[Perioperative management of transthoracic oesophagectomies : Fundamentals of interdisciplinary care and new approaches to accelerated recovery after surgery]. / Perioperatives Management der transthorakalen Ösophagektomie : Grundlagen der interdisziplinären Patientenversorgung und neue Konzepte zur beschleunigten postoperativen Erholung.

Locally advanced carcinomas of the oesophagus require multimodal treatment. The core element of curative therapy is transthoracic en bloc oesophagectomy, which is the standard procedure carried out in most specialized centres. Reconstruction of intestinal continuity is usually achieved with a gastric sleeve, which is anastomosed either intrathoracically or cervically to the remaining oesophagus. This thoraco-abdominal operation is associated with significant postoperative morbidity, not least because of a vast array of pre-existing illnesses in the surgical patient. For an optimal outcome, the careful interdisciplinary selection of patients, preoperative risk evaluation and conditioning are essential. The caseload of the centres correlates inversely with the complication rate. The leading surgical complication is anastomotic leakage, which is diagnosed endoscopically and usually treated with the aid of endoscopic procedures. Pulmonary infections are the most frequent non-surgical complication. Thoracic epidural anaesthesia and perfusion-orientated fluid management can reduce the rate of pulmonary complications. Patients are ventilated protecting the lungs and are extubated as early as possible. Oesophagectomies should only be performed in high-volume centres with the close cooperation of surgeons and anaesthesia/intensive care specialists. Programmes of enhanced recovery after surgery (ERAS) hold further potential for the patient's quicker postoperative recovery. In this review article the fundamental aspects of the interdisciplinary perioperative management of transthoracic oesophagectomy are described.

Molecular analysis of the carboxy terminus of the beta and gamma subunits of the epithelial sodium channel in patients with end-stage renal disease.

BACKGROUND: Mutations in the carboxy termini of the beta subunit (hbetaENaC) and the gamma subunit (hgammaENaC) of the human epithelial sodium channel have been identified in patients with Liddle syndrome. Moreover polymorphisms have been described in these genes, the clinical relevance of which for progression to end-stage renal disease (ESRD) is unknown. We, therefore, have screened ESRD patients for putative variants of these genes. METHODS: We investigated 256 chronic hemodialysis patients, including 123 patients with a history of hypertension as a cause of ESRD. Screening for mutations in the carboxy termini of hbetaENaC and hgammaENaC was accomplished by polymerase chain reaction amplification followed by single-strand conformation polymorphism analysis. RESULTS: In 231 patients single-strand conformation polymorphism analysis of the polymerase chain reaction fragments of the hbetaENaC and hgammaENaC genes showed a similar migration pattern as compared with negative control subjects. In 25 patients a band shift was observed. However, sequence analysis in all these patients revealed wild-type sequence. CONCLUSIONS: The present study demonstrates the absence of genetic variants in the carboxy terminus of the hbetaENaC and hgammaENaC genes in Austrian patients with ESRD maintained on chronic hemodialysis treatment. Thus, mutations in these genes are unlikely to be associated with ESRD.

Mutations in the carboxy terminus of the beta and gamma subunits of the epithelial sodium channel are not present in patients with hypertensive crisis.

BACKGROUND: The pathophysiology of hypertensive crises is poorly understood. To date, no information is available about genetic determinants underlying the individual risk for development of hypertensive urgencies or emergencies. Recently, mutations in the beta subunit (h beta ENaC) and the gamma subunit (h gamma ENaC) of the human epithelial sodium channel (hENaC) have been shown to result in excessive elevation of blood pressure in patients with Liddle's syndrome. METHODS: Using polymerase chain reaction and direct sequencing of amplification products we have screened 90 consecutive out-patients with hypertensive urgency or hypertensive emergency for the presence of mutations in the carboxy terminus of these genes. Furthermore, serum potassium concentrations were determined in all 90 patients, and serum aldosterone levels and plasma renin activity were measured in a subset of 34 patients. RESULTS: Among 71 patients with hypertensive urgency (78.9%) and 19 patients with hypertensive emergency (21.1%) not one individual showed a mutation in genomic DNA extending from codon 532 to codon 637 of h beta ENaC and from codon 525 to codon 651 of h gamma ENaC. Twelve of 90 patients showed mild hypokalaemia (13.3%), 16 of 34 patients had a plasma renin activity below the lower normal range (47.1%) and one of 34 patients had a low serum aldosterone concentration (2.9%). CONCLUSIONS: The present study clearly demonstrates the absence of mutations in the carboxy terminus of the h beta ENaC and h gamma ENaC gene of hENaC in an Austrian cohort of 90 patients suffering from hypertensive crisis.

Synthesis and evaluation of 3-modified 1D-myo-inositols as inhibitors and substrates of phosphatidylinositol synthase and inhibitors of myo-inositol uptake by cells.

A number of 3-substituted 1D-myo-inositols were synthesized and evaluated as substrates for phosphatidylinositol synthase and uptake by intact cells. 1D-3-Amino-, -3-chloro-, and -3-(acetylthio)-3-deoxy-myo-inositols were all synthesized by nucleophilic displacement of the 6-O-(trifluoromethyl)sulfonyl group of 1L-1,2:3,4-di-O-cyclohexylidene-5-O-methyl-6-O-[(trifluoromethyl)-sulfon yl] - chiro-inositol (which was prepared from L-quebrachitol), respectively, by reaction with LiN3, followed by reduction of the azido function, and with LiCl and KSAc to give the O-protected compounds. O-Demethylation using BBr3 and concomitant acetal hydrolysis furnished the free-hydroxy 3-amino- and 3-chloro-3-deoxy-1D-myo-inositols. The 3-mercapto analogue was obtained by removal of the acetal groups of the acetylthio analogue, followed by acetylation and purification of the peracetate, and subsequent O-demethylation and deacetylation. The 3-deoxy derivative was synthesized from the 6-O-(imidazol-1-ylthiocarbonyl) compound via Barton-McCombie deoxygenation. The 3-azido derivative was directly synthesized from 1L-1-O-tosyl-chiro-inositol via displacement with azide. The 3-keto analogue was prepared by Pt-catalyzed air oxidation of 1L-chiro-inositol. The compounds were all evaluated as substrates for phosphatidylinositol (PtdIns) synthase from mouse brain. The 3-NH2, 3-F, 3-deoxy, and 3-keto analogues all showed activity as substrates, as measured by liberation of cytidine monophosphate. These compounds also showed inhibition of the reaction of myo-[3H]inositol with PtdIns synthase. These results taken together indicate that these compounds are likely to be incorporated into phospholipids. As a further indication that these compounds might be useful as probes for the PtdIns pathway, it was demonstrated that the 3-NH2, 3-F, and 3-deoxy compounds are taken up by intact fibroblast cells as evidenced by their competing with myo-[3H]inositol uptake.