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Biomedical subjects

G Follea

Publications and source records attributed to G Follea.

17 recordsLinked to original sources

[Comparison of mechanical qualities of cortical bone preserved by various freezing methods].

The purpose of this study was to compare the mechanical properties of the human cortical bone following three deep-freezing techniques: addition of D.M.S.O. (di-methyl-sulfoxide) and staged decrease of temperature with immersion into liquid nitrogen, immersion into nitrogen without cryoprotection, deep freezing in an electric device, down to -80 degrees C. Axial loading tests performed on two femurs (88 samples) allowed to determine the strain of failure fmax and the Young's modulus E. Torsion tests were undertaken on four femur (66 samples) to obtain the strain failure tmax and the Young's modulus G. We have taken several samples from the cortex, that we randomly divided into four groups, three of them being deep-frozen with one of the methods studied, the fourth being tested "fresh", after standard sample manufacturing. The results obtained at the fresh state were comparable with those published in the literature (fmax = 158 MPa, E = 9000 MPa, tmax = 60 MPa, G = 4000 MPa). The results obtained after deep freezing both in axial loading and in torsion, demonstrated significant differences, ever though of low value. The surgeon may use one of either freezing method, without fearing any deterioration of the mechanical properties that could threaten the primary stability of the graft. However, only liquid nitrogen permits a long lasting storage, and only the use of cryoprotection can give the hope of preservation of the chondrocytes in case of diaphyseal-epiphyseal grafts.

Bone Transplantation

Apheresis-elutriation program for adoptive immunotherapy with autologous activated monocytes in cancer patients.

Human blood monocytes (Mo) and monocyte-derived macrophages (M phi) are known to be potent antitumor cytotoxic effector cells through activation with recombinant human interferon gamma (rIFN-gamma), bacterial muramyldipeptide or the synthetic derivative muramyltripeptide phosphatidylethanolamine entrapped in liposomes (L-MTP-PE). Large-scale generation of ex vivo activated Mo from the blood of cancer patients proved feasible. We report our experience with a fixed rotor speed counterflow centrifugation elutration (CEE) procedure using the newly available Beckman high capacity JE-5.0 rotor system that reproducibly isolates up to 1.0-1.5 x 10(9) Mo with greater than 90% purity, in suspension and functionally intact derived from peripheral blood mononuclear cell-enriched suspensions obtained by leukapheresis (LP) from healthy volunteers and cancer patients. The semiclosed, easy to handle CCE system, was adapted to a sterile technique that permitted clinical trials in adoptive monocyte immunotherapy. Freshly isolated Mo did not lose morphological or functional integrity and had no spontaneous activation. Their abilities to become activated to the cytotoxic state after 18-h stimulation with 500 U/ml rIFN-gamma or 1 microgram/ml L-MTP-PE and to differentiate into matured M phi in vitro were not altered. The system was therefore used to isolate large numbers of Mo for a phase I clinical trial of intraperitoneal immunotherapy with L-MTP-PE activated autologous Mo in nine patients with peritoneal carcinomatosis. Each patient received weekly Mo infusions (n = 5) with an intrapatient dose escalation schedule (from 10(7) to 10(9) Mo). Toxicities were mild including fever, chills and abdominal pain. There was no treatment-induced thromboembolic event or capillary leak syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylmuramyl-Alanyl-Isoglutamine

A randomized study of on-line plasma perfusion over protein A-sepharose and 5-fluorouracil chemotherapy in patients with metastatic colorectal carcinoma.

To evaluate the safety of on-line plasma perfusion over protein-A sepharose and the therapeutic advantage of combining plasma perfusion (PP) over protein-A sepharose with 5-fluorouracil (5-FU) chemotherapy in patients with metastatic colorectal carcinoma (MCRC), thirty patients were randomized after surgery of primary CRC to receive a combination of 5-FU and PP over protein-A sepharose (group A), or a combination of 5-FU and PP over sepharose (group B), or 5-FU alone (group C). Bi-weekly on-line PP over 200 ml protein-A sepharose gel (group A) or 200 ml sepharose gel (group B) were performed with a Cobe 2997 blood cell separator for a maximum of 19 treatments per patient. 5-FU was given at 1000 mg/m2/d on days 1-5 of a 4-weekly cycle until progression. PP was well tolerated and no severe or life-threatening toxicity was observed. Mild clinical side-effects consisted of fever and chills (36% in group A, 23% in group B). The most common biological effects of PP over protein-A sepharose were significant drops in IgG (66% of pre-PP values), CH50 and C3 (73% of pre-PP values) and a significant generation of C3a and C5a anaphylatoxins. Tumor response rates were 40% for group A, 0% for group B and 20% for group C. The median survival times tended to be longer in group A (17 months) than in group B (10 months) and in group C (9 months). This is the first randomized trial showing some therapeutic advantage in combining PP over protein-A sepharose with conventional chemotherapy in MCRC.

Chromatography, Gel

A randomized study of combined 5-fluorouracil and plasma perfusion over protein A-sepharose in human advanced colorectal carcinoma.

To evaluate the advantage with regard to toxicity, response rate, time to progression and survival of combination chemoimmunotherapy over single-agent chemotherapy in patients with metastatic colorectal carcinoma (CRC), 30 patients were randomized to receive a combination of 5-fluorouracil (5-FU) by continuous i.v. infusion and plasma perfusion (PP) over protein A-Sepharose (group A), or a combination of 5-FU and PP over sepharose (group B) or 5-FU alone (group C). 5-FU was given at 1,000 mg/m2/d on days 1-5 of a 4-weekly cycle until progression. Patients of groups A and B received bi-weekly on-line PPs until disease progression or for a maximum of 19 treatments. PP was well tolerated and no severe or life-threatening toxicity was observed. The response rates were 10% for the group A (1 PR), 0% for the group B and 20% for the group C (1 CR + 1 PR). The times to tumor progression for patients in groups A and C were 22 months, 12 and 11 months, respectively and the median survival times were 17 months, 10 months and 9 months. Although the time to progression and survival tended to be higher in patients treated with protein A. PP, these differences were not statistically significant. This is the first report of a randomized trial showing some therapeutic advantage in combining protein A. PP with 5-FU in CRC patients. Further randomized studies are required to demonstrate the real true value of this chemoimmunotherapeutic approach.

Adult

Intravenous high-dose IgG therapy induced alterations of spleen lymphocyte IgM secretion and T cell subsets in patients with idiopathic thrombocytopenic purpura.

High-dose intravenous (IV) IgG therapy is an effective possible means of raising platelet counts in patients with idiopathic thrombocytopenic purpura (ITP). In order to elucidate further the mechanism of action of such treatment we comparatively studied spleen mononuclear cells (SMC) from two groups of ITP patients. Group I consisted of 9 patients who had not received any recent treatment before splenectomy. The 8 patients in group II had received IV IgG infusions 1-5 days before splenectomy. The SMC were cultured either unstimulated or stimulated by pokeweed-mitogen (PWM), and proliferation (as assessed by 3H-thymidine uptake), and IgG and IgM secretion were measured. In addition T lymphocyte subsets were determined in the SMC by indirect immunofluorescence using monoclonal antibodies (OKT3,4,8). By comparison with group I SMC, our results in group II SMC mainly showed a significant decrease in proliferation and IgM secretion, in both unstimulated and PWM stimulated cultures. In addition, a significant decrease in the proportion of T helper-inducer lymphocytes (OKT4+ cells) was also found in group II SMC, as compared to group I SMC. However, these immunological alterations in group II SMC were paradoxically more pronounced in those patients who failed to respond to IV IgG infusions. Thus, these results suggest that, although immune suppression takes place in the SMC of ITP patients following IV IgG therapy, it has not a pronounced effect on the increase of platelet.

Adolescent

Pharmacokinetic studies of standard heparin and low molecular weight heparin in patients with chronic renal failure.

The disappearance of the anticoagulant activities of a standard commercial heparin and of a low molecular weight (LMW) heparin (PK 10169), administered as single intravenous injections, was studied in patients with chronic renal failure. Heparin and LMW heparin anticoagulant activities were determined by activated partial thromboplastin time (APTT) and chromogenic assays of anti-Xa and anti-IIa activities. Following heparin injection, a fast initial decay of anticoagulant activities preceded a slow convex disappearance curve, in semilogarithmic plots. These experimental data are in agreement with a model based on a predominant saturable mechanism of elimination of heparin in patients with renal failure. The disappearance of LMW heparin anti-Xa activity was obviously different, with linear or concave elimination curves, and longer apparent half-life. Taken together, our kinetic data and those previously reported in normal subjects strongly suggest that the mechanism of elimination of the LMW heparin studied is not saturable (at least for the tested dosages), and that the kidneys play a minimal role in the elimination.

Adolescent

Intravenous plasmin-treated gammaglobulin therapy in idiopathic thrombocytopenic purpura. Results in 40 patients.

A study of the effects of high-dose IV plasmin-treated IgG was undertaken in 40 patients (30 children and 10 adults) with idiopathic thrombocytopenic purpura (ITP). After a first course of treatment, a success therapy (platelet counts greater than 100 X 10(9)/l) was observed in 21 patients. The results after additional courses of pH 4 treated IgG in 7 patients tended to indicate that the 2 kinds of concentrates might induce similar platelet responses. No significant side-effects were observed. Platelet associated (PA), IgG, IgM and C3 levels were determined before therapy and on the 7th day after the first infusion (day 8) in 27 patients (36 courses). In spite of great variability, overall results showed a significant decrease in PA IgG (P less than 0.05), PA IgM (P less than 0.01) and PA C3 (P less than 0.001) at day 8. A significant inverse relationship was found between either PA IgG, or PA IgM or PA C3 levels, and platelets counts (respectively, r = -0.57, -0.55, -0.66, P less than 0.001). Our results also showed that pretreatment platelet counts were higher in patients with success therapy (25.8 +/- 16.9 X 10(9)/l) than in others (11.3 +/- 12.1 X 10(9)/l, P less than 0.001). This suggested that pretreatment platelet counts could help predicting the platelet response.

Adolescent

[Severe postpartum hemorrhage].

The authors report 95 cases of post-partum haemorrhage estimated at one litre or more seen in the Department of Obstetrics between 1979 and 1982 for 11 662 deliveries. Classical treatment combining artificial delivery or uterine manual evacuation-oxytocics led to the arrest of bleeding in 73 cases. Severe haemorrhage persisted in 22 cases, including 13 patients who were found to be suffering from a coagulopathy. Treatment of these severe forms is based upon: local haemostasis (in the presence of inertia, prostaglandins must be used before surgery) and correction of the coagulation disorder by substitution therapy providing the missing factors.

Female

[Antiplatelet drugs (author's transl)].

Acetyl salicylic acid, sulfinpyrazone, dipyridamole, hydroxychloroquine, ticlopidine, clofibrate, nicergoline are the most used antiplatelet drugs. A. S. A. and sulfinpyrazone have been tested in several large scale clinical trials. A. S. A. seems beneficial in the prevention of cerebral ischemia for patients, specially men who have previously had a transient cerebral ischemic attack. Sulfinpyrazone appears to be effective in reducing cardiac deaths during the first year after myocardial infarction.

Aspirin

Antithrombin III deficiency in diabetes mellitus: influence on vascular degenerative complications.

Plasma Antithrombin III (At III), a natural inhibitor of coagulation, was determined using a single radial immunodiffusion technique. In 116 diabetics, plasma At III levels were significantly decreased (26.6 +/- 0.4 mg/100 ml) compared with those in 64 controls (31.0 +/- 0.3 mg/100 ml, P less than 0.001). An elevation of plasma fibrinogen degradation products in 42 per cent of our patients, and a positive linear relationship between platelet counts and At III levels ( r = 0.29, P less than 0.01), provided additional evidence for chronic disseminated intravascular clotting in diabetes mellitus. Diabetic retinal complications were more frequent in patient with low plasma At III levels (50.6 per cent of cases) than in those exhibiting At III concentrations within a normal range: 32.4 per cent of cases (X2 = 6.09, P less than 0.02). It is postulated that the low levels of At III encountered in diabetes result from excessive consumption, and that the deficiency may be responsible for the onset and/or aggravation of intravascular clotting. At III deficiency may therefore contribute to vascular degenerative complications, particularly those leading to diabetic retinopathy.

Adolescent

A multicenter study on the efficiency of white cell reduction by filtration of red cells.

To evaluate accurately the current performance of filtration, the French Produits Sanguins Labiles study group, composed of 21 transfusion teams, conducted a large-scale 6-month study involving over 1400 filtrations and 3000 controls. Some 745 standard red cell concentrates (RBC concentrates) and 690 concentrates previously white cell (WBC)-reduced by removal of buffy coat (BC-poor RBC concentrates) were filtered using six commercially available filters: at least 170 results were collected per filter, spread among a minimum of three teams. Prefiltration controls show that the removal (manual and automated) of the buffy coat results in an initial WBC reduction of approximately 63 percent, along with a hemoglobin loss of 4 g (7%). After filtration, residual WBCs were counted in the Nageotte manual counting chamber. The reliability of this counting method, which is simple and adapted to low WBC concentrations, was characterized in this study by a 25-percent coefficient of variation (CV) for a concentration of 2.5 WBCs per microL (i.e, 0.6 x 10(6) WBCs/filtered unit). The analysis of the results shows that, for five of six filters (1 filter was excluded), the postfiltration median value of residual WBCs was 1.1 x 10(6) in filtered RBC concentrates (n = 590), whereas it was 0.34 x 10(6) in filtered BC-poor RBC concentrates (n = 581). The difference is significant (p less than 10(-8), Wilcoxon test). Hemoglobin loss due to filtration varies according to the filter, from 5.7 +/- 2.2 to 17.3 +/- 2.5 g.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Component Removal