Cervical biomarkers as predictors of successful induction of labour by Foley catheter

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Autonomic nerves in myocardial sleeves around caval veins : Potential role in cardiovascular mortality?

Background: Quantitative changes in the cardiac autonomic nervous system may play an important role in the pathogenesis of various cardiovascular diseases. In the present morphological analysis, we aimed to study autonomic nerve density in myocardial sleeves and surrounding fibro-fatty tissue around caval veins. We correlated the nerve distribution with cardiovascular mortality and a history of atrial fibrillation. Materials and Methods: A total of 24 autopsied adult hearts were excised together with the superior and inferior vena cava and grouped according to the immediate and underlying causes of death (cardiovascular vs. non-cardiovascular), and documented heart rhythm history (atrial fibrillation vs. sinus rhythm). The density of autonomic nerves was quantified by measuring the area of immunohistochemical staining for sympathetic (tyrosine hydroxylase, TH) and parasympathetic (choline acetyltransferase, CHAT) nerves and ganglia. Growth-associated protein 43 (GAP43) was used as a neural growth marker. Results: The mean density of TH-positive nerves in the superior vena cava myocardial sleeves was significantly decreased between groups with documented underlying cardiovascular vs. non-cardiovascular cause of death (mean density ± standard deviation (SD): 704.81±1016.41 µm2/mm2 vs. 2391.01±1841.37 µm2/mm2; P =.008). Similarly, the nerve density of GAP43-positive nerves in the superior vena cava myocardial sleeves was significantly lower in subjects with documented underlying cardiovascular cause of death (mean density ± SD: 884.74±1240.16 µm2/mm2 vs. 2132.89±1845.89 µm2/mm2; P =.040). The mean age was significantly higher in subjects with documented underlying cardiovascular vs. non-cardiovascular cause of death (mean age ± SD: 69.2±11.9 years, vs. 57.5±11.2 years, P =.016). No differences were found in nerve densities of TH-positive (953.01±1042.93 µm2/mm2 vs. 919.26±1677.58 µm2/mm2), CHAT-positive (180.8±532.9 µm2/mm2 vs. 374.22±894.76 µm2/mm2), and GAP43-positive nerves (593.58±507.97 µm2/mm2 vs. 1337.34±1747.69 µm2/mm2) in myocardial sleeves around the inferior vena cava between groups with documented immediate cardiovascular vs. non-cardiovascular cause of death. Similarly, no differences were found between groups with documented underlying cardiovascular vs. non-cardiovascular cause of death (TH: 717.23±887.31 µm2/mm2 vs. 1365.51±2149.10 µm2/mm2; CHAT: 256.18±666.86 µm2/mm2 vs. 368.53±959.47 µm2/mm2; GAP43: 661.21±839.51 µm2/mm2 vs. 1759.90±2008.80 µm2/mm2). Moreover, there was no association found in nerve densities between subjects with documented atrial fibrillation vs. sinus rhythm (TH: 235.07±425.69 µm2/mm2 vs. 1166.08±1563.84 µm2/mm2; CHAT: 648.59±1017.33 µm2/mm2 vs. 175.31±641.65 µm2/mm2; GAP43: 990.17±1315.18 µm2/mm2 vs. 1039.86±1467.23 µm2/mm2). Conclusions: Decrease of superior vena cava myocardial sleeve sympathetic nerves may be associated with cardiovascular mortality and/or aging. No difference in autonomic innervation was found between subjects with documented atrial fibrillation vs. sinus rhythm.publishedVersionPeer reviewe

Ascending aortic wall degeneration in patients with bicuspid versus tricuspid aortic valve

Background: The magnitude of ascending aortic degeneration in patients with bicuspid aortic valves (BAV) is controversial. Methods: The aim of this study was to investigate ascending aortic wall degeneration in patients with BAV as compared with tricuspid aortic valves (TAV). The ascending aortic wall of 67 consecutive patients was processed for histology and immunohistochemistry. The extent of surgery and wall degeneration were investigated. Unadjusted survival was evaluated by Kaplan–Meier analysis. Median follow-up for patients with BAV and TAV was 3.8 years (interquartile range [IQR] 3.5–4.1) and 3.7 years (IQR 3.4–3.9), respectively. Results: There were 33 patients with BAV and 34 with TAV. Mid-ascending aorta diameter was 54 mm (IQR 50–60). Replacement of the aortic valve, together with an ascending aortic prosthesis, was more frequent in BAV vs TAV patients (24% vs. 3%, P = 0.013). However, medial fibrosis, elastic fiber thinning, incremental medial degeneration and smooth muscle cell nuclei loss were less prominent in BAV vs TAV patients (0.1 ± 0.4 vs. 0.8 ± 1.4, P = 0.016; 0.6 ± 1.4 vs. 1.6 ± 2.0, P = 0.027; 1.7 ± 0.7 vs. 2.2 ± 0.8, P = 0.045 and 2.3 ± 1.5 vs. 3.2 ± 1.3, P = 0.026, respectively). Conclusions: Since degeneration of the ascending aortic wall was seldom prominent, histopathology alone may not support the need for surgery of the dilated ascending aorta in BAV patients as compared with TAV patients.publishedVersionPeer reviewe

Complement activation in astrocytomas: deposition of C4d and patient outcome

Background C4d is a cleavage product of complement component C4 and is considered to serve as a marker for the site of complement activation. In this study C4d staining of grade I-IV astrocytic tumors was studied to explore if there is an association between complement activation and the grade of tumor, or patient survival. Methods Tissue micro-array samples of 102 astrocytomas were stained immunohistochemically. The material consisted of 9 pilocytic astrocytomas and 93 grade II-IV astrocytomas, of which 67 were primary resections and 26 recurrent tumors. The intensity of C4d staining as well as extent of C4d and CD34 staining were evaluated. The intensity of C4d staining was scored semiquantitatively. The extent of the staining was counted morphometrically with a point counting grid yielding a percent of C4d and CD34 positive area of the sample. Results The intensity and extent of C4d staining increased in grade II-IV diffusely infiltrating astrocytoma tumors in line with the malignancy grade (p = 0.034 and p = 0.016, respectively, Kruskal-Wallis test). However, C4d positive tumor area percentages were higher in grade I pilocytic astrocytomas than in grade II-IV diffusely infiltrating astrocytomas (p = 0.041, Mann–Whitney test). There was a significant correlation between CD34 positive and C4d positive endothelial area fraction in diffusely infiltrating astrocytomas (p < 0.001, Pearson correlation). In these tumors, the increasing intensity of C4d staining was also associated with worsened patient outcome (p = 0.014, log-rank test). Conclusion The worsening of patient outcome and malignant progression of tumor cells seem to be connected to microenvironmental changes evoked by chronically activated complement. Keywords: Astrocytoma; Glioblastoma; C4d; Complement; Inflammation; Survival;BioMed Central open acces

Overexpression of HSP27 and HSP70 is associated with decreased survival among patients with esophageal adenocarcinoma

BACKGROUND Overexpression of heat shock proteins (HSPs) is associated with several malignancies and contributes to the development, progression, and metastasis of cancer, in addition to the inhibition of cellular death. In recent years, there has been active research into using HSP inhibitors in several malignancies. Due to the poor prognosis of esophageal adenocarcinoma (EAC), it would be valuable to find new biomarkers for the development of cancer treatments. AIM To evaluate the expressions of HSP27 and HSP70 and their effect on survival in EAC. METHODS Immunohislochemical analyses and evaluations of HSP27 and HSP70 expression were performed on all available samples from 93 patients diagnosed with EAC between 1990 and 2007 at two university hospitals. Fifteen cases with Barrett's metaplasia and 5 control cases from the same patient population were included in the analysis. HSP expression was quantitatively assessed and classified as high or low. Kaplan-Meier analyses and Cox regression models adjusting for age and sex as well as tumor site, stage, and grade were used to evaluate the effect on survival. RESULTS Tumor stage and surgical treatment were the main prognostic factors. High HSP27 expression in cancer cases was a strong negative predictive factor, with a mean survival of 23 mo compared to the 49 mo in cases with a low expression (P = 0.018). The results were similar for HSP70, with a poorer survival of 17 mo in cases with high HSP70 expression, in contrast to 40 mo (P = 0.006) in cases with a low expression. A Cox regression survival analysis was performed, adjusting for possible confounding factors, and higher HSP27 and HSP70 expressions remained an independent negative prognostic factor. The HSPs' correlation with survival was not affected by cancer treatments. When the analysis was adjusted for all factors, the odds ratios for HSP27 and HSP70 were 3.3 (CI: 1.6-6.6, P = 0.001) and 2.2 (CI: 1.2-3.9, P = 0.02), respectively. CONCLUSION HSP27 and HSP70 overexpression is associated with poor survival in EAC, which is, to the best of our knowledge, reported for the first time.Peer reviewe

Human Pulmonary Vein Myocardial Sleeve Autonomic Neural Density and Cardiovascular Mortality

Myocardial sleeves around pulmonary veins (PVs) are highly innervated structures with heterogeneous morphological and electrophysiological characteristics. Autonomic nerve dysfunction in the myocardium may be associated with an increased risk of cardiovascular morbidity and mortality. This article studied autonomic neural remodeling in myocardial sleeves around PVs and atrial-PV ostia with immunohistochemical and morphometric methods with clinicopathological correlations. PVs were collected from 37 and atrial-PV ostia from 17 human autopsy hearts. Immunohistochemical analysis was performed using antibodies against tyrosine hydroxylase (TH), choline acetyltransferase (CHAT), and growth-associated protein 43 (GAP43). In the PV cohort, subjects with immediate cardiovascular cause of death had significantly decreased sympathetic nerve density in fibro-fatty tissue vs those with non-cardiovascular cause of death (1624.53 vs 2522.05 µm2/mm2, p=0.038). In the atrial-PV ostia cohort, parasympathetic nerve density in myocardial sleeves was significantly increased in subjects with underlying cardiovascular cause of death (19.48 µm2/mm2) than subjects with underlying non-cardiovascular cause of death with no parasympathetic nerves detected (p=0.034). Neural growth regionally varied in sympathetic nerves and was present in most of the parasympathetic nerves. Heterogeneous autonomic nerve distribution and growth around PVs and atrial-PV ostia might play a role in cardiovascular morbidity and mortality. No association in nerve density was found with atrial fibrillation.acceptedVersionPeer reviewe

Absent Toll-like receptor-9 expression predicts poor prognosis in renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Toll-like receptor 9 (TLR9) is a cellular DNA-receptor whose activation with cognate ligands triggers an immune reaction, with increased production of inflammatory cytokines. The aim of this study was to examine the expression of TLR9 in renal cell carcinoma (RCC), which is generally renowned of its immunogenic nature. We also evaluated the prognostic value of TLR9 in RCC.</p> <p>Methods</p> <p>TLR9 expression in RCC was characterized with immunohistochemistry in a retrospective study population of 152 RCC patients who underwent renal surgery. The TLR9 staining intensity was compared with clinical parameters.</p> <p>Results</p> <p>Of the studied tumours, 112 (81%) exhibited cytoplasmic TLR9 immunostaining. No association was detected between cytoplasmic TLR9 immunoexpression intensity and stage, nuclear grade, histological subtype or tumour necrosis. Cytoplasmic TLR9 immunoexpression was, however, a marker of favourable RCC specific survival both in univariate analysis and in multivariate regression model.</p> <p>Conclusions</p> <p>We conclude that TLR9 expression is an independent prognostic marker of RCC and the absence of TLR9 expression is related to poorer prognosis in RCC.</p