Endoscopic retrograde cholangiopancreatography in the orthotopic liver transplant patient

BACKGROUND AND STUDY AIMS: Diagnostic imaging of the biliary tract is often required in liver transplant recipients, preoperatively to assess extent of biliary tract disease and postoperatively in patients with a suspected biliary complication due to an abnormal postoperative course. PATIENTS AND METHODS: Over a six-year period, 115 patients received 127 liver transplantations at our institution. Twenty-three preoperative ERCPs were performed in 17 patients, while 25 ERCPs were performed on 15 patients after liver transplantation. RESULTS: Preoperative ERCP in seven of 17 patients revealed a dominant biliary stricture as a result of primary sclerosing cholangitis (PSC); five of these patients were managed successfully with the placement of biliary endoprosthesis. An additional nine patients with PSC underwent brush cytology of the extrahepatic bile ducts to rule out coexisting cholangiocarcinoma; there were no positive results, although three were found to have coexisting cholangiocarcinoma after examination of the explanted liver. Postoperatively, nine of 15 patients were found to have biliary tract disease. These included five biliary strictures (three treated successfully by endoscopic dilation and stent therapy), two biliary leaks (treated by biliary endoprosthesis), one biloma (treated by percutaneous drainage) and one intraductal stone (treated successfully by sphincterotomy and stone extraction). The remaining six patients showed no abnormality at ERCP, and were subsequently diagnosed with allograft rejection. CONCLUSIONS: Diagnosis of biliary complications after hepatic transplantation is often problematic. Definitive characterization frequently requires cholangiography. Interventional biliary procedures, both endoscopic and percutaneous, can be used successfully to treat these complications; however, surgical revision and retransplantation are sometimes required.     

The hemodynamic changes during the intraperitoneal hyperthermic perfusion under induced hypothermia

We investigated the whole body oxygen consumption (VO2) and the hemodynamic changes during the intraperitoneal hyperthermic perfusion (IPHP), which was coupled with induced hypothermia to prevent the cerebral disorder. IPHP was carried out for 90-120 min with 45-47 degrees C perfusate after the operation. We induced hypothermia using the surface cooling method and the infusion of triflupromazin. In no patient, the pulmonary artery temperature (PAT) rose above 40 degrees C. In the IPHP, there was a significant correlation between VO2 and PAT. If PAT reached 42 degrees C during the IPHP, VO2 would increase to 130-140% of the value at 37-38 degrees C. This rise is smaller than that during the total body hyperthermia (TBH), in which VO2 at 42 degrees C reached 130-190% of the value at 38 degrees C. Heart rate increased in proportion to the rising rate of body temperature. During the IPHP, PAT sometimes rose remarkably about 8 degrees C (from 32 degrees C to 40 degrees C) with a marked rise in heart rate. This rising rate of PAT is greater than that of TBH, in which PAT rose about 4-5 degrees C (from 37-38 degrees C to 42 degrees C). We consider that IPHP is not applicable to the patients with ischemic heart disease. During the rise of PAT, other circulatory parameters related to IPHP, changed in the same direction as those related to TBH. The rate of change of these parameters related to IPHP was smaller than that of the TBH, because during the IPHP the highest PAT was lower than that during TBH.     

Blood concentrations of dopexamine in patients during and after orthotopic liver transplantation

Blood concentrations of dopexamine were measured in five female patients during and after orthotopic liver transplantation. Each patient received a continuous infusion of the drug (2 micrograms kg-1 min-1), starting at induction of anaesthesia and finishing 48 h afterwards. Blood concentrations of dopexamine increased rapidly at the start of the infusion, to a mean (range) value of 64 (40-150) ng ml-1 after 20 min. Blood concentrations of dopexamine increased further during the anhepatic period of surgery, to 236 (180-410) ng ml-1. On reperfusion of the donor liver, concentrations of dopexamine decreased rapidly, reaching similar values to the maximum seen during the dissection period. Steady-state was not reached during either the dissection or anhepatic periods. From 1-2 h after revascularisation the mean (range) steady-state concentration was 85 (69-102) ng ml-1 corresponding to a mean (range) clearance of 24 (20-29) ml min-1 kg -1. These results suggest that the liver plays a significant role in the clearance of dopexamine.     

The effect of acute hypocapnia on middle cerebral artery transcranial Doppler velocity during orthotopic liver transplantation: changes at reperfusion

This study examines the effects of acute hypocapnia, instituted prior to reperfusion of the graft liver, on the middle cerebral artery (MCA) Doppler blood flow velocity response to reperfusion during orthotopic liver transplantation in humans. Seventeen patients with chronic liver disease underwent continuous, noninvasive Doppler imaging of the MCA. Hyperventilation to an end-tidal Pco2 of 25 +/- 1 mm Hg was associated with a decrease in mean MCA flow velocity (FVm) from 51.6 +/- 5.7 to 37.0 +/- 3.3 cm/s (P < 0.05). After reperfusion, the Paco2 increased from 32 +/- 1 to 40 +/- 1 mm Hg (P < 0.05), mean arterial pressure (MAP) decreased from 76 +/- 3 to 60 +/- 2 mm Hg, and the FVm increased from 37.0 +/- 3.3 to 54.0 +/- 4.7 cm/s (P < 0.05). FVm increased postreperfusion despite prior hyperventilation, decreased MAP, and abrupt increases in central venous and pulmonary artery pressure, but FVm did not exceed the prereperfusion level. In 10 of the 17 patients, the baseline FVm versus Paco2 response slopes and Paco2 measured postreperfusion were used to predict the FVm response to Paco2 after reperfusion. The slopes were similar to those reported for anesthetized patients without liver disease. Predicted FVm exceeded measured FVm in 9 of the 10 patients. We conclude that mild hyperventilation prior to reperfusion of the graft liver prevents FVm increases above prereperfusion baseline level.     

Sequential hemodynamic changes in end-stage renal disease and the anephric state during volume expansion

The sequence of hemodynamic events during periods of salt- and water-loading was studied in anephric patients and those with end-stage kidney disease. The 10 patients studied showed four different sequential hemodynamic patterns: 1) no significant increase in blood pressure (BP) in two patients; 2) increase in BP associated with an increase in cardiac output and without change in total peripheral resistance in two patients; 3) increase in BP associated with an increase in total peripheral resistance from the beginning without an increase in cardiac output in five patients; and 4) increase in BP associated with an initial increase in cardiac output followed by an increase in total peripheral resistance in one patient. There was a significant positive correlation between BP and blood volume and between BP and total exchangeable sodium in the patients in whom salt- and water-loading increased the BP. It is concluded that during salt- and water-loading an initial rise in cardiac output is not necessary to increase BP and that a sustained rise in cardiac output does not always increase the total peripheral resistance. Mechanisms other than whole-body autoregulation play a role in increasing BP during salt- and water-loading in patients deprived of renal excretory function.     

Comparative analysis of changes in respiration and systemic hemodynamics during activation of GABA receptors in cats and rats]

Rat liver mitochondrial alanine aminotransferase (mALT) is known to be a very unstable enzyme, a property that has hindered efforts to purify it. In this report we examine the possibility of stabilizing mALT with ethanol, trehalose, and protease inhibitors. The presence of ethanol was shown to slow down the inactivation of mALT, increasing its half-life from 1 to 4 h. Trehalose was found to greatly enhance the stability of mALT in a concentration-dependent manner. In the presence of 36.5% trehalose, the half-life of mALT was 85 h. Of the protease inhibitors tested only antipain and chymostatin slowed down the inactivation of mALT but only within the first 24 h following preparation of the crude enzyme. It is concluded that the inclusion of ethanol and trehalose in purification protocols could aid the purification of the enzyme. It is also concluded that the inclusion of protease inhibitors in purification protocols of mALT may not be necessary as its inactivation does not seem to be due to protease activity.     

Use of esmolol to prevent hemodynamic changes during intubation in general anesthesia

Regeneration-competent urodele Amphibia are highly resistant to spontaneous development of neoplasms, in comparison with other vertebrates which do not exhibit great regenerative power. This observation implies that at least one growth parameter of urodele cells might be subject to different developmental mechanisms than the cells of animals incapable of epimorphic regeneration. Therefore, keeping records concerning the incidence of tumors in urodeles and investigating those exceptional cases might prove invaluable in understanding the basic biological principles governing organ regeneration and carcinogenesis, and might therefore help in cancer therapy. The present report depicts a case of two spontaneous, dermal, melanoma-like tumors found in an adult newt Triturus cristatus. Both tumors were located in the pelvic region. Histological examinations and tumor transplantations were conducted. It was found that the tumors were melanomata. When allografted within the body cavity, their mass was progressively eliminated.     

Infective endocarditis of the tricuspid valve in an orthotopic heart transplant recipient

A 43-year-old orthotopic heart transplant recipient had coagulase-negative staphylococcus endocarditis 26 weeks after the operation. A diagnosis of endocarditis was confirmed and followed up by serial transoesophageal echocardiography. Treatment with intravenous gentamycin and vancomycin cured her endocarditis, and a 2.5 cm vegetation regressed significantly. She has been well since and, at 14 months after transplantation, was back to her normal activities. Although repeated blood culture yielded only intermittent light growths of coagulase-negative staphylococci, there were several positive samples. In a setting of infective features, light growths of coagulase-negative staphylococcus should be taken seriously if repeatedly positive in heart transplant recipients or other immunocompromised patients. Transesophageal echocardiography offers significant advantages over the transthoracic modality in suspected endocarditis.     

Role of prostaglandins in the mediation of systemic tachyphylaxis to angiotensin II

Angiotensin-induced prostaglandin release has been implicated in the deveolpment of tachyphylaxis to angiotensin in vitro. Based on these findings and evidence that prostaglandins modulate the angiotensin reposne locally, experiments were done to investigate the role of prostaglandins in the systemic tachyphylaxis to angiotensin. Rats were given intravenous infusions of 1-asparaginyl-5-valyl and 1-aspartyl-5-isoleucyl andiotensin II at two different doses. Using systemic blood pressure as a parameter, varying degrees of tachyphylaxis were produced and the aspartyl analog was found to be more tachyphylactic. When rats were given indomethacin, a prostaglading synthesis inhibitors, the response to intravenous infusion of aspartyl angiotensin was not significantly altered.     

Pharmaceutical and pharmacological development of antitumor prostaglandins]

The stoichiometry of the interaction between Erythrina variegata chymotrypsin inhibitor ECI and chymotrypsin was reinvestigated by analysis of their complex with ultracentrifugation and with amino acid analysis of the components separated. The amino acid analysis clearly showed that the stoichiometry of ECI and chymotrypsin was 1:1, though the apparent molecular mass of the complex was estimated to be 60 kDa. To examine the contribution of Leu64 (the P1 residue) to the inhibitory activity of ECI, a complete set of mutated inhibitors in which the amino acid at position 64 was replaced by 19 other amino acid residues was constructed by means of site-directed mutagenesis. Potent inhibitory activities (Ki, 1.3-4.6 x 10(-8) M) exceeding that of the wild-type ECI (Ki, 9.8 x 10(-8) M) were present in the mutant proteins L64F, L64M, L64W, and L64Y. The inhibitory activity of the mutant L64R was practically identical to that of the wild-type ECI. All other mutants exhibited slightly decreased inhibitory activities with Ki values of 1.9-4.6 x 10(-7) M. These results indicate that ECI-chymotrypsin interaction involves not only the P1 site residue but also other residue(s) of ECI. A series of individual alanine mutations was then constructed in residues Gln62 (P3), Phe63 (P2), Ser65 (P1'), Thr66 (P2'), and Phe67 (P3') in order to evaluate the contribution of each residue in the primary binding loop to the inhibitory activity. Replacement of Gln62, Phe63, and Phe67 with Ala residues decreased the inhibitory activity, the Ki values being increased by approximately 3-4-fold; but replacement of Ser65 and Thr66 had relatively little effect. This suggests that the P2, P3, and P3' residues, together with the P1 residue, in the primary binding loop play an important role in the inhibitory activity toward chymotrypsin.     

High levels of extracellular glutamate are present in retina during neonatal development

The three major classes of neurons which comprise the primary visual pathway in retina are glutamatergic. These cells are generated in two separate developmental stages, with one subclass of photoreceptors (cones) and ganglion cells generated before birth; and the other subclass of photoreceptors (rods) and bipolar cells generated during the first week after birth. Gas chromatography/mass spectroscopy analysis coupled with a new method for collecting small samples of extracellular fluids from retina were used to determine the levels of endogenous glutamate present during differentiation and synaptogenesis of these different cell types. As expected the total retinal content of glutamate increased during the postnatal period in synchrony with the generation and maturation of glutamatergic cells. However, a significant proportion of the endogenous pool was found extracellularly at birth. Intracellular glutamate is localized within cell bodies and growing processes of cones and ganglion cells at this time but few glutamatergic synapses are present. The extracellular concentration of glutamate actually declined during the most active period of synaptogenesis, reaching very low levels in the adult. The high concentrations of extracellular glutamate in neonatal retina could play an important role in a variety of developmental events such as dendritic pruning, programmed cell death and neurite sprouting.