ABSTRACT
In addition to its role in erythropoiesis, erythropoietin (Epo) plays a role in tissue protection, which includes cardioprotective, nephroprotective and neuroprotective effects. The presence of Epo and its receptor (Epo-R) in pulmonary tissue also suggests a cytoprotective effect of Epo in the lung. Our project aims to document this role in a murine model under-expressing Epo. The obtained results will lead to a better understanding of the cytoprotective effects of Epo and will also give an appreciation of its beneficial effects in cases of lung injury.
Subject(s)
Acute Lung Injury/pathology , Cytoprotection , Erythropoietin/pharmacology , Erythropoietin/physiology , Kidney , Animals , Cytoprotection/drug effects , Cytoprotection/genetics , Disease Models, Animal , Erythropoietin/genetics , Hematopoiesis/drug effects , Hematopoiesis/genetics , Humans , Kidney/drug effects , Kidney/pathology , Lung/drug effects , Lung/pathology , Lung/physiology , MiceSubject(s)
Aneurysm, False/complications , Femoral Artery/pathology , Psoas Muscles/pathology , Spasm/etiology , Aged , Aged, 80 and over , Aneurysm, False/diagnosis , Femoral Artery/diagnostic imaging , Humans , Iliac Artery/diagnostic imaging , Iliac Artery/pathology , Male , Psoas Muscles/diagnostic imaging , Spasm/diagnosis , Tomography, X-Ray Computed , Ultrasonography, Doppler , Ultrasonography, Doppler, DuplexABSTRACT
BACKGROUND: Despite intensive research into the molecular abnormalities associated with colorectal cancer (CRC), no diagnostic tests have emerged which usefully complement standard histopathological assessments. AIMS: To assess the feasibility of using immunohistochemistry to detect replication error (RER) positive CRCs and determine the incidence of RER positivity within distinct patient subgroups. METHODS: 502 CRCs were analysed for RER positivity (at least two markers affected) and/or expression of hMSH2 and hMLH1. RESULTS: There were 15/30 (50%) patients with metachronous CRCs, 16/51 (31%) with synchronous CRCs, 14/45 (31%) with a proximal colon carcinoma, and 4/23 (17%) who developed a CRC under the age of 50 showed RER positivity. However, 0/54 patients who developed a solitary carcinoma of the rectum/left colon over the age of 50 showed RER positivity. Immunohistochemical analysis revealed that 66/66 (100%) RER positive carcinomas were associated with complete lack of expression of either hMSH2 or hMLH1. This correlation was confirmed using a further 101 proximal colon carcinomas. Patients with a mismatch repair defective carcinoma showed improved survival but a 5.54 times relative risk of developing a metachronous CRC. A prospective immunohistochemical study revealed 13/117 (11%) patients had a mismatch repair defective carcinoma. A fivefold excess of hMLH1 defective cases was noted. CONCLUSIONS: All RER positive carcinomas were identified by the immunohistochemical test. This is the first simple laboratory test which can be performed routinely on all CRCs. It will provide a method for selecting patients who should be investigated for HNPCC, offered long term follow up, and who may not respond to standard chemotherapy regimens.
Subject(s)
Biomarkers, Tumor/metabolism , Colorectal Neoplasms/diagnosis , DNA Repair , DNA-Binding Proteins , Neoplasm Proteins/metabolism , Adaptor Proteins, Signal Transducing , Adult , Carrier Proteins , Colorectal Neoplasms/genetics , Feasibility Studies , Follow-Up Studies , Humans , Immunoenzyme Techniques , Microsatellite Repeats , Middle Aged , MutL Protein Homolog 1 , MutS Homolog 2 Protein , Neoplasm Proteins/genetics , Nuclear Proteins , Polymerase Chain Reaction , Prospective Studies , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolismABSTRACT
The aim of this study was to measure the effects of heparin therapy in patients undergoing vascular surgery, and to monitor the effectiveness of continuous intravenous heparin therapy in ward-based patients. In addition, we compared results from a new portable device with those from the standard laboratory assay. A prospective comparison of the two methods in patients undergoing peripheral vascular surgery, and in ward-based patients who were receiving intravenous heparin infusions was undertaken. Fifty patients who were undergoing vascular surgery and receiving a bolus dose of intravenous heparin, and 22 patients receiving a continuous heparin infusion, were recruited. Blood samples were taken 10 and 40 min following bolus heparin administration or after > 12 h of a continuous heparin infusion. Plasma activated partial thromboplastin times (APTTp) measured by the haematology laboratory were compared with whole blood (APTT(B)) ascertained with the CoaguChek Plus Device (Boehringer Mannheim UK Diagnostics and Biochemicals Limited) at each time point. The results from the two methods were compared using the method of Bland and Altman (Lancet, 1986, 307-310). We found a good level of agreement between the two methods (at induction, mean bias was -0.050, limits of agreement -0.46 - 0.36; heparin infusions, mean bias was -0.283, limits of agreement -1.64 - 1.07). In addition we discovered that many of our patients appeared to be excessively anticoagulated during surgery (10 min following heparin bolus 47/50 patients had an APTT(B) > 150 s, 45/50 had an APTTp > 250 s; at 40 min 45/50 had an APTT(B) > 150 s, 39/50 had an APTTp > 250 s). In conclusion, whole blood APTT measurement allows rapid and accurate assessment of the effects of heparin therapy when compared with laboratory APTT measurement and may prevent both excessive and suboptimal anticoagulation.
