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Biomedical subjects

P Herve

Publications and source records attributed to P Herve.

At least 91 records · Page 5Linked to original sources

Control of the transmembrane phospholipid distribution in eukaryotic cells by aminophospholipid translocase.

The aminophospholipid translocase is a plasma membrane Mg2(+)-ATPase which selectively pumps the aminophospholipids (phosphatidylserine and phosphatidylethanolamine) from the outer to the inner monolayer in eukaryotic cells and is predominantly responsible for the asymmetric phospholipid distribution of the plasma membrane. Similar ATP-dependent transport of phospholipid takes place in some organelles such as chromaffin granules. On the other hand, the phospholipid flippase of rat liver endoplasmic reticulum does not require ATP and has a low lipid specificity. The biological implications of these phospholipid flippases are discussed.

Carrier Proteins↗

High dose melphalan and autologous marrow rescue in advanced epithelial ovarian carcinomas: a retrospective analysis of 35 patients treated in France.

We retrospectively evaluated the feasibility and antitumour efficacy of high dose melphalan (HDM) followed by autologous marrow rescue in 35 patients with common epithelial ovarian cancers. All patients initially had advanced disease (FIGO III-IV) and received HDM after extensive surgery and a median of 6 cycles of cis-DDP containing regimens CAP or CHAP. All, except three patients who showed evidence of progression, had a second surgical exploration before high dose chemotherapy. Melphalan was given at a dosage greater than or equal to 140 mg/m2 followed 24 h later by autologous marrow rescue. Severe but reversible aplasia and mucositis were the most common toxicities: three patients died from the procedure, two from infection and one from secondary leukaemia. HDM was effective in 75% of evaluable patients; this was evidence of activity in patients who failed to respond to first line chemotherapy. The duration of response was short, particularly for patients treated with progressive disease at the time of high dose chemotherapy rather than in partial or complete remission. With a median follow-up of 23 months (range 8-54) after high dose chemotherapy, 19 patients are alive (15 with non-progressive disease) with a projected survival of 47% between 2 and 5 years.

Adult↗

Almitrine decreases the distensibility of the large pulmonary arteries in man.

Almitrine improves blood gas values in patients with COPD, primarily through better ventilation-perfusion matching. The improvement comes largely from a vasomotor effect of the drug. The vasomotor mechanism is unknown. We suspected that decreased distensibility of the large pulmonary arteries was one probable effect of the drug. If present, reduced distensibility would explain many of the hemodynamic alterations produced by almitrine. To test this idea, we measured the diameter of the right pulmonary artery during systole and diastole both before and after almitrine administration in nine patients who were undergoing pulmonary cineangiography. Our calculations of the distensibility of the right pulmonary artery showed that almitrine caused a 60 percent decrease. This significant alteration in the stiffness of the large pulmonary arteries can account for the rise in systolic pressure, a change that would be expected to redistribute pulmonary blood flow upwards and thereby improve ventilation-perfusion balance.

Adult↗

[Human grafts preserved at +37 degrees C. Initial clinical results].

This study reports the clinical use of donor corneas stored at +37 degrees C in organ culture medium. Twenty-five penetrating keratoplasties were performed. The mean storage time of organ-cultured donor corneas was 12.3 days (3-21). The follow up of the patients was 12 months. The criteria for the survival of corneal grafts was mean central corneal thickness, clarity of the cornea and mean endothelial cell density. The graft survival was 92% at 12 months. The mean central corneal thicken was 0.54 mm. The mean endothelial cell density was 1625 cells/mm2. The mean decrease in endothelial cell density at 12 months was 40.6%.

Cornea↗

[Medium-term preservation of human corneas in an enriched culture medium at +37 degrees Centigrade].

A study of 36 penetrating keratoplasties using donor corneas stored at +37 degrees C in organ culture incubation for an average of 12 days prior to transplantation is reported. The criteria for the survival of corneal grafts were mean central corneal thickness, clarity of the cornea and mean endothelial cell density. A total of 86% of the grafts remained clear after 12 months follow-up time. The mean central corneal thickness was 0.47 mm. The mean endothelial cell density was 1452 cells/mm2. Based on the results of this study, organ culture reported here appears to be a safe and efficient method of medium to long-term corneal storage.

Adult↗

Marrow transplantation from HLA non-identical family donors for the treatment of leukaemia: a pilot study of 15 patients using additional immunosuppression and T-cell depletion.

Fifteen patients with high-risk leukaemia were given T-cell depleted marrow transplants from HLA non-identical related donors. They were treated with a combination of total body irradiation (TBI), high-dose cytosine arabinoside (Ara-C) and high-dose melphalan in an attempt to prevent a host-versus-graft reaction. Antilymphocyte globulins were given prior to transplantation for additional immunosuppression to 13 patients and in-vivo monoclonal antibody anti-human LFA1 to two. Engraftment and chimaerism assessed by HLA typing were achieved in 14 patients. Seven developed acute graft-versus-host disease (two fatal), one failed to engraft. Six patients died in complete remission from cytomegalovirus (CMV) interstitial pneumonitis and three remain alive in complete remission 2, 3 and 13 months after transplant. We conclude that aggressive immunosuppression allows for sustained engraftment of T-cell depleted HLA non-identical marrow. The incidence and severity of GVHD are acceptable and CMV pneumonitis remains the major problem.

Adolescent↗

Early neutrophil alveolitis after rechallenge in drug induced alveolitis.

A patient with drug induced alveolitis due to an antidepressant drug, nomifensine, is described. After an inadvertent rechallenge by the patient sequential bronchoalveolar lavage was carried out. Twenty four hours after the rechallenge the lavage fluid contained a high cell count with neutrophils predominating. Seven days after challenge the cells were predominantly lymphocytes.

Alveolitis, Extrinsic Allergic↗

Relaxation of the diaphragm muscle: influence of ryanodine and fatigue.

Relaxation of rat diaphragm was shown to be sensitive to load, as previously described for adult mammalian ventricular muscle, because the time course of isotonic relaxation could be changed by changing the load: the lighter the load, the greater the shortening, the quicker the relaxation. Maximum velocity of isotonic relaxation was linearly related to the extent of shortening (r = 0.90). To quantify the degree of load sensitivity, we measured the tRi, i.e., the ratio of time at which the isometric relaxation of the twitch afterloaded at 50% of the isometric peak active tension began to time at which the isometric twitch was relaxed to 50% of the isometric peak active twitch tension. tRi was 0.76 +/- 0.03 (SE) in control conditions but significantly increased to 0.91 +/- 0.02 after ryanodine, which is an inhibitor of the sarcoplasmic reticulum (SR) function, and to 0.89 +/- 0.03 after fatigue. These results suggest that in adult rat diaphragm, as in cardiac muscle, the load sensitivity of relaxation requires a well-functioning SR and that the relaxation abnormalities observed in fatigued diaphragm are related to a dysfunction of the SR.

Alkaloids↗

Mild isocapnic hypoxia enhances the bronchial response to methacholine in asthmatic subjects.

We studied the effect of mild isocapnic hypoxia (FIO2 = 15.5%) on lung mechanics, heart rate, circulating plasma catecholamines, and bronchial responsiveness to methacholine in ten asthmatic adults. Hypoxia did not alter lung mechanics (i.e., dynamic pulmonary compliance [CLdyn], pulmonary resistance [RL]) nor did it increase plasma catecholamines, but it significantly increased bronchial responsiveness to aerosolized methacholine, as assessed by the fall in forced expiratory volume in one second (FEV1: 1.2 +/- 0.18 versus 0.9 +/- 0.14 L/s, p less than 0.05), the rise in RL (RL: 19.1 +/- 1.4 versus 8.4 +/- 1 cm H2O/L/s, p less than 0.05), and the steeper slope of the dose-response curve to methacholine. We concluded that the hypoxic characteristic of asthmatic attacks may aggravate airflow obstruction.

Adult↗

Preclinical studies of a panel of 12 monoclonal antibodies in view of bone marrow purging in acute lymphoblastic leukemia.

We analysed the optimal conditions for autologous bone marrow purging using complement binding monoclonal antibodies (mAbs). Twelve mAbs belonging to four clusters (CD9, CD10, CD19, CD24), alone or combined were evaluated by using direct cytotoxicity and clonogenic assays. We observed the following data: (1) optimal cytotoxicity was reached with doses of 1-10 micrograms mAbs for 10(7) cells, (2) the concentration of the cell suspension had to be below 3 X 10(7)/ml, (3) combinations of mAbs were more effective than a single mAb treatment, (4) in the case of an IgM isotype, there seems to be a clear dissociation between the amount needed for optimal toxicity and that for antigenic saturation measured by cytofluorometry.

Antibodies, Monoclonal↗

Recurrence of pulmonary embolism during anticoagulant treatment: a prospective study.

The risk of early recurrence of pulmonary embolism in patients with venous thromboembolic disease treated by anticoagulants is not well established. To determine the risk linked to contemporary proximal deep venous thrombosis, a prospective study was organised to give clinical and scintigraphic surveillance to 50 patients with angiographically proved pulmonary embolism plus phlebographically proved proximal deep vein thrombosis during the first 15 days of anticoagulant treatment. Perfusion lung scans were performed initially and on days 3, 7, and 15. Only two patients had a recurrence of pulmonary embolism during this period; both episodes were revealed by new symptoms, and one recurrence was fatal. The systematic performance of angiography in four patients found to have new scintigraphic defects led to the diagnosis of "spurious scintigraphic recurrence" in three of them. It is concluded that (a) adjusted anticoagulant treatment showed an effectiveness of 96% for preventing early recurrence of pulmonary embolism in this group of supposed high risk patients, and (b) in patients with recent pulmonary embolism new defects on systematic perfusion lung scans are not specific indicators of recurrent pulmonary embolism.

Adult↗

[Preservation of human corneas in an enriched culture medium at +37 degrees Centigrade: histological and biochemical analyses].

Using the methods of Doughman, Sperling and Pels 66 human corneas were preserved up to five weeks in a modified tissue culture medium at +37 degrees C. The organ culture medium consisted of the following ingredients: Dulbecco Iscov's medium, 2% fetal calf serum, penicillin 100 IU/ml, Streptomycin 0.5 mg/ml, and fungizone 5 mg/ml. After culture the corneal endothelium was examined by light microscopy after staining with trypan blue 0.3% and alizarin red 1%. The number of dead cells was counted and the morphological alterations were described at 7, 14, 21 and 35 days. Biochemical analysis of the medium (pH, lactate, glucose) during storage has allowed the comparison of three kinds of storage: 50 ml, 20 ml, and 20 ml with 10 ml substitution weekly. After culture the number of dead cells did not exceed 1% at each period indicating that no dead cell was present at that time. Alteration of the cell shape and formation of rosette and joint meetings of 5 to 8 cells were the dominating morphological changes of the endothelial cells. The endothelial layer was intact and coherent on to 35 days culture. Endothelial cells loses during culture were not determined. The biochemical studies have shown the better quality (pH stability, anaerobic ratio) of storage in 50 ml medium or 20 ml 50% weekly substitution medium. This last kind of storage has given the best metabolic conditions for the preserved corneas. However for long period of storage up to 3-4 weeks, renewing 50% of the medium is found appropriate. At the end of this study a clinical trial is proposed.

Cornea↗