Photobiological properties of nabumetone (4-[6-methoxy-2-naphthalenyl]-2-butanone), a novel non-steroidal anti-inflammatory and analgesic agent.

The photolability of nabumetone (NB, 1, 4-[6-methoxy-2-naphthalenyl]-2-butanone) and its photobiological properties were studied under aerobic and anaerobic conditions using a variety of in vitro phototoxicity assays: photohemolysis, photoperoxidation of linoleic acid, and photosensitized degradation of histidine and thymine. The photodegradation rate of NB in methanol and phosphate buffered saline (PBS) was enhanced under oxygenated media. NB was phototoxic in vitro. The photohemolysis rate was enhanced by deuterium oxide and inhibited by the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO), butylated hydroxyanisole (BHA), sodium azide (NaN3) and reduced gluthathione (GSH). The induced photoperoxidation of linoleic acid was inhibited significantly by sodium azide and reduced gluthathione. Histidine and thymine were photodegraded by a photosensitized reaction induced by NB. A mechanism involving singlet oxygen, radicals and photoproducts is suggested for the observed photoxicity.

[Collection and freezing of blood stem cells in acute nonlymphoblastic leukemia]. / Collection et congélation des cellules souches sanguines au cours des leucémies aiguës non lymphoblastiques.

Blood-derived hemopoietic stem cells were collected using a continuous (10 patients) or a semi-continuous flow separator (2 patients) in some patients with acute non-lymphocytic leukemia. For ten out of those patients, five to seven leukaphereses were performed during a short period (median = 11 days) of marrow recovery following severe aplasia induced by an intensive chemotherapy. The mean number of CFU-GM cells collected per leukapheresis and per patient respectively was 6.7 X 10(4)/kg and 38.5 X 10(4)/kg. This latter number was similar to that obtained during a marrow harvest performed for a bone marrow transplantation, suggesting that high numbers of hemopoietic stem cells can be collected from the peripheral blood in leukemic patients and used for autologous transplantation.

Successful autologous transplantation with peripheral blood hemopoietic cells in a patient with acute leukemia.

One patient with acute nonlymphocytic leukemia (ANLL) in remission was given intensive chemotherapy (DAT regimen) as late intensification treatment. Seven leukaphereses were performed during the period of marrow recovery following aplasia induced by the DAT regimen. High numbers of nucleated cells (7.8 X 10(8)/kg) and granulocyte-macrophage precursors (9.5 X 10(4)/kg) were collected and then cryopreserved and stored in liquid nitrogen. When he relapsed, the patient was treated with etoposide (600 mg/m2), cyclophosphamide (120 mg/kg), and total body irradiation (1000 rad), followed by the transfusion of thawed autologous leukocytes. The time to reach 0.5 X 10(9) granulocytes/liter and 50 X 10(9) platelets/liter was 16 and 35 days, respectively. This observation demonstrates that circulating hemopoietic stem cells are capable of complete hemopoietic reconstitution after marrow-ablative therapy with supralethal doses of chemoradiotherapy.

Technical aspects of different donor plasmapheresis systems and biological results obtained in collected plasma.

Four plasmapheresis systems were comparatively studied: a centrifugation system (Haemonetics Model 50) and three filtration ones (Dideco BT 810, Organon Teknika PLASMAPUR and HemaScience Autopheresis Plasmacell). For each separator we studied the technical conditions for plasma separation, the biological characteristics of the collected plasma and the in vitro recovery of factor VIIc after preparation of cryoprecipitates. Concerning the plasma extraction rate, the HemaScience apparatus was the most efficient but values were quite similar to those obtained with the Organon Teknika machine. Contaminating cells were only found in plasma separated with the Haemonetics. Total protein and immunoglobulin levels were higher in plasma collected with the Haemonetics and HaemaScience systems. Factor VIIIc activity was comparable in plasma separated by filtration or by centrifugation while fibrinopeptide A levels were higher in plasma collected by Haemonetics. Whatever the machine, no statistical difference was observed when in vitro recovery of factor VIII was studied.

[Bilateral prosthesis of the knee in a hemophilia A patient with an inhibitor]. / Prothèse bilatérale de genou chez un hémophile A avec inhibiteur.

A forty-one year old severe haemophiliac A (factor VIII less than 1%) complicated by an antifactor VIII inhibitor was operated on for a bilateral arthroplasty of the knees. Substitutive treatment was started by giving anti-haemophilic A cryoprecipitate at a dose of 40 IU . kg-1. The anamnestic response occurred at day 6. Consumption of the inhibitor begun with the injection of 50,000 IU of concentrated factor VIII. This method proved to be insufficient for mastering the haemorrhagic syndrome, because the antibody titre quickly reached 10 IU Oxford. Treatment was continued with Autoplex (100 IU . kg-1), during three weeks, without any clinical or biological complications. It is suggested that Autoplex be used as the substitutive treatment in cases of major surgery in severe haemophilia complicated by a factor VIII inhibitor.

[Acute transformation of chronic myeloid leukemia: disappearance of the Philadelphia chromosome after autograft]. / Transformation aiguë de leucémie myéloïde chronique: disparition du chromosome Philadelphie après autogreffe.

Two patients with chronic granulocytic leukemia (C.G.L.) undergoing transformation were treated by high dose chemotherapy and total body irradiation followed by autografting of hematopoietic stem cells collected and cryo-preserved at the time of diagnosis. Recovery of hematopoiesis was characterized by disappearance of the Philadelphia chromosome in most metaphases. A new approach of the management of C.G.L. is discussed.

[Isolation from a pregnant woman of a serum protein responsible for inhibiting an in vitro cytotoxicity reaction]. / Isolement chez la femme enceinte d'une protéine sérique responsable de l'inhibition d'une réaction de cytotoxicité in vitro.

A non specific immunosupressive factor able to block an in vitro cytotoxicity reaction is demonstrated in the serum of pregnant women. A solution containing this blocking factor is obtained by gel filtration and precipitation of plasma by polyethylene glycol 4 000. Then after immunisation of rabbits the immune serum can be used for affinity chromatography. An alpha 2 glycoprotein has been separated which inhibits the in vitro cytotoxicity reaction and whose molecular weight determined by gel filtration and polyacrylamide gel is about 200 000 daltons.

[Comparison of platelets frozen with different cryoprotective agents]. / Etude comparative des plaquettes congelées avec différents cryoprotecteurs.

A comparative study was performed on platelets frozen with dimethyl-sulfoxide (D.M.S.O.), glycérol and dimethyl-acetamide (D.M.A.C.). The results of tests realized in vitro (platelet yields after thawing platelet aggregation, hypotonic stress, release of enzymes and ultrastructure), and in vivo (life span and recoveries after transfusion) have clearly shown that D.M.S.O. is the best cryoprotective agent. The results obtained with glycerol were less interesting and more clinical data are needed in order to study the hemostatic effectiveness of platelets preserved with this agent. Dimethyl-acetamide gave the worse results and in our opinion, must not be used for the cryopreservation of platelets.

[In vitro study of comparative immunosuppressive activity of sera from pregnant women on an in vitro cellular cytotoxic reaction]. / Etude in vitro de l'activité immunosuppressive comparée de sérums de Femmes enceintes sur une réaction de cytotoxicité cellulaire in vitro.

By means of an adaptation of a well-known in vitro cellular cytotoxic reaction we can demonstrate: 1. a strong immunosuppressive non-specific activity of sera from pregnant women; 2. a decrease or an absence of immunosuppressive activity of sera from pregnant women submitted to several spontaneous abortions; 3. we propose a reliable and simple test allowing us to predict the outcome of abortions.

[Value of a technical modification for the detection of syphilis on Technicon BT 15. Study on 10.076 samples tested with 2 "VDRL-carbon" antigens]. / Intérêt d'une modification technique apportée au dépistage de la lyphilis sur Technicon BT 15. Essair sur 10.076 échantillons testés avec deux antigènes de type "VDRL-Chabon".

Previously described Manifold for routine detection of Syphilis using charcoal particles with Auto-Analyzer did not appear satisfactory to the authors. A modified Manifold is described which includes a longer time of incubation and decantation, without any saline addition. Two charcoal antigen suspensions (K-Ag, ART) were tested on 10.076 samples from blood donors, comparatively with 13.614 samples tested through manual Kline and VDRL methods: no significative difference was noted in detection of Syphilis. Differences between both antigen suspensions (ART antigen gives more positive resultats than K-Ag) can be attributed to "false positive" reactions.

[Rapid and simultaneous screening and quantitation of antitetanus and anti-HBs antibodies using Laurell's method]. / Titrages et dépistages rapides simultanés des anticorps anti-tétaniques et anti-HBs par la technique de Laurell.

Every transfusion Center which must hunt out anti-tetanus and anti-HBs antibodies to obtain specific corresponding immunoglobulins, is submitted to rapidity, precision and low cost necessity. In order to satisfy these obligations, the authors describe a simple and rapid method, allowing use of the same serum, through a single stage, and simultaneously, screening and quantitation of anti-tetanus antibodies (according to Laurells' method) and of fractionation suitable anti-HBs antibodies (through electro immunodiffusion). Technical conditions exposed in this paper allow direct quantitation of anti-tetanus antibodies from 1 to 30-40 IU; dilutions can be made for upper titers. False negative reactions due to zone effect, as observed in EID and passive haemagglutination do not occur while using this method. Its routine use contributes to the increase of the percentage of fractionation suitable plasmas, without overloading the screening laboratory's tash.

[Alpha-1 antitrypsin and idiopathic respiratory distress of the newborn infant. Study in serum and lungs]. / Alpha-1 antitrypsine et detresse respiratoire idiopathique du nouveau-ne. Etude dans le serum et dans les poumons

Serum level of alpha-1-antitrypsin is significantly reduced in newborns with idiopathic respiratory distress when compared to matched controls. This decrease was predominantly due to the group of infants who died from I.R.D., provided that alpha-1-antitrypsin determination was carried out on the first day of life. Alpha-1-antitrypsin was demonstrable by indirect immunofluorescence in hyaline membranes whereas fluorescence was negative in the alveolae of infants who had no hyaline membranes.

[Cytogenetic study of 30 couples having had several spontaneous abortions]. / Etude cytogénétique de 30 couples ayant présenté plusieurs avortements spontanés

In 30 couples consulting after two or more failed pregnancies, the authors detected two women with reciprocal translocation in the heterozygous condition: t (5 ; 6) (q 35 ; q 21) in one case. t (5 ; 10) (q 15 ; q 25) in the other case. In both cases, there was, later, birth of a normal boy of karyotype 46, XY. It thus appears obvious that the balanced structural changes which occur in the fertility of these couples, reduces the latter.