On the Allocation of Cardiac Allografts from Blood Group-O Donors

An organ allocation policy, in which hearts from blood group-O donors are used to transplant recipients with other blood groups (ABO-compatible, non-identical transplantations), may affect blood group-O patients on the waiting list. We investigated how blood group affiliation influences potential recipients on the waiting list. In the case of patients with blood group O, fewer patients were transplanted, waiting list mortality was higher and waiting time to transplantation was longer. Patients with blood group O awaiting cardiac transplantation are affected considerably by an organ allocation policy in which ABO-compatible, non-identical transplantations are performed.     

OP-1 for cervical spine fusion: Bridging bone in only 1 of 4 rheumatoid patients but prednisolone did not inhibit bone induction in rats

We used OP-1 (also called BMP-7) on a collagen type-1 carrier in atianto-axial posterior fusions to promote bony healing after wire fixation. 4 patients who had instability between the atlas and axis due to rheumatoid disease received the implants. The patients were examined with conventional radiography postoperatively at 2, 6 and 10 months. In 3 patients, no new bone formation was detectable. In 1 patient, new bone bridged the fusion site at 6 months. 3 patients were on chronic steroid treatment, including the patient in whom bone formation was detected. To determine whether steroid treatment could be responsible for the low rate of bone induction, 24 rats each received OP-1 implants in an abdominal muscle pouch. They were divided into 3 groups receiving saline, 0.1 or 1.0 mg/kg BW of prednisolone daily until they were killed 3 weeks postoperatively. Specimens were decalcified for histology and the amount of calcium in the decalcifying solution was measured. All groups showed ossicles induced by OP-1, and no effect of prednisolone was detected. Thus the failures in the patients may have causes other than prednisolone treatment.     

The prevention of arterial collaterals after repeated temporary blockade of the hepatic artery in pigs

Hepatic dearterialization and permanent hepatic artery ligation can induce tumor necrosis but only of limited duration, partly due to a rapid development of arterial collaterals. The aim of this study was to determine if collateral formation could be reduced or prevented by repeated, transient dearterialization.Three groups of pigs were repeatedly and transiently dearterialized daily for 2 hours (n=5), 4 hours (n=5), and 6 hours (n=4), respectively, over a 4-week-period by means of a totally implantable vascular occluder described earlier by us. These pigs were compared with a group having permanent hepatic dearterialization (n=4). An additional group (n=3) served as a control and did not have dearterialization. After 4 weeks of treatment, hepatic angiograms were taken and absolute hepatic arterial blood flow was measured according to the reference sample method with radiolabeled microspheres. There were no demonstrable collaterals in the 2-hour group, formation of some small collaterals in the 4-hour group, and a fully developed collateral network in the 6-hour group, with similar findings in the permanently dearterialized group. Absolute hepatic arterial blood flow was significantly lower in the 4-hour group with obstructed hepatic artery compared to permanent hepatic dearterialization (p<0.01, Wilcoxon rank sum test) and highly significantly lower in the 2-hour group (p<0.0001, Wilcoxon rank sum test). Thus, repeated and brief dearterialization seems to prevent the formation of arterial collaterals and makes repeated arterial ischemia of the liver possible which could be of value in the treatment of liver tumors. In addition, a patent artery makes continuous intra-arterial cytostatic infusion possible.

---

Resumen La desarterialización hepática y ligadura permanente de la arteria hepática puede inducir necrosis tumoral, pero sólo de duración limitada, en parte debido al rápido desarrollo de colaterales arteriales. El propósito de este estudio fue determinar si la formación de colaterales puede ser reducida o evitada mediante desarterializaciones repetidas y transitorias.Tres grupos de cerdos fueron sometidos a desarterialización repetida y transitoria por periodos de 2 horas (n=5), 4 horas (n =5), y 6 horas (n=4), respectivamente, en un periodo de 4 semanas, por medio de un método de oclusión vascular previamente descrito por nosotros. Estos cerdos fueron comparados con un grupo que había sido sometido a desarterialización hepática permanente (n=4). Un grupo adicional (n=3), no sometido a desarterialización, sirvió como control. Después de 4 semanas de tratamiento se tomaron angiogramas hepáticos y el flujo arterial hepático absoluto fue medido por medio del método de microesferas radiomarcadas. No se encontraron colaterales demostrables en el grupo de 2 horas, se observó la formación de algunas colaterales pequeñas en el grupo de 4 horas, y se observó el desarrollo de una bien formada red de colaterales en el grupo de 6 horas, con hallazgos similares en el grupo de desarterialización permanente. El flujo arterial hepático absoluto apareció significativamente menor en el grupo de 4 horas con la arteria hepática obstruída en comparación con los animales con desarterialización hepática permanente (p<0.01, prueba de adición del rango de Wilcoxon) y significativamente menor en el grupo de 2 horas (p< 0.0001).Por consiguiente, la desarterialización breve y repetida parece evitar la formación de colaterales arteriales y hace posible realizar la isquemia arterial repetida del hígado, lo cual puede ser útil en el tratamiento de los tumores del hígado. Además la presencia de una arteria hepática permeable permite la infusión intraarterial continua de agentes citostásicos.

---

Résumé La désartérialisation hépatique ou la ligature permanente de l'artère hépatique peut provoquer des phénomènes de nécrose mais leur durée est limitée en raison du développement rapide d'une circulation artérielle collatérale. Le but de cette étude est de déterminer si la formation du réseau collatéral peut être réduite ou empêchée par désartérialisations intermittentes répétées.Trois groupes de cochons ont été respectivement soumis quotidiennement à cette méthode pendant 2 heures (n=5), 4 heures (n=5), et 6 heures (n=4) pendant une période de plus de 4 semaines à l'aide de l'appareil occlusif implantable décrit antérieurement par les auteurs. Ces animaux ont été comparés à un groupe de cochons (n=4) soumis à une désartérialisation hépatique permanente. Enfin un dernier groupe (n=3) d'animaux qui n'ont pas subi de désartérialisation a constitué un groupe de contrôle. Après 4 semaines des angiogrammes hépatiques ont été pratiqués et le flux sanguin artérial hépatique global a été mesuré à l'aide de microsphères radio marquées. Les constatations furent les suivantes: absence de collatérales dans le premier groupe, formation de quelques collatérales dans le second, réseau complet de collatérales dans le troisième identique à celui observé chez les animaux soumis à une désartérialisation permanente. Le flux artériel hépatique fut significativement plus bas dans le second groupe (4 heures) par rapport au groupe soumis à une désartérialisation permanente (p<0.01, test de Wilcoxon) et encore plus bas dans le premier groupe (p<0.0001, test de Wilcoxon).En conséquence il semble que la désartérialisation brève et répétée empêche la formation de collatérales artérielles en provoquant une ischémie artérielle répétée susceptible d'exercer une action utile dans le traitement des tumeurs du foie. En outre la préservation de la perméabilité artérielle permet l'injection continue intra-artérielle d'agents cytostatiques.

     

Glucose utilisation in the lungs of septic rats

Sequestration and degranulation of leucocytes in the pulmonary microcirculation is considered to be a key event in the development of acute respiratory distress syndrome in patients with sepsis. Glucose serves as the main source of energy in activated leucocytes. The aim of this study was to assess whether glucose utilisation in the lungs can be used as an indicator of pulmonary leucocyte accumulation in an experimental model of sepsis of intra-abdominal origin. Sepsis was induced in rats by abdominal implantation of a gelatine capsule containing bacteria and rat colonic contents. Empty gelatine capsules were implanted in control animals. Animals were studied 6 and 12 h after sepsis induction. Glucose utilisation was measured as the tissue uptake of fluorine-18-fluorodeoxyglucose (¹⁸FDG) 1 h after intravenous injection of the tracer. Micro-autoradiography was also performed after injection of tritiated deoxyglucose. We found increased uptake of ¹⁸FDG in the lungs of septic animals. The uptake also increased with time after sepsis induction. ¹⁸FDG uptake in circulating leucocytes was increased in septic animals compared with controls, and micro-autoradiography showed intense accumulation of deoxyglucose in leucocytes in the lungs of septic animals. We conclude that glucose utilisation is increased in the lungs of septic rats. Measurements of pulmonary glucose utilisation as an index of leucocyte metabolic activity may open new possibilities for studies of the pathophysiology of sepsis and for evaluation of therapeutic interventions. Received 15 February and in revised form 28 April 1999     

High-dose therapy and peripheral blood progenitor cell transplantation: effects of recombinant human granulocyte-macrophage colony-stimulating factor on the autograft

Between June 1989 and June 1992, 144 patients participated in sequential clinical trials using peripheral blood progenitor cells (PBC) as their sole source of hematopoietic rescue following high-dose chemotherapy. All patients had received prior extensive combination chemotherapy and had marrow defects that precluded autologous bone marrow transplantation (ABMT). PBC were collected according to a single apheresis protocol. The initial 86 patients (group 1) had PBC collected without mobilization. Beginning in April 1991, PBC were mobilized solely with recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). Thirty-four patients (group 2) received rHuGM-CSF at a dose of 125 micrograms/m2/d by continuous intravenous infusion, and 24 patients (group 3) received rHuGM-CSF at a dose of 250 micrograms/m2/d by continuous intravenous infusion. Patients underwent at least six aphereses and had a minimum of 6.5 x 10(8) mononuclear cells (MNC)/kg collected. Cytokines were not routinely administered immediately after transplantation. A median of nine aphereses were required to collect PBC in group 1 and seven aphereses for groups 2 and 3 (P = .03). The time required to recover 0.5 x 10(9)/L granulocytes after transplant was significantly shorter (P = .0004) for the mobilized groups; the median time to recovery was 26 days for group 1, 23 days for group 2, and 18 days for group 3. Transplantation of PBC mobilized with rHuGM-CSF resulted in a shorter time to platelet (P = .04) and red blood cell (P = .01) transfusion independence. Mobilization with rHuGM-CSF alone resulted in efficient collection of PBC, that provided rapid and sustained restoration of hematopoietic function following high-dose chemotherapy. Mobilization of PBC with rHuGM-CSF alone is an effective method for patients who have received prior chemotherapy and have bone marrow abnormalities.