Refractory Type Research Articles

Polymerase gamma deficiency (POLG): Clinical course in a child with a two stage evolution from infantile myocerebrohepatopathy spectrum to an Alpers syndrome and neuropathological findings of Leigh’s encephalopathy

AimsDescription of the clinical course in a child compound heterozygous for POLG1 mutations, neuropathology findings and results of dietary treatment based on fasting avoidance and long chain triglycerides (LCT) restriction. ResultsAt 31/2 months of age the patient presented with severe hypoglycemia, hyperlactatemia, moderate ketosis and hepatic failure. Fasting hypoglycemia occurred 8 h after meals. The hypoglycemia did not respond to glucagon. She was supplemented with IV glucose and/or frequent feedings, but developed liver insufficiency which was reversed by long-chain triglyceride (LCT) restriction. Alpha-foeto-protein (AFP) levels were elevated and returned to low values after dietary treatment. Liver biopsy displayed cirrhosis, bile ductular proliferation, steatosis, isolated complex IV defect in part of the liver mitochondria, and mitochondrial DNA depletion (27% of control values). Two heterozygous mutations (p. [Ala467Thr] + p. [Gly848Ser]) were found in the POLG1 gene. At 3 years of age she progressively developed refractory mixed type seizures including a focal component and psychomotor regression which fulfilled the criteria of Alpers syndrome (AS) although the initial presentation was compatible with infantile myocerebrohepatopathy spectrum (MCHS). She died at 5 years of age of respiratory insufficiency. Neuropathologic investigation revealed lesions in the right striatal area and the inferior colliculi typical for Leigh’s encephalopathy. ConclusionThe present patient showed an evolution from infantile MCHS to AS, and dietary treatment seemed to slow the progression of liver failure. In spite of the late clinical features of AS, it extends the neuropathological spectrum of AS and polymerase gamma deficiency (POLG) to Leigh syndrome lesions.

HsTRAIL/Apo2L Induces Apoptosis in Enteropathy-Associated T-Cell Lymphoma

Abstract 1665EATL is an intestinal tumor of aberrant intraepithelial T-lymphocytes (IELs) and may be preceded by refractory celiac disease type II (RCD II). Current therapies include surgery, chemotherapy and autologous and/or allogeneic stem cell transplantation. Despite these therapies, the overall outcome of EATL is very poor with 1- and 5-year survival rates in the range of 31–39% and 8–20%, respectively. Therefore, new therapeutic options are needed. Human soluble tumor necrosis factor-related apoptosis-inducing ligand, hsTRAIL/Apo2L, a member of the TNF family, has proven to selectively kill tumor cells via an alternative, death-receptor mediated apoptosis pathway. In this present study we evaluated if hsTRAIL/Apo2L induces apoptosis in both isolated lymphoma cells of EATL biopsies and isolated cells of RCD II biopsies.hsTRAIL/Apo2L induced apoptosis in isolated EATL lymphoma cells. RCD II cells were less sensitive to hsTRAIL/Apo2L compared to EATL cells. hsTRAIL/Apo2L induced apoptosis in EATL cells was caspase-9 dependent, but unexpectedly active caspase-8 involvement could not be detected. RT-MLPA analysis on EATL samples confirmed this observation by showing increased levels of c-Flip in EATL cells, which suggests a blockage in the extrinsic apoptosis pathway. Both EATL and RCDII cells showed expression of TRAIL receptors R1 and R2 and almost no expression of R3 and R4.In conclusion, our study showed that hsTRAIL/Apo2L induces apoptosis in EATL cells through the intrinsic apoptosis pathway. Moreover, we showed that TRAIL receptor R1 and R2 are expressed in EATL cells. Based on these results, hsTRAIL/Apo2L may be a new therapeutic option for EATL patients. Disclosures:No relevant conflicts of interest to declare.

Refractory of Furnaces to Reduce Environmental Impact

The energy load of furnaces used in the manufacturing process of ceramics is quite large. Most of the environmental impact of ceramics manufacturing is due to the CO2 produced from this high energy load. To improve this situation, R&D has focused on furnace systems and techniques of control in order to reduce energy load. Since furnaces are comprised of refractory, consideration of their mechanical and thermal characteristics is important. Herein are described several refractory types which were chosen through comparison of the characteristics which contribute to heat capacity reduction, heat insulating reinforcement and high emissivity, thereby improving thermal radiation heat transfer efficiency to the ceramic articles. One selected refractory material which will reduce the environmental impact of a furnace, chosen considering low heat capacity and high emissivity characteristics, is SiC. In this study, thermal radiation heat transfer efficiency improvement and its effect on ceramic articles in the furnace and oxidation behaviour were investigated at 1700K. A high density SiC refractory, built into the furnace at construction, has relatively high oxidation durability and has the ability to reduce environmental impact-CO2 by 10 percent by decreasing the furnace's energy load. However, new oxidation prevention techniques for SiC will be necessary for long-term use in industrial furnaces, because passive to active oxidation transition behaviour of commercial SiC refractory is coming to close ideal.

Sulthiame in refractory paediatric epilepsies: An experience of an ‘old’ antiepileptic drug in a tertiary paediatric neurology unit

Purpose Sulthiame is an old antiepileptic drug primarily used in a few European countries for the treatment of benign epilepsy of childhood with central temporal spikes. Other studies suggest that it might be effective in children and adults with a range of refractory seizure types. Methods A retrospective case note review was undertaken to evaluate the efficacy and safety of sulthiame as adjunctive therapy in children with refractory epilepsies. Results Twenty patients (10 female) were evaluated, aged 10.7 (range 2.1–17) years. The median duration of treatment with sulthiame was 18 (range 2–37) months. Fifty five percent of patients showed at least a 50% reduction in seizure frequency and two patients were seizure-free at the end of follow-up. Patients with focal seizures responded best. Seven patients reported side effects, leading to withdrawal of the drug in two (10%). Conclusion Sulthiame was reasonably effective and well-tolerated in a heterogeneous group of 20 children with refractory epilepsies. Although an ‘old’ antiepileptic drug it should be considered in a similar population.

Effective method of service life extension for glass furnaces

A technology has been developed for high-temperature ceramic welding for the purpose of repairing the lining in glass furnaces without stopping and cooling the furnace. This maintenance method makes it possible to restore damaged refractory articles and, if necessary, to change their properties toward higher heat-resistance as well as resistance to corrosive media and mechanical actions. The main and auxiliary equipment for ceramic welding have been developed and repair pastes for restoring different types of refractories obtained.

Encephalitis Associated With Glutamic Acid Decarboxylase Autoantibodies in a Child

To increase the recognition of glutamic acid decarboxylase autoantibodies-related encephalitis in childhood. Case report and review of the literature. A 6-year-old girl who had developed refractory seizures, developmental regression, and type 1 diabetes mellitus at age 25 months. Blood analysis, electroencephalogram, cerebral magnetic resonance imaging, positron emission tomography scan, lumbar puncture, and measurement of glutamic acid decarboxylase activity were performed. Treatment with repeated plasmapheresis and rituximab, with concomitant antiepileptic drugs, was administered. Highly elevated titers of glutamic acid decarboxylase autoantibodies were found in the serum, as well as in the cerebrospinal fluid. Major clinical improvement in parallel with a decrease in the levels of serum and cerebrospinal fluid antibodies was observed with treatment. Encephalitis associated with glutamic acid decarboxylase autoantibodies is a severe epileptic disorder that occurs in young children as well as adults. It may be partially reversible with aggressive immunomodulatory treatment, including plasmapheresis and rituximab. Studies are warranted to determine whether early treatment leads to complete remission.

A Historical Perspective of Aluminium Casthouse Furnace Developments

This paper provides an historical perspective of aluminium casthouse furnace evolution over the past 30 years or so with a view towards explaining the reasons for those innovations, and the success or otherwise of some of the changes which were tried. The paper covers electrically energized furnaces such as channel and coreless induction furnaces as well as “glo-bar” heated furnaces. It goes on to discuss fuel fired furnaces including melters of many varieties including side charged, top charged, sidewell, and multichamber designs. Additionally it includes melter/holders and conventional holding (casting furnaces). The drivers for change have been many and varied, and have included the need to cope with capacity creep, reduced specific energy consumption, improved asset utilization, greatly enhanced process intensity, reduced melt loss, improved furnace reliability, acceptance of the benefits of automation, and always the concern for improved safety in all aspects of furnace operation. Accordingly the paper covers related matters such as major changes in burner choices; furnace charging and tending; refractory type and design; furnace enlargement; forced convection stirring; dealing with difficult scraps; the demise of stationary casting furnaces, recognition of the need for improved metal cleanliness; and the challenge to deal with a wider range of difficult alloys. Additionally there has been a much greater understanding of furnace functionality by computer modelling of heat transfer as well as modelling of furnace stress design by FEA as well as some physical modelling and full scale tests to validate computer model assumptions. One of the most significant aspects of improved science has been the manner in which furnaces are operated to maximize productivity, reduce energy cost and melt loss, and by the adoption of purpose built tending vehicles. Finally the paper discusses prospects for future technological development and other aspects of improved productivity through achieving target composition first time as well as by better production planning, together with the aid of dynamic simulation for optimisation of activities.

Unexpected cutaneous toxicity of IGEV regimen in patients with Hodgkin lymphoma.

e18543 Background: IGEV (ifosfamide, gemcitabine, vinorelbine, and prednisolone) is an active regimen increasingly used in relapsed/refractory Hodgkin lymphoma (HL) before autologous stem cell transplantation with CR and adequate CD34+ cell collection rate of more than 50% and 90%, respectively. No substantial non-hematological toxicity had been reported so far. Methods: Between December 2009 and October 2010, 12 patients (pts): 5 female and 7 male, median age of 35, range: 23-51, with refractory HL received IGEV regimen. 10 pts were diagnosed with refractory classical HL NS type, one male pts had HL transformed from follicular lymphoma, one female pts had classical HL partly transformed to diffuse large B-cell lymphoma and additionally received rituximab. Results: Of a total of 44 cycles followed by G-CSF support, 4 (9%) were delayed and dose reduced due to grade 3/4 hematologic toxicity. 6 pts, 5 female and 1 male (50%) experienced cutaneous toxicity including grade 3/4 reactions in 4/6 pts (60%). Skin symptoms included rash, maculopapular pruritic eruptions and vesicular erythema with serous effusion in 2 pts. Lesions were itchy or burning, located on the trunk and extremities. Skin symptoms occurred repeatedly after each cycle and resolved within 10-14 days with glucocorticoid and antihistaminic treatment. In 1 case, IGEV chemotherapy was terminated due to prolonged itching and burning sensations. Of 11 evaluable pts, 7 responded (64%) with CR in 4 pts (36%). Conclusions: Reportedly, rate of cutaneous adverse events related to gemcitabine monotherapy is up to 30%. Unexpectedly high incidence of skin events in our pts might have resulted from peculiar toxic synergy of combination agents. The only clinical characteristic apparently related to skin toxicity of gemcitabine was female sex.

Applicability of Different Endovascular Methods for Treatment of Refractory Budd–Chiari Syndrome

The study's objective was to evaluate the applicability of different endovascular methods for treatment of refractory type of Budd-Chiari syndrome (BCS) under specific scenarios frequently encountered in patients. The treatment methods were evaluated in 197 patients with the following four types of refractory BCS: lesions of the inferior vena cava (IVC) including a special shape diaphragm (e.g., a knife- or a vertically shaped diaphragm, etc.), occlusion of the long segment of IVC, IVC obstruction combined with thrombosis, and occlusion of the hepatic vein. The choice of endovascular treatment depended on the degree of difficulty to puncture the membrane after spatial orientation. There was a need to adjust the curvature of the device to fit the natural angle of IVC. When IVC lesions were combined with thrombosis, the treatment was adjusted depending on the freshness of the thrombus. Different routes were used to rupture the membrane and expand the lesion. The majority of patients recovered without complications. The few complications observed were the following: 1 case of death due to a postoperative stress ulcer, 1 case of a successfully treated pericardial tamponade, 1 case of stent migration, and 3 cases of failure to stent and re-occlusion that occurred in the follow-up period. To conclude, BCS is preferably treated via endovascular intervention; however, the particular choice depends on individual circumstances.

Variation of Poisson's ratio of refractory materials with thermal shocks

Investigations into the changes of Poisson's ratio as well as other mechanical properties of selected types of refractories subjected to thermal shocks have been carried out. The investigations included several types of porous refractory materials e.g. magnesia, magnesia–spinel, magnesia–chrome, chrome–magnesia, mullite, silica and low cement chamotte castable. The Poisson's ratio value of the examined materials decreased after each thermal shock. Decreasing of Poisson ratio caused by a stronger drop in Young's modulus than that for shear modulus was explained. It was found that some tested materials were characterized by low values of Poisson's ratio, which after series of severe thermal shocks decreased even to negative values. In order to explain the observed phenomenon, an attempt to correlate the obtained results with the microstructure of materials before and after a series of thermal shocks was undertaken. A hypothetical model of the microstructure of a porous ceramic material with negative Poisson ratio was proposed.

Is their a Role for Capsule Endoscopy in Patients with Coeliac Disease and Persisting Symptoms?

IntroductionUp to one third of patients with coeliac disease fail to have a symptomatic response to gluten-free diet (GFD), or relapse after initial response. Causes include inadvertent gluten exposure and...

1 Norepinephrine Infusion for Treatment of Type 1 Hepatorenal Syndrome

NOREPINEPHRINE INFUSION FOR TREATMENT OF TYPE 1 HEPATORENAL SYNDROME Sabeen Abid, Nauman Shahid, David Sass, Kenneth Rothstein, David Reich, Karthik Ranganna , Ziauddin Ahmed. Drexel University College of Medicine, Philadelphia PA Hepatorenal syndrome Type 1 (HRS-1) is a complication of advanced liver cirrhosis associated with high mortality and a median survival of 2 weeks. Treatment of HRS-1 and reversal of the underlying pathophysiology is extremely important for patients awaiting liver transplantation (OLT). Terlipressin is the treatment of choice for type 1 HRS but it is expensive and not approved by FDA. Norepinephrine (NE) has been shown to be equally effective and safe in two RCT. We report a case of 27 year old white male with Child’s C cirrhosis who was listed for OLT. His disease was complicated by refractory ascites and HRS type 2 at baseline. He was admitted for an acute change in mental status with a MELD score of 30 and serum creatinine (Scr) of 1.9 mg/dl. The Scr continued to rise to 2.7 mg/dl by hospital day 7 despite adequate volume expansion with normal saline and albumin. A diagnosis of HRS-1 was made after carefully ruling out other causes of renal dysfunction. A combination of octreotide and midodrine was initiated however the patient failed to respond with a continued rise in Scr to 3.5 mg/dl by day 11. At this point the above therapy was discontinued and an infusion of NE was started at 10 mcg/hr. Within 48 hours his urine output increased from 1445 ml on day 0 to 3575 ml on day 1and 3725 ml on day two, Scr decreased from 3.5 mg/dl to 2.8 mg/dl at day 2. The patient tolerated the infusion well. At this time a liver became available and the patient underwent a successful OLT. At a recent follow up visit, 9 months post OLT, the patient had a stable Scr of 1.0 mg/dl. Infusion of NE can be an effective treatment of HRS-1. It should be considered as a primary therapy in patients whom are awaiting OLT due to its availability, cost and comparable efficacy to Terlipressin.

Long-term effects of biological amnion combined with glaucoma valve implantation for neovascular glaucoma

Background Neovascular glaucoma is a type of refractory glaucoma.Biological amnion combined with glaucoma valve implantation is a primary therapy and its long-term effectiveness is noticeable. Objective The goal of this Survey was to evaluate the effectiveness of biological amnion combined with glaucoma valve implantation for neovascular glaucoma and compare the clinical outcome with simple glaucoma valve implantation. Methods This was a retrospective observational case series.The clinical data of 44 eyes of 44 patients received biological amnion combined with glaucoma valve implantation for neovascular glaucoma and 43 eyes of 43 patients received simple glaucoma valve implantation for neovascular glaucoma were retrospectively analyzed and compared.The age,sex and disease-cause were matched between these two groups.Patients were followed-up for 24 months after operation.Surgery success was identified as the intraocular pressure(IOP) 0.05). Conclusion The biological amnion combined with glaucoma valve implantation surgery may be more effective and safe for the treatment of neovascular glaucoma than with glaucoma va]ve only. Key words: Biological amnion; Glaucoma valve; Glaueoma/neovascular

High temperature mechanical behavior of Al 2O 3–MgO–C refractories for steelmaking use

The advantages of Al 2O 3–MgO–C (AMC) refractories are achieved mainly by the incorporation of graphite and the formation of spinel by solid reaction between alumina and magnesia. Regarding other members of oxide-C refractories (such as MgO–C bricks) and others properties (such as the slag corrosion resistance or the PLC), the information about the mechanical behavior of this type of refractories is scarce. In this work, the mechanical behavior of commercial AMC brick used in steelmaking ladles was studied by stress–strain curves in compression at RT and 1000 °C (nitrogen atmosphere). Before the mechanical testing, a comprehensive characterization of AMC materials was performed by several techniques: XRD, DTA/TGA, SEM/EDS, aggregate size distribution analysis and densities, porosities and thermal expansion measurements. Mechanical parameters such as fracture strength and strain, yield stress and Young modulus were determined together with the main characteristics of the fracture. In order to study the transformations occurred during the stay at high temperature, the specimens tested at 1000 °C were analyzed by the same techniques used for the as-received bricks characterization (with the exception of the thermal expansion analysis). The AMC refractories displayed differences in the mechanical behavior and its dependence on the testing temperature. These results were explained considering the differences in the composition and microstructure of both refractories and in their thermal transformations.

Small Intestinal Release Mesalamine for the Treatment of Refractory Celiac Disease Type I

The goal of this study is to evaluate the safety and efficacy of Small intestinal release mesalamine (SIRM) for symptom relief in refractory celiac disease (RCD). Therapeutic options for the RCD are inadequate and treatment with corticosteroids and immunosuppressants is limited by side effects. SIRM has been shown to have local antiinflammatory action and excellent tolerability. We reviewed records of the RCD patients who received SIRM in an open-label therapeutic trial. Data included demographics, disease characteristics, dose and duration of SIRM therapy, and response. Response was categorized as complete if there was complete resolution of symptoms, partial if there was at least 50% improvement, and nonresponsive if there was less than 50% improvement. Four patients were treated with SIRM alone and 6 received SIRM and oral budesonide. Within 4 weeks, 50% had complete response and an additional 10% had partial response. Two of the 6 patients were able to discontinue budesonide. One patient discontinued SIRM owing to headaches. SIRM seems to be a safe and efficacious treatment option in patients with RCD. Larger, controlled trials of this agent are warranted.

Evaluation of Cladribine treatment in refractory celiac disease type II

To evaluate cladribine [2-chlorodeoxyadenosine (2-CdA)] therapy in refractory celiac disease (RCD) II. An open-label cohort-study of RCD II patients treated with 2-CdA was performed between 2000 and 2010. Survival rate, enteropathy associated T-cell lymphoma (EATL) occurrence, clinical course, and histological and immunological response rates were evaluated. Overall, 32 patients were included with a median follow-up of 31 mo. Eighteen patients responded well to 2-CdA. Patients responsive to 2-CdA had a statistically significant increased survival compared to those who were unresponsive. The overall 3- and 5-year survival was 83% in the responder and 63% and 22% in the non-responder group, respectively. The overall 2-year clinical, histological and immunological response rates were 81%, 47% and 41%, respectively. Progression into EATL was reported in 16%, all of these patients died. Treatment of RCD II with 2-CdA holds promise, showing excellent clinical and histological response rates, and probably less frequent transition into EATL.

Electroclinical Features of Lennox-Gastaut Syndrome in Adulthood and Adolescence

Introduction: Lennox- Gastaut Syndrome (LGS) is characterized by seizures which may have inconspicuous semiological features so they may be unrecognized while patients are continuously deteriorating. To confirm its clinical and electrographic characteristics is mandatory, which has therapeutic and prognostic implications. Those features have not been completely elucidated in LGS in adulthood. Purpose: We performed a descriptive study to investigate seizure types, interictal and ictal EEG characteristics and cognitive outcome in adult LGS subjects. Methods: We evaluated 28 cases with development impairment and several refractory seizure types, which included tonic seizures, in order to make a screening of LGS. We confirm LGS diagnosis in 24 patients older than 12 years who were assessed by video-EEG, particularly to record seizure types and EEG findings as well as cognitive outcome. Results: During this stage of the disease, all patients presented tonic seizures (TS) during wakefulness and sleep, 12/24 had atypical absences, more rarely other seizure types. Some cases (5/24) have evolved from West syndrome and in 62.5% aetiology was cryptogenic. Interictal EEG showed normal background activity in 13/24 patients, slow spike-wave discharges during wakefulness was diffuse just in 4/24; bursts of diffuse fast rhythms (DFR) in sleep were seen in all patients. A moderate to severe cognitive impairment was observed in 18/24 patients, but all of them experience deterioration after the epilepsy had begun. Conclusions: In adult LGS patients a standard waking EEG may be normal. TS during sleep and the presence of DFR are paramount to confirm the diagnosis.

Dexmedetomidine for the treatment of acute pain from complex regional pain syndrome

Dexmedetomidine for the treatment of acute pain from complex regional pain syndrome

Mineralogy, composition and PGM of chromitites from Pefki, Pindos ophiolite complex (NW Greece): evidence for progressively elevated fAs conditions in the upper mantle sequence

The Pindos ophiolite complex, located in the northwestern part of continental Greece, hosts various chromite deposits of both metallurgical (high-Cr) and refractory (high-Al) type. The Pefki chromitites are banded and sub-concordant to the surrounding serpentinized dunites. The Cr# [Cr/(Cr + Al)] of magnesiochromite varies between 0.75 and 0.79. The total PGE grade ranges from 105.9 up to 300.0 ppb. IPGE are higher than PPGE, typical of mantle hosted ophiolitic chromitites. The PGM assemblage in chromitites comprises anduoite, ruarsite, laurite, irarsite, sperrylite, hollingworthite, Os-Ru-Ir alloys including osmium and rutheniridosmine, Ru-bearing oxides, braggite, paolovite, platarsite, cooperite, vysotskite, and palladodymite. Iridarsenite and omeiite were also observed as exsolutions in other PGM. Rare electrum and native Ag are recovered in concentrates. This PGM assemblage is of great petrogenetic importance because it is significantly different from that commonly observed in podiform mantle-hosted and banded crustal-hosted ophiolitic chromitites. PGE chalcogenides of As and S are primary, and possibly crystallized directly from a progressively enriched in As boninitic melt before or during magnesiochromite precipitation. The presence of Ru-bearing oxides implies simultaneous desulfurization and dearsenication processes. Chemically zoned laurite and composite paolovite-electrum intergrowths are indicative of the relatively high mobility of certain PGE at low temperatures under locally oxidizing conditions. The PGM assemblage and chemistry, in conjunction with geological and petrologic data of the studied chromitites, indicate that it is characteristic of chromitites found within or close to the petrologic Moho. Furthermore, the strikingly different PGM assemblages between the high-Cr chromitites within the Pindos massif is suggestive of non-homogeneous group of ores.

Metal Stents and Biliary Obstruction Secondary to Lymphoma: A Tale of Caution

We read with great interest the recent article by Ross et al. [1] reporting one cancer center’s experience with the treatment of obstructive jaundice in patients with lymphoma. This article describes outcomes for 35 patients who underwent biliary decompression endoscopically or percutaneously; biliary stents were placed in 43 of the 50 ERCP’s completed, and all but four of these stents were plastic. As quoted by Ross et al. [1], the need for a permanent metal stent in cases of biliary obstruction secondary to lymphoma is less prevalent given the increased chemoresponsiveness of many lymphomas when compared to other more refractory types of malignant biliary obstruction. The authors conclude that metal stents should be reserved for patients with lymphomas refractory to treatment who are expected to live more than 6 months. Based on experiences at our institution, we fully agree with the placement of plastic biliary stents for obstructive lymphomas, but would also urge more caution when considering uncovered metal stent placement in these cases, given the potential complications which can ensue due to the difficult (if not impossible) removal of such stents. We have two cases that illustrate this point.