Search

Calcium channel blockers (CCB) are widely prescribed anti-hypertensive agents. The commonest side-effect, peripheral oedema, is attributed to a larger arterial than venous dilatation causing increased fluid filtration. Whether CCB treatment is detrimental to human lymphatic vessel function and thereby exacerbates oedema formation is unknown. We observed that spontaneous lymphatic contractions in isolated human vessels (thoracic duct and mesenteric lymphatics) maintained under isometric conditions were inhibited by therapeutic concentrations (nanomolar) of the CCB nifedipine while higher than therapeutic concentrations of verapamil (micromolar) were necessary to inhibit activity. Nifedipine also inhibited spontaneous action potentials measured by sharp microelectrodes. Furthermore, noradrenaline did not elicit normal increases in lymphatic vessel tone when maximal constriction was reduced to 29.4 ± 4.9% of control in the presence of 20 nmol l(-1) nifedipine. Transcripts for the L-type calcium channel gene CACNA1C were consistently detected from human thoracic duct samples examined and the CaV1.2 protein was localized by immunoreactivity to lymphatic smooth muscle cells. While human lymphatics ex vivo were highly sensitive to nifedipine, this was not apparent in vivo when nifedipine was compared to placebo in a randomized, double-blinded clinical trial: conversely, lymphatic vessel contraction frequency was increased and refill time was faster despite all subjects achieving target nifedipine plasma concentrations. We conclude that human lymphatic vessels are highly sensitive to nifedipine in vitro but that care must be taken when extrapolating in vitro observations of lymphatic vessel function to the clinical situation, as similar changes in lymphatic function were not evident in our clinical trial comparing nifedipine treatment to placebo.

Complications to oesophageal and junctional cancer surgery are common and have not diminished much during the past ten years. An unusually high occurrence of anastomotic dehiscence occurred in Denmark in 2009 and 2010 as seen in the national database for oesophagus, cardiac and gastric (ECV) cancer.In accordance with national guidelines, all patients resected for oesophageal and junctional cancer in Denmark from 2003 were prospectively entered into a national database. Data concerning anaesthesia, peri- and post-operative course, complications, re-operations and time spent in intensive care unit were obtained retrospectively from hospital records. An in-depth analysis of data from two high-volume centres performing ECV cancer surgery according to national guidelines was performed.A total of 881 patients (Centre 1: 438; Centre 2: 443) were resected for oesophageal and junctional cancer. A total of 79 patients with anastomotic insufficiency (AI) were detected (Centre 1: 36; Centre 2: 43). By using a grading system, it was shown that AI was more severe and occurred earlier in one centre than in the other. Possible factors of influence are discussed, including neoadjuvant oncological therapy, use of thoracoscopically performed anastomosis and perioperative inotrophic drugs.Thanks to the establishment of a nationwide database in pursuance of national guidelines, it was possible to detect variations in quality of surgery over time, evaluate serious complications early and undertake an in-depth analysis of possible aetiological factors. Particularly, comparison was facilitated by the use of a standardised grading system for complications.not relevant.not relevant.

Small (K(Ca) 2) and intermediate (K(Ca) 3.1) conductance calcium-activated potassium channels (K(Ca) ) may contribute to both epithelium- and endothelium-dependent relaxations, but this has not been established in human pulmonary arteries and bronchioles. Therefore, we investigated the expression of K(Ca) 2.3 and K(Ca) 3.1 channels, and hypothesized that activation of these channels would produce relaxation of human bronchioles and pulmonary arteries.Channel expression and functional studies were conducted in human isolated small pulmonary arteries and bronchioles. K(Ca) 2 and K(Ca) 3.1 currents were examined in human small airways epithelial (HSAEpi) cells by whole-cell patch clamp techniques.While K(Ca) 2.3 expression was similar, K(Ca) 3.1 protein was more highly expressed in pulmonary arteries than bronchioles. Immunoreactive K(Ca) 2.3 and K(Ca) 3.1 proteins were found in both endothelium and epithelium. K(Ca) currents were present in HSAEpi cells and sensitive to the K(Ca) 2.3 blocker UCL1684 and the K(Ca) 3.1 blocker TRAM-34. In pulmonary arteries contracted by U46619 and in bronchioles contracted by histamine, the K(Ca) 2.3/ K(Ca) 3.1 activator, NS309, induced concentration-dependent relaxations. NS309 was equally potent in relaxing pulmonary arteries, but less potent in bronchioles, than salbutamol. NS309 relaxations were blocked by the K(Ca) 2 channel blocker apamin, while the K(Ca) 3.1 channel blocker, charybdotoxin failed to reduce relaxation to NS309 (0.01-1 µM).K(Ca) 2.3 and K(Ca) 3.1 channels are expressed in the endothelium of human pulmonary arteries and epithelium of bronchioles. K(Ca) 2.3 channels contributed to endo- and epithelium-dependent relaxations suggesting that these channels are potential targets for treatment of pulmonary hypertension and chronic obstructive pulmonary disease.

Treatment of cancer of the upper part of the oesophagus is challenging. Even after intended curative treatment, less than half of the patients are alive after five years. This retrospective study evaluates all the patients who had the upper oesophagus reconstructed by use of a free jejunal transfer following cancer resection from February 2000 to May 2008 at the University Hospital of Aarhus.Twenty patients aged 46-75 years were included. In all 20 cases, the diagnosis was squamous cell carcinoma, T3 or T4. All patients suffered from severe dysphagia prior to surgery. The median follow-up time was 23 months at 31 January 2010.No perioperative mortality was experienced. Thirteen patients are now dead; nine due to the cancer of the oesophagus and four due to other causes. The median survival time of the 13 diseased patients was 15.3 months. The seven patients who remain alive have a median survival time of 40.2 months. None of these patients have shown signs of recurrence of the oesophageal cancer. All the patients regained their capacity to swallow and thereby increased their quality of life. No complications were experienced in relation to the abdominal procedure of harvesting the jejunal transfer. Three patients developed a fistula and in one case this required minor surgery. Eight patients needed to have a dilatation procedure performed.Reconstruction of the oesophagus with a free jejunal transfer is a suitable treatment for selected patients with cancer in the upper oesophagus.