Complement component C5a predicts restenosis after superficial femoral artery balloon angioplasty.

PURPOSE: To investigate whether balloon angioplasty of the superficial femoral artery (SFA) increases serum levels of C5a and whether C5a predicts risk of restenosis. METHODS: C5a antigen was measured at baseline and 8 hours after intervention in 131 consecutive patients (76 women; median age 72 years) with intermittent claudication who underwent successful primary SFA balloon angioplasty. Patients were followed for a median 10 months [interquartile range (IQR) 6 to 14] for the occurrence of >50% restenosis by duplex ultrasound. RESULTS: Median C5a levels increased significantly from 39.7 ng/mL (IQR 27.8 to 55.0) at baseline to 53.8 ng/mL (IQR 35.6 to 85.1, p<0.001) 8 hours post intervention. During the follow-up period, 70 (53%) patients developed restenosis. Increasing levels of C5a (quartiles) at baseline were significantly associated with an increased risk for restenosis (p=0.0092). Adjusted hazard ratios (95% confidence intervals) for restenosis with increasing quartiles of baseline serum C5a levels were 1.24 (0.60 to 2.58), 1.93 (0.95 to 3.93), and 2.08 (1.02 to 4.21), respectively, compared to the lowest quartile. This effect was independent of nonspecific inflammation as reflected by plasma levels of C-reactive protein. CONCLUSION: Inflammatory mechanisms play a major role in the development of restenosis after angioplasty. The complement component C5a exerts strong chemotactic and proinflammatory effects. Enhanced complement activation prior to PTA, as measured by higher levels of C5a, was significantly associated with restenosis after SFA balloon angioplasty. Pathways of complement inhibition thus may be worth investigating with respect to improving patency rates.     

In vitro effects of detergent sclerosants on coagulation, platelets and microparticles.

OBJECTIVES: To investigate the in vitro effects of Sodium Tetradecyl Sulphate (STS) and Polidocanol (POL) on clotting tests, clotting factors, platelets and microparticles. MATERIALS AND METHODS: Platelet rich (PRP) and platelet poor (PPP) plasmas were incubated with varying concentrations of STS and POL. Clotting tests, platelet/plasma turbidity, and microparticle studies were performed. Specimens were mixed with individual factor deficient plasmas and clotting factor activities were studied. RESULTS: STS at high concentrations (>0.3%) destroyed platelets, microparticles and the clotting factors V, VII and X. It prolonged all clotting tests including prothrombin time (PT), activated partial thromboplastin time (APTT), non-activated partial thromboplastin time (NAPTT), thrombin time (TT), factor Xa clotting time (XACT) and surface activated clotting time (SACT). Higher concentrations of POL were required to achieve some anticoagulant activity. Low sclerosant concentrations shortened XACT and SACT, and induced release of procoagulant platelet derived microparticles. Increased exposure time resulted in increased procoagulant activity. STS at concentrations higher than 0.5% precipitated a complex containing apolipoprotein b and fibrinogen. CONCLUSIONS: Detergent sclerosants affect the clotting mechanism by interfering with clotting factor activities, procoagulant phospholipids and platelet derived microparticles. STS has more anticoagulant activity than POL in high concentrations. Low concentration sclerosants demonstrate procoagulant activity.     

Immunoadsorption in Severe C4d-Positive Acute Kidney Allograft Rejection: A Randomized Controlled Trial

Antibody-mediated rejection (AMR) frequently causes refractory graft dysfunction. This randomized controlled trial was designed to evaluate whether immunoadsorption (IA) is effective in the treatment of severe C4d-positive AMR. Ten out of 756 kidney allograft recipients were included. Patients were randomly assigned to IA with protein A (N = 5) or no such treatment (N = 5) with the option of IA rescue after 3 weeks. Enrolled recipients were subjected to tacrolimus conversion and, if indicated, 'anti-cellular' treatment. All IA-treated patients responded to treatment. One death unrelated to IA occurred after successful reversal of rejection. Four control subjects remained dialysis-dependent. With the exception of one patient who developed graft necrosis, non-responders were subjected to rescue IA, however, without success. Because of a high graft loss rate in the control group the study was terminated after a first interim analysis. Even though limited by small patient numbers, this trial suggests efficiency of IA in reversing severe AMR.     

The effect of seated positioning quality on typical 6- and 7-year-old children's object manipulation skills.

OBJECTIVE: The purpose of this study was to examine the effect of optimal seated positioning in individually fitted furniture versus suboptimal seated positioning in standard classroom furniture on typical 6- and 7-year-old children's object manipulation skills as measured by the In-hand Manipulation Test (IMT). METHOD: An experimental research design was used to compare IMT performance of two groups of 20 children. One group was positioned in standard, too-large classroom furniture that did not support an optimal seated position, and one group was positioned optimally in furniture fitted to each child for tabletop activities, which allowed for hip flexion to 90 degrees, and foot placement on the floor, and the table to be at flexed elbow height. RESULTS: Independent groups' t tests indicated that children who were optimally positioned performed significantly better (t = -2.77, df = 38, p < .01) than children who were tested in the too-large standard classroom furniture. The difference between groups was greater on the more difficult object manipulation items (t = -3.29, df = 38, p = .001) than on the easier items (t = -1.38, df = 38, p = .08). Age and gender may have differentially affected the results. CONCLUSION: The study's results suggest that the fit of furniture relative to the child's size may have a significant impact on a young, typical child's object manipulation skills. Complex hand skills, such as those involving in-hand manipulation with stabilization, appear to be more affected by the quality of the child's seated position than are simpler, more well-established skills. Findings suggest that test administrators should strive to test young children in the most optimal seated position possible, particularly when the test involves complex hand skills. Further study is needed to assess the impact of the fit of furniture on hand skills in children with disabilities and on children's performance of other tasks.     

Metastatic bone disease from occult carcinoma: a profile

Summary To assess the general profile of metastatic bone disease from occult primary carcinoma, the records of 172 patients with skeletal metastases seen between 1965 and 1985 were reviewed. In 51 patients (30%), the origin of the primary could not be identified when bone metastases were first diagnosed. This group were predominantly male with a high incidence of spinal metastases, cord compression and pathological fractures, and a significantly shorter (P<0.1) survival compared with bony metastases when the primary was known. The site of the primary was established in 33 patients (65%), mostly at autopsy. Lung carcinoma was by far the most common primary tumour in 52% of the cases, while it accounted for only 7% of those with a diagnosed primary. We believe that the onset of bony metastases from an occult source must initially raise the possibility of lung carcinoma. If the primary remains undetected, it appears justifiable to assume it to be in the lung, since the probability of a missed lung tumour being responsible for the metastases is high.

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Résumé Les auteurs ont revu les observations de 172 malades porteurs de métastases osseuses, vus entre 1965 et 1985, afin d'apprécier l'aspect général des métastases provenant d'un cancer primitif méconnu. Chez 51 malades (30%) l'origine du cancer primitif n'avait pu être découverte lors du diagnostic de métastase osseuse. Ce groupe était à prédominance masculine, comportant un nombre élevé d'atteintes vertébrales, de compressions médullaires et de fractures pathologiques, et un taux de survie significativement plus court (P<0,1) comparativement à celui des métastases d'un cancer primitif connu. La localisation du cancer primitif a été découverte dans 33 cas (65%), la plupart du temps à l'autopsie. Le cancer du poumon était le plus fréquemment en cause (52%), alors qu'il n'était responsable que de 7% des cas quand le cancer primitif était connu. Il semble que l'apparition de métastases osseuses d'origine inconnue doive faire évoquer d'emblée la possibilité d'un cancer du poumon. Si le cancer primitif ne peut être découvert il est vraisemblable qu'il siège au niveau du poumon, la probabilité d'un cancer du poumon méconnu, responsable des métastases, étant élevée.

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Presented in part at the International Symposium on Bone Metastases, Rome, Italy, June 1986     

The Cellular Lesion of Humoral Rejection: Predominant Recruitment of Monocytes to Peritubular and Glomerular Capillaries

Accumulation of inflammatory cells within capillaries is a common morphologic feature of humoral renal allograft rejection and is most easily appreciated if it occurs in glomeruli. The aim of our study was to determine the amount and composition of immune cells within glomeruli and peritubular capillaries (PTC) in cellular and humoral allograft rejection. Immunofluorescent double-labeling for CD31 and CD3 or CD68 was used for phenotyping and enumerating immune cells within glomeruli and PTC. The major findings are: (1) accumulation of immune cells in PTC is far more common than it would be anticipated based on the assessment by conventional histology; (2) it is not the absolute number of immune cells accumulating within capillaries, but rather the composition of the intracapillary cell population that distinguishes humoral rejection from cellular rejection and (3) in C4d positive biopsies a predominantly monocytic cell population accumulates not only within glomeruli but also within PTC. The median value of monocyte/T-cell ratio within PTC was 2.3 in C4d positive biopsies but only 1 (p = 0.0008) in C4d negative biopsies. Given their prominent presence within capillaries and their extensive biological versatility monocytes might contribute to the capillary damage observed in acute and chronic allograft rejection.     

Hydroxyethyl starch does not improve pancreas preservation with HTK

The effect of hydroxyethyl starch on pancreas preservation with cardioplegic histidine-tryptophan-ketoglutarate solution (HTK) was investigated. The study was performed using an in vitro reperfusion system of the porcine pancreas. During organ preservation pancreatic weight, arterial pressure, volume flow, and washout of amylase and lactate were quantified. Addition of hydroxyethyl starch did not affect arteriovenous volume flow or washout of amylase and lactate during protective perfusion after pancreas preparation. However, hydroxyethyl starch in HTK prevented an increase in pancreatic weight at the end of the protective perfusion (102.2 ± 4.55% vs 127.8 ± 4.62% in controls; p < 0.005) and after 24 h cold ischemia (72.9 ± 3.91 % vs. 83.5 ± 3.49 % in controls; p < 0.05). Hydroxyethyl starch did not affect postischemic organ quality assessed during reperfusion in a perfusion chamber by pancreatic vascular resistance, amylase and lactate release, insulin secretion, and oxygen consumption. We conclude that hydroxyethyl starch does not bring about any further improvement in immediate postischemic organ quality assessed in an in vitro reperfusion system.

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Hydroxyäthylstärke bringt keine verbesserung der pankreaskonservierung mit HTK-Lösung

Zusammenfassung Der Effekt von Hydroxyäthylstärke auf die Pankreaskonservierung mit der kardioplegischen Histidin-Tryptophan-Ketoglutarat-Lösung (HTK) wurde untersucht. Die Studie wurde an einem Reperfusionssystem des in vitro perfundierten Pankreas vom Schwein durchgeführt. Während der Organprotektion wurden das Pankreasgewicht, der arterielle Perfusionsdruck, die Volumenstromstärke sowie Amylase und Laktat im Perfusat bestimmt. Der Zusatz von Hydroxyäthylstärke bewirkte keine Änderung der Volumenstromstärke oder der Amylase- und Laktatauswaschung aus dem Organ während der Protektion. Allerdings konnte eine Zunahme des Organgewichts am Ende der protektiven Perfusion (102,2 ± 4,55% vs. 127,8 ± 4,62%in Kontrollen; p < 0,005) und nach 24 h kalter Ischamie (72,9 ± 3,91 vs. 83,5 ± 3,49% in Kontrollen; p < 0,05) durch Hydroxyathylstärke in der HTK-Lösung verhindert werden. Hydroxyäthylstärke hatte keinen Einfluß auf die postischämische Organqualität, die während der Reperfusion in einer Perfusionskammer anhand von Gefäßwiderstand, Amylase- und Laktatfreisetzung, Insulinsekretion und Sauerstoffverbrauch abgeschätzt wurde. Wir schließen daraus, daß Hydroxyäthylstärke die sofort nach einer Ischämie in einem In-vitro-Reperfusionssystem bestimmte Pankreasfunktion nicht weiter verbessert.

     

Naphthalimido derivatives as antifolate thymidylate synthase inhibitors

A new series of N-(substituted)benzyl-1,8-naphthalimides 4, structurally related to the previously reported thymidylate synthase (TS) inhibitor naphthaleins 3, were synthesized and compounds tested for their inhibition of several species of TS. Moreover, their in vitro cytotoxicity together with antimycotic and antibacterial properties were assayed. While no activity was detected in the antibacterial tests, the m-nitro (4ae) and the p-nitro (4af) derivatives were found able to partially inhibit TS at low micromolar concentrations. Introduction of nitro or (substituted)-amino groups in position 4 of the naphthalic ring always led to less active compounds.