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Biomedical subjects

C Richard

Publications and source records attributed to C Richard.

At least 91 records · Page 5Linked to original sources
PubMed1999

Clinical use of respiratory changes in arterial pulse pressure to monitor the hemodynamic effects of PEEP.

In ventilated patients with acute lung injury (ALI) we investigated whether respiratory changes in arterial pulse pressure (DeltaPP) could be related to the effects of PEEP and fluid loading (FL) on cardiac index (CI). Measurements were performed before and after application of a PEEP (10 cm H2O) in 14 patients. When the PEEP-induced decrease in CI was > 10% (six patients), measurements were also performed after FL. Maximal (PPmax) and minimal (PPmin) values of pulse pressure were determined over one respiratory cycle and DeltaPP was calculated: DeltaPP (%) = 100 x ((PPmax - PPmin)/ ([PPmax + PPmin]/2)). PEEP decreased CI from 4.2 +/- 1.1 to 3.8 +/- 1.3 L/min/m2 (p < 0.01) and increased DeltaPP from 9 +/- 7 to 16 +/- 13% (p < 0.01). The PEEP-induced changes in CI correlated with DeltaPP on ZEEP (r = -0.91, p < 0.001) and with the PEEP-induced increase in DeltaPP (r = -0.79, p < 0.001). FL increased CI from 3.5 +/- 1.1 to 4.2 +/- 0.9 L/min/m2 (p < 0.05) and decreased DeltaPP from 27 +/- 13 to 14 +/- 9% (p < 0.05). The FL-induced changes in CI correlated with DeltaPP before FL (r = 0.97, p < 0.01) and with the FL-induced decrease in DeltaPP (r = -0.85, p < 0.05). In ventilated patients with ALI, DeltaPP may be useful in predicting and assessing the hemodynamic effects of PEEP and FL.

Adult↗
PubMed1999

Regulation of c-Myc and Max in megakaryocytic and monocytic-macrophagic differentiation of K562 cells induced by protein kinase C modifiers: c-Myc is down-regulated but does not inhibit differentiation.

We have studied the regulation and role of c-Myc and Max in the differentiation pathways induced in K562 cells by 12-O-tetradecanoyl phorbol-13 acetate (TPA) and staurosporine, an activator and inhibitor, respectively, of protein kinase C (PKC). We found that staurosporine induced megakaryocytic differentiation, as revealed by the cellular ultrastructure, platelet formation, and DNA endoreduplication. In contrast, TPA induced a differentiated phenotype that more closely resembled that of the monocyte-macrophage lineage. c-myc expression was down-regulated in K562 differentiated by both TPA and staurosporine, whereas max expression did not change in either case. Although PKC enzymatic activity was low in cells terminally differentiated with TPA and staurosporine, inhibition of PKC activity by itself did not induce c-myc down-regulation. We conclude that the c-myc gene is switched off as a consequence of the differentiation process triggered by these drugs in a manner independent from PKC. Ectopic overexpression of c-Myc in K562 cells did not affect the monocytic-macrophagic and megakaryocytic differentiation, indicating that c-Myc suppression is not required for these processes in K562. Similarly, both differentiation pathways were not affected by Max overexpression or by concomitant overexpression of c-Myc and Max. This result is in contrast with the inhibition of erythroid differentiation of K562 exerted by c-Myc, suggesting divergent roles for c-Myc/Max, depending on the differentiation pathway.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed1999

[Fenfluramines and cardiac valvular lesions].

We report cardiac valvulopathy occurring after prolonged intake of anorectic drugs containing fenfluramine (Fen) and/or dexfenfluramine (D-Fen) in 14 patients whose evolution was followed by Doppler echocardiography. A relation between these drugs and valvular regurgitation was first suspected after 4 cases reported in 1991-1992 and confirmed after 3 more patients in 1993-94-95, who were taken D-Fen or Fen alone. All were women, aged 42 to 73 years. Patient 1 to 7 had been taking Fen and/or D-Fen for 14 to 52 months. Patients 8 to 14 had been taking a mixture of Fen and/or D-Fen, diethylpropion and chinese-herbs for 3 to 69 months. These last 7 patients developed renal failure requiring hemodialysis or peritoneal dialysis in 5 and subsequent renal transplantation in 4. All presented with cardiac murmur(s) and some with dyspnea or palpitations. An initial echocardiography was performed at the time of diagnosis, and was repeated annually for a follow-up period extending to 8 years. We conclude that a relation between Fen and/or D-Fen and the outbreak of valvular heart disease is identified in our patients, confirming previous findings. The nephrotoxicity observed in 7 patients is due to the "chinese-herbs". When Fen and/or D-Fen are stopped and proper therapy initiated, the cardiac symptoms may stabilize or even subside, though slowly. Hemodynamic unstability and/or infection appear to be an aggravating factor. These patient's follow up must be prolonged for several years and is readily achieved with echocardiography. Systematic screening of all patients having taken Fen and/or D-Fen must be performed, as renal and urinary screening for all patients having taken chinese-herbs. Endocardial prophylaxis must always be prescribed.

Adult↗
PubMed1998

Spi-1/PU.1 proto-oncogene induces opposite effects on monocytic and erythroid differentiation of K562 cells.

Spi-1/PU.1 is a hematopoietic transcription factor of the Ets family. To analyze the effects of ectopic expression of spi-1 on the proliferation/differentiation of human myeloid leukemia cells, K562 cells were stably transfected with a spi-1 expression vector. The transfected cell lines expressed elevated levels of spi-1 mRNA and protein and high Spi-1-DNA binding activity. The spi-1 transfected cells showed reduced growth rates and reduced clonogenic cell growth. When the erythroid and monocytic differentiation markers were analyzed, spi-1 overexpression resulted in opposite effects: erythroid differentiation was significantly inhibited in spi-1 transfectants, while spi-1 overexpression increased the monocytic differentiation of cells. These results indicate a differential role of Spi-1 on the differentiation of human myeloid leukemia cells.

Antigens, CD↗
PubMed1998

Expression of Bcl-x in erythroid precursors from patients with polycythemia vera.

BACKGROUND: Deregulating the expression of Bcl-xL, an inhibitor of apoptosis, in an erythropoietin-dependent erythroblast cell line averts apoptosis induced by the withdrawal of erythropoietin. Since in polycythemia vera an abnormal clone of erythroid progenitors is independent of erythropoietin, we investigated whether the endogenous expression of Bcl-xL was deregulated in these cells. METHODS: Erythroid colonies from patients with polycythemia vera and normal subjects were cultured in the presence and absence of erythropoietin and assessed by immunocytochemical and flow-cytometric analysis with anti-Bcl-x antibodies that recognize the two species of Bcl-x (Bcl-xL and Bcl-xS). Reverse-transcriptase-polymerase-chain-reaction analysis was used to determine which one of the two species was responsible for anti-Bcl-x staining. Bone marrow mononuclear cells from 8 healthy bone marrow donors, 14 patients with polycythemia vera, 19 patients with other myeloproliferative syndromes, and 12 patients with secondary erythrocytosis were analyzed by flow cytometry with antibodies against Bcl-x and glycophorin A, an erythroid marker. RESULTS: Erythroid cells from patients with polycythemia vera survived in vitro without erythropoietin, and this finding correlated with the expression of Bcl-x protein (Bcl-xL messenger RNA was the main species of Bcl-x found), even in mature erythroblasts that normally do not express Bcl-x. The mean (+/-SD) percentage of cells positive for both glycophorin A and Bcl-x in the 14 patients with polycythemia vera (21.8+/-3.6 percent) was significantly higher than that in 8 normal donors (6.62+/-1.58 percent), 12 patients with secondary erythrocytosis (6.87+/-1.95 percent), 9 patients with essential thrombocythemia (3.81+/-0.97 percent), and 10 patients with chronic myeloid leukemia (2.7+/-0.41 percent). CONCLUSIONS: Deregulated expression of Bcl-x may contribute to the erythropoietin-independent survival of erythroid-lineage cells in polycythemia vera and thereby contribute to the pathogenesis of this disease.

Adolescent↗
PubMed1998

Molecular pathology of galactosialidosis in a patient affected with two new frameshift mutations in the cathepsin A/protective protein gene.

Galactosialidosis is a recessively inherited lysosomal storage disease characterized by the combined deficiency of neuraminidase and beta-galactosidase secondary to the genetic deficiency of cathepsin A/protective protein. In lysosomes, cathepsin A forms a high-molecular-weight complex with beta-galactosidase and neuraminidase that protects these enzymes against intralysosomal proteolysis. In a patient affected with late infantile form of galactosialidosis, we found two new cathepsin A mutations, a two-nucleotide deletion, c517delTT and an intronic mutation, IVS8+9C-->G resulting in abnormal splicing and a five-nucleotide insertion in the cathepsin A cDNA. Both mutations cause frameshifts and result in the synthesis of truncated cathepsin A proteins, which, as suggested by structural modeling, are incapable of dimerization, complex formation, and catalysis. However, enzymatic assays, gel-filtration, and Western blot analysis of the patient's cultured skin fibroblast extracts showed the presence of a small amount of normal-size, catalytically active cathepsin A and cathepsin A-beta-galactosidase 680 kDa complex, suggesting that a low amount of cathepsin A mRNA is spliced normally and produces the wild-type protein. This may contribute to the relatively mild phenotype of the patient and illustrates the importance of critically comparing molecular results with clinical and biochemical phenotypes.

Adolescent↗
PubMed1998

Joint time and time-frequency optimal detection of K-complexes in sleep EEG.

Automated detection of waveforms such as delta and K-complex in the EEG is an important component of sleep stage monitoring. The K-complex is a key feature that contributes to sleep stages assessment. However, its automated detection is still difficult due to the stochastic nature of the EEG. In this paper, we propose a detection structure which can be interpreted as joint linear filtering operations in time and time-frequency domains. We also introduce a method of obtaining the optimum detector from training data, and we show that the resulting receiver offers better performances than the one obtained via the Fisher criterion maximization. The efficiency of this approach for K-complexes detector design is explored. It results from this study that the obtained receiver is potentially the best one which can be found in the literature. Finally, it is emphasized that this methodology can be advantageously used to solve many other detection problems.

Algorithms↗
PubMed1998

Relation between dicrotic notch and mean pulmonary artery pressure studied by using a Swan-Ganz catheter in critically ill patients.

OBJECTIVE: It has been recently shown that there is a match between dicrotic notch and mean pulmonary artery (PA) pressures in spontaneously breathing patients studied by means of high-fidelity pressure catheters. The aim of the study was to analyze the relation between mean PA pressure and PA pressure at the incisura by using a Swan-Ganz catheter in critically ill, mechanically ventilated patients. MEASUREMENTS AND RESULTS: Fluid-filled PA pressures were obtained over four ventilatory cycles in 32 consecutive, mechanically ventilated patients in the intensive care unit. We measured mean PA pressure and dicrotic notch pressure. We also calculated the widely used approximation of mean PA pressure (mean PAPapprox = diastolic + 1/3 pulse pressure). Cardiac output was measured in triplicate by using the thermodilution technique. Dicrotic notch was clearly identified in 30 of 32 patients. Mean PA pressure (32.1 +/- 10.2 mm Hg) and PA dicrotic notch pressure (31.8 +/- 10.4 mm Hg) were linearly related (r = 0.989, p < 0.001). Agreement between dicrotic notch and mean PA pressures was suggested (mean difference +/- SD = -0.3 +/- 1.5 mm Hg). Similar agreement was found between mean PAPapprox and mean PA pressure (mean difference +/- SD = -0.7 +/- 0.8 mm Hg; p = 0.20). CONCLUSION: By using a Swan-Ganz catheter we found that dicrotic notch pressure equalled mean PA pressure in the critically ill, mechanically ventilated patients studied. This indicated that right-sided ejection was completed at a PA pressure equal to mean PA pressure in these patients.

Aged↗
PubMed1998

Purification and determination of the action pattern of Haliotis tuberculata laminarinase.

The major laminarinase activity (EC 3.2.1.39) from the gastropodean marine mollusc Haliotis tuberculata was purified to homogeneity by cation exchange chromatography and its action pattern was investigated by HPAEC-PAD analysis of the degradation of various laminarin samples. It consists of a 60 kDa protein capable of depolymerizing the unbranched portions of the beta-(1-->3), beta-(1-->6)-glucan, down to laminaritriose. The enzyme operates via a molecular mechanism retaining the anomeric configuration. As the purified protein does not cleave the beta-(1-->6) linkages, it can be used for the structural analysis of laminarins.

Amino Acid Sequence↗
PubMed1998

Characterization of a polyclonal anti-Galalpha1-3Gal antibody from chicken.

A polyclonal antibody was raised against the Galalpha1-3Gal carbohydrate epitope, which is expressed by all mammals (except man and the closest primate species) by immunizing hens with rabbit erythrocyte membranes. IgY was isolated from egg yolks, and affinity-purified on a Galalpha1-3Gal-Synsorb column. Two percent of the initial IgY fraction was recovered. The specificity of the affinity-purified antibody was characterized by: absorption with human, rabbit and pig erythrocytes; by using Synsorb columns; by inhibition with different saccharides; and by immunostaining of glycolipids separated on thin layer chromatograms. A weak reactivity was found toward blood group B or blood group Pk determinant, depending on the assay system used. Such reactivities were abolished after absorption by the appropriate sorbents, yielding a polyclonal anti-Galalpha1-3Gal antibody with narrow specificity.

Animals↗
PubMed1998

Pneumococcal pericarditis with cardiac tamponade in a patient with chronic graft-versus-host disease.

We report a case of pneumococcal pericarditis in a 13-year-old boy following allogeneic BMT from an HLA-identical unrelated donor. The post-transplant course was complicated by chronic GVHD which led to reinstitution of immunosuppressive therapy. Eight months after BMT the patient developed pericarditis with cardiac tamponade, and Streptococcus pneumoniae was isolated in the pericardiocentesis fluid. This is the first reported case of pneumococcal pericarditis after BMT. Although pericardial effusions after allogeneic BMT are often sterile and related to conditioning therapy or associated with chronic GVHD, rapid microbiological investigation and empirical treatment with antibiotics are necessary. Prophylaxis for pneumococcal infection in patients with chronic GVHD is recommended.

Adolescent↗
PubMed1998

Value of the venous-arterial PCO2 gradient to reflect the oxygen supply to demand in humans: effects of dobutamine.

OBJECTIVE: To test the value of venous-arterial PCO2 gradient (deltaPCO2) measurements to reflect the adequacy of cardiac index (CI) to oxygen demand in patients submitted to rapid changes of CI and oxygen demand. DESIGN: Prospective, comparative study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Ten patients with congestive heart failure exhibiting low baseline CI (< or =2.5 L/min/m2) but no evidence of global tissue hypoxia, as attested by the absence of clinical signs of shock and by normal blood lactate concentrations. INTERVENTIONS: Infusion of incremental doses of dobutamine: 0 (D0), 5 (D5), 10 (D10), and 15 (D15) microg/kg/min. MEASUREMENTS AND MAIN RESULTS: The CI increased by a linear fashion from D0 (1.6+/-0.1 L/min/m2) to D15 (2.4+/-0.2 L/min/m2) (p< .05). The mixed venous oxygen saturation (SVO2) increased from D0 (49+/-2%) to D10 (61+/-2%) (p < .05) and remained unchanged from D10 to D15 (60+/-2%). The oxygen extraction ratio (O2 ER) and the deltaPCO2 decreased from D0 (48+/-2% and 9+/-1 torr [1.2+/-0.3 kPa], respectively) to D10 (36+/-2% and 5+/-1 torr [0.7+/-0.1 kPa], respectively) (p < .05 for both comparisons) and remained unchanged from D10 to D15 (36+/-2% and 6+/-1 torr [0.8+/-0.1 kPa], respectively). The biphasic courses of SVO2, O2 ER, and deltaPCO2 were related to the course of oxygen consumption that remained constant from D0 (113+/-9 mL/min/m2) to D10 (112+/-8 mL/min/m2) and significantly increased from D10 to D15 (127+/-10 mL/min/m2) (p <.05). CONCLUSIONS: deltaPCO2 can be reliably used at the bedside for informing on the adequacy of CI with respect to a given metabolic condition, and particularly for detecting changes in oxygen demand (e.g., the changes accompanying drug-induced changes in CI). In this regard, deltaPCO2, together with O2 ER and SVO2, can help to assess the adequacy of CI to global oxygen demand.

Adult↗
PubMed1998

Effects of catecholamines on the pulmonary venous bed in sheep.

OBJECTIVE: To assess the effects of various catecholaminergic agents on pulmonary venous tone. DESIGN: Prospective, randomized, controlled, experimental study. SETTING: Physiology laboratory of a university hospital. SUBJECTS: Thirty anesthetized, mechanically ventilated adult sheep. INTERVENTIONS: Four groups of six animals received 1-hr infusions of norepinephrine (0.5 microg/kg/min), epinephrine (0.5 microg/kg/ min), dopamine (10 microg/kg/min), or dobutamine (10 microg/kg/min). MEASUREMENTS AND MAIN RESULTS: A 7-Fr pulmonary artery catheter was placed in a proximal location to measure cardiac output and pressure in a large pulmonary vein (Ppw) after balloon inflation. Another catheter wedged in a small pulmonary artery measured pressure in a small pulmonary vein (Pdw). A third catheter measured left atrial pressure (PLA ). This method was able to detect the pulmonary venoconstrictive effects of histamine in a separate group of six animals. Pdw-PLA increased from a mean of 2.0+/-1.7 to 3.0+/-1.5 (SD) cm H2O (p < .01), 2.3+/-1.6 to 4.4+/-1.3 cm H2O (p < .01), and 1.7+/-1.0 to 3.5+/-2.2 cm H2O (p < .05) with norepinephrine, epinephrine, and dopamine, respectively. All of these drugs increased Pdw-Ppw, but only norepinephrine and epinephrine increased Ppw-PLA . No change in either pressure difference was observed with dobutamine. Elevation of cardiac output alone could not account for these findings since the increase in cardiac output induced by fluid infusion did not change the pressure differences. CONCLUSION: Norepinephrine, epinephrine, and dopamine at doses commonly used in humans increase pulmonary venous tone in sheep.

Animals↗
PubMed1998

Characterization of a murine monoclonal antibody specific for swine beta1 integrin.

Murine monoclonal antibodies were raised against porcine platelets in order to provide tools for investigating interactions of human blood cells and natural antibodies with porcine tissues. Hybridomas were screened by cellular ELISA on porcine platelets and endothelial cells. Positive clones were tested by flow cytometry for reactivity with isolated endothelial cells. One clone, NaM160-1A3, produced an antibody that stained porcine but not human endothelial cells and lymphocytes. The antibody bound to a 116 kDa glycoprotein on Western blot of both platelets and endothelial cells. The antigen was purified from a platelet lysate by affinity chromatography, first on a ConA column and then on a column presenting the immobilized NaM160-1A3 antibody. Two glycoproteins were obtained: one (116 kDa) was recognized by the antibody and one (150 kDa) was not. The 116 kDa protein had an internal decapeptide identical with human beta 1 integrin, and the 150 kDa protein had an internal amino acid sequence belonging to porcine alpha 2 integrin. Therefore, the NaM160-1A3 antibody was directed against porcine beta 1 integrin and allowed the purification of the complex alpha 2 beta 1, also termed Very Late Antigen 2 (VLA-2). It did not recognize human beta 1 integrin.

Amino Acid Sequence↗