Right living donor liver transplantation: an option for adult patients: single institution experience with 74 patients

OBJECTIVE: To present an institutional experience with the use of right liver grafts in adult patients and to assess the practicability and efficacy of this procedure by analyzing the results. SUMMARY BACKGROUND DATA: Living donor liver transplantation (LDLT) for the pediatric population has gained worldwide acceptance. In the past few years, LDLT has also become feasible for adult patients due to technical evolution in hepatobiliary surgery and increased experience with reduced-size and split-liver transplants. Nevertheless, some graft losses remain unexplained and are possibly due to unrecognized venous outflow problems. METHODS: From April 1998 to September 2002, we performed 74 right LDLTs (segments 5-8). The 74 donors were selected from 474 candidates according to standard protocol. The median age of the donors was 35 years (range 18-58 years) and 51 years (range 18-64 years) in recipients. Standard and extended indications for transplantation were considered. Over the period reported, technical modifications in the bile duct anastomosis (duct-to-duct, end-to-end, or end-to-side) and a new graft implantation technique that provides maximized venous outflow, leading to outcome improvement, were developed. RESULTS: 64.9% of patients had liver cirrhosis and 35.1% had malignancy. While 44 donors (59.5%) presented an uneventful postoperative course, 27% minor (pleural effusion, pneumonia, venous thrombosis, wound infection, incisional hernia) and 13.5% major (biliary leakage, death of a donor due to unrecognized hereditary liver disease, and consecutive liver insufficiency) complications were documented. In recipients, 23% biliary complications and 6.8% hepatic artery thrombosis occurred. The overall patient and graft survival rate after 1 year was 79.4% and 75.3%, respectively. In cases with extended indication, the patient survival rate was 74% and the graft survival rate 68% at 12 months. Using technical modifications in the last 10 recipients, including 2 critically decompensated cirrhotics, the survival rate was 100% at a median follow-up of 3.5 months. CONCLUSIONS: In our transplant program, living donor liver transplantation has become a standard option in the adult patient population. The critical issue of this procedure is donor morbidity. Technical improvements in the harvesting and implantation of right grafts can also offer hope to patients with challenging forms of end-stage liver disease or malignant liver tumors.     

Current determinants of operative mortality in 1400 patients requiring aortic valve replacement

BACKGROUND: Determinants of operative mortality after aortic valve replacement vary with a changing patient population due to advances in operative management and increasing life expectancy. In order to predict current groups of high risk patients, a statistically valid large study population base recruited over a short period of time is required. METHODS: Between January 1996 and June 2001, 1408 aortic valves were replaced in 1400 patients (572 of them with simultaneous coronary artery bypass grafting). The data were analyzed by multivariate logistic regression to evaluate the operative risk. Mean age of the study population was 68 +/- 11 years (range 19 to 90 years old, 44% female). RESULTS: Overall operative mortality (within 30 days) was 3.8%. Independent predictive factors for operative mortality were previous bypass surgery, emergency operation, simultaneous mitral valve replacement, renal dysfunction, more than 80 years old, simultaneous bypass surgery in female patients with a body mass index greater than 29 kg/m(2), and height smaller than 1.57 m for patients more than 71 years old. Simultaneous coronary artery bypass grafting in general (p = 0.6), previous aortic valve replacement (p = 0.59), and implantation of stented bioprostheses (p = 0.39) or stentless bioprostheses (p = 0.7) were not identified as independent risk factors. CONCLUSIONS: Certain groups of patients with a high operative risk were identified: patients more than 80 years old, women with a body mass index greater 29 kg/m(2) undergoing simultaneous coronary artery bypass surgery, and "small" patients more than 71 years old.     

Repetitive short-term bile duct obstruction and relief causes reproducible and reversible bile acid regurgitation

BACKGROUND: Long-term bile duct obstruction causes sinusoidal regurgitation of bile acids, a shift in bile acid metabolism, and alterations of liver histology. In this study we investigated the regurgitation of bile acids during short-term bile duct obstruction and its reversibility and reproducibility. In addition, the biotransformation of taurodeoxycholate and its appearance in bile and perfusate effluent were studied as well as liver histology. METHODS: Rat livers (n = 5) were perfused in vitro with 32 nmol/min/g liver taurodeoxycholate over 85 min with the bile duct being intermittently closed for 30 and 20 min, respectively. RESULTS: Within the first 5 min after bile duct obstruction bile acids started to regurgitate to the perfusate effluent amounting to approximately 15% of hepatic uptake until the end of the perfusion period. After relief of obstruction, bile flow and biliary bile acid excretion showed an overshoot phenomenon and were almost doubled compared to preobstruction. In contrast, sinusoidal bile acid regurgitation declined. The same phenomenon was observed during the second closure/opening cycle of the bile duct. Regurgitated bile acids consisted of significantly more taurodeoxycholate metabolites (approximately 70%) than did biliary bile acids (approximately 30%). Histology of liver parenchyma was preserved. CONCLUSIONS: During repetitive short-term bile duct obstruction bile acid regurgitation is reversible and reproducible. The absence of altered mechanical barriers suggests that specific pathways are involved in the regurgitation process of bile acids.     

Experimental lung preservation with Perfadex: effect of the NO-donor nitroglycerin on postischemic outcome

OBJECTIVE: Optimal preservation of postischemic graft function is essential in lung transplantation. Antegrade flush perfusion with modified Euro-Collins solution represents the standard technique worldwide. However, growing evidence suggests the superiority of extracellular-type Perfadex solution (Vitrolife AB, Gothenburg, Germany) over Euro-Collins solution. During ischemia and reperfusion, endogenous pulmonary nitric oxide synthesis is decreased, and therefore therapeutic stimulation of the nitric oxide pathway might be beneficial in ameliorating ischemia-reperfusion damage. However, research mainly focuses on nitric oxide supplementation of intracellular solutions, and no studies exist in which the effect of nitroglycerin on Perfadex preservation quality is evaluated. METHODS: Eight rat lungs each were preserved with Perfadex solution with or without nitroglycerin (0.1 mg/mL) and compared with low-potassium Euro-Collins solution. Postischemic lungs were reventilated and reperfused, and oxygenation capacity, pulmonary vascular resistance, and peak inspiratory pressures were monitored continuously. Stereological analysis was used for evaluation of pulmonary edema and assessment of the vasculature. Statistics were performed by using different analysis of variance models. RESULTS: The oxygenation capacity of the Perfadex-preserved groups was higher compared with that of the low-potassium Euro-Collins solution group (P <.03). By using nitroglycerin, flush-perfusion time was reduced, and Perfadex solution with nitroglycerin-protected lungs showed superior oxygenation capacity compared with that seen in Perfadex solution-protected organs (P <.01). Furthermore, pulmonary vascular resistance and peak inspiratory pressures were improved in the nitroglycerin group (P <.01). Stereology revealed comparable intrapulmonary edema between groups and a trend toward less vasoconstricted vasculature in Perfadex with nitroglycerin-protected lungs. CONCLUSIONS: Perfadex solution provides superior lung preservation in terms of postischemic oxygenation capacity than Euro-Collins solution. Supplementation of the nitric oxide pathway by nitroglycerin further enhances functional outcome of Perfadex-preserved organs and might be an easily applicable tool in clinical lung transplantation.     

Unreamed tibia nail (UTN) bending: case report and problem solution

Background An unreamed tibia nail (UTN), implanted for operative stabilization of the tibia after a distal shaft fracture of the lower leg, was bent by excessive load prematurely applied during the healing process, whereby the cross-section-dependent maximum torque permitted in the edge fiber of the UTN during bending load was exceeded. Straightening of the bent, not broken UTN by hand was impossible. Therefore, the bent UTN could only be removed by causing additional damage to the tibia, which is why bending of the nail must be avoided.Conclusion Our analysis shows that modification of the arrangement of the locking holes by 45° increases bending load capacity of the UTN, which can minimize the probability of the occurrence of a bent nail.     

EEG abnormalities associated with antipsychotics: a comparison of quetiapine, olanzapine, haloperidol and healthy subjects

In this study the effects of the atypical antipsychotics quetiapine and olanzapine, and the typical antipsychotic haloperidol on EEG patterns were retrospectively investigated in 81 patients under stable monotherapy with either drug (quetiapine: n=22, olanzapine: n=37, haloperidol: n=22). These three subgroups were compared with a control group of healthy subjects (n=30) which were matched regarding sex and age. Diagnoses of patients were schizophrenia (DSM-IV 295.xx, n=61), brief psychotic disorder (DSM-IV 298.8, n=9), schizoaffective disorder (DSM-IV 295.70, n=8) and delusional disorder (DSM-IV 297.1, n=3). There were no statistically significant differences regarding demographic characteristics between the groups. Digital EEG recordings were retrieved from a database and visually assessed by two independent investigators, and one blinded regarding medication. One patient from the quetiapine group (5%), 13 olanzapine patients (35%), five of the haloperidol patients (23%) and two subjects of the control group (7%) had an abnormal EEG. Epileptiform activity was observed in four patients (11%) of the olanzapine group, and none in the others. EEG abnormalities were statistically significantly increased with dose in the olanzapine group, in contrast to patients treated with haloperidol, quetiapine or healthy subjects. In conclusion, EEG abnormalities seem to occur rarely in patients treated with quetiapine comparable to the control group, but significantly more often with haloperidol and olanzapine, possibly due to different receptor profiles of these substances. To our knowledge, this is the first electrophysiological investigation comparing the new atypical antipsychotics quetiapine, haloperidol, olanzapine with healthy subjects.     

Bupropion and 4-OH-bupropion pharmacokinetics in relation to genetic polymorphisms in CYP2B6

Bupropion is applied in depression and smoking cessation. Genetic polymorphisms in cytochrome P450 2B6 (CYP2B6) may cause variability in bupropion pharmacokinetics since hydroxylation is known to be mediated by CYP2B6. Bupropion may be a probe drug for CYP2B6 activity in humans. Bupropion pharmacokinetics were studied after a single oral dose of 150 mg in 121 healthy male volunteers. The amino acid polymorphisms R22C, Q172H, S259R, K262R and R487C were analysed by polymerase chain reaction and restriction fragment length polymorphism and plasma concentrations were measured by high-performance liquid chromatography. Pharmacokinetic analysis was performed by non-parametric methods and by population pharmacokinetic modelling. A unimodal distribution of bupropion and hydroxybupropion kinetic parameters was detected with a mean (range) area under the curve (AUC) of 3.64 (0.89-8.14) micromol.h/l for bupropion and 25.5 (6.72-75.3) micromol.h/l for hydroxybupropion. Population kinetic analysis revealed that bupropion total clearance via CYP2B6 alleles *1, *2, *5 and *6 did not differ, but clearance via allele *4 was 1.66-fold higher compared to wild-type allele *1 (P=0.001). Corresponding to the high clearance of bupropion, carriers of the CYP2B6 genotype *1/*4 had significantly higher Cmax of hydroxybupropion compared to all other genotypes (P=0.03). Only a minor fraction of the variability in bupropion and hydroxybupropion kinetics could be explained by the known CYP2B6 amino acid variants, in particular by the CYP2B6*4 allele. The role of this allele should also be studied in other CYP2B6 substrates, including cyclophosphamide, halothane, mianserin, promethazine and propofol.     

Long-term results following pars plana vitrectomy with platelet concentrate in pediatric patients with traumatic macular hole

PURPOSE: To describe the long-term clinical course in children with a traumatic macular hole after vitrectomy with platelet concentrate. DESIGN: Interventional case series. METHODS: Four pediatric patients with a mean age of 13.2 years (range, 10-15 years) underwent pars plana vitrectomy with platelet concentrate, internal limiting membrane peeling, and SF6 gas tamponade for stage 3 traumatic macular hole repair. RESULTS: Primary closure was achieved by a single intervention in all patients with a marked visual improvement of three to seven lines after surgery. The surgically achieved visual improvement remained stable and no vision-threatening complications occurred during the mean follow up of 35.2 months (range, 27-51 months). CONCLUSION: We regard pars plana vitrectomy with platelet concentrate and SF6 gas instillation as safe and effective and, therefore, as the therapy of choice for traumatic macular holes particularly in children after a period of observation no longer than 3 to 4 months.