Long term improvement in the treatment of canine leishmaniosis using an antimony liposomal formulation.

Pharmacokinetic and clinical effectiveness of liposome-encapsulated N-methylglucamine antimoniate (LMA) was performed in dogs suffering from experimental leishmaniosis. LMA was compared with N-methylglucamine antimoniate (MGA), the same drug in its free form. Sb plasma concentrations for LMA were always higher than those for MGA. Mean residence time (MRT), half-life time (t(1/2)) and clearance (Cl) showed that Sb was eliminated slower after liposome administration. The high volume of distribution (Vd) obtained with LMA suggests that Sb could achieve therapeutic concentrations in parasite-infected tissues. Average plasma concentration at steady state (Css(ave)) shows that Sb body concentrations after LMA treatment (9.8 mg/kg Sb, each 24h) would be effective in Leishmania infantum canine infection. Comparing LMA with MGA in a 1-year follow-up we observed no relapses for LMA and total protein and gammaglobulin concentrations were within normal range, while for MGA both began to rise 3 months after treatment. Use of antimonial liposomal formulations may restore effectiveness to an existing drug and reduce toxicity.

Acute biliary pancreatitis: sphincter of Oddi and choledochal pressure.

Twenty four patients with biliary pancreatitis were divided into three groups: A (18 subjects underwent surgery on the biliary tract seven days after admission to hospital when acute signs disappeared); B (3 cases were operated two months later), and C (3 patients underwent emergency surgery for acute cholescistitis with simultaneous acute pancreatitis). A cholecistectomy-choledochostomy through a Kehr tube was performed in all patients. Pressure in the main biliary duct (MBD) was measured. Only group A was significant (18 cases). As a control, another group, group D was considered (52 biliary cholecysto-choledochal lithiasis patients without pancreatitis and without transduodenal sphincterotomy). Group A: 1) The mean pressure in MBD on the fourth postoperative day (11 days after onset of pancreatitis) was low (p < 0.0001) in relation to that of group D with Oddi's sphincter (SO) normal; 2) in group A, no significant differences (p-NS) were found in relation to positions: during fasting, 4.4 +/- 4 cm H2O in the upright position, and 5.3 +/- 2 when lying (in group D, 9.9 +/- 4.1 cm H2O upright, and 7.76 +/- 3.6 lying with p = 0.0001), and 3) a slow improvement of pressure was observed and, on the 25th day after operation, it was nearly normal (9 cm H2O upright and 7 cm lying with p < 0.001). Group B: biliary surgery at 2 months; mean pressure in MBD meartly normal. Group C: 1) 4 days after emergency surgery, the pressure in MBF (15 cm H2O upright and 11.7 lying) was higher than in subjects with normal SO, probably due to compression of the distal part of MBD by the inflamed pancreas, and 2) from the 11th day the pressure followed the same evolution as that of group A. In conclusion, in patients with acute biliary pancreatitis, operated on the biliary tract when acute signs disappeared, MBD pressure is low (p < 0.0001) in reference to normal on the fourth post-operatory day (11 days after onset of pancreatitis) and no significant differences were found in relation to positions (upright and lying). The pressure changes are transient (4-5 weeks) and most probably due to the lesions and malfunction of the SO related to pancreatitis.

[Cholelithiasis. Post-choledochostomy intraductal pressure (without and with sphinctero-infundibulostomy]. / Colelitiasis. Presiones intraductales poscoledocotomía (sin y con esfinteroinfundibulotomía).

In 72 patients operated on for lithiasis of the main biliary duct (MBD), the intraductal pressure was measured through the choledochostomy T-tube. This measure was done, both in upright and lying positions, fasting and after lunch. Two groups were considered: A (of 52 cases) and B (of 20 cases). In both groups a choledochotomy was performed, and only in group B a long, although partial, sphincterotomy was also done. Three patients in group B had the upper part of the sphincter of Oddi (SO) dilated by big stones. 1) When groups A and B were compared, no significant differences of pressures in MBD was found. 2) Highly significant differences (p = 0.0001) were always found when paired data related to positions were compared: in the upright position pressures in MBD were higher than on the lying position. Group A, during fasting (9.90 +/- 4.1 cm H2O, in upon position, and 7.76 +/- 3.6 when lying) and group B, also at fasting (8.95 +/- 3.0 in the upright position and 6.57 +/- 3.0, when lying). The three patients included in group B with big stones impacted in the upper part of SO, showed low pressures in MBD, specially one (2 and 1 cm H2O, upright lying positions), but the group is too small have statistical significance. We conclude that the long but partial sphincterotomy does not modify significantly the pressures in MBD whether upright or lying, and when paired data related to positions were compared, upright pressures were always higher than on the lying position (p = 0.0001).

[Somatostatin and choleresis in human beings during the digestive phase]. / Somatostatina y coleresis en el ser humano durante la fase digestiva.

The effect of somatostatin on human choleresis has been poorly studied. Nearly all present knowledge comes from animal research (dog). In the human being, the effect is known in fasted patients. But no data are available of its action during digestion. In the present study, before removing the choledochostomy T-tube from 73 patients operated on for biliary disease, the bile output (40% of the total choleresis) was measured for 4 hours, at 30 min intervals: during fasting, lunch and after lunch: 1) at fasting (A) 10.5 +/- 2.2 cc; at lunch (B) 18.6 +/- 5.4 cc, and after lunch (C) 16.8 +/- 4.5 cc. These differences were highly significant: A vs B p < 0.0001, and A vs C p < 0.0001. In a second part, 10 of these patients received subcutaneously 0.1 mg of SMS 201-995 (a somatostatin's analogue) 30 min before lunch. In all patients the bile output was significantly reduced: 1) prandial phase (D) 9.6 +/- 2.6 cc, and 2) post-prandial phase (E) 5.1 +/- 2.2 cc. Flow in E was significantly reduced when compared to A. Action of 0.1 mg SMS lasted about 120 min. We conclude that SMS decreases prandial and postprandial choleresis in humans.

[Trans-Kehr postoperative cholangiography in upright and horizontal positions: the morphofunctional aspects of the biliary tract]. / La colangiografía postoperatoria trans Kehr en posiciones orto y horizontal: aspectos morfológico-funcionales de las vías biliares.

To change from the lying position to the upright position, in patients without their gallbladder, causes: a) a rapid and partial emptying of the biliary ducts towards the duodenum by the amplification of the opening phasic waves activity of the sphincter of Oddi (S. O.); b) an important reduction caliber of the main biliary duct (M. B. D) and c) stability of the intraductal pressure with slight raising in upright position. These physiological concepts allow a better cholangiographic exploration by means of a drip of 60 to 70 drops per minute of diluted tri-iodic in: 1) Upright position, which gives a good image regarding the terminal choledochus; of the biliary duodenal flow, and of the reduction of the caliber of the MBD. 2) In lying down position which allows: the filling up of the complete biliary-tree with possible scarcity of information about the distal choledochus-duct; the appreciation of the degree of the expansion of the MBD, and the measuring of the delay of the emptying out of the X-ray-opaque substance in relation to what was found in the upright position. The elasticity of the walls of the biliary ducts acts efficiently in the compliance of the container and contained. In normal choledochal ducts, the top level images in the upright position do not go beyond the hepatic duct. When there are problems with the flow through the S. O., there is a filling up of the intrahepatic biliary ducts with the contrast substance introduced in the upright position.

Comparison of high-performance liquid chromatography and high-performance capillary electrophoresis for the determination of cicletanine in plasma.

A sensitive and selective high-performance capillary electrophoresis (HPCE) procedure was developed for the determination of total cicletanine in human plasma. The procedure consisted in extraction of the drug with diethyl ether and analysis by micellar electrokinetic capillary chromatography in a fused-silica capillary using sodium dodecyl sulphate in the run buffers and ultraviolet detection. The concentrations of cicletanine obtained by this method were compared with those obtained by a high-performance liquid chromatographic (HPLC) method used routinely. The within-run precision of the methods, expressed as relative standard deviation, ranged from 1.6 to 7.8% for HPLC and from 6.4 to 11.1% for HPCE. Both methods showed an adequate level of accuracy; the relative errors ranged from 0.02 to 3.25% for HPLC and from 0.21 to 2.90% for HPCE. The HPCE method required less than half the time taken by the HPLC method, making HPCE a useful alternative technique for the routine determination of cicletanine in plasma. Both methods were used to follow the time course of total cicletanine in human plasma after a single oral therapeutic dose of the drug.

Determination of cicletanine enantiomers in plasma by high-performance capillary electrophoresis.

A sensitive and selective high-performance capillary electrophoresis procedure was developed for the determination of S(+) and R(-) enantiomers of cicletanine in human plasma. The procedure consisted in extraction of the drug with diethyl ether and analysis by micellar electrokinetic capillary chromatography in a fused-silica capillary using gamma-cyclodextrins in the run buffers and ultraviolet detection. The method was linear from 10 to 500 ng/ml and the limit of detection was 10 ng/ml for each enantiomer in plasma samples. The within-run precision of the method, expressed as relative standard deviation, was 10.4 and 9.6% at 25 ng/ml for S(+) and R(-) cicletanine, and 4.2 and 4.6% at 500 ng/ml, respectively. This method has been used to follow the time course of the concentrations of the cicletanine enantiomers in human plasma after a single therapeutic dose of cicletanine given by mouth.

[Physiopathologic concepts related to patients undergoing total gastrectomy]. / Conceptos fisiopatológicos referentes a los pacientes sometidos a gastrectomía total.

Total gastrectomy due, principally, to malignant diseases, has two aims: a) to carry out an adequate oncological operation, and b) to perform a simple reconstruction of the digestive tract which must avoid biliary esophageal reflux. All other functional disturbances may be controlled by adequate diet. Pseudogastric jejunal pouches are, at present, being abandoned. The reduced intestinal malabsorption--favored by the loss of the stomach and the bacterial proliferation--is kept under control, it seemed, by the function of the "ileal brake", which, when certain fat acids and other substances reach the ileum, produce hypomotility of the jejunum with slowing up of the intestinal flow. In such patients, an important catabolism prolongs for some weeks after the operation, and lose also weight due to poor appetite and not eating enough. In view of this, it is considered justified the application of an enterostomy tube during the operation, in order to provide a supplement of food by direct intestinal way, which should begin to be used only after the first postoperative days (five-six).

[Biliary secretion. Significance of hypercholeresis from the surgical point of view]. / La secreción biliar. Significación de la hipercoleresis desde el punto de vista quirúrgico.

In patients carrying a Kehr tube choledochostomy, the surgeon may observe, but rarely, important hypercholeresis, non-bile-acid dependent, in people with severe advanced chronic hepatic diseases or persistent cholestasis. The amount of bile flowing to the outside can reach two liters and more daily. We have seen this in two patients with compensated hepatic disorders and in another suffering from light cholestasis produced by choledocholithiasis. We have also found the same in three other people with liver and the main biliary extrahepatic tract completely normal. This hypercholeresis is continuous and subject to rapid increases relative to the ingestion of food. Such increases are related to gastrointestinal hormones, specially secretin, which is produced when portions of gastric chyme enters the duodenum.