Early accumulation of the terminal complement-complex in the ischaemic myocardium after reperfusion

The terminal, membrane-damaging complement complex C5b-9 accumulatesin the infarcted myocardium. In experimental myocardial infarction,we investigated the time course of C5b-9 deposition and theinfluence of reperfusion. In a group of 17 rabbits (group 1),the circumflex coronary artery was occluded for different timeperiods ranging from 0•5 to 29 h without subsequent reperfusion.A second group of 23 rabbits (group 2) underwent coronary arteryocclusion for periods ranging from 0•5 to 6 h followedby reperfusion. C5b-9 was determined in transmural myocardialbiopsies by immunohistochemistry and by ELISA. In group 1, C5b-9accumulation in the ischaemic myocardium was found only after5 to 6 h of coronary artery occlusion. In group 2 (ischaemiaand reperfusion), significant C5b-9 deposition was already observedafter 30 min of myocardial ischaemia. We conclude that in the absence of reperfusion C5b-9 accumulationoccurs as a late event when most of the jeopardized myocardiumhas probably already become necrotic. In the presence of reperfusion,however, the complement system is activated rapidly and thiscould play a role in the pathogenesis of reperfusion injury.     

EFFECTS OF SEGMENTAL THORACIC EXTRADURAL ANALGESIA ON SYMPATHETIC BLOCK IN CONSCIOUS DOGS

To test the hypothesis that segmental thoracic extradural blockcauses sympathetic denervation caudally beyond dermatomes renderedanalgesic, we have measured regional skin temperatures in sixconscious dogs after upper thoracic, mid thoracic, and lumbarextradural injection of 0.5% bupivacaine 0.5, 1 and 2 ml cumulatively(total dose: 3.5 ml) given at 45-min intervals. Dogs were studiedat constant ambient and rectal temperatures. Upper thoracicextradural injections resulted in a significant increase inskin temperatures on both the front (+ 1.4 (SEM 0.2) °C)and hind paw (+ 1.4 (0.3) °C), while the area of analgesiawas confined to the upper trunk. With lumbar extradural injection,skin temperatures increased significantly (+2.0 (0.5) °C)on the lower extremities only. Mid thoracic injection significantlyincreased both front (+2.4 (0.9) °C) and hind paw (+2.2(0.6) °C) skin temperatures, but decreased temperatureson the thorax (–0.9 (0.2) °C) and abdomen (–1.0(0.2) °C), reversing the normal temperature gradient alongthe body axis. Irrespective of the injection site, skin temperatureson the trunk failed to increase or even decreased significantly.These data suggest that small doses of local anaesthetics appliedto the extradural space of conscious dogs cause increased lowerextremity skin temperatures caudal to areas unresponsive topinprick stimulation when injected at a high thoracic level,and decreased trunk skin temperature even in analgesic areas,so that skin temperature measurements are unlikely to reflectpurely sympathetic efferent activity on the trunk. Upper thoracicsegmental extradural analgesia induced a decrease in sympathetictone distal to the area of analgesia.     

PLACENTAL TRANSFUSION IN INFANTS OF DIABETIC MOTHERS ELUCIDATED BY PLACENTAL RESIDUAL BLOOD VOLUME

The influence of the method of delivery and the clamping technique on the placental transfusion is investigated by measurement of the placental residual blood volume in 58 infants of diabetic mothers and in 65 infants of nondiabetic mothers. It is shown that infants of diabetic mothers delivered vaginally compared with infants of diabetic mothers delivered by caesarean section, have a larger placental residual blood volume, if early clamping is employed. This relation suggests that also in infants of diabetic mothers, a temporary deposition of the distribution of the foeto-placental blood volume between the infant and the placenta occurs during vaginal delivery, because of the impaired venous backflow to the infant. The difference in the placental residual blood volume is more pronounced for infants of diabetic mothers than for infants of non-diabetic mothers. Further, it is shown that the placental residual blood volume is significant larger in infants of diabetic mothers but only after vaginal delivery with early clamping, compared with the same group of infants of non-diabetic mothers.     

Synthesis,biological activity and isomerism of guanylate cyclase C-activating peptides guanylin and uroguanylin

Recently, the peptides guanylin and uroguanylin were identified as endogenous ligands of the membrane-bound guanylate cyclase C (GC-C) that is mainly expressed in the intestinal epithelium. In the present study, bioactive guanylin and uroguanylin have been prepared by solid-phase methodology using Fmoc/HBTU chemistry. The two disulfide bonds with relative 1/3 and 2/4 connectivity have been introduced selectively by air oxidation of thiol groups and iodine treatment of Cys(Acm) residues. Using this strategy, several sequential derivatives were prepared. Temperature-dependent HPLC characterization of the bioactive products revealed that guanylin-related peptides exist as a mixture of two compounds. The isoforms are interconverted within approximately 90 min, which prevents their separate characterization. This effect was not detected for uroguanylin-like peptides. Synthetic peptides were tested for their potential to activate GC-C in cultured human colon carcinoma cells (T84), known to express high levels of GC-C. The results obtained show that both disulfide bonds are necessary for GC-C activation. The presence of the amino-terminally neighboring residues of Cys104 for guanylin and Cys100 for uroguanylin has been found to be essential for GC-C stimulation. Unexpectedly, a hybrid peptide obtained from substitution of the central tripeptide AYA of guanylin by the tripeptide VNV of uroguanylin was not bioactive. © Munksgaard 1997.     

THE INFLUENCE OF THE METHOD OF DELIVERY AND THE CLAMPING TECHNIQUE ON THE RED CELL VOLUME IN INFANTS OF DIABETIC AND NON-DIABETIC MOTHERS

The red cell volume has been investigated in 35 infants of diabetic mothers and in 18 infants of non-diabetic mothers. It is shown that not only the clamping technique but also, the method of delivery has an influence on the red cell volume of the infant. Thus the red cell volume is less in infants delivered vaginally with early clamping, compared with infants delivered by caesarean section with early clamping. These findings support the theory that during vaginal delivery a temporary change in It is suggested that IDM during vaginal delivery with early clamping deposit more blood in the placenta than do the non-IDM, since we found a smaller red cell volume per kg the distrfbution of. the foeto-placental blood volume between placenta and child occurs.     

Predicting malignancy in mediastinal lymph nodes by endobronchial ultrasound: A new ultrasound scoring system

Background and objective: Endobronchial ultrasound (EBUS) is now widely used in patients with resectable non‐small‐cell lung cancer to sample mediastinal lymph nodes (LN) for preoperative staging. The aim of this study was to investigate prospectively the utility of six ultrasound criteria to predict malignancy in mediastinal LN. Methods: EBUS was performed in patients with mediastinal lymphadenopathy irrespective of the underlying disease. The following criteria were expected to predict malignancy: short axis >1 cm, heterogeneous pattern, round shape, distinct margin, absence of a central hilar structure and high blood flow in a LN. A sum score prediction model for malignancy was built. If more than two criteria were present, LN was classified as high risk for malignancy. Moreover, interrater variability of two blinded investigators was evaluated. Results: Two hundred eighty‐one LN in 145 patients were analysed. Forty‐four percent of LN were found malignant, 10% revealed sarcoidosis, and 10% revealed tuberculosis. Interobserver agreement was very good. Positive predictive value was best for heterogeneity (73%), with a negative predictive value of more than 80%. The sum score resulted in an odds ratio of 15.5 if more than two criteria were positive (P < 0.00001). Conclusions: The assessment of ultrasound criteria during routine EBUS examinations is feasible and reproducible with very good interrater agreement. If less than three of the described criteria are present, a LN has a very low chance of being malignant. The best single criterion to predict malignancy is heterogeneity. The introduction of the sum score of ultrasound criteria could potentially increase diagnostic accuracy.