Complete surgical resection of lung tumor decreases exhalation of mutated KRAS oncogene

Exhaled breath condensate (EBC) contains extracellular DNA that may originate from pathological lesions of the respiratory tract and can be a genetic marker of pulmonary malignancy. We tested whether complete surgical excision of lung cancer will decrease exhalation of mutated KRAS oncogene. Fifty seven patients with clinical diagnosis of lung cancer and detectable KRAS mutations in pre-surgery EBC-DNA were qualified for surgical treatment. Point mutations at codon 12 of KRAS oncogene were detected using mutant-enriched PCR technique in DNA from pre-surgery blood, EBC collected before, 7 and 30 days after surgery and from specimens of resected tumor and normal pulmonary parenchyma. The ratio of mutated to wild type KRAS DNA (R mut/wild KRAS) was calculated for each specimen after electrophoresis and densitometry of the final amplification and digestion product. In 46 patients non-small cell lung cancer (NSCLC) and in 11 benign lesion (BL) were confirmed. All blood and tumor specimens were positive for KRAS mutations, while 41 specimens of normal pulmonary parenchyma were negative. In NSCLC patients pre-surgery EBC R mut/wild KRAS of 0.20?±?0.03 decreased by 1.3- and 3.7-times (p?相似文献   

Hyporesponsiveness to Erythropoietin Therapy in Hemodialyzed Patients: Potential Role of Prohepcidin,Hepcidin, and Inflammation

Hepcidin is the key regulator of iron metabolism. Iron supplementation is often introduced in dialyzed patients to replete or to maintain iron stores, particularly in patients treated with erythropoietic-stimulating agents. The present study was aimed to assess possible relation between hepcidin and erythropoietin therapy, with particular attention being paid to erythropoietin-hyporesponsiveness in hemodialyzed patients. Prohepcidin and hepcidin were studied using commercially available kits from DRG Instruments GmbH, Germany (ELISA method) and Bachem, UK (RIA method). TNFα and IL-6 were studied using kits from and R&D (Abington, UK), and hsCRP was studied using kits from American Diagnostica, USA. Hyporesponsive patients to erythropoietin therapy had significantly lower serum albumin, cholesterol, LDL, hemoglobin, hematocrit, and residual renal function, and significantly higher serum ferritin, hsCRP, IL-6, TNFα, and erythropoietin dose. The difference in serum prohepcidin and hepcidin did not reach statistical significance; however, there was a tendency toward higher values of both prohepcidin and hepcidin in hyporesponsive patients. In conclusion, though hyporesponsiveness to erythropoietin therapy occur in dialyzed patients, it is mainly associated with subclinical inflammation than with hepcidin excess. Further studies are needed to develop a reliable and reproducible assay to elucidate the potential contribution of hepcidin to hyporesponsiveness during erythropoietin therapy.     

Bone graft incorporation after revision hip arthroplasty in patients with rheumatoid arthritis, seventy eight revisions using bone allografts with or without metal reinforcements

Purpose

The aim of the study was to assess bone graft incorporation after revision hip arthroplasty in patients with rheumatoid arthritis (RA).

Methods

We report an acetabular reconstruction using impacted, morselized, frozen, radiation sterilized bone allografts in 71 patients suffering from RA. There were sixty-six women and five men at a mean age of 57.5 years. Reconstruction was performed in 78 revision total hip arthroplasties (THAs) for aseptic loosening of acetabular component. The mean follow-up was five years and four months. In 38 cases, a revision was done with use of reinforcement devices.

Results

In four revised hips (10 %) without reinforcement implants, resorption of the allografts was noticed. All Mueller rings and 50 % of unscrews cages (Link, Howmedica) were revised because of aseptic loosening and bone graft resorption. In all of 17 hips with the Burch-Schneider cage, no measurable migration or bone allografts resorption occurred. There were no major general complications.

Conclusions

Acetabular reconstruction with use of morselized, frozen, radiation sterilized bone allografts and the Burch-Schneider cage can be highly successful in managing massive deficiency of acetabular bone stock in revision hip arthroplasty in RA patients.     

Experience with intraoperative high frequency Doppler sonography in neurosurgical practice

Abstract

The method of blood flow velocity (BFV) evaluation by intraoperative application of the high frequency Doppler is presented. The device is used to estimate BFV changes in small caliber arteries by direct placement of the probe upon the examined vessel. BFVexaminations were performed on the site during aneurysm operations, during transsphenoidal approaches to identify the intracavernous portion of leA embedded in the tumor mass and in patients after encephalodurosynangiosis evaluated on the outpatient basis. Technical characteristics of the flowmeter used are described and examples of the BFV pictures in cerebral arteries are presented. The device allows a precise BFVevaluation in the selected vessel and detection of changes in BFV patterns particularly useful during aneurysms surgery. This method of identifying cerebral vessels may become applicable in other types of neurosurgical operations. [Neural Res 1998; 20: 655–657]     

Impact and persistence of cirrhotic cardiomyopathy after liver transplantation

Cirrhotic cardiomyopathy causes variable degree of systolic and diastolic dysfunction (DD) and conduction abnormalities. The primary aim of our study was to determine whether pre‐transplant DD and prolonged corrected QT (QTc) predict a composite of mortality, graft failure, and major cardiovascular events after liver transplantation. We also evaluated the reversibility of cirrhotic cardiomyopathy after transplantation. Adult patients who underwent liver transplantation at our institution from January 2007 to March 2009 were included. Data were obtained from institutional registry, medical record review, and evaluation of echocardiographic images. Among 243 patients, 113 (46.5%) had grade 1 DD, 16 (6.6%) had grade 2 DD, and none had grade 3 DD. The mean pre‐transplant QTc was 453 milliseconds. After a mean post‐transplant follow‐up of 5.2 years, 75 (31%) patients satisfied the primary composite outcome. Cox regression analysis did not show any significant association between DD and the composite outcome (P=.17). However, longer QTc was independently associated with the composite outcome (HR: 1.01, 95% confidence interval: 1.00–1.02, P=.05). DD (P<.001) and left ventricular mass index (P=.001) worsened after transplantation. In conclusion, QTc prolongation appears to be associated with worse outcomes. Although DD did not impact outcomes, it significantly worsened after transplantation.     

Low-level laser irradiation effect on endothelial cells under conditions of hyperglycemia

Diabetes mellitus is considered to be a very serious lifestyle disease leading to cardiovascular complications and impaired wound healing observed in the diabetic foot syndrome. Chronic hyperglycemia is the source of the endothelial activation. The inflammatory process in diabetes is associated with the secretion of inflammatory cytokines by endothelial cells, e.g., tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6). The method of phototherapy using laser beam of low power (LLLT—low-level laser therapy) effectively supports the conventional treatment of diabetic vascular complications such as diabetic foot syndrome. The aim of our study was to evaluate the effect of low-power laser irradiation at two wavelengths (635 and 830 nm) on the secretion of inflammatory factors (TNF-α and IL-6) by the endothelial cell culture—HUVEC line (human umbilical vein endothelial cell)—under conditions of hyperglycemia. It is considered that adverse effects of hyperglycemia on vascular endothelial cells may be corrected by the action of LLLT, especially with the wavelength of 830 nm. It leads to the reduction of TNF-α concentration in the supernatant and enhancement of cell proliferation. Endothelial cells play an important role in the pathogenesis of diabetes; however, a small number of studies evaluate an impact of LLLT on these cells under conditions of hyperglycemia. Further work on this subject is warranted.     

Anti-tumor action of tumor necrosis factor against Bomirski Ab melanoma in hamsters

Introduction: Tumor necrosis factor (TNF) is a cytokine able to exert anti-tumor activity in various models and modes of applications. However, the exact mechanism mediating the in vivo anti-tumor effect of TNF has not yet been clarified. Materials and Methods: The effects of intratumoral injection of rat TNF into hamsters bearing Bomirski Ab amelanotic melanoma, a fast growing tumor of high metastatic potential, were tested. Subcutaneous injections of the anti-angiogenic compound TNP-470 allowed analysis of its influence on the effects of TNF administration. Results: TNF application resulted in a significant inhibition of tumor growth and changes in metastasis pattern. Accelerated hemorrhagic necrosis was also observed, indicating the effect of the cytokine on tumor vessels. Moreover, the synergistic anti-tumor effect of TNF and anti-angiogenic agent TNP-470 suggested a cooperative activity of both substances on tumor vasculature. Microscopically, the effect of TNF injections was expressed by an increase in the amount of tumor cells with nuclear pyknosis and karryorrhexis. In vitro assays indicated a direct cytotoxic effect of TNF against Ab melanoma cells, most probably as an outcome of apoptosis. Intratumoral application of TNF also caused some modulation of cytokine response in melanoma-bearing hamsters as evidenced by increased levels of IL-6 in blood serum. Conclusions: This study established Bomirski Ab melanoma as a useful model for complex analysis of the anti-tumor activity of TNF.     

Evaluation of selected parameters of the antioxidative system in patients with type 2 diabetes in different periods of metabolic compensation

Introduction: The aim of the study was to evaluate some selected parameters of the antioxidative system in patients with type 2 diabetes. Materials and Methods: Eighty-one type 2 diabetes patients took part in the study (39 patients with metabolically balanced and 42 with metabolically unbalanced diabetes). The control group consisted of 30 healthy people. The total antioxidant capacity of plasma was measured fluorometrically using phycoerythrin. To calculate the low-molecular-weight antioxidant concentration in the plasma samples, the duration of Trolox activity as a function of its concentration in the sample was measured. The activity of antioxidative enzymes in red blood cells was determined using the Misra and Fridovich method and Beers and Sizer method. Results: The total plasma antioxidant capacity and the low-molecular-weight antioxidant concentration in the group of patients with metabolically compensated type 2 diabetes were statistically significantly higher than in the group of patients with metabolically uncontrolled diabetes. The activity of antioxidative enzymes was found to be higher in the group of type 2 diabetes patients at the stage of metabolic balance. Conclusions: The obtained results confirm the thesis of glucose toxicity and intensification of oxidative stress in patients with diabetes.