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Treatment of tuberculosis has many side effects. Thrombocytopenia is a serious side effect of such treatment and occurs mostly due to rifampicin (RIF). There are very few reported cases of thrombocytopenia due to isoniazid (INH). An 18-year-old female patient was diagnosed with smear-positive pulmonary tuberculosis. A four-drug regimen INH, RIF, ethambutol (EMB), and pyrazinamide (PZA) was given. After the development of thrombocytopenia, the drug treatment was stopped, and a thrombocyte suspension was given until a normal thrombocyte count was obtained.

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After several start-stop trials, first INH and then RIF were identified as the possible causes of thrombocytopenia and were removed from the regimen. The patient was treated with EMB, streptomycin, PZA, and moxifloxacin with no further development of thrombocytopenia. The current case shows that antituberculosis drugs other than RIF and PZA may be responsible for the development of thrombocytopenia. BackgroundTuberculosis is a chronic granulomatous infection that has caused mortality and morbidity for centuries. Treatment of this disease is problematic because of its long duration and compliance problems.

One of the most important factors causing low compliance is the adverse effects of the drugs. Some of them are self-limiting, but some require treatment cessation.

Common adverse effects are hepatotoxicity, hypersensitivity reactions, loss of vision, loss of hearing, flu-like syndrome, hemolytic anemia, acute renal failure, shock, neuropathy, arthralgia, and thrombocytopenia. Although rare, severe thrombocytopenia may be life-threatening. Here we describe the case of a patient affected with thrombocytopenia caused by isoniazid (INH) and rifampicin (RIF). Case presentationAn 18-year-old female with no known disease history was admitted to another center with complaints of coughing with sputum and weight loss. Chest x-ray and microscopic examination of the sputum enabled a diagnosis of smear-positive pulmonary tuberculosis. A four-drug regimen (INH, 300 mg/day; RIF, 450 mg/day; ethambutol EMB, 1,250 mg/day; and pyrazinamide PZA, 1,500 mg/day) was started according to her weight of 50 kg. While normal at the start of therapy (300,000/mm 3), her thrombocyte count began to decrease during the second day of treatment (18,000/mm 3).

The therapy was stopped, and after transfusions of fresh frozen plasma and a thrombocyte suspension, her thrombocyte count became normal. Rifampicin was assumed to be the causative factor of thrombocytopenia, and therapy was restarted with INH, PZA, and EMB. However, thrombocytopenia relapsed during this regimen. The treatment was stopped and the patient was referred to our hospital.When the patient was admitted to our hospital, her main complaint was coughing. No important previous history was present. Physical examination findings were normal with the exception of bilateral ecchymoses on her lower extremities.

Chest X-ray showed a cavity with peripheral infiltration in the left upper zone. Laboratory findings revealed; sedimentation rate: 46 mm/hr, CRP: 24 mg/lt, WBC: 9,910/mm 3, hemoglobin: 10 gr/dl, hematocrit: 31%, and thrombocytes: 135,000/mm 3. Other parameters were noncontributory.Because of the recurrent thrombocytopenia, we planned to start a treatment with a single agent and add the others one by one. The treatment was initiated in our hospital with INH at 300 mg/day, but this resulted in thrombocytopenia (30,000/mm 3) on the third day, and the therapy was stopped.

As soon as the thrombocyte count became normal, we began a three-drug regimen according to the patient’s weight: PZA, 1,500 mg/day; streptomycin (SM), 750 mg/day; and EMB, 1,250 mg/day. Because the thrombocyte count was normal (225,000/mm 3), INH was again added to the regimen, but on the second day of INH initiation, the thrombocyte count decreased to 10,000/mm 3. The INH was stopped and the patient underwent a consultation in the Hematology Department. Then a thrombocyte suspension and methylprednisolone (1 mg/kg/day) were given. During the follow up, the thrombocyte count became normal and the methylprednisolone therapy was stopped. After re-initiation of the three-drug regimen (EMB, PZA, and SM), RIF at 450 mg/day was added to the therapy as the fourth drug. On the third day of RIF therapy, the thrombocyte count decreased to 34,000/mm 3 and RIF was ceased.Because of thrombocytopenia caused by both INH and RIF, moxifloxacin at 400 mg/day was added to the treatment regimen.

Without INH and RIF, patient had no further thrombocytopenia development during the period of therapy. After the first month of the therapy, her sputum smear was negative.

There were no clinical or laboratory abnormalities during follow up examinations. After cessation of SM in the second month, the antituberculosis treatment regimen was continued and completed with three drugs (EMB, 1250 mg/day; PZA, 1500 mg/day; and moxifloxacin, 400 mg/day) without any further complications. Discussion and conclusionsAlthough there are reports of thrombocytopenia during antituberculosis treatment, only few case reports of INH-induced thrombocytopenia are reported -, but none where the hematologic disorder was at the same time caused by INH and RIF.

Our patient had recurrent episodes of thrombocytopenia due to INH and RIF, either together or separately.A thrombocyte count of. Blumberg HM, Burman WJ, Chaisson RE, Daley CL, Etkind SC, Friedman LN, Fujiwara P, Grzemska M, Hopewell PC, Iseman MD, Jasmer RM, Koppaka V, Menzies RI, O'Brien RJ, Reves RR, Reichman LB, Simone PM, Starke JR, Vernon AA. American Thoracic Society, Centers for Disease Control and Prevention and the Infectious Diseases Society. American thoracic society/centers for disease control and prevention/infectious diseases society of America: treatment of tuberculosis.

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UpToDate version 19.3. Last topic update 27 September, 2011. 2011. George JN, Raskob GE, Shah SR, Rizvi MA, Hamilton SA, Osborne S, Vondracek T. Drug induced thrombocytopenia a systematic review of published case reports. Ann Intern Med.

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.Mo, Kun; Miao, Yinbin; Yun, Di2015-09-30This activity is supported by the US Nuclear Energy Advanced Modeling and Simulation (NEAMS) Fuels Product Line (FPL) and aims at providing experimental data for the validation of the mesoscale simulation code MARMOT. MARMOT is a mesoscale multiphysics code that predicts the coevolution of microstructure and properties within reactor fuel during its lifetime in the reactor.

It is an important component of the Moose-Bison-Marmot (MBM) code suite that has been developed by Idaho National Laboratory (INL) to enable next generation fuel performance modeling capability as part of the NEAMS Program FPL. In order to ensure the accuracy of the microstructuremore » based materials models being developed within the MARMOT code, extensive validation efforts must be carried out. In this report, we summarize our preliminary synchrotron radiation experiments at APS to determine the grain size of nanograin UO 2. The methodology and experimental setup developed in this experiment can directly apply to the proposed in-situ grain growth measurements.

The investigation of the grain growth kinetics was conducted based on isothermal annealing and grain growth characterization as functions of duration and temperature. The kinetic parameters such as activation energy for grain growth for UO 2 with different stoichiometry are obtained and compared with molecular dynamics (MD) simulations.« less.Mo, Kun; Miao, Yinbin; Yun, Di2015-09-30This activity is supported by the US Nuclear Energy Advanced Modeling and Simulation (NEAMS) Fuels Product Line (FPL) and aims at providing experimental data for the validation of the mesoscale simulation code MARMOT. MARMOT is a mesoscale multiphysics code that predicts the coevolution of microstructure and properties within reactor fuel during its lifetime in the reactor. It is an important component of the Moose-Bison-Marmot (MBM) code suite that has been developed by Idaho National Laboratory (INL) to enable next generation fuel performance modeling capability as part of the NEAMS Program FPL. In order to ensure the accuracy of the microstructuremore » based materials models being developed within the MARMOT code, extensive validation efforts must be carried out. In this report, we summarize our preliminary synchrotron radiation experiments at APS to determine the grain size of nanograin UO 2.

The methodology and experimental setup developed in this experiment can directly apply to the proposed in-situ grain growth measurements. The investigation of the grain growth kinetics was conducted based on isothermal annealing and grain growth characterization as functions of duration and temperature.

The kinetic parameters such as activation energy for grain growth for UO 2 with different stoichiometry are obtained and compared with molecular dynamics (MD) simulations.« less.Hales, Stephen J. (Inventor); Claytor, Harold Dale (Inventor); Alexa, Joel A. (Inventor)2015-01-01The present invention provides a process for suppressing abnormal grain growth in friction stir welded aluminum alloys by inserting an intermediate annealing treatment ('IAT') after the welding step on the article. The IAT may be followed by a solution heat treatment (SHT) on the article under effectively high solution heat treatment conditions. In at least some embodiments, a deformation step is conducted on the article under effective spin-forming deformation conditions or under effective superplastic deformation conditions.

The invention further provides a welded article having suppressed abnormal grain growth, prepared by the process above. Preferably the article is characterized with greater than about 90% reduction in area fraction abnormal grain growth in any friction-stir-welded nugget.Miao, Yinbin; Yao, Tiankai; Lian, JieHere, we report on the study of grain growth kinetics in nano- grained UO 2 samples. Dense nano- grained UO 2 samples with well-controlled stoichiometry and grain size were fabricated using the spark plasma sintering technique. To determine the grain growth kinetics at elevated temperatures, a synchrotron wide-angle X-ray scattering (WAXS) study was performed in situ to measure the real-time grain size evolution based on the modified Williamson-Hall analysis. The unique grain growth kinetics of nanocrystalline UO 2 at 730 °C and 820 °C were observed and explained by the difference in mobility of various grain boundaries.Miao, Yinbin; Yao, Tiankai; Lian, Jie.2017-01-09Here, we report on the study of grain growth kinetics in nano- grained UO 2 samples. Dense nano- grained UO 2 samples with well-controlled stoichiometry and grain size were fabricated using the spark plasma sintering technique. To determine the grain growth kinetics at elevated temperatures, a synchrotron wide-angle X-ray scattering (WAXS) study was performed in situ to measure the real-time grain size evolution based on the modified Williamson-Hall analysis.

The unique grain growth kinetics of nanocrystalline UO 2 at 730 °C and 820 °C were observed and explained by the difference in mobility of various grain boundaries.Kapadia, C. M.; Leipold, M. H.1972-01-01The theory of grain boundary migration as a thermally activated process is reviewed, the basic mechanisms in ceramics being the same as in metals. However, porosity and non-stochiometry in ceramic materials give an added dimension to the theory and make quantitative treatment of real systems rather complex. Grain growth is a result of several simultaneous (and sometimes interacting) processes; these are most easily discussed separately, but the overall rate depends on their interaction. Sufficient insight into the nature of rate controlling diffusion mechanisms is necessary before a qualitative understanding of boundary mobility can be developed.Bennett, Tricia A.Abnormal grain growth (AGG) was studied in an Fe-1%Si alloy using automated Electron Backscattered Diffraction (EBSD) to determine the driving force for this phenomenon.

Experiments were performed with the knowledge that there are several possible driving forces and, the intent to determine the true driving force by elimination of the other potential candidates. These potential candidates include surface energy anisotropy, anisotropic grain boundary properties and the stored energy of deformation. In this work, surface energy and grain boundary anisotropies as well as the stored energy of deformation were investigated as the possible driving forces for AGG. Accordingly, industrially processed samples that were temper rolled to 1.5% and 8% were annealed in air for various times followed by quenching in water. The results obtained were compared to those from heat treatments performed in wet 15%H2-85%N2 at a US Steel facility. In addition, for a more complete study of the effect of surface energy anisotropies on AGG, the 1.5% temper-rolled material was heat-treated in other atmospheres such as 5%H2-95%Ar, 98%H2-2%He, 98%H2-2%H 2S, and 98%H2-2%N2 for 1 hour followed by quenching in water.

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The character of the grain boundaries in the materials was also examined for each set of experiments conducted, while the influence of stored energy was evaluated by examining intragranular orientation gradients. AGG occurred regardless of annealing atmosphere though the most rapid progression was observed in samples annealed in air. In general, grains of varying orientations grew abnormally. One consistently observed trend in all the detailed studies was that the matrix grains remained essentially static and either did not grow or only grew very slowly. On the other hand, the abnormally large grains (ALG), on average, were approximately 10 times the size of the matrix. Analysis of the grain boundary character of the interfaces between abnormal grains and the matrix showed no.Rios, P. R.; Glicksman, M.

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E.2015-07-01Reduction in stored free energy provides the thermodynamic driving force for grain and bubble growth in polycrystals and foams. Evolution of polycrystalline networks exhibit the additional complication that grain growth may be controlled by several kinetic mechanisms through which the decrease in network energy occurs.

Polyhedral boundaries, triple junctions (TJs), and quadruple points (QPs) are the geometrically distinct elements of three dimensional networks that follow Plateau's rules, provided that grain growth is limited by diffusion through, and motion of, cell boundaries. Shvindlerman and co-workers have long recognized the kinetic influences on polycrystalline grain growth of network TJs and QPs. Moreover, the emergence of interesting polycrystalline nanomaterials underscored that TJs can indeed influence grain growth kinetics. Currently there exist few detailed studies concerned either with network distributions of grain size, number of faces per grain, or with ' grain trajectories', when grain growth is limited by the motion of its TJs or QPs.

By contrast there exist abundant studies of classical grain growth limited by boundary mobility. This study is focused on a topological/geometrical representation of polycrystals to obtain statistical predictions of the grain size and face number distributions, as well as growth 'trajectories' during steady-state grain growth. Three limits to grain growth are considered, with grain growth kinetics controlled by boundary, TJ, and QP mobilities.Tan, Y.; Maniatty, A. M.; Zheng, C.; Wen, J. T.2017-09-01This work investigated the development of a Monte Carlo (MC) simulation approach to modeling grain growth in the presence of non-uniform temperature field that may vary with time. We first scale the MC model to physical growth processes by fitting experimental data. Based on the scaling relationship, we derive a grid site selection probability (SSP) function to consider the effect of a spatially varying temperature field.

The SSP function is based on the differential MC step, which allows it to naturally consider time varying temperature fields too. We verify the model and compare the predictions to other existing formulations (Godfrey and Martin 1995 Phil.

A 72 737-49 Radhakrishnan and Zacharia 1995 Metall. A 26 2123-30) in simple two-dimensional cases with only spatially varying temperature fields, where the predicted grain growth in regions of constant temperature are expected to be the same as for the isothermal case. We also test the model in a more realistic three-dimensional case with a temperature field varying in both space and time, modeling grain growth in the heat affected zone of a weld. We believe the newly proposed approach is promising for modeling grain growth in material manufacturing processes that involves time-dependent local temperature gradient.van Aken, D. C.; Krajewski, P.

Chevalier Et Camelot Isoniazid For Sale

E.; Vyletel, G. M.; Allison, J. E.; Jones, J. W.1995-06-01Recrystallization and grain growth in a 2219/TiC/15p composite were investigated as functions of the amount of deformation and deformation temperature. Both cold and hot deformed samples were annealed at the normal solution treatment temperature of 535 °C. It was shown that large recrystallized grain diameters, relative to the interparticle spacing, could be produced in a narrow range of deformation for samples cold-worked and those hot-worked below 450 °C. For cold-worked samples, between 4 to 6 pct deformation, the recrystallized grain diameters varied from 530 to 66 μm as the amount of deformation increased.

Subsequent grain growth was not observed in these recrystallized materials and noncompact grain shapes were observed. For deformations greater than 15 pct, recrystallized grain diameters less than the interparticle spacing were observed and subsequent grain growth produced a pinned grain diameter of 27 μm.

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The pinned grain diameter agreed well with an empirical model based on three dimensional (3-D) Monte Carlo simulations of grain growth and particle pinning in a two-phase material. Tensile properties were determined as a function of grain size, and it was shown that grain size had a weak influence on yield strength. A maximum in the yield strength was observed at a grain size larger than the normal grain growth and particle-pinned diameter.Militzer, M.; Giumelli, A.; Hawbolt, E.B.1996-11-01Austenite grain growth kinetics have been investigated in three Al-killed plain carbon steels.

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Experimental results have been validated using the statistical grain growth model by Abbruzzese and Luecke, which takes pinning by second-phase particles into account. It is shown that the pinning force is a function of the pre-heat-treatment schedule. Extrapolation to the conditions of a hot-strip mill indicates that grain growth occurs without pinning during conventional processing. Analytical relations are proposed to simulate austenite grain growth for Al-killed plain carbon steels for any thermal path in a hot-strip mill.