Sustained unresponsiveness development in wheat oral immunotherapy: predictive factors and flexible regimen in the maintenance phase.

Summary: Background. Immunotherapy may induce sustained unresponsiveness (SU )in which the patient can tolerate the allergen without any severe symptoms after discontinuing immunotherapy. The present study evaluated serum and cutaneous markers for predicting SU in patients with wheat anaphylaxiswho underwent oral immunotherapy. We investigated the effectiveness of a flexible regimen of 5 to 10 g wheat protein (WP) in the maintenance phase of oral immunotherapy (OIT). Methods.This study was conducted on 19 patients with wheat anaphylaxis who underwent OIT. The results of the skin prick test (SPT), besides specific serum IgE (sIgE) and IgG4 (sIgG4) to WP, were evaluated before the desensitization. The maintenance dose started from the preferred dose of 5 to 10 g WP after the build-up phase, if the patient could tolerate it. All patients were recruited 7 to 9 months after undergoing this flexible regimen, and the results of SPT and sIgE, and sIgG4l evels were obtained once more. The patients underwent oral food challenge (OFC) after a 3-4-week avoidance to evaluate SU. Results. There was anassociation between mean IgE reduction and SU (p < 0.0006), while no association was observed between the mean increase in specific IgG4 (p = 0.1), and the mean wheal diameter decrease (p = 0.29). A 50% reductionin sIgE was associated with SU. Thirteen patients were considered to havea SU. There was no association between the flexible regimen and the desensitization rate. Conclusions.The reduction of 50% sIgE is a predictive factor for SU in patients with IgE-mediated wheat allergy.

Assessment of IgE- and cell-mediated immunity in pediatric patients with eosinophilic esophagitis.

Summary: Eosinophilic esophagitis (EoE) is a chronic allergen/immune-mediated disease leading to esophageal dysfunction. Food allergens play critical roles in the pathogenesis and treatment of EoE via different mechanisms. This study aimed to present the characteristics and evaluate the ability of skin prick test (SPT), skin prick to prick test (SPP) (IgE-mediated), and atopic patch test (APT) (cell-mediated) individually or simultaneously to diagnose food allergy in patients suffering from EoE. This prospective study was conducted on 58 patients with EoE. Seven patients (12.1%) were positive to only one, 3 (5.2%) were simultaneously positive to two, and 32 (55.2%) were simultaneously positive to three tests. Single and double sensitizations were totally 10.4% in IgE-mediated reactions, while 36.5% in cell-mediated reactions. In contrast, poly sensitization (> 2 allergens) was 51.7% in IgE-mediated tests and 20.7% in the cell-mediated test. Multiple sensitization findings showed egg white, milk, yolk, and soy were the most frequent allergens. Our findings indicate that EoE is early onset and associated with multiple food sensitizations, particularly via IgE-mediated mechanisms. These immune-mediated responses encompass both IgE-mediated (SPT and SPP) and cell-mediated (APT) reactions simultaneously not individually. Therefore, employing multiple assays may strengthen the diagnosis of food sensitization.

Investigating the Effect of Air Cavities of Sinuses on the Radiotherapy Dose Distribution Using Monte Carlo Method.

BACKGROUND: Considering that some vital organs exist in the head and neck region, the treatment of tumors in this area is a crucial task. The existence of air cavities, namely sinuses, disrupt the radiotherapy dose distribution. The study aims to analyze the effect of maxillary, frontal, ethmoid and sphenoid sinuses on radiotherapy dose distribution by Monte Carlo method. MATERIAL AND METHODS: In order to analyze the effect of the cavities on dose distribution, the maxillary, frontal, ethmoid and sphenoid sinus cavities were simulated with (3×3.2×2) cm3, (2×2×3.2) cm3, (1×1×1.2) cm3 and (1×1×2) cm3 dimensions. RESULTS: In the analysis of the dose distribution caused by cavities, some parameters were observed, including: inhomogeneity of dose distribution in the cavities, inhomogeneity of dose on the edges of the air cavities and dispersion of the radiations after the air cavity. The amount of the dose in various situations showed differences: before the cavity a 0.64% and a 2.76% decrease, a 12.06% and a 17.17% decrease in the air zone, and a 2.25% and a 5.9% increase after the cavity. CONCLUSION: The results indicate that a drop in dose before the air cavities and in the air zone occurs due to the lack of scattered radiation. Furthermore, the rise in dose was due to the passage of more radiation from the air cavity and dose deposition after the air cavity. The changes in dose distribution are dependent on the cavity size and depth. As a result, this has to be noted in the treatment planning and MU calculations of the patient.

Evaluation of thyroid gland as an organ at risk after breast cancer radiotherapy: a systematic review and meta-analysis

Background: Radiotherapy can often lead to thyroid dysfunction. Some studies demonstrated that treatment of breast cancer by RT can expose thyroid gland to high doses of radiation. The aim of this systematic review is to evaluate consideration of thyroid gland as an organ at risk. Methods: In this systematic review and meta-analysis to select initial studies, a comprehensive search by two independent reviewers was performed. Electronical databases following: Web of Science, Google Scholar, Scopus, PubMed, Elsevier, Embase, ProQuest and Persian databases such as Iranmedex, Magiran, and SID were searched. All searches were restricted to English language between 1985 and 2017. A random effect meta-analysis is applied to estimate pooled effect size across initial studies. Funnel plot with Egger’s test is used to assess potential publication bias. Results: Totally, five studies (478 samples) were included in meta-analysis. The meta-analyses of result showed that thyroid gland is affected by radiotherapy significantly and the TSH increased after radiotherapy (z = 2.68, P = 0.007). The pooled estimate of difference mean for TSH was 0.90 (95% CI 0.24, 1.55). In studies among patients with breast cancer RT, hypothyroidism was reported more than other thyroid disorders. There was not showed possibility publication bias among studies (P > 0.05). Conclusion: This study demonstrated that thyroid gland is affected by radiotherapy significantly and the TSH increased after radiotherapy. Protecting thyroid gland during radiation and follow-up of patients with breast cancer RT are suggested for the assessment of thyroid gland dysfunction

No disponible

Analysis of the effect of subcutaneous injection of omental-derived cells on the healing of third degree burns in rats: a preliminary study.

Burn injury is considered a global health issue. Third degree burn wounds do not heal spontaneously and require skin grafts. Some factors could contribute to wound healing. In this study we assessed the effect of non-fatty omental cells in burn wound healing. Similar third degree burn wounds were induced on the back of 192 rats. Forty-eight of these rats were put in a control group that did not receive any treatment. The rest of the rats were put in 3 groups, each receiving a different treatment regime. Rats in group 2 had a daily application of silver sulfadiazine; group 3 rats were injected with omental cells, and group 4 rats were injected with phosphate buffer saline (PBS) once, followed by daily application of Vaseline to the burned region. Parameters such as open epidermis length, number of epidermal cell layers, granulation tissue thickness (GTT) and neutrophil density were evaluated in each group. The average open epidermis length in the omental cell group was less than in the other groups on days 10 and 20 (P<0.05). The thickness of epidermal cell layers in the group receiving cells was greater than in the other groups on all days. On the 20th day, there was a significant difference in GTT between the four groups (P<0.05). The injection of non-fatty omental cells has a positive effect on third degree burn wounds in rats.

Les brûlures sont un problème de santé publique. Celles du 3ème ne peuvent guérir spontanément et requièrent des greffes cutanées. Certains facteurs pourraient contribuer à la cicatrisation. Nous avons évalué l'effet des cellules épiploïques non adipocytaires sur la cicatrisation des brûlures. Des brûlures similaires, du 3ème degré au niveau du dos ont été infligées à 192 rats. Quatre vingt huit d'entre eux, contrôles (groupe 1), n'ont reçu aucun traitement. Les autres ont été répartis en 3 groupes recevant chacun un type de traitement. Le groupe 2 a reçu chaque jour une application de sulfadiazine argentique ; le groupe 3 a reçu une injection de cellules épiploïques ; le groupe 4 une injection de sérum salé suivis d'application journalière de vaseline. La longueur non épidermisée, le nombre de couches de cellules épidermiques, l'épaisseur du tissu de granulation et la densité de neutrophiles ont été évalués. La longueur non épidermisée à J10 et J20 était plus courte dans le groupe 3 (p<0,05). L'épaisseur des couches épidermiques était constamment supérieure dans ce groupe. À J20, les différences d'épaisseur du tissu de granulation étaient significatives entre tous les groupes. L'injection de cellules épiploïques non adipocytaires a un effet favorable sur l'évolution de brûlures du 3ème degré chez le rat.

Evaluation of thyroid gland as an organ at risk after breast cancer radiotherapy: a systematic review and meta-analysis.

BACKGROUND: Radiotherapy can often lead to thyroid dysfunction. Some studies demonstrated that treatment of breast cancer by RT can expose thyroid gland to high doses of radiation. The aim of this systematic review is to evaluate consideration of thyroid gland as an organ at risk. METHODS: In this systematic review and meta-analysis to select initial studies, a comprehensive search by two independent reviewers was performed. Electronical databases following: Web of Science, Google Scholar, Scopus, PubMed, Elsevier, Embase, ProQuest and Persian databases such as Iranmedex, Magiran, and SID were searched. All searches were restricted to English language between 1985 and 2017. A random effect meta-analysis is applied to estimate pooled effect size across initial studies. Funnel plot with Egger's test is used to assess potential publication bias. RESULTS: Totally, five studies (478 samples) were included in meta-analysis. The meta-analyses of result showed that thyroid gland is affected by radiotherapy significantly and the TSH increased after radiotherapy (z = 2.68, P = 0.007). The pooled estimate of difference mean for TSH was 0.90 (95% CI 0.24, 1.55). In studies among patients with breast cancer RT, hypothyroidism was reported more than other thyroid disorders. There was not showed possibility publication bias among studies (P > 0.05). CONCLUSION: This study demonstrated that thyroid gland is affected by radiotherapy significantly and the TSH increased after radiotherapy. Protecting thyroid gland during radiation and follow-up of patients with breast cancer RT are suggested for the assessment of thyroid gland dysfunction.

An Analytical-empirical Calculation of Linear Attenuation Coefficient of Megavoltage Photon Beams.

BACKGROUND: In this study, a method for linear attenuation coefficient calculation was introduced. METHODS: Linear attenuation coefficient was calculated with a new method that base on the physics of interaction of photon with matter, mathematical calculation and x-ray spectrum consideration. The calculation was done for Cerrobend as a common radiotherapy modifier and Mercury. RESULTS: The values of calculated linear attenuation coefficient with this new method are in acceptable range. Also, the linear attenuation coefficient decreases slightly as the thickness of attenuating filter (Cerrobend or mercury) increased, so the procedure of linear attenuation coefficient variation is in agreement with other documents. The results showed that the attenuation ability of mercury was about 1.44 times more than Cerrobend. CONCLUSION: The method that was introduced in this study for linear attenuation coefficient calculation is general enough to treat beam modifiers with any shape or material by using the same formalism; however, calculating was made only for mercury and Cerrobend attenuator. On the other hand, it seems that this method is suitable for high energy shields or protector designing.

Evaluation of electron contamination in cancer treatment with megavoltage photon beams: monte carlo study.

BACKGROUND: Megavoltage beams used in radiotherapy are contaminated with secondary electrons. Different parts of linac head and air above patient act as a source of this contamination. This contamination can increase damage to skin and subcutaneous tissue during radiotherapy. Monte Carlo simulation is an accurate method for dose calculation in medical dosimetry and has an important role in optimization of linac head materials. The aim of this study was to calculate electron contamination of Varian linac. MATERIALS AND METHOD: The 6MV photon beam of Varian (2100 C/D) linac was simulated by Monte Carlo code, MCNPX, based on its company's instructions. The validation was done by comparing the calculated depth dose and profiles of simulation with dosimetry measurements in a water phantom (error less than 2%). The Percentage Depth Dose (PDDs), profiles and contamination electron energy spectrum were calculated for different therapeutic field sizes (5×5 to 40×40 cm(2)) for both linacs. RESULTS: The dose of electron contamination was observed to rise with increase in field size. The contribution of the secondary contamination electrons on the surface dose was 6% for 5×5 cm(2) to 27% for 40×40 cm(2), respectively. CONCLUSION: Based on the results, the effect of electron contamination on patient surface dose cannot be ignored, so the knowledge of the electron contamination is important in clinical dosimetry. It must be calculated for each machine and considered in Treatment Planning Systems.

Hypercalcemia in glioblastoma multiforme.

Hypercalcemia is commonly associated with cancer, occurring in around 10-20% of cancer patients. Hypercalcemia is usually related to solid and non-solid malignancies specifically breast cancer, lung cancer and multiple myeloma. Hypercalcemia has been reported to occur in association with astrocytomas, and uncommonly in gliomas. We report a case of a previously healthy man presenting with glioblastoma multiforme . He was found to have persistently elevated serum calcium and calcitriol with normal parathyroid function. This is the first reported case of hypercalcemia associated with glioblastoma multiforme.

Effects of oncostatin M on human cerebral endothelial cells and expression in inflammatory brain lesions.

Oncostatin M (OSM) is a member of the interleukin (IL)-6 cytokine family and modulates inflammatory responses. Here we investigated the role of OSM as an immunoregulatory factor for human cerebral endothelial cells (HCEC). Using RT-PCR we detected transcripts of the receptor components involved in OSM signaling, gp130, OSM receptor (OSMR)-beta, and leukemia inhibitory factor receptor (LIFR), in HCEC. A parallel FACS analysis revealed surface expression of gp130 and OSMR-beta, but not of LIFR on these cells. Functionally, OSM upregulated intercellular adhesion molecule-1, but did not induce vascular cell adhesion molecule-1 in HCEC. Further, OSM upregulated IL-6 and monocyte chemoattractant protein (MCP)-1, whereas IL-8 was unaffected. Combined application of tumor necrosis factor (TNF)-alpha and OSM synergistically enhanced IL-6 and MCP-1 production, but downregulated TNF-alpha-induced IL-8. As OSM regulated molecules relevant in inflammatory brain diseases, we investigated its expression in normal and pathological human brains. OSM was detected by immunohistochemistry in brains from multiple sclerosis patients in microglia, reactive astrocytes, and infiltrating leukocytes, whereas in normal brains and noninflammatory neurological diseases. immunoreactivity was absent from the parenchyma. These data suggest that immunoregulatory functions in human cerebral endothelial cells may be a mechanism by which OSM participates in the pathophysiology of inflammatory brain disease.

Ret oncogene signal transduction via a IRS-2/PI 3-kinase/PKB and a SHC/Grb-2 dependent pathway: possible implication for transforming activity in NIH3T3 cells.

Multiple endocrine neoplasia 2A (MEN 2A) is an inherited disease caused by mutations of the Ret proto-oncogene. Although many different Ret mutations have been described, little is known about the signaling pathways triggered by the Ret oncogene. In this study, we have determined the signaling properties of a Ret-9bp duplication encoding amino acids 634-636, which was recently identified in a patient with all clinical features of the MEN 2A syndrome. The Ret-9bp duplication leads to constitutive activation of the Ret tyrosine kinase. Furthermore, Ret-9bp increased mitogenic and transforming activity demonstrated by thymidine incorporation as well as colony formation in soft agar. Studying intracellular signaling pathways, which may be involved in malignant transformation of Ret-9bp expressing NIH3T3 cells, we could demonstrate Ret-9bp dependent phosphorylation of insulin receptor substrate-2 (IRS-2) with consecutive activation of phosphatidylinositol 3-kinase (PI 3-kinase) and protein kinase B (PKB/AKT). Moreover, Ret-9bp induces phosphorylation of SHC resulting in growth factor receptor binding protein-2 (Grb-2) binding and activation of the mitogen activating protein (MAP) kinase pathway. In addition to these postreceptor cytoplasmic signaling events, we have studied nuclear signal by Ret-9bp and found activation of c-jun and jun-D, two members of the jun/AP-1 family of transcription factors. In summary, an oncogenic 9bp duplication of Ret causes Ret dimer formation and ligand independent activation of the tyrosine kinase. Besides the signaling steps leading to MAPK activation, we could demonstrate that Ret-9bp induced constitutive activation of a signaling pathway involving IRS-2, PI 3-kinase and PKB/AKT which could transduce the oncogenic Ret signal to increased gene transcription via activation of the jun/AP-1 transcription factor family.

Estrogen dependence of synthesis and secretion of apolipoprotein B-containing lipoproteins in the chicken hepatoma cell line, LMH-2A.

The chicken hepatoma cell line LMH-2A, which permanently overexpresses the chicken estrogen receptor, was used to study the synthesis and secretion of lipoproteins in response to treatment with estrogen. In the absence of the hormone, only small amounts of apolipoprotein B (apoB) and no apolipoprotein VLDL II (apoII) were found in cell extracts. After treatment of cells with moxestrol, a stable estrogen derivative, for 24 to 48 h, a dramatic increase in the quantities of these lipoproteins was observed both in cell extracts and in the medium. As determined by pulse-chase experiments, both proteins also showed enhanced rates of synthesis after estrogen induction, and secretion of the newly synthesized proteins was essentially complete by 6 h. The secreted apoB-containing lipoprotein particles have a density corresponding to that of very low density lipoprotein (VLDL). Furthermore, in estrogen-stimulated cells, the secreted particles also contain apoII, as shown by co-immunoprecipitation of apoII, and apoB. It appears that vitellogenin, the product of another estrogen-regulated gene in egg-laying species, is not synthesized by LMH-2A cells. Taken together, the data suggest that LMH-2A cells provide a new and promising cell system to investigate lipoprotein synthesis, assembly, and secretion in an estrogen-dependent manner.

Advanced glycation endproducts stimulate the MAP-kinase pathway in tubulus cell line LLC-PK1.

Advanced glycation endproducts (AGEs) are suggested to play an important role in diabetic nephropathy. They induce specific cellular responses such as the release of cytokines in different cell lines. The effect of AGEs on signal transduction pathways was investigated in the renal tubulus cell line LLC-PK1. Using a serine-phosphate-specific antibody AGE-induced cellular responses associated with phosphorylation/dephosphorylation events were demonstrated. In particular, the p42MAP kinase and its downstream target, the AP-1 complex, are shown to be activated by AGE-BSA but not by BSA. In contrast, only partial phosphorylation is observed for the p70S6-kinase. Thus, AGEs appear to induce specific signal transduction pathways.

Pruritus in chronic hepatitis C: association with high serum bile acids, advanced pathology, and bile duct abnormalities.

Pruritus is a common symptom of chronic cholestatic liver diseases but is considered rare in chronic hepatitis. We observed pruritus to be an unusually common complaint in patients with advanced chronic hepatitis C. We reviewed the records of 175 chronic hepatitis C patients to identify patients with severe, diffuse, unexplained pruritus; 12 consecutive prospective patients undergoing liver biopsy for chronic hepatitis C served as controls. Assessment included laboratory biochemical tests and assessment of liver pathology by stage, grade, hepatic activity index, and a bile duct score. Pruritus was present in nine (5.1%) patients. Serum AST, ALT, alkaline phosphatase, GGTP, total bilirubin, and ferritin were similar in pruritics and controls. Pruritics had higher serum bile acids (2028.4 +/- 223.1 mmol/liter vs 423.1 +/- 194.3, P < 0.001), higher transferrin saturation (57.5 +/- 6.8% vs 33.2 +/- 3.3, P < 0.01), and lower HCV RNA by bDNA (24.5 +/- 12.7 x 10(5) vs 172.7 +/- 54.1 x 10(5), P < 0.05). Pathology revealed cirrhosis in 6/9 (66.6%) pruritics vs 1/12 (8.3%) controls (P < 0.01). Pruritics had higher pathologic stage (3.7 +/- 0.2 vs 2.2 +/- 0.4, P < 0.01), grade (4.4 +/- 0.2 vs 2.1 +/- 0.2, P < 0.001), activity index (14.3 +/- 1.9 vs 8.6 +/- 1.9, P < 0.025), and bile duct score (7.6 +/- 0.6 vs 4.7 +/- 0.4, P < 0.01). Of eight pruritics treated with IFN-alpha2b, two had complete ALT response and one relapsed. Pruritus followed a relapsing course and only three patients partially responded despite a variety of interventions. In conclusion, pruritus is a common complication of advanced CHC. Its presence is associated with high serum bile acids, advanced pathology and bile duct abnormalities. The clinical course of pruritus is relapsing and response to therapy is inconsistent. These features suggest that pruritus in CHC has a pathogenesis that may vary from that of chronic cholestatic diseases.

[The unmasking of secondary adrenal insufficiency and central diabetes insipidus by a highly febrile acute Hantaan virus infection]. / Demaskierung einer sekundären Nebennierenrindeninsuffizienz und eines Diabetes insipidus centralis durch eine hochfieberhafte akute Hantaan-Virus-Infektion.

CASE REPORT: A 32-year-old obese patient was admitted to our hospital as an emergency with very severe abdominal pain. Routine examinations initially failed to establish a diagnosis. The patient then went on to develop a high fever that was associated with polydipsia and polyuria. Serological studies revealed an acute infection with the Hantaan virus. Laboratory investigations showed hypofunction of the anterior and posterior lobes of the pituitary, with complete absence of ACTH, which was caused by two germinomas located intracranially. CONCLUSION: The clinical symptoms had thus been the result of acute secondary insufficiency of the adrenal cortex, which was unmasked by the acute, highly febrile Hantaan viral infection.

Upregulation of cholesterol synthesis after acute reduction of low density lipoprotein by apheresis in normocholesterolaemic subjects: evidence for a threshold effect.

The influence of low density lipoproteins (LDL) in the plasma on the regulation of cholesterol biosynthesis is not clear. We studied the changes in plasma mevalonic acid (MVA) concentration and the lathosterol/cholesterol (L/C) ratio, which are well established indices of whole body cholesterol synthesis, in four normocholesterolaemic subjects after each had undergone LDL apheresis on two occasions. LDL apheresis of 75% of the calculated plasma volume reduced LDL-cholesterol by 44% to 1.5 +/- 0.2 mmol/l without changing plasma MVA levels or L/C ratios. Apheresis of 125% of the calculated plasma volume decreased plasma LDL-cholesterol by 69% to 0.9 +/- 0.2 mmol/l, with significant increases in plasma MVA and L/C ratio on the day after the procedure. These results imply that LDL-cholesterol is an integral part of the sterol regulatory pool and suggest that plasma levels cannot be lowered below 1-1.4 mmol/l in normal subjects without upregulating cholesterol biosynthesis.

Detection of the apolipoprotein B-100 arg(3500) > gl mutation in familial defective apoB-100 by temperature-gradient gel electrophoresis.

Familial defective apolipoprotein B-100 (FDB) is caused by a point mutation in exon 26 of the apolipoprotein B gene leading to a decreased binding to the LDL-receptor. Patients with FDB have hypercholesterolemia and atherosclerotic disease. Since other mutations of apoB-100 could also cause binding abnormalities we established a temperature-gradient gel electrophoresis (TGGE) method and started to screen hypercholesterolemic patients for the presence of point mutations in this region. 4 of 43 patients were positive according to TGGE and subsequent sequencing showed the familiar guanine to adenine transition in codon 3500 in all cases.

Mutations of the ret protooncogene in German multiple endocrine neoplasia families: relation between genotype and phenotype. German Medullary Thyroid Carcinoma Study Group.

It has been suggested that not only the position but also the nature of the mutations of the ret protooncogene strongly correlate with the clinical manifestation of the multiple endocrine neoplasm type 2 (MEN 2) syndrome. In particular, individuals with a Cys634-Arg substitution should have a greater risk of developing parathyroid disease. We, therefore, analyzed 94 unrelated families from Germany with inherited medullary thyroid carcinoma (MTC) for mutation of the ret protooncogene. In all but 1 of 59 families with MEN 2A, germline mutations in the extracellular domain of the ret protein were found. Some 81% of the MEN 2A mutations affected codon 634. Phenotype-genotype correlations suggested that the prevalence of pheochromocytoma and hyperparathyroidism is significantly higher in families with codon 634 mutations, but there was no correlation with the nature of the mutation. In all but 1 of 27 familial MTC (FMTC) families, mutations were detected in 1 of 4 cysteines in the extracellular domain of the ret protooncogene. Half of the FMTC mutations affected codon 634. Mutations outside of codon 634 occurred more often in FMTC families than in MEN 2A families. In all but 1 of 8 MEN 2B patients, de novo mutations in codon 918 were found. These data confirm the preferential localization of MEN 2-associated mutations and the correlation between disease phenotype and the position of the ret mutation, but there was no correlation between the occurrence of hyperparathyroidism or pheochromocytoma and the nature of the mutation.