[Palliative therapy of complex hilar biliary obstructions using self-expanding metal stents]. / Palliativtherapie komplexer hilärer biliärer Obstruktionen mit selbstexpandierenden Metall-Stents.

Implantation of self-expandable metal stents was planned for 21 patients (12 women, 9 men; mean age 64.7 +/- 11.6 [38-80] years) with malignant obstructive jaundice due to complex hilar biliary obstruction (Bismuth II: n = 5, Bismuth III: n = 13, Bismuth IV: n = 1, state after hepaticojejunostomy: n = 2). Stents were implanted bilaterally in 18 patients (one each on the right and left, n = 12; two stents on right, one stent on left, n = 6), one patient had three stents on one side, another had one unilateral stent. Thus there was a 93.3% success rate (46 of 49 planned stent implantations). The mean bilirubin level fell from 14.7 +/- 7.7 mg/dl before stent implantation to 3.9 +/- 5.4 mg/dl afterwards (P = 0.0001). One patient experienced late bleeding with haemorrhagic shock and consumption coagulopathy after a failed drainage attempt. She died despite superselective embolization, operative suturing of the puncture site, and wide-ranging intensive care measures. Procedure-related death rate was thus 4.8%, the 30-day death rate 9.5%. During the follow-up period, averaging 145 +/- 152 (16-529) days, jaundice recurred in six patients (30%) and was successfully treated by re-intervention in five. 13 patients died after a mean survival time of 98 +/- 119 (16-432) days. It is concluded from these data that self-expandable metal stents provide minimally invasive palliative treatment of complex biliary hilar obstruction in the type of case in which plastic stents are known to fail.

Evaluation by reverse phase HPLC of [3H]acetylcholine release evoked from the myenteric plexus of the rat.

Myenteric plexus-longitudinal muscle strips isolated from the small intestine of rats were incubated with [3H]choline to measure the synthesis and the release of [3H]acetylcholine. To separate different radioactive compounds (acetylcholine, choline, phosphorylcholine) from both the tissue and the overflow a new method, the reverse phase HPLC, was used. The radiochromatogram following the injection of a [3H]choline-standard and a [14C]acetylcholine-standard onto the HPLC showed a clear separation of both isotopes with a recovery rate of roughly 100%. Incubation of the muscle strips with [3H]choline caused the synthesis of [3H]acetylcholine (30,000 dpm/preparation) that increased 2-fold, when the electrical field stimulation during labelling was increased from 0.2 Hz to 1 Hz. Electrical field stimulation (3 Hz, 2 min) caused an increase in tritium efflux that was abolished by the removal of extracellular calcium or by the addition of tetrodotoxin. Analysis by reverse phase HPLC of the overflow showed that the stimulated increase in tritium overflow was balanced by the enhanced release of [3H]acetylcholine. whereas the overflow of [3H]choline was not affected by the electrical field stimulation. Oxotremorine (1 mumol/l) suppressed the release of [3H]acetylcholine by 60%. Scopolamine (0.1 mumol/l) prevented this inhibition and, given alone, enhanced the release of [3H]acetylcholine by 43%. The release of [3H]acetylcholine evoked at 0.2, 2 or 20 Hz did not consistently decline at increasing frequencies. The present experiments show the synthesis and the calcium-dependent release of [3H]acetylcholine from the myenteric plexus-longitudinal muscle preparation of rats correspondingly to the same in-vitro preparation isolated from guinea-pigs. Muscarinic autoinhibition operates also in the small intestine of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential effects of calcium channel antagonists (omega-conotoxin GVIA, nifedipine, verapamil) on the electrically-evoked release of [3H]acetylcholine from the myenteric plexus, phrenic nerve and neocortex of rats.

Electrically-evoked release of [3H]acetylcholine from autonomic neurons (myenteric plexus), motoneurons (phrenic nerve) and the central nervous system (neocortex) was investigated in the presence and absence of the calcium channel antagonists omega-conotoxin GVIA, nifedipine and verapamil, whereby the same species (rat) was used in all experiments. Release of [3H]acetylcholine was measured after incubation of the tissue with [3H]choline. omega-Conotoxin GVIA markedly reduced (70%) the evoked release of [3H]acetylcholine from the myenteric plexus of the small intestine (IC50: 0.7 nmol/l) with a similar potency at 3 and 10 Hz stimulation. An increase in the extracellular calcium concentration attenuated the inhibitory effect of omega-conotoxin GVIA. Release of [3H]acetylcholine from the rat neocortex was also inhibited (90%) by omega-conotoxin GVIA, but the potency was 19-fold lower (IC50: 13 nmol/l). However, the release of [3H]acetylcholine from the phrenic nerve was not reduced by omega-conotoxin GVIA (100 nmol/l) at 1.8 mmol/l calcium (normal concentration), whereas omega-conotoxin GVIA inhibited evoked [3H]acetylcholine release by 47% at 0.9 mmol/l calcium. Neither nifedipine (0.1 and 1 mumol/l) nor verapamil (0.1, 1 and 10 mumol/l) modified the evoked release of [3H]acetylcholine from the myenteric plexus and the phrenic nerve. Acetylcholine release from different neurons appears to be regulated by different types of calcium channels. N-type channels play the dominant role in regulating acetylcholine release from both the myenteric plexus and the neocortex, whereas acetylcholine release from motor nerves is regulated by calcium channel(s) not yet characterized.