[Lung metastases of pancreatic adenocarcinoma: Watch for the second train!] / Adénocarcinome pancréatique métastatique aux poumons : un train peut en cacher un autre !

Pulmonary metastases due to a pancreatic cancer are difficult to diagnose and demonstrate a wide range of radiological patterns. We report the case of a 37-year-old female patient, without past medical history, with multicystic lung disease in a context of chronic abdominal pain, fatigue and weight loss. After several months of diagnostic delay, pathological examination of surgical lung biopsies led to the diagnosis of secondary deposits of pancreatic cancer. The clinical and radiogical situation deteriorated quickly with the development of alveolar consolidation and Aspergillus superinfection was then diagnosed. This case illustrates the value of an early decision to undertake surgical lung biopsy in the work-up of multicystic lung disease when cancer is suspected. In addition, in the specific context of cancer, faced with clinical and/or radiological deterioration, it is essential to look for infection, particularly aspergillosis.

Large scale detection of IgA deficient blood donors.

An automated technique using passive haemagglutination inhibition was developed on Groupamatic equipment for the screening of IgA deficient blood donors. Positive controls were also assayed by a manual haemagglutination inhibition test and solid-phase radioimmunoassay. Fourty-two blood donors totally deficient in IgA were detected in the systematic screening of 108,000 blood samples. Thirty-three were partially deficient and 2 other blood donors had an associated anti-IgA class-specific antibody. These donors now belong to a national panel of IgA deficient blood donors and their blood is used for the preparation of various IgA deficient blood components.

Physiological effects of high-P50 erythrocyte transfusion on piglets.

Rightward shifts of the O2 dissociation curve (ODC) were experimentally obtained in lysed and resealed erythrocytes following encapsulation of inositol hexaphosphate (IHP). This continuous lysing and resealing procedure led to in vitro P50 (Po2 at 50% hemoglobin saturation) increases up to 80 Torr (pH, 7.40; Pco2, 40 Torr; temp, 37 degrees C) for both human and pig erythrocytes. The Hill number of the transformed blood decreased when IHP was fixed on the hemoglobin, but the sigmoid shape of the ODC was maintained. The O2 hemoglobin binding capacity and the mean corpuscular hemoglobin content were found unchanged by the experimental procedure in human and pig erythrocytes. Isovolumic exchange transfusion of high-P50 erythrocytes in anesthetized and ambient air-ventilated piglets (n = 6) led to substantial in vivo P50 increases (range, 8-19 Torr). The rightward shift of the ODC was concomitant with an increase of the arterial Po2 and of the arteriovenous O2 content difference, 19 and 59% respectively above their control values. The mixed-venous Po2 (PVO2) remained unchanged. The cardiac output was shown to be inversely related to the P50 value. In spite of the O2-transport reduction (37%), O2 consumption was maintained due to enhanced O2 extraction.

Erythrocytes as carriers for L-asparaginase. Methodological and mouse in-vivo studies.

L-Asparaginase has been encapsulated in Swiss mouse or human erythrocytes by hypotonic haemolysis followed by isotonic resealing and reannealing. The details of incorporation and properties of carrier erythrocytes are presented. When L-asparaginase loaded into 51Cr-labelled erythrocytes, was infused intravenously, the same half-life was found for asparaginase and 51Cr. In addition, L-asparaginase loaded into erythrocytes was much more effective in eliminating plasma asparagine compared with the same dose of free L-asparaginase injected in solution, during a sustained period (14 days).

Erythrocytes as carriers of new anti-opioid prodrugs: in vitro studies.

In using a reversed hypoosmotic lysis and resealing process, internalization of Naloxone or Naltrexone prodrugs as new opioid antagonists into red blood cells (RBC) can be obtained. We describe the entrapment method and haematological parameters of such RBC carriers. Percentages of internalization range between 35% and 70%, depending on the prodrug. The stability of the different prodrugs within RBC, after in vitro internalization have been compared at 4 degrees C and 37 degrees C. These studies were performed in order to screen and choose the most interesting prodrugs for in vivo studies. Some prodrugs tested appeared to be stable after 24 hours of incubation, but others were not. The intracellular ATP and 2,3 BPG concentrations of RBC carriers were similar to the control.

Engineered erythrocytes: influence of P50 rightward shift and oxemia on oxygen transport to tissues.

The red blood cell (RBC) membrane may be reversibly opened using a lysis-resealing continuous flow method. The technology was adapted to the internalisation of an allosteric effector of haemoglobin, Inositol-Hexaphosphate (IHP). This molecule, occupying the allosteric site of 2,3 Bis-Phosphoglycerate with a very large affinity, induces a rightward shift of the oxyhaemoglobin dissociation curve (ODC). From ODC parameters in human volunteers, the potential effect of P50 (oxygen pressure at 50% haemoglobin saturation) on oxygen exchangeable fraction (OEF%), for various oxygen partial pressures (oxemia) was evaluated. For hyperoxic or normoxic arterial oxygen pressure (paO2), rightward shift greatly improved OEF%. In optimised conditions, engineered erythrocytes were potentially able to deliver two to three times more oxygen than normal cells. For patients with decreased paO2, as observed in chronic obstructive pulmonary deficiency (COPD), the reduction in arterial oxygen saturation (saO2%) reduces the benefit of the treatment for paO2 values between 60 and 80 mmHg. Below 60 mmHg, the saO2% reduction cannot be compensated by a corresponding reduction in svO2%, particularly for organs with physiologically low svO2%. In these organs, deleterious effects could be observed for a very large rightward shift of the ODC. Such engineered cells have unique properties for oxygen transport improvement and may be used for the treatment of patients suffering from diseases associated with hypoxia and ischemia.

Enhanced O2 transportation during cardiopulmonary bypass in piglets by the use of inositol hexaphosphate loaded red blood cells.

A continuous lysing and resealing of erythrocytes permitted internalization of inositol hexaphosphate (IHP), a strong allosteric effector of Hb, leading to significant rightward shifts of the HbO2 dissociation curve. Twelve piglets were put on cardiopulmonary bypass (CPB) with the heart beating, cooled to 25 degrees C then rewarmed to 37 degrees C before weaning off CPB. AoP, LV pressure, PAP, and cardiac output (CO) were monitored. Blood samples were taken before CPB, at 25 degrees C, at 30 degrees C, at 37 degrees C and after CPB for assessment of blood gases, arterio-venous difference in O2 content, lactates, P50 (partial pressure of O2 at 50% Hb saturation), and ionogram. Control group I included five pigs where the CPB circuit was primed with Ringer's lactate solution and porcine blood. In group II (n = 5), priming was done with Ringer's lactate solution and IHP loaded erythrocytes. P50 was significantly higher during CPB than before surgery in group II (20%), but not in group I (1%). There was a significant increase in VO2 in group II (6.02 ml/min) compared to group I (4.03 ml/min) (p less than 0.05) after CPB. Hemodynamics improved after CPB in group II (mean AoP 42 mmHg and syst LVP 70 mmHg) compared to group I (AoP 25 mmHg and syst LVP 22.5 mmHg). These preliminary results show that O2 transportation at the end of CPB is enhanced and myocardial function is improved in piglets with the use of IHP erythrocytes.

[Acquired B antigen]. / L'antigène B acquis

Many cases of acquired B antigens, always observed in group A subjects have been so far reported. Most of them were found in patients with digestive tract disease, essentially colonic cancer. An investigation on 200 patients in a gastroenterology department showed that this B-like antigen was quite frequent (10,6%); it occurred only in A1 individuals and was related to infectious syndrome. Immunological and serological studies of many cases had shown that this B-like antigen differs from that of normal B cells. Groupe A1 cells transfused to patients acquired B activity; on the contrary group A2 and O cells remained unchanged. Likewise, only A1 cell became active when incubated in vitro with C. Tertium A., known to contain a deacetylase. In 1970, we postulated that a deacetylase enzyme could be responsible for this B-like antigen: this enzyme could transform the N-acetylgalactosamine (A specific sugar) into galactosamine, which could cross react with anti-B sera. The relationship between the acquired B antigen and a deacetylase was recently confirmed: A1 acquired B cells, chemically acetylated lost their B reactivity and enhanced their A1 activity. A polyagglutinability, different from that associated with T, Tn, Cad, Hempas has been always found in acquired B cells; nervertheless, because of its weakness, it could sometimes be unnoticed. Besides, it disappeared prior to B reactivity in case of recovery. Like acquired B activity, it decreased in low pH medium of after acetylation of the cells. Nevertheless, this polyagglutinability appears, contrarly to acquired B antigen, in vitro, on all the cells, irrespective of their ABO phenotypes. A deacetylation of N-acetyl-neruaminic acid could explain such a phenomenon.

Effects of proteolytic enzymes and neuraminidase on the I and i erythrocyte antigen sites. Quantitative and thermodynamic studies.

The effects of neuraminidase and proteolytic enzymes on I and i reactivities was studied with I and i adult red cells, using radioimmunological methods. An enhanced reactivity after enzyme treatment is not exclusively due to a membrane charge reduction. The increase in site numbers and association constants bring about the gain of the cold agglutinin fixation. The release of N-acetylneuraminic acid residues gradually increases the I antigen site density of I red cells and the i site density of i red cells. Similar behaviour was observed after proteolytic enzyme treatment with papain, bromelin or ficin. The proteolytic treatment of I erythrocyte reveals underlying i receptors on these cells. Following membrane glycoprotein chain removal, anti-i antibodies are specifically fixed on I erythrocytes. The accessibility to antibodies of the determinants responsible for I and i erythrocyte activities was influenced significantly by steric hindrance factors. While N-acetylneuraminic acid release increased antibody affinities for the antigenic receptor, the removal of glycopeptide chains greatly diminished steric hindrance and brought about higher affinity constants. After enzyme treatment, the antigenic structures become more homogeneous in their reaction with antibodies. The heterogeneity of binding constants observed with antigenic determinants of non-treated erythrocytes is probably due to the wide range of spatial distribution of these receptors within the membrane.

Quantitative and thermodynamic measurements on I and i antigens of human red blood cells.

Different homogeneous IgM cold agglutinins (two anti-I, two anti-i and one anti-Il cross-reacting antibodies) have been used to determine the antigen site densities of adult I and i erythrocytes and of cord red cells. The equilibirium constants and the thermodynamic constants of these reactions have been determined. The two anti-I antibodies, which did not combine with i or cord red blood cells, recognized two different determinants on I red cells. The antigen density of the I Fla. receptor was 120,000 sites per erythrocyte and the standard enthalpy change (-deltaH degrees) of the reaction was 18 to 25 kcal/mole. The antigen density of the I Loi. determinant varied according to the red cells tested and the enthalpy change (-deltaH degrees) of these reactions was 50-65 kcal/mole. The i and cord erythrocytes reactive structures were more heterogeneous than those present on I erythrocytes. The equilibrium constants rapidly decreased as the temperature rose and the standard enthalpy changes (-deltaH degrees) ranged from 50 to 90 kcal/mole. Two types of i determinants were observed; one of the anti-i antibodies reacted mainly with an i component present on cord erythrocytes, the other antibody reacted with a different i component present on i adult red-cells. The determinants, recognized by the cross -reacting antibody on I red cells, differed fromthose on i or cord red cells in equilibrium constant, thermodynamic constants, index of heterogeneity of the reaction and in their sensitivity to formalin treatment.