Regulation of MAC-1 (CD11b/CD18) expression on circulating granulocytes in endurance runners

PURPOSE: We tested the hypothesis that degranulation of granulocytes and upregulation of the granulocyte integrin MA-1 (CD11b/CD18) are related to exercise duration and/or intensity. We also investigated whether or not the expression of MAC-1 would be influenced by body temperature or dehydration. Moreover, we tested the hypothesis that changes in leukocyte counts and changes in MAC1 expression with endurance exercise are independently regulated. METHODS: In eight amateur runners, MAC-1 (CD11b/CD18) surface expression on granulocytes was determined by fluorescent antibody cell sorting, before and after an incremental maximal treadmill test, a moderate 3-h run, and a competitive marathon race. RESULTS: Expression CD11b on granulocytes was increased by 10+/-9.6% (P < 0.05) after the maximal treadmill test and by 84+/-76% (P < 0.01) after the marathon run. There was no change in CD11b expression after the moderate 3-h run. CD18 expression was not significantly changed after any of the exercise protocols. CONCLUSION: Expression of CD11b on granulocytes is increased with intense endurance exercise, either incremental maximal treadmill testing or competitive marathon running, but not in moderate endurance training. Thus, exhaustive exercise may be one mechanism for the upregulation of integrin adhesive receptors on granulocytes. This phenomenon could be in part responsible for increased adhesion of granulocytes to endothelial cells and could facilitate tissue infiltration after endurance exercise.     

Exceptional performance in heart preservation with an amino acid—Containing perfusion fluid

This is a report of a study aimed at putting into practice a new theory for hypothermic preservation of viable organs. A perfusion fluid elaborated according to this theory was applied in preservation of the heart, and resulted in storage of the heart for up to 72 hours with preservation of its functions (rhythm, presystolic ventricular pressure, systolic ventricular pressure, cardiac work, coronary blood pressure, sensitivity to drugs) and its morphology. An important finding was that repeated heart storage for 24 hours alternating with functional testing for 5–7 hours could be performed without irreversible alterations of cardiac function and fine structure. Furthermore, during functional testing following storage the hearts consistently demonstrated improvement of function in time, suggesting that the preserved myocardial tissues were able to rapidly achieve metabolic reequilibration. The results of this study provide the possibility of developing a system for efficient ex vivo heart conditioning before transplantation.

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Résumé Nous avons testé la valeur d'une nouvelle théorie sur la préservation d'organes en hypothermie. Un liquide de perfusion conforme à cette théorie a été utilisé pour la préservation cardiaque. Il permet de conserver le coeur pendant 72 heures, sans altérations de ses fonctions (rythme, pression ventriculaire pré-systolique et systolique, travail cardiaque, pression coronaire, sensibilité aux médicaments) ni de sa morphologie. De plus, le coeur peut-être, à plusieurs reprises, conservé pendant 24 heures, avec des intervalles de reprise fonctionnelle de 5–7 heures, sans que sa fonction ni sa structure fine ne soient altérées de façon irréversible. Enfin, l'étude fonctionnelle montre qu'après conservation la fonction cardiaque s'améliore avec le temps, suggérant donc une rééquilibration métabolique rapide du tissu myocardique. Les résultats de cette étude permettront la mise au point d'un système efficace de conservation cardiaque ex-vivo en vue de la transplantation.

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Supported by the German Heart Center, Munich, and the German Academy Department for Foreign Scientific Relationships, Bonn.     

Prevention and treatment of thromboembolic and ischemic complications associated with endovascular procedures: Part II--Clinical aspects and recommendations

We reviewed the incidence, risk factors, and clinical features of thromboembolic and ischemic events associated with diagnostic cerebral angiography, endovascular treatment of aneurysms using coils or balloons, angioplasty and stent placement to treat extracranial carotid artery stenosis, and embolization of arteriovenous malformations using glue or other embolic agents. We performed a cumulative analysis to determine the frequency and characteristics of these events and a subset analysis (whenever possible) to determine the benefits of various strategies for complication avoidance. Of the 1,547 patients who underwent Guglielmi detachable coil treatment, thromboembolic events were observed for 127 (8.2%), consisting of asymptomatic events for 12 patients, transient ischemic attacks for 29, and strokes for 86. The outcomes for the 86 patients with strokes were categorized as full recovery for 15, good recovery for 27, partial recovery for 19, no recovery for 11, death for 12, and undetermined outcome for 2. Of the 834 patients who underwent carotid angioplasty and stent placement, thromboembolic events were observed for 73 (8.8%), consisting of transient ischemic attacks for 26 patients and strokes for 47. The outcomes for the patients with strokes were categorized as full recovery for 20, good recovery for 15, partial recovery for 6, no recovery for 2, and death for 4. High rates of thromboembolic events were also observed with balloon occlusion of aneurysms (11%) or parent arteries (19%) and carotid angioplasty alone (5.9%). Arteriovenous malformation embolization was associated with an ischemic event/procedure rate of 9.4%. High rates of thromboembolic and ischemic complications, with subsequent morbidity and death, are associated with most endovascular procedures. Further research and the formulation of standard preventive guidelines may help to reduce these risks and improve the overall success of these procedures.     

Ischemia-reperfusion injury in renal transplantation is independent of the immunologic background

BACKGROUND: Adhesion molecule expression is important to early transplant failure. However, whether or not adhesion molecule-facilitated inflammation is antigen-dependent is unknown. We tested this hypothesis. METHODS: Rat renal grafts were four-hours cold-preserved in University of Wisconsin (UW) solution, transplanted to syngeneic or allogeneic recipients, and harvested after 2, 6, 12, 24, and 48 hours and after 1 week. The first allogeneic group receive no immunosuppression; two additional groups received either low (1.5 mg/kg) or standard (5 mg/kg) cyclosporine A (CsA). Renal function and morphology were determined; frozen sections were immunostained for P-selectin, L-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1), leukocyte function associated molecule-1 (LFA-1), very late antigen-4 (VLA-4), as well as for neutrophils and monocytes. RESULTS: Selectins increased rapidly at 2 hours and quickly decreased by 12 hours. While P-selectin was expressed on vasculature, L-selectin was found on inflammatory cells. Neutrophil influx and that of LFA-1-positive cells occurred early, peaked between 12 and 24 hours, and paralleled the maximal impairment in renal function. ICAM-1 and PECAM-1 showed similar kinetics and a diffuse distribution. VCAM-1 increased more slowly after 12 hours, peaked at 24 hours, and was localized predominantly on the endothelium of elastic vessels. Between 24 hours and 1 week, all grafts progressively developed dense VLA-4-positive monocytic infiltrates adjacent to vessels expressing VCAM-1. Functional, morphological, and immunohistochemical parameters did not differ between isografts and allografts at one week. However, by day 10, allografts showed severe vascular and cellular rejection, while injury in isografts resolved. Immunosuppression with CsA did not reverse the inflammation induced by ischemia-reperfusion injury. CONCLUSIONS: The early inflammation after ischemia-reperfusion injury is largely independent of the immunologic background. We suggest that initial injury prevention should receive the highest priority.     

Turkish pepper (extra hot)

A 38 year old female office worker was admitted with a newly discovered blood pressure of 250/110 mm Hg. Evaluation for secondary forms of hypertension was negative and treatment was begun. Sodium excretion was markedly reduced, plasma aldosterone was normal, and plasma renin activity was low. Therefore, presence of an aldosterone-like activity was suspected. Eventually, the patient confessed to abusing "Turkish Pepper", a brand of Scandinavian liquorice candies and "Fisherman's Friend", another brand of liquorice candies, concurrently. After eliminating liquorice from her diet, the hypertension disappeared thus allowing her antihypertensive treatment to be stopped.     

Molecular monitoring of tumour load kinetics predicts disease progression after non-myeloablative allogeneic stem cell transplantation in multiple myeloma.

BACKGROUND: Non-myeloablative allogeneic stem cell transplantation followed by immunomodulatory therapies is considered a potentially curative approach in the treatment of multiple myeloma and most effective in a minimal residual disease setting. PATIENTS AND METHODS: The aim of this study was to find the most sensitive real-time PCR assay (TaqMan), based on the IGH rearrangement, to quantify the tumour load of 11 patients with multiple myeloma after non-myeloablative allogeneic transplantation. Patient-allele specific primers (ASO) and the TaqMan probe were derived from CDR2 and CDR3 hypervariable regions of IGH, while consensus primers were located within the FR3 and FR4/JH regions. Four different approaches of primer combinations were tested. RESULTS: ASO-forward and -reverse primers together with the clone-specific TaqMan probe were the most sensitive approach compared with the JH (P=0.071) or the FR3 consensus primer (P <0.001). The detection limit amounted to 1/10(4)-1/10(5) cells. Consecutively, 120 samples from 11 patients prior and post allogeneic transplantation were analysed. Three patients reached complete clinical remission accompanied by molecular remission. Disease progression or relapse was seen in six patients. In five, molecular progressive disease was detected prior to the clinical diagnosis of progression or relapse. CONCLUSION: Patient-specific real-time IGH-PCR provides the opportunity for earlier treatment intervention.