Biliary disease after liver transplantation: the experience of the King Faisal Specialist Hospital and Research Center, Riyadh

BACKGROUND AND AIM: The biliary tract has been referred to as the "Achilles heel" of liver transplantation. The aim of this study was to document the frequency, clinical presentation and management of biliary complications after liver transplantation in the King Faisal Specialist Hospital and Research Center (KFSH&RC), Riyadh, Saudi Arabia. METHODS: The liver transplant clinic at KFSH&RC has registered and followed 220 patients (150 male and 70 female patients; age 40.6 +/- 18.6 years; pediatric 33, adult 187) during the period from 1987 to June 2003. A total of 235 transplants were carried out on these patients. Cadaveric liver transplants had been carried out on 202 patients, non-heart beating liver transplant in three patients, live donor liver transplants in 11 and split transplant in four. Biliary reconstruction was duct-to-duct anastomosis in 147 patients and Roux-en-Y in 73. Biliary complications were suspected on clinical and biochemical parameters and confirmed using imaging techniques. RESULTS: Forty patients (18.2%) developed 53 biliary complications. These included bile leak in 16, strictures in 25, calculi in eight, and sphincter of Oddi dysfunction and possible recurrence of primary sclerosing cholangitis in the donor duct in two patients each. Bile leaks were observed in the early postoperative period (median period 30 days, range 1-150 days, 95% confidence interval [CI] 8-51). Leakage occurred at the anastomotic site in 13 patients. Patients presented with bilious drainage (n = 6), abdominal pain at T-tube removal (n = 3), fever (n = 2), sepsis (n = 1), dyspnea (n = 1) and abnormal liver tests (n = 3). Eleven patients had intra-abdominal bilious collections. Two patients were treated conservatively, eight patients had ultrasound-guided aspiration of biloma, five had biliary stenting at endoscopic retrograde cholangiopancreatography and two patients needed surgery. There were four deaths, two of which were related to bile leak, one patient was left with permanent external biliary drainage and four patients had biliary strictures in the follow-up period. Biliary strictures occurred at a median period of 360 days (range 4-2900 days; 95% CI 50-670) after the transplant. Hepatic artery thrombosis caused biliary strictures in three, while 21 strictures were localized to the anastomotic site. Biliary strictures presented with elevated liver tests in five patients, progressive cholestasis in five, cholangitis (with septicemia in five) in 11, abdominal pain in two and acute pancreatitis in three patients. Repeat sessions of endoscopic or percutaneous dilatation and stenting (mean sessions 4.4/patient, range 3-7) were attempted in 20 patients to relieve strictures, with success in only nine patients. Seven patients had surgery. Four patients with biliary strictures died. Biliary calculi developed late in the follow-up period and had the appearance of biliary casts in five and sludge in three patients. Eleven (27.5%) patients with biliary disease died compared with 35 (19.4%) patients without biliary disease. CONCLUSIONS: Biliary complications occurred in 18.2% of patients after liver transplantation and included biliary leak and biliary strictures with or without calculi. Management involved a combination of endoscopic, radiologic and operative procedures. Biliary complications caused considerable morbidity and mortality in liver transplant patients.     

Comparison of human skeletal myoblasts and bone marrow-derived CD133+ progenitors for the repair of infarcted myocardium

OBJECTIVES: The present study was designed as a face-to-face functional comparison of human skeletal myoblasts (SMs) and CD133(+) bone marrow-derived hematopoietic progenitors in an animal model of semichronic myocardial infarction. BACKGROUND: Compared with SMs, bone marrow-derived cells have the advantage of plasticity and might more effectively regenerate ischemic cardiac tissue. However, few data exist on the comparative efficacy of these two cell types in semichronic infarcts. METHODS: A myocardial infarction was created by coronary ligation in 32 nude rats. Ten days later, rats received in-scar injections of human SMs, CD133(+) progenitors, or culture medium. Left ventricular function was assessed before and one month after transplantation by echocardiography and pressure-volume loops. Immunofluorescence, polymerase chain reaction, and in situ hybridization were used to detect cells grafted in the hearts. RESULTS: One month after transplantation, left ventricular ejection fraction decreased by 8 +/- 4% in controls, whereas it increased by 7 +/- 3% in CD133(+)-grafted hearts (p = 0.0015 vs. controls) and further by 15 +/- 5% in SM-treated hearts (p = 0.008 vs. controls). Systolic indices yielded by pressure-volume loops paralleled these data. Engrafted myotubes were identified in all SM-treated hearts by immunofluorescence, whereas in CD133(+)-grafted hearts, few human cells were only detected by polymerase chain reaction. CONCLUSIONS: In the setting of postinfarction scars, the transplantation of bone marrow-derived CD133(+) progenitors improves cardiac function, but this benefit is not superior to that afforded by myogenic cells.     

Neointimal hyperplasia after stenting in a human mammary artery organ culture

Although the use of stents has limited the incidence of restenosis, in-stent restenosis remains an important problem. In-stent restenosis is the result of a healing process that induced neointimal hyperplasia through mechanisms that are still not understood. The aim of this study was to analyze the histological consequences of the healing process following stent implantation. Internal mammary arteries from atheroslerotic patients undergoing coronary artery bypass surgery were stented and maintained in culture for 0-28 days. Stent implantation after predilatation induced an extensive loss of endothelial cells whereas direct stenting preserved endothelium between the struts. Morphometric analysis shows that stent placement induced neointimal thickening. Smooth muscle alpha-actin labeling indicates that neo-intimal formation was mainly due to proliferation and migration of smooth muscle cells. Smooth muscle cell proliferation, assessed by MIB-1 staining, was maximal at day 14 after stent insertion. Human mammary artery organ culture thus provides valuable information on histological consequences of stent implantation with or without predilatation regarding endothelial cell disappearance and neointimal hyperplasia. These data also demonstrate that neointimal thickening induced by stent implantation comprises an intrinsic component resulting from the vessel wall response to stent insertion and suggest that blood factors could play an amplifying but not necessary role.     

Immediate and long-term results of percutaneous mitral balloon valvotomy in asymptomatic or minimally symptomatic patients with severe mitral stenosis.

The purpose of this study was to evaluate the safety and value of percutaneous mitral balloon valvotomy (PMBV) in asymptomatic or minimally symptomatic patients with severe mitral stenosis (MS). There are very limited data supporting the concept of PMBV in asymptomatic or minimally symptomatic patients with severe MS. We analyzed the results of 539 consecutive patients with severe MS who underwent PMBV at our hospital. Patients were divided according to their symptoms at the time of PMBV into group A (55 patients), who had few or no symptom (NYHA class 1 or 2), and group B (484 patients), who had severe symptom (NYHA class 3 or 4). Patients had clinical and echocardiographic follow-up for 0.5-15 years. There was no significant difference in baseline characteristics between the two groups. The immediate mitral valve area (MVA) was equal in both groups. The follow-up MVA was larger in group A (1.9 +/- 0.38 vs. 1.7 +/- 0.4 cm(2); P = 0.002), and restenosis occurred in 11% in group A vs. 23% in group B (P = 0.023). Actuarial freedoms from restenosis at 5, 10, and 13 years were significantly higher for group A than for group B (97% +/- 2%, 77% +/- 9%, 77% +/- 9% vs. 85% +/- 1%, 62% +/- 3%, 39% +/- 5%; P = 0.0018). Atrial fibrillation at follow-up was encountered in 11% in group A vs. 20% in group B (P = 0.042). There was a significant reduction of the left atrial size in both groups. Event-free survivals at 5, 10, and 13 years were higher for group A than for group B (97% +/- 2%, 80% +/- 9%, 80% +/- 9% vs. 86% +/- 1%, 65% +/- 3%, 42% +/- 3%; P = 0.0018). This study demonstrated excellent immediate results of PMBV in asymptomatic or minimally symptomatic patients with severe MS and long-term results are better compared to the reported natural history of such patients. We recommend mitral balloon valvotomy (MBV) for patients with severe MS with few or no symptoms, provided the valve morphology is suitable for MBV.     

Frailty in older Mexican Americans

OBJECTIVES: To identify sociodemographic characteristics and health performance variables associated with frailty in older Mexican Americans. DESIGN: A prospective population-based survey. SETTING: Homes of older adults living in the southwest. PARTICIPANTS: Six hundred twenty-one noninstitutionalized Mexican-American men and women aged 70 and older included in the Hispanic Established Populations for Epidemiologic Study of the Elderly participated in a home-based interview. MEASUREMENTS: Interviews included information on sociodemographics, self-reports of medical conditions (arthritis, diabetes mellitus, heart attack, hip fracture, cancer, and stroke) and functional status. Weight and measures of lower and upper extremity muscle strength were obtained along with information on activities of daily living and instrumental activities of daily living. A summary measure of frailty was created based on weight loss, exhaustion, grip strength, and walking speed. Multivariable linear regression identified variables associated with frailty at baseline. Logistic regression examined variables predicting frailty at 1-year follow-up. RESULTS: Sex was associated with frailty at baseline (F=4.28, P=.03). Predictors of frailty in men included upper extremity strength, disability (activities of daily living), comorbidities, and mental status scores (Nagelkerke coefficient of determination (R(2))=0.37). Predictors for women included lower extremity strength, disability (activities of daily living), and body mass index (Nagelkerke R(2)=0.29). At 1-year follow-up, 83% of men and 79% of women were correctly classified as frail. CONCLUSION: Different variables were identified as statistically significant predictors of frailty in Mexican-American men and women aged 70 and older. The prevention, development, and treatment of frailty in older Mexican Americans may require consideration of the unique characteristics of this population.     

Tonsillar actinomycosis: a clinicopathological study

Actinomycosis has been known to involve virtually every anatomic site in the body. Although actinomycosis has been identified in resected tonsils, its possible role in adeno-tonsillar disease has received little attention. A clinicopathological study of 302 patients who had adeno-tonsillar surgery is presented. Tonsillar actinomycosis was present in 86 (28.5%) patients. The statistical analysis revealed a significant association (P<0.0001) of actinomycosis and tonsillar hypertrophy (56.8%) compared to only 10.3% in the recurrent tonsillitis group. A statistically significant association (P<0.0001) of tonsillar actinomycosis and sickle cell anaemia, beta thalassaemia, bronchial asthma and beta haemolytic streptococcal infections was also seen. This data supports a predisposition of the above conditions to tonsillar actinomycosis and adeno-tonsillar hypertrophy and a possible etiopathologic role of this organism in adeno-tonsillar hypertrophy and disease. Although the clinical association of actinomycosis and tonsillar hypertrophy and beta haemolytic streptococcal infection has been described before the association of actinomycosis with sickle cell anaemia, beta thalassaemia and bronchial asthma is being observed for the first time in literature.     

Progression of primary APS (Hughes syndrome) into serological SLE: case report

An Arab woman presented with a history of multiple foetal losses and spontaneous venous thromboembolism, which recurred on several occasions. The presence of antiphospholipid antibodies in the absence of other clinical and serological features of systemic lupus erythematosus (SLE), including negative antinuclear antibodies (ANA), confirmed the diagnosis of primary antiphospholipid syndrome (PAPS). More than 15 years after the beginning of clinical events and 10 years after diagnosis, she progressed into the immunological domain of SLE without concurrent clinical features. The patient exhibited weakly positive ANA of a speckled pattern, strongly positive anti (ds) DNA antibodies and false positive VDRL. Lymphopenia has not been observed at any stage of the follow-up. Although the evolution of PAPS into SLE has been infrequently reported, this seems to be another case suggesting that PAPS in some patients may be an early manifestation of lupus. Received: 10 April 2000 / Accepted: 15 June 2000     

Amino acid challenge in patients with cirrhosis: a model for the assessment of treatments for hepatic encephalopathy.

BACKGROUND/AIMS: To mimic episodic hepatic encephalopathy after gastrointestinal bleeding under controlled conditions, cirrhotic patients were challenged with an amino acid mixture of comparable composition to haemoglobin. METHODS: Basal EEG, psychometric score (HE test), reaction times and venous blood ammonia were recorded. Following a 54 or 108 gm oral amino acid challenge, blood ammonia levels and EEG were recorded at 30-min intervals, and psychometric testing was repeated at 180 min. Ten controls (57 +/- 2) and 31 cirrhotics (52 +/- 2) of which 21 were Child's grade A or B and 10 grade C underwent the challenge. Nine had a transjugular intrahepatic porta-systemic shunt in situ. RESULTS: Seventeen patients had abnormal baseline HE scores. Basal blood ammonia and reaction time A were significantly greater in patients (52 +/- 5 micromol/l and 478 +/- 20 ms, respectively) than controls (19 +/- 2 micromol/l and 372 +/- 14 ms) (P < 0.001). Following the challenge, in patients with advanced liver disease (Child's grade B and C) the slowing of reaction time A (+85 +/- 38 and +71 +/- 31 ms, respectively; P < 0.03) and EEG (ratio of slow to fast wave activity +0.31 +/- 0.12 and +0.58 +/- 0.19; P < 0.02) were significantly greater than in controls (-3.3 +/- 8 ms and 0.00 +/- 0.03, respectively). Patients with an abnormal basal HE score had the most pronounced changes (reaction time A +110 +/- 39 ms, P < 0.01, EEG +0.52 +/- 13, P < 0.01, respectively). The change in EEG ratio correlated with the dose of amino acid administered (r = 0.96; P < 0.008). CONCLUSION: The amino acid challenge constitutes a reproducible human model of episodic, Type C hepatic encephalopathy unaffected by the complications usually encountered in clinical practice.     

Does the presence of hibernating myocardium in patients with impaired left ventricular contraction affect QT dispersion?

BACKGROUND: Hibernating myocardium is associated with increased cardiovascular events. Increased QT dispersion on the surface electrocardiogram is a marker for serious ventricular arrhythmias. In this study, we determine whether hibernating myocardium is associated with increased QT dispersion in patients with coronary artery disease and impaired left ventricular contraction. METHODS: Positron emission tomography with (13)N-ammonia and (18)F-fluorodeoxyglucose determined the presence of metabolic-perfusion mismatch defect. QT dispersion was measured by means of a digitizing tablet with validated software. QT intervals were measured on two separate occasions by two investigators blinded to the result of the positron emission tomography scans. RESULTS: Forty-two patients with impaired left ventricular contraction were studied. They were divided into two groups: group A was made up of patients with mismatch defects (n = 26) and group B was made up of patients with no mismatch defects (n = 16). The mean (SD) QT dispersion measurements were 61.7 +/- 29.8 ms and 70 +/- 24.6 ms for groups A and B, respectively (not significant). When the patients were divided according to the dominant viability status of the impaired myocardial segment, a similar result was found. The patients whose impaired myocardium was dominantly hibernating (n = 19) had a mean QT dispersion of 66.4 +/- 31.9 ms compared with 63.6 +/- 24.8 ms in the patients whose impaired myocardium was mainly scarred (not significant). CONCLUSIONS: QT dispersion is not affected by the presence of hibernating myocardium and is therefore not clinically useful in identifying patients with this phenomenon. This is in contrast with recent reports by other groups and calls for further investigation of this dichotomy.     

Emergence of multidrug-resistant Gram-negative bacteria during selective decontamination of the digestive tract on an intensive care unit

OBJECTIVES: During treatment with selective decontamination of the digestive tract (SDD), four multidrug-resistant (MDR) strains, three different Escherichia coli and one Klebsiella pneumoniae, were isolated from four patients not known as carriers of such MDR strains before their admission to the intensive care unit (ICU) in the Academic Medical Center (AMC) in Amsterdam. These isolates were extended-spectrum beta-lactamase (ESBL)-positive. We investigated whether this was due to interspecies transfer of resistance genes. METHODS: The MDR strains were typed by amplified fragment length polymorphism (AFLP) analysis. The plasmids from these strains were characterized by restriction fragment length polymorphism and the resistance genes were characterized by PCR and sequence analysis. RESULTS: The strains were genetically unrelated and contained identical plasmids with ESBL genes. CONCLUSIONS: We identified an outbreak of plasmid-mediated ESBL genes during SDD treatment in the ICU. The use of third-generation cephalosporins in SDD is associated with the emergence of ESBLs. We conclude that identification of emerging MDR Gram-negative bacteria and recognition of resistance plasmid transfer during SDD treatment are crucial for optimal application of this regimen in ICUs.