Budd-Chiari Syndrome-A Single Center Experience From the United Kingdom.

Pediatric Budd-Chiari syndrome (BCS) is a rare cause of portal hypertension and liver disease in Europe and North America. In order to understand the long-term effect of radiological intervention on BCS we performed a single center retrospective review. Fourteen cases were identified; 6 of 14 (43%) had a congenital thrombophilia with many having multiple prothrombotic mutations. Two were managed with medical anticoagulation alone and two required super-urgent transplant for acute liver failure. The remaining 10 of 14 (71%) underwent radiological intervention: 1 of 14 thrombolysis, 5 of 14 angioplasty, and 4 of 14 transjugular intrahepatic portosystemic shunt (TIPS). Six of 14 (43%) patients required repeat radiological intervention (1 angioplasty, 5 TIPS) but none required surgical shunts or liver transplantation for chronic liver disease. The time between diagnosis and treatment did not predict the need for repeat radiological intervention. These data show that radiological intervention can be highly effective, and reduces the need for surgery, though it requires specialist multidisciplinary teams for monitoring.

The tellurium-based immunomodulator, AS101 ameliorates adjuvant-induced arthritis in rats.

Despite undeniable improvement in the management of rheumatoid arthritis (RA), the discovery of more effective, less toxic and, ideally, less immune suppressive drugs are much needed. In the current study, we set to explore the potential anti-rheumatic activity of the non-toxic, tellurium-based immunomodulator, AS101 in an experimental animal model of RA. The effect of AS101 was assessed on adjuvant-induced arthritis (AIA) rats. Clinical signs of arthritis were assessed. Histopathological examination was used to assess inflammation, synovial changes and tissue lesions. Very late antigen-4 (VLA-4)+ cellular infiltration was detected using immunohistochemical staining. Enzyme-linked immunosorbent assay (ELISA) was used to measure circulating anti-cyclic citrullinated-peptide autoantibody (ACPA) and real-time polymerase chain reaction (PCR) was used to measure the in-vitro effect of AS101 on interleukin (IL)-6 and IL-1ß expression in activated primary human fibroblasts. Prophylactic treatment with intraperitoneal AS101 reduced clinical arthritis scores in AIA rats (P < 0·01). AS101 abrogated the migration of active chronic inflammatory immune cells, particularly VLA-4+ cells, into joint cartilage and synovium, reduced the extent of joint damage and preserved joint architecture. Compared to phosphate-buffered saline (PBS)-treated AIA rats, histopathological inflammatory scores were significantly reduced (P < 0·05). Furthermore, AS101 resulted in a marked reduction of circulating ACPA in comparison to PBS-treated rats (P < 0·05). Importantly, AS101 significantly reduced mRNA levels of proinflammatory mediators such as IL-6 (P < 0·05) and IL-1ß (P < 0·01) in activated primary human fibroblasts. Taken together, we report the first demonstration of the anti-rheumatic/inflammatory activity of AS101 in experimental RA model, thereby supporting an alternative early therapeutic intervention and identifying a promising agent for therapeutic intervention.

Erratum to "halo naevus or malignant melanoma: A case report" [JPRAS open volume 16, June 2018, pages 98-99].

[This corrects the article DOI: 10.1016/j.jpra.2018.03.003.].

Halo naevus or malignant melanoma: A case report.

This is a report describing the case of a 66-year-old male with development of halo naevi. A biopsy of one of these naevi revealed a malignant melanoma with extensive regression. The purpose of this report is to identify that development of halo naevi outside of childhood or adolescence should raise suspicion and may require biopsy.

Experimental and Numerical Study of Micropitting Initiation in Real Rough Surfaces in a Micro-elastohydrodynamic Lubrication Regime.

Micropitting is a form of surface fatigue damage that happens at the surface roughness scale in lubricated contacts in commonly used machine elements, such as gears and bearings. It occurs where the specific film thickness (ratio of smooth surface film thickness to composite surface roughness) is sufficiently low for the contacts to operate in the mixed lubrication regime, where the load is in part carried by direct asperity contacts. Micropitting is currently seen as a greater issue for gear designers than is regular pitting fatigue failure as the latter can be avoided by control of steel cleanliness. This paper describes the results of both theoretical and experimental studies of the onset of micropitting in test disks operated in the mixed lubrication regime. A series of twin disk mixed-lubrication experiments were performed in order to examine the evolution of micropitting damage during repeated cyclic loading of surface roughness asperities as they pass through the contact. Representative measurements of the surfaces used in the experimental work were then evaluated using a numerical model which combines a transient line contact micro-elastohydrodynamic lubrication (micro-EHL) simulation with a calculation of elastic sub-surface stresses. This model generated time-history of stresses within a block of material as it passes through the contact, based on the instantaneous surface contact pressure and traction at each point in the computing mesh at each timestep. This stress time-history was then used within a shear-strain-based fatigue model to calculate the cumulative damage experienced by the surface due to the loading sequence experienced during the experiments. The proposed micro-EHL model results and the experimental study were shown to agree well in terms of predicting the number of loading cycles that are required for the initial micropitting to occur.

Eppur Si Muove: ferritin is essential in modulating inflammation.

Ferritin, which was only discovered in the last century, has stirred a formidable debate. Ferritin has long been appreciated as a non-specific acute-phase reactant. Several years ago, we hypothesized the contributory role of ferritin as a pathogenic molecule rather than being a product of inflammation. The latest emerging evidence provides support to this notion. Such revelation provides a step forward towards the understanding of disease conditions associated with hyperferritinaemia, and hence provide new targets for treatment modalities.

Anterior ST-elevation myocardial infarction induced by rituximab infusion: A case report and review of the literature.

WHAT IS KNOWN AND OBJECTIVES: Rituximab is a chimeric monoclonal anti-CD20 antibody approved for the treatment of some lymphoid malignancies as well as for autoimmune diseases including rheumatoid arthritis (RA), idiopathic thrombocytopenic purpura (ITP) and vasculitis. Generally, rituximab is well tolerated; nevertheless, some patients develop adverse effects including infusion reactions. Albeit rare, these reactions may in some cases be life-threatening conditions. Rituximab cardiovascular side effects include more common effects such as hypertension, oedema and rare cases of arrhythmias and myocardial infarction. CASE SUMMARY: In this article, we report a case of a 58-year-old man with a history of overlap syndrome including RA and limited scleroderma who was treated with rituximab and developed a dramatic ST-elevation myocardial infarction (STEMI) during the drug administration. WHAT IS NEW AND CONCLUSION: This report underlines previous published reports emphasizing the awareness of such an association. This communication also warrants the importance of screening for ischaemic heart disease in selected cases of patients treated with rituximab.

Frequencies and phenotypic consequences of association of α- and ß-thalassemia alleles with sickle-cell disease in Bahrain.

INTRODUCTION: Bahrain has high prevalence rates of sickle cell and thalassemia in the population. This study reports the frequencies and phenotypic characteristics of α- and/or ß-thalassemia associated with sickle-cell disease (SCD) in a tertiary care hospital. METHODS: Adult SCD patients (n = 200) were screened for the common α- and ß-thalassemia alleles prevalent in the region using molecular techniques. Results of CBC, hemoglobin analysis, and average annual frequencies of severe pain episodes and numbers of transfused red cell units were documented. RESULTS: Patients were grouped on the basis of molecular studies as sickle-cell anemia (SS, n = 131), SS/α-thalassemia with three normal genes (n = 27), SS/α-thalassemia with two normal genes (n = 11), sickle-ß-thalassemia (Sß, n = 23), and Sß with co-inherited α-thalassemia (n = 8). Identified α-thalassemia determinants were -α3.7 (n = 52), -α4.2 (n = 4), αT-Saudi α (n = 1), and αHph α (n = 1). All ß-thalassemia alleles were ß0 defects. Sickle-thalassemia association resulted in higher hemoglobin, hematocrit, and erythrocyte counts with reduced MCV and reticulocytes. Significant clinical associations were as follows: increased severe pain frequency with α-thalassemia (three-gene group); red cell transfusion with ß-thalassemia alleles and female gender. CONCLUSION: One-third of patients with SCD co-inherited α- and/or ß-thalassemia alleles and these associations explained some of the observed phenotypic variability. A low prevalence of nondeletion α-thalassemia alleles was observed in these patients. The most significant disease amelioration occurred in SCD associated with two α-thalassemia alleles.

Successful long-term outcome of liver transplantation in late-onset lysosomal acid lipase deficiency.

Late-onset LAL deficiency, previously referred to as cholesteryl ester storage disorder, is a rare lysosomal storage disorder characterized by accumulation of cholesteryl esters. It has a heterogeneous clinical phenotype including abdominal pain, poor growth, hyperlipidemia with vascular complications and hepatosplenomegaly. End-stage liver disease may occur, but there are few reports of successful LT. There are also concerns that systemic manifestations of the disease might persist post-LT. We report a case with excellent outcome eight yr following LT. The subject was noted to have asymptomatic hepatosplenomegaly during an intercurrent illness, and LAL deficiency was confirmed with compound heterozygosity in the LIPA. Despite dietary fat restriction, he developed signs of progressive liver disease and subsequently developed hepatopulmonary syndrome. He underwent cadaveric LT at the age of nine and a half yr and recovered with prompt resolution of hepatopulmonary syndrome. Eight yr post-transplant he has normal growth, normal lipid profile, and liver and renal function tests. Liver histology showed no evidence of disease recurrence at this stage. LT in this subject resulted in an excellent functional correction of late-onset LAL deficiency.

The thermoluminescence glow curve and the deconvoluted glow peak characteristics of erbium doped silica fiber exposed to 70-130 kVp x-rays.

In regard to thermoluminescence (TL) applied to dosimetry, in recent times a number of researchers have explored the role of optical fibers for radiation detection and measurement. Many of the studies have focused on the specific dopant concentration, the type of dopant and the fiber core diameter, all key dependencies in producing significant increase in the sensitivity of such fibers. At doses of less than 1 Gy none of these investigations have addressed the relationship between dose response and TL glow peak behavior of erbium (Er)-doped silica cylindrical fibers (CF). For x-rays obtained at accelerating potentials from 70 to 130 kVp, delivering doses of between 0.1 and 0.7 Gy, present study explores the issue of dose response, special attention being paid to determination of the kinetic parameters and dosimetric peak properties of Er-doped CF. The effect of dose response on the kinetic parameters of the glow peak has been compared against other fiber types, revealing previously misunderstood connections between kinetic parameters and radiation dose. Within the investigated dose range there was an absence of supralinearity of response of the Er-doped silica CF, instead sub-linear response being observed. Detailed examination of glow peak response and kinetic parameters has thus been shown to shed new light of the rarely acknowledged issue of the limitation of TL kinetic model and sub-linear dose response of Er-doped silica CF.

Multivariate analysis of PRISMA optimized TLC image for predicting antioxidant activity and identification of contributing compounds from Pereskia bleo.

Multivariate analysis of thin-layer chromatography (TLC) images was modeled to predict antioxidant activity of Pereskia bleo leaves and to identify the contributing compounds of the activity. TLC was developed in optimized mobile phase using the 'PRISMA' optimization method and the image was then converted to wavelet signals and imported for multivariate analysis. An orthogonal partial least square (OPLS) model was developed consisting of a wavelet-converted TLC image and 2,2-diphynyl-picrylhydrazyl free radical scavenging activity of 24 different preparations of P. bleo as the x- and y-variables, respectively. The quality of the constructed OPLS model (1 + 1 + 0) with one predictive and one orthogonal component was evaluated by internal and external validity tests. The validated model was then used to identify the contributing spot from the TLC plate that was then analyzed by GC-MS after trimethylsilyl derivatization. Glycerol and amine compounds were mainly found to contribute to the antioxidant activity of the sample. An alternative method to predict the antioxidant activity of a new sample of P. bleo leaves has been developed.

Early and late complications after liver transplantation for propionic acidemia in children: a two centers study.

Propionic acidemia (PA) is a severe metabolic disorder with cardiac and neurologic complications and a poor quality of life. Liver transplantation (LT) was thus proposed in PA to increase enzyme activity. We studied retrospectively LT in PA in two European centers. Twelve patients underwent 17 LTs between 1991 and 2013. They developed severe, unusual and unexpected complications, with high mortality (58%). When present, the cardiomyopathy resolved and no acute metabolic decompensation occurred allowing dietary relaxation. Renal failure was present in half of the patients before LT and worsened in all of them. We suggest that cardiac and renal functions should be assessed before LT and monitored closely afterward. A renal sparing immunosuppression should be used. We speculate that some complications may be related to accumulated toxicity of the disease and that earlier LT could prevent some of these consequences. As kidney transplantation has been performed successfully in methylmalonic acidemia, a metabolic disease in the same biochemical pathway, the choice of the organ to transplant could be further discussed.

Thermoluminescence characteristics of Ge-doped optical fibers with different dimensions for radiation dosimetry.

Important thermoluminescence (TL) properties of five (5) different core sizes Ge-doped optical fibers have been studied to develop new TL material with better response. These are drawn from same preform applying different speed and tension during drawing phase to produce Ge-doped optical fibers with five (5) different core sizes. The results of the investigations are also compared with most commonly used standard TLD-100 chips (LiF:Mg,Ti) and commercial multimode Ge-doped optical fiber (Yangtze Optical Fiber, China). Scanning Electron Microscope (SEM) and EDX analysis of the fibers are also performed to map Ge distribution across the deposited region. Standard Gamma radiation source in Secondary Standard Dosimetry Lab (SSDL) was used for irradiation covering dose range from 1Gy to 10Gy. The essential dosimetric parameters that have been studied are TL linearity, reproducibility and fading. Prior to irradiation all samples ∼0.5cm length are annealed at temperature of 400°C for 1h period to standardize their sensitivities and background. Standard TLD-100 chips are also annealed for 1h at 400°C and subsequently 2h at 100°C to yield the highest sensitivity. TL responses of these fibers show linearity over a wide gamma radiation dose that is an important property for radiation dosimetry. Among all fibers used in this study, 100µm core diameter fiber provides highest response that is 2.6 times than that of smallest core (20µm core) optical fiber. These fiber-samples demonstrate better response than commercial multi-mode optical fiber and also provide low degree of fading about 20% over a period of fifteen days for gamma radiation. Effective atomic number (Zeff) is found in the range (13.25-13.69) which is higher than soft tissue (7.5) however within the range of human-bone (11.6-13.8). All the fibers can also be re-used several times as a detector after annealing. TL properties of the Ge-doped optical fibers indicate promising applications in ionizing radiation dosimetry.

Selenium homocholic acid taurocholate scanning, selenium-75-labeled bile acid, a novel method for testing the function of the terminal ileum in small bowel transplant recipients: a pilot study.

INTRODUCTION: The terminal ileum (TI) is important for the active reabsorption of bile salts and is the site of allograft rejection; disruption of enterohepatic circulation (EHC) may give insights to inflammatory and other physiologic processes at the TI. SUBJECTS AND METHODS: Four children aged 5 to 12 years who had received small bowel transplantation (SBTx), 3 recovering from post-transplant lymphoproliferative disease (PTLD) and 1 with acute rejection, were studied. Two of the 4 had stoma reversal. Another child (15 years) with progressive familial intrahepatic cholestasis (PFIC) and pruritus, despite liver transplantation and biliary diversion, was studied. Selenium homocholic acid taurocholate scanning ((75)SeHCAT) capsule was given orally (n = 3) or via introducer during endoscopy (n = 2); a baseline whole-body gamma camera scan was done 4 hours later and on days 1 to 5. RESULTS: The normal 3-day bile salt retention is 30% to 70% of baseline and normal adult biological half-life, t½ is 62 ± 17 hours. The results in children with a stoma were very low (0.1% at 7.6 hours; 5% at 17 hours). The children with reversed stoma had retention and t½ closer to the reference range (18% at 29 hours; 22% at 33 hours). The child with PFIC + biliary diversion had an initial very high gamma emission from the stoma bag suggesting excellent reabsorption of bile salts from his TI, but retention was 0.6% and t½ 9.8 hours, demonstrating efficient biliary diversion. CONCLUSION: These results confirm children with stomas malabsorb bile acids, which can be ameliorated after stoma closure. SeHCAT demonstrated that the biliary diversion was working well and may be helpful in preoperative assessment of abnormal EHC. The role of SeHCAT in SBTx requires further evaluation.

Rejection is less common in children undergoing liver transplantation for hepatoblastoma.

To compare the incidence of acute histologically proven rejection in children who have had a liver transplant for hepatoblastoma with a control group of children transplanted for biliary atresia (EHBA). A retrospective case notes based study was performed. Twenty patients were identified with hepatoblastoma who were transplanted at a single unit between 1991 and 2008. These were matched as closely as possible for age, gender, year of transplant and type of immunosuppression used to the control group transplanted for biliary atresia (n = 60). There was a significant decrease in rate of acute rejection as assessed by the rejection activity index (RAI) in the hepatoblastoma group (75% vs. 50%, respectively, p < 0.04). Chronic rejection was rare in both groups, but twice as common in the biliary atresia group. Equal levels of immunosuppression were achieved in both groups. Renal function was noted to be reduced one yr post-transplant in both groups, as previously reported. A modified immunosuppression regimen could be considered in children with hepatoblastoma undergoing liver transplantation.

Use of tissue expansion to facilitate liver and small bowel transplant in young children with contracted abdominal cavities.

Liver and small bowel transplant is an established treatment for infants with IFALD. Despite organ reduction techniques, mortality on the waiting list remains high due to shortage of size-matched pediatric donors. Small abdominal cavity volume due to previous intestinal resection poses a significant challenge to achieve abdominal closure post-transplant. Seven children underwent tissue expansion of abdominal skin prior to multiorgan transplant. In total, 17 tissue expanders were placed subcutaneously in seven children. All seven subjects underwent re-exploration to deal with complications: hematoma, extrusion, infection, or port related. Three expanders had to be removed. Four children went on to have successful combined liver and small bowel transplant. Two children died on the waiting list of causes not related to the expander and one child died from sepsis attributed to an infected expander. Tissue expansion can generate skin to facilitate closure of abdomen post-transplant, thus allowing infants with small abdominal volumes to be considered for transplant surgery. Tissue expansion in children with end-stage liver disease and portal hypertension is associated with a very high complication rate and needs to be closely monitored during the expansion process.

Staged abdominal closure after small bowel or multivisceral transplantation.

Following paediatric SBMT, size discrepancy between the recipient's abdomen and the graft may lead to ACS, graft dysfunction, and death. We report our experience with SAC in these patients. Between 04/1993 and 03/2009, 57 children underwent 62 SBMTs. When abdominal wall tension seemed excessive for safe PAC, SAC was performed, using a Silastic® sheet and a vacuum occlusive dressing. Transplantations with SAC (23 combined liver and small bowel [CLB]) were compared with those with PAC [14 ISB and 25 CLB]. Indications for transplantation, preoperative status (after stratification for ISB/CLB transplants), age at transplantation, donor-to-recipient weight ratio, reduction in bowel and/or liver, and incidence of wound complications were not different in both groups. Post-operative intubation, stay in intensive care unit, and hospital stay were prolonged after SAC. Two deaths were related to ACS after PAC, none after SAC. Since 2000, one-yr patient survival is 73% after ISB transplantation and 57% vs. 75% after CLB transplantation with PAC vs. SAC, respectively (NS). SAC safely reduces severe ACS after paediatric SBMT and can be combined with graft reduction for transplantation of small recipients.

Long-term outcomes of isolated liver transplantation for short bowel syndrome and intestinal failure-associated liver disease.

BACKGROUND AND AIM: A select group of children with short bowel syndrome (SBS) and intestinal failure-associated liver disease (IFALD) fulfill the criteria for isolated liver transplantation (iLTx). Long-term results in this group of patients have not been reported. METHODS: A retrospective study of the medical records of 8 survivors of 14 children who underwent iLTx for SBS and IFALD from 1998 to 2005, managed by a multidisciplinary intestinal rehabilitation team at our institution. RESULTS: Median follow-up is 107.5 months (range 89-153 months). Five of 8 children were weaned from parenteral nutrition (PN) to enteral nutrition (EN) in a median of 10 months after iLTx (range 3-32 months). Three of 5 children were subsequently weaned from EN to full oral feeding in 13, 24, and 53 months after stopping PN, whereas the remaining 2 are still receiving EN 118 and 74 months after stopping PN. These 5 children maintain their weight median z scores with a median increase of 1.59 (range 1.24-1.79) compared with the pretransplant z score, whereas the height z scores show fluctuations through the years with a median change of 0.12 (range -0.29 to 0.36). The other 3 of 8 children developed progressive intestinal failure; 2 underwent isolated small bowel transplantation 112 and 84 months after iLTx and the third is receiving PN. CONCLUSIONS: Children with SBS and IFALD who have the potential for adaptation in the residual bowel can undergo iLTx, but it is a treatment option to be exercised with extreme caution. These children need close follow-up with an experienced multidisciplinary team to monitor nutritional outcomes and may need consideration for transplant or nontransplant surgery in the long term.

Predictive modelling of fatigue failure in concentrated lubricated contacts.

Reducing frictional losses in response to the energy agenda will require use of less viscous lubricants causing hydrodynamically-lubricated bearings to operate with thinner films leading to "mixed lubrication" conditions in which a degree of direct interaction occurs between surfaces protected only by boundary tribofilms. The paper considers the consequences of thinner films and mixed lubrication for concentrated contacts such as those occurring between the teeth of power transmission gears and in rolling element bearings. Surface fatigue in gears remains a serious problem in demanding applications, and its solution will become more pressing with the tendency towards thinner oils. The particular form of failure examined here is micropitting, which is identified as a fatigue phenomenon occurring at the scale of the surface roughness asperities. It has emerged recently as a systemic difficulty in the operation of large scale wind turbines where it occurs in both power transmission gears and their support bearings. Predictive physical modelling of these contacts requires a transient mixed lubrication analysis for conditions in which the predicted lubricant film thickness is of the same order or significantly less than the height of surface roughness features. Numerical solvers have therefore been developed which are able to deal with situations in which transient solid contacts occur between surface asperity features under realistic engineering conditions. Results of the analysis, which reveal the detailed time-varying behaviour of pressure and film clearance, have been used to predict fatigue and damage accumulation at the scale of surface asperity features with the aim of improving understanding of the micropitting phenomenon. The possible consequences on fatigue of residual stress fields resulting from plastic deformation of surface asperities is also considered.