ABSTRACT
The carotid bodies tend to enlarge after long-standing cardiopulmonary disease. Our objective was to investigate whether cardiac hypertrophy is associated with carotid body hyperplasia. Fifteen autopsy cases with combined left and right ventricular hypertrophy were examined and compared with two control groups (16 cases). The study involved a meticulous dissection of carotid bifurcations, thin serial sections, and morphometric analysis of carotid body volume and cell types (progenitor, dark, light, and sustentacular). There was a significant increase in sustentacular cells in all individuals with cardiac hypertrophy, which was not drug-induced, and accompanied by a similar increase in carotid body volume. Dark or light cell accumulation was detected focally and only in three instances. It appears that the generalized sustentacular cell hyperplasia is the result of long-standing hypoxia, while a superimposed focal prominence of dark or light cells may be proliferative or metaplastic in nature and attributed to short-term hypoxia.
Subject(s)
Carotid Body/pathology , Hypertrophy, Left Ventricular/pathology , Hypertrophy, Right Ventricular/pathology , Aged , Aged, 80 and over , Case-Control Studies , Cell Count , Female , Forensic Pathology , Humans , Hyperplasia/etiology , Hypertension/complications , Hypoxia/pathology , Male , Microscopy , Middle AgedABSTRACT
INTRODUCTION: Fever/rash is a side-effect of amifostine that demands immediate interruption of the drug. Here, we focus on the role of C-reactive protein (CRP) as a putative marker linked with amifostine fever/rash. MATERIALS AND METHODS: The CRP serum values were analyzed in 496 patients receiving radiotherapy supported with amifostine (500-1000 mg/d). CRP levels were recorded before the onset of radiotherapy (day 0), on day 15 and when the fever/rash appeared. For 121 out of 496 patients, CRP values on day 7 were also available. About 79 patients (15.9%) developed fever/rash symptoms. RESULTS: The CRP levels before the onset of therapy were 0 to 20.7 mg/dL (normal, ≤0.5 mg/dL). For patients who did not develop fever/rash, the CRP levels increased from a median of 0.30 to 0.50 on day 15; P = 0.001. Patients who developed fever/rash showed a more than 7-fold increase of the median CRP levels (median, 3.50; P < 0.0001). This sharp CRP rise was specific for amifostine-related fever/rash. Initially abnormal CRP levels were linked with a 2-fold risk for fever/rash (P = 0.01), while abnormal levels on day 7 were linked with a 3-fold higher risk (P = 0.08). The occurrence of fever/rash was independent of the amifostine dose level. CONCLUSIONS: Sharp rise of CRP levels on the day after the fever/rash development suggest amifostine-related etiology of fever/rash. Abnormal initial CRP levels and/or high CRP levels on day 7 should be considered as an alert signal as the probability to develop fever/rash reaches the 30%.
Subject(s)
Amifostine/adverse effects , C-Reactive Protein/metabolism , Dose Fractionation, Radiation , Drug Eruptions/etiology , Fever/chemically induced , Radiation-Protective Agents/adverse effects , Radiotherapy/methods , Adult , Aged , Amifostine/administration & dosage , Biomarkers/blood , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Radiation-Protective Agents/administration & dosageABSTRACT
Erythropoietin receptors (EpoRs) are expressed in a large percentage of cells in many human malignancies, including endometrial adenocarcinoma. In such tumors, administration of recombinant human erythropoietin (rhEpo) during radiotherapy and chemotherapy may oppose tumor progression by interfering with growth and invasion pathways. In the present study, a strong EpoR expression was demonstrated in 58.8% of 72 stage I endometrial adenocarcinomas, and this pattern was linked with a high degree of tumor differentiation (p=0.01), deep myometrial invasion (p=0.04) and, marginally, with poor prognosis (p=0.06). In addition, a strong association with the immunohistochemical expression of hypoxia-inducible factor 1alpha (HIF1alpha) and the downstream angiogenic protein vascular endothelial growth factor (VEGF) was noted. In multivariate analysis, HIF1alpha, but not EpoR, was associated with the depth of myometrial invasion (p=0.04) and marginally with prognosis (p=0.07). It is concluded that EpoR are common constituents of endometrial adenocarcinomas and are related to tumor aggressiveness, although this is probably a result of their involvement in an active HIF pathway.
Subject(s)
Adenocarcinoma/metabolism , Endometrial Neoplasms/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Receptors, Erythropoietin/metabolism , Vascular Endothelial Growth Factor A/metabolism , Adenocarcinoma/pathology , Endometrial Neoplasms/pathology , Female , Fluorescent Antibody Technique, Indirect , Humans , Neoplasm Invasiveness , Neoplasm Staging , PrognosisABSTRACT
High levels of CRP relate with advanced disease and poor prognosis of cancer patients. CRP serum levels were measured in 684 cancer patients who had undergone complete surgery or inoperable patients. Patients with inoperable tumors had significantly higher CRP levels (1.21 +/- 2.2 vs. 0.40 +/- 0.4 mg/dL; p < 0.0001). No association with gender, diabetes, autoimmune disease, thyroid disease or allergy was noted. Significantly higher CRP levels were noted in operated patients with hypertension (0.55 +/- 0.5 vs. 0.35 +/- 0.4; p = 0.001), coronary disease (0.73 +/- 0.8 vs. 0.39 +/- 0.4; p = 0.01) and obesity (0.51 +/- 0.5 vs. 0.37 +/- 0.4; p = 0.04). On the contrary, analysis in the group of inoperable patients showed that hypertensive patients had significantly lower CRP levels (0.64 +/- 1.0 vs. 1.36 +/- 2.4; p = 0.008). Although the tumor itself is the main factor defining increased CRP levels in cancer patients, hypertension, coronary disease and obesity are also linked with high CRP levels. Anti-hypertensive drugs appear as potent suppressors of the tumor-induced CRP production.
