method is far from being settled and these discussions do not resolve the problem. The use of finger plethysmographic techniques (Finapress-Ohmeda) is an interesting approach but limited for the time being by the necessity of confinement to a laboratory and recordings of short durations requiring strict conditions of ambient temperature. Future developments using ultrasonic techniques may provide a solution to these problems.

Ambulatory Care↗

Spironolactone and altizide used in combination with enalapril: twenty-four-hour ambulatory recording of blood pressure.

The addition of enalapril or acebutolol to a regimen of altizide + spironolactone in patients with moderate hypotension was investigated in a multicenter study of 53 patients. The patients underwent semiambulatory 24-hour blood pressure monitoring, especially to observe hypotensive episodes. In the 25 patients uncontrolled with altizide + spironolactone alone, enalapril and acebutolol were about equally effective in reducing blood pressure. The incidence of hypotension was low and comparable for both treatment groups, provided that the initial dose of angiotensin-converting enzyme inhibitor was low (5 mg).

Acebutolol↗

Stable expression and function of EBV/C3d receptor following genomic transfection into murine fibroblast L cells.

The Epstein-Barr virus (EBV) and the C3d component of complement bind to the same cell surface receptor (EBVR/CR2) which is part of the B lymphocyte differentiation antigen recognized by the monoclonal antibodies (mAb) of the cluster of differentiation 21 (CD21). To analyze EBV and C3d binding to this receptor, mouse fibroblasts were transfected with human genomic DNA and rare CD21-positive cells were selected and cloned by cell sorting. The presence of the human gene in host cell DNA as well as its transcription product were assayed with a cloned EBVR/CR2 cDNA by Southern and Northern blotting analysis, respectively. A glycoprotein of apparent molecular mass of 140 kDa, similar to that found in human B lymphocytes, was immunoprecipitated with anti-CD21 mAb and proved to be functional since both C3d and EBV bound efficiently and specifically to mouse cells expressing EBVR/CR2. However, no expression of EBV nuclear antigens, early antigens and viral capsid antigens was detected in cells exposed to EBV. This indicates that the presence of EBVR/CR2 is not sufficient to allow full infection of mouse fibroblasts.

Animals↗

Pre-clinical evaluation of anti-lacto-N-fucopentaose III (CD15) monoclonal antibodies for ex vivo bone marrow purging in acute myeloid leukemia.

In order to eliminate residual leukemic cells from the marrow of patients with acute myeloid leukemia (AML) prior to autologous bone marrow transplantation, the optimal conditions of utilization of three CD15 murine monoclonal antibodies (MoAb) were investigated. The VIM-D5 MoAb was used with rabbit complement (C'), whereas the 8.27 and SMY15A MoAbs were used in the presence of human C'. These antibodies were also tested after fixation on magnetic beads. In a culture assay in semi-solid medium with a mixture of normal marrow and 1% HL60 cells, a lysis of clonogenic cells greater than 99% was achieved with the three antibodies and two rounds of complement, or with antibody-coated magnetic beads. Cultures of leukemic clonogenic cells (CFU-L) were performed in 47 cases. An inhibition equal to or greater than 90% was achieved in seven cases with VIM-D5, 16 cases with 8.27 and 11 cases with SMY15A and C'. The correlation with cytotoxicity of fresh cells was low. Twenty cases were purged with antibody-coated beads. An inhibition equal to or greater than 90% was observed in 10 cases with VIM-D5, 11 cases with 8.27 and 12 cases with SMY15A. The mean recovery of normal CFU-GM was higher than 70% and that of BFU-E higher than 95% with any method of treatment. It is concluded that efficient marrow purging of clonogenic AML cells can be achieved in some cases without toxicity for normal progenitors. The addition of other MoAbs seems necessary to obtain a significant purge in a majority of cases.

Antibodies, Monoclonal↗

Effects of an anti HLA-DR immunotoxin on leukaemia cells and hematopoietic progenitors.

An anti HLA-class II immunotoxin has been prepared by coupling to ricin A-chain (RTA) and anti-DR-DP monoclonal antibody (2G5-MoAb). Protein synthesis inhibition assays showed that 2G5-RTA immunotoxin is: highly cytotoxic to B-cell lymphoid neoplastic cells, and variable so to ALL cells, while AML cell lines display a generally poor susceptibility. Toxicity of 2G5-RTA on normal hematopoietic cells (HPC) was found to be dose-dependent, and to increase significantly with the addition of NH4Cl, used as an activating agent. After 4 h of incubation with 2G5-RTA (10(-8) M), without NH4Cl, percentages of CFU-GM and CFU-GEMM (colony forming units-granulo-monocytes and -multipotent, respectively) progenitor cell recovery were in the order of 50% and 30% respectively. In the same treatment conditions, 2G5-RTA induced a 6 log kill on RAJI cells--measured by clonogenic assay. Finally, this study shows that anti-DR immunotoxins may represent an original, efficient, and relatively safe approach for bone marrow purging of DR positive malignant B-cell populations; while their clinical potential pertaining to ALL and AML remains uncertain.

Animals↗

Interest of simultaneous ultrastructural characterization of morphology, cytochemistry and immune phenotype in a case of putative hybrid acute leukaemia.

A case of acute leukaemia is reported in which blast cells expressed some B-related antigens (namely the CALLA antigen) and no peroxidase activity at the optical level; however, some mature granular cells contained Auer rods. Simultaneous characterization of ultrastructural morphology, cytochemistry and immune phenotype was performed. There was an apparent mutual exclusion in the expression of myeloperoxidase activity and the CALLA antigen, and a heterogeneity in the CALLA expression among the blastic population. These results disagree with the hypothesis of a true biphenotypic leukaemia and demonstrate a complete heterogeneity between the lymphoblastoid cells and the myeloid ones. The interest of such a simple combined method in a case of putative hybrid acute leukaemia is emphasized.

Acute Disease↗

[Calcium intestinal absorption in normotensive and essential hypertensive subjects before and after nicardipine].

The part played by calcium in genesis of essential hypertension may be suspected. Yet, the whole of epidemiological research as well in the animal as in man is still not very convincing. The objective of such a research has been to appreciate the calcium intestinal absorption before and after nicardipine treatment in 11 subjects (5 M/6 F) aged between 32 and 82. The group is made up of 7 hypertensive patients (2 M/5 F) and 4 normotensive ones (3 M/1 F). Subjects showing bone disease, kidney insufficiency and stone in kidneys or under such a treatment as to interfere with calcium metabolism had been excluded. Dosage of calcium and phosphate, Na, K, aldosterone, in blood and urine and PTH and PRA in blood had been effectuated. Estimation of true calcium absorption has been made by double isotope deconvolution method. Blood pressure has been measured by semi-ambulatory monitoring method. Similar evaluation has been made after four weeks treatment (60 mg of nicardipine a day). Without any treatment, normotensive subjects have a lower intestinal absorption coefficient than the hypertensive ones, which is normal (non significative statistical results: NS). Under nicardipine, hypertensive patients seem to get lower intestinal absorption (NS); other clinical, biological parameters show no change, except a rise of apoprotein A after nicardipine treatment (P less than or equal to 0.05). So, the intestinal absorption of calcium would become higher in hypertensive subjects and diminished by calcium antagonist treatment.

Aged↗

Phenotypic analysis of human myeloma cell lines.

Multiple myeloma (MM) is a B-cell malignancy characterized by the accumulation, primarily in bone marrow, of a clone of plasma cells. The nature of the stem cells feeding the tumoral compartment is still unknown. To investigate this special point, we have studied the phenotypes of nine well-known human myeloma cell lines (HMCLs) and compared them with those of normal lymphoblastoid cell lines (LCLs). Twenty-four clusters of differentiation involved in B lymphopoiesis were investigated using a panel of 65 monoclonal antibodies (MoAbs). For each cluster, the percentage of positive cells and the antigen density were determined, giving rise to a "quantitative phenotype". We thus classified the HMCLs into two different groups: those with cytoplasmic mu chains (c mu+) and those without (c mu-). In the first (c mu+) group, comprising seven cell lines, the HMCLs had a phenotype of pre-B/B cells close to that of Burkitt's lymphoma cell lines. They expressed low densities of surface mu chains, without detectable cytoplasmic or surface light chains. Three of them were infected with the Epstein Barr virus (EBV). These c mu+ HMCLs bore most of the B-cell antigens except CD23. They expressed the CALLA antigen (CD10) and lacked the plasma-cell antigen PCA1. In contrast, LCLs expressed surface light chains, high densities of CD23, low densities of PCA1 antigen, and no CD10 antigen. The c mu- HMCLs had a plasma-cell phenotype, lacking most of the B-cell antigens and expressing high densities of PCA1 antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Differentiation, B-Lymphocyte↗

Acute monocytic leukemia with B cell markers expression following B chronic lymphocytic leukemia.

A case of chronic lymphocytic leukemia (CLL) treated with chlorambucil, followed by the development of an acute monoblastic leukemia, is described. Cytofluorometric quantitative immunophenotype was determined during the blastic phase. Whereas small lymphocytes displayed a CD19+; CD24+; CD37+; CD5+ phenotype, the blastic population exhibited, besides CD13, CD14 and CD15 positivity, which is usually noted in such a monoblastic leukemia, definite CD9, CD10, CD22, CD24, CD37, CD5 and CD4 staining. Such results argue against a complete independence between the two clones, although their similarity could not be demonstrated.

Aged↗

[Congenital diaphragmatic hernia. Therapeutic re-evaluation].

Twenty-eight patients with "High-Risk" diaphragmatic hernia were treated without postoperative ipsilateral chest drains. Overall survival was 71%. This study suggests that, in cases of complete absence of the diaphragm, the use of a mesh pervious to air is as noxious postoperatively as an underwater chest drain. This idea is supported by experiments in cats with a left pneumonectomy, in which part of the diaphragm was replaced either by a macroporous mesh or by a microporous prosthesis impervious to air at normal pressures. Moreover, barotrauma may occur preoperatively and when assisted ventilation is required, inspiratory pressure must be strictly limited.

Animals↗

Increase of class II HLA molecules on the membrane of B lymphocytes from patients with rheumatoid arthritis.

Using a novel cytofluorometric method of cellular antigen quantification, we examined peripheral blood mononuclear cells (PBMC) from patients suffering from rheumatoid arthritis (RA) for quantitative modification of class II human leucocyte antigen (HLA) molecules expressed on the surface. Class II HLA molecules were detected by indirect immunofluorescence with a monomorphic monoclonal antibody. No change was observed in the density of class II HLA molecules at the surface of monocytes of RA patients as compared to that of paired healthy subjects. We confirmed that the percentage of class II HLA-bearing T cells was slightly increased in RA patients versus controls, but the density of class II antigens per cell could not be determined accurately. An increase in the density of class II HLA molecules on RA B cells was shown, suggesting that a chronic activation stage of this population contributes to the disease.

Antigens, Surface↗

[Trial of typological classification of the blood pressure profile over 24 hours in aged patients by Fourier analysis].

The profiles of 24-hour systolic and diastolic arterial pressures and heart rates obtained with the Bard-Sentron system were studied in 36 untreated subjects (24 women and 12 men, aged from 65 to 89 years) with normal or borderline blood pressure. Each profile was modelized by a Fourier's serie. Multivariate analysis showed that 4 first harmonics were sufficient for a good description of the values observed. A programme of redistribution in subgroups, using McQueen's reallocation method and based on diastolic pressure spectrum, divided the subjects into two groups (A and B) such that the diastolic pressure spectrum of subjects in the same group were "similar" and those of subjects in different groups were "dissimilar". Subjects in both groups were of the same age and had the same man/woman ratio. The diastolic profile of group A showed marked day-night variations, while that of group B had almost the same level day and night. The same method can be applied to systolic pressure. Although the exact role of ambulatory blood pressure as a risk factor remains to be determined, a strong day-night variation of pressure observed in a given subject ought to be closely watched by the clinician. This study suggests a method to evaluate the different types of arterial pressure and heart rate profiles in any population of subjects and to identify a group at higher cardiovascular risk, if it is present.

Aged↗

Rationale for the selection of ricin A-chain anti-T immunotoxins for mature T cell depletion.

A series of 25 different ricin A-chain immunotoxins (IT) were prepared with monoclonal antibodies reacting with several T cell antigens belonging to different clusters of differentiation (CD) to select the most appropriate immunotoxins (IT) for mature T cell depletion. Our screening procedure was performed in 2 steps. First, IT were evaluated using protein synthesis inhibition assay on clonogenic malignant cells in order to determine the most active IT for a given CD. Second, IT thus selected were evaluated for both mature T cell killing efficacy and tolerance on hematopoietic progenitor cells (HPC). This study showed that (1) different IT directed against the same CD antigen displayed a wide range of activity, suggesting the need for a large screening of IT to determine the most appropriate antibody for a given target antigen; (2) anti-CD3 and anti-CD5 ricin A-chain IT are the most active, displaying a cytoreduction of more than 2 logs on mature T cells; (3) the 3 different anti-CD2 ricin A-chain IT evaluated in this study induced poor mature T cell cytoreduction despite their relative efficacy on leukemic cells; (4) anti-CD8 ricin A-chain IT showed almost no efficacy on relevant target cells; (5) no toxicity on HPC was found for concentrations up to 10(-8) of A-chain whatever the IT used.

Antibodies, Monoclonal↗

[Reliability of the measurement of arterial pressure in the forearm in the obese subject].

The measurement of the blood pressure of corpulent persons often leads to over-estimation. We have therefore compared, for 10 over-weight women (body mass index = 38.04 +/- 1.32 kg/m2) whose average age was 54 +/- 4 years, the blood pressure figures obtained by the invasive method (humeral artery) with values measured automatically by the Bard-Sentron apparatus (B.S.) on the one hand, and the mercury sphygmomanometer (S. Hg) on the other hand. The cuff (bladder = 25 X 12.5 cm) was placed on the same side of the forearm. (table; see text) We have compared the values obtained by invasive and Bard-Sentron methods (I), invasive and mercury sphygmomanometer methods (II), and Bard-Sentron and mercury sphygmomanometer (III) respectively. (Table: see text). The correlations are excellent for the systolic blood pressure, as the Bard-Sentron over-estimates by 5.5 p. 100. They are not so good for the diastolic blood pressure as the Bard-Sentron over-estimates by 33 p. 100. The mercury sphygmomanometer over-estimates the diastolic blood pressure by about 43 p. 100. For conclusion: The blood pressure measurement taken on the forearm of corpulent persons by auscultation or by automatic methods is reliable for the systolic blood pressure, but the diastolic blood pressure is largely over-estimated.

Adult↗

Expression of Tac antigen in B cell lymphomas.

In a series of 55 cases of B cell derived non-Hodgkin's lymphoma the reactivity of two distinct anti-Tac monoclonal antibodies was examined using a sensitive immunoperoxidase technique on cryostat sections. Eighteen out of the thirty-five cases of B cell lymphomas of low or intermediate grade of malignancy were found to be reactive while six out of 20 cases of high-grade malignancy lymphomas showed a positive immunostaining. No correlation was found between anti-Tac reactivity and surface immunoglobulin phenotype, T65 antigen, or calla expression. These findings showed that IL2 receptor expression is not restricted to activated T cells, and raise the question of the possible role of IL2 in the regulation of malignant B cell clone expansion.

Antigens, Neoplasm↗