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.     

Anti-epileptogenic effect of beta-carotene and vitamin A in pentylenetetrazole-kindling model of epilepsy in mice

Vitamin A (Vit A) and its derivatives have recently been reported to be implicated in synaptic plasticity. In this study, the possible effect of Vit A and its precursor, beta-carotene on acute seizure and kindling, induced by pentylenetetrazole (PTZ) was assessed. Vit A and beta-carotene were evaluated for their ability to: (1) elevate the threshold of clonic seizures induced by i.v. infusion of PTZ; (2) suppress the seizures (clonic and tonic) and lethality induced by i.p. PTZ in PTZ-kindled mice (anticonvulsant effect); (3) attenuate the development of sensitization to convulsive and lethal effects of i.p. PTZ in kindled mice (anti-epileptogenic effect). Diazepam was employed as positive control. All the drugs showed anti-epileptogenic effect against PTZ-induced tonic seizures and lethality. Vit A and beta-carotene had no effect on clonic seizures threshold and also on tonic seizures and lethality induced by PTZ in kindled mice. Non-genomic and genomic mechanisms could be involved in the anti-epileptogenic effect of Vit A and beta-carotene.     

Global gene expression analysis of keloid fibroblasts in response to electron beam irradiation reveals the involvement of interleukin-6 pathway

Keloid is a dermal fibroproliferative lesion of unknown etiology that commonly recurs after surgical excision. Post-operative adjuvant electron beam (EB) irradiation has been successfully used to reduce keloid recurrences. To provide new insights into the molecular mechanism behind the effect of EB irradiation, we used a cDNA microarray screening of more than 5000 genes to assess early changes in gene expression between EB-irradiated and non-irradiated keloid and non-lesional dermal fibroblasts. Primary fibroblast cultures from keloid and associated non-lesional dermis obtained from five patients were exposed to 15 Gy EB irradiation and analyzed after 15 min incubation. Early response to EB irradiation showed that 96 (1.8%) genes were modulated 2-fold or more in keloid fibroblasts. Upregulated genes accounted for 29.2% (28 genes), whereas downregulated genes comprised 70.8% (68 genes), indicating a silencing of many genes in keloid fibroblasts after EB irradiation. Many of the downregulated genes play roles in the enhancement of cell proliferation and extracellular matrix production, whereas several of the upregulated genes involves in the promotion of apoptosis and extracellular matrix (ECM) degradation. Using emerging bioinformatic tools and further corroboration, the interleukin 6 (IL-6) signaling pathway was found to be mainly involved in EB irradiation response. We also showed co-expression of IL-6 and its specific receptor (IL-6Ralpha) in keloid fibroblasts that points to the existence of an IL-6 autocrine loop in these cells. These results suggested that at the molecular level, EB irradiation might hinder keloid formation by regularizing disturbances in the homeostatic equilibrium between inducer and inhibitor activities in the matrix system most likely through the IL-6 pathway. Our study provides clues for the molecular mechanism(s) behind the beneficial effect of EB irradiation in reducing keloid recurrences and may help develop alternative strategies for the therapy and prophylaxis of this lesion.     

Histopathologic changes related to fibrotic oviduct occlusion after genital tract infection of mice with Chlamydia muridarum

OBJECTIVES: We sought to determine if intraluminal occluding fibrosis of the oviduct occurs after urogenital Chlamydia muridarum infection in mice. STUDY: Oviduct occlusion was assessed by infusing dye into the distal uterus and tracking the diffusion of the dye into the oviduct. We also conducted histologic assessment of the affected tissues using hematoxylin and eosin (H&E) and Masson trichrome stains. RESULTS: All previously infected susceptible mice had occluded oviducts compared with 17.5% of previously uninfected mice. Oviduct occlusion correlated with hydrosalpinx formation and infertility. Intraluminal oviduct fibrosis was observed in several sections of tissue displaying hydrosalpinx but not in tissues without hydrosalpinx. Fibrosis was localized to the oviduct isthmus and oviduct proper, proximal to the uterus. CONCLUSION: Intralumenal occluding fibrosis of the oviduct is a sequela of infection with C. muridarum in this model. These observations support the use of the murine model to study pathogenesis of chlamydial upper genital tract infection.     

White matter hyperintensities and chronicity of depression

OBJECTIVE: White matter hyperintensities (WMHs) on T(2)-weighted magnetic resonance imaging (MRI) of the brain are associated with advanced age and late-life depression. Most investigations predominantly found these lesions in frontal lobe and basal ganglia supporting the hypothesis of a fronto-striatal dysfunction in depression. A prospective study was undertaken to investigate the association between extent of WMHs and clinical outcome in elderly depressed patients. METHODS: Thirty-one non-demented depressed subjects underwent a 1.5 T cranial MRI scan. The MRI scans were analysed in consensus by two experienced radiologists. Each MRI scan was assessed for presence and extent of WMHs, which are differentiated in periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs). A total of 21 patients of the original cohort of 31 patients were re-assessed 5 years after baseline assessment. We ascertained the severity of depressive symptoms, the longitudinal course of depression, the cognitive decline and the global assessment of functioning at follow-up visit. RESULTS: (1) Subjects with greater extent of WMHs had a significant higher Hamilton Depression Rating Scale (HAM-D) score, (2) had more severe longitudinal courses of depression (3) and had a lower Mini-Mental State Examination (MMSE) score. CONCLUSIONS: WMHs on MRI are associated with poorer outcome in elderly depressed subjects. Further studies are needed to evaluate WHMs as prognostic factor for an appropriate treatment decision-making.     

A Family History Study of Asperger Syndrome

Asperger syndrome (AS) is a childhood-onset disorder often described as a mild variant of autism. Although classified as a distinct disorder in the DSM-IV, its overlap with autism continues to be a matter of ongoing debate. While the family genetic origins of autism are well established, few studies have investigated this topic in AS using current operational criteria. In this report, we examined the family psychiatric history of 58 subjects with AS diagnosed according to DSM-IV criteria (48 males; mean age 13.34; mean full scale IQ 104.87). All subjects had a history of mild autistic social deficits; focused special interests; normal level of intelligence; and an odd and often pedantic manner of speaking. None had a previous diagnosis of autism. Of the 58 subjects with Asperger syndrome, three had first degree relatives with AS; nine (15%) had a family history of schizophrenia; and 35 (60%) had a family history of depression. Of the 64 siblings, four had a diagnosis of AS and none of autism. Compared with a group of 39 subjects with normal intelligence autism (high functioning autism, HFA; 33 males; mean age 15.34; mean full scale IQ 85.89) subjects with AS were more likely to have relatives with depression; schizophrenia; and the broader autistic phenotype. Possible reasons for and implications of these findings are discussed.