bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet Activation Markers in Patients with Venous Thromboembolism without Predisposing Factors
Authors: Gerdsen Frank , Weber Martin , Langer Florian , Eifrig Barbara , Lindhoff-Last Edelgard
Published: February 2006

A constant in vitro hypersensitivity of platelets (adenosine diphosphate) has been suggested as a risk factor for arterial and even venous thrombosis. Our aim was to determine phenotypic and functional alterations of platelets by flow cytometry as potential prothrombotic risk factors in patients with a history of unexplained spontaneous venous thrombosis. Forty-nine patients with a history of spontaneous venous thrombosis and no inherited or acquired thrombophilic risk factors were compared with a reference group of 39 healthy volunteers. Flow cytometry (FACS) was used to analyze the surface expression of CD62 (P-selectin) and CD63 in nonactivated platelets and after in vitro stimulation with adenosine diphosphate and thrombin receptor activator peptide 6. Mean fluorescence intensity of CD62 and CD63 surface expression as well as percentage of CD62 and CD63 positive cells and binding index differed in patients with a history of thrombosis compared with the reference group, but failed to reach statistical significance. Similar results were observed after in vitrostimulation with adenosine diphosphate and thrombin receptor activator peptide 6. In conclusion, the expression of CD62 and CD63 of resting and in vitro activated platelets could not be established as a risk factor for spontaneous venous thromboembolism.
Long-Term Prospective Study of Recurrent Venous Thromboembolism in Patients Younger than 50 Years
Authors: García-Fuster María-José , Forner María-José , Fernández Conrado , Gil Joaquín , Vaya Amparo , Maldonado Luis
Published: February 2006

Long-term incidence of recurrent venous thromboembolism (VTE) in patients younger than 50 years, not affected by a malignancy or chronic diseases, are poorly characterized. After the initial episode of VTE and cessation of oral anticoagulation, 98 patients, mean age 32.2 ± 9.2 years were followed for a median of 117 months (range 6–165). Congenital risk factors for VTE were present in 36% of patients, acquired persistent (positive antiphospholipid antibodies during the whole follow-up) in 19%, and acquired transitory in 44%. Thirty episodes of recurrent VTE were documented. The cumulative incidence of VTE after 1 year of follow-up was 5.1%, 9.8% after 2 years, 14% after 4 years, and 34.2% after 8 years. In the univariate analysis, the relative risk of recurrent VTE was 2.66 [95% confidence interval (CI) 1.03–6.90] for congenital risk factors, 4.97 (95% CI 1.75–14.0) for persistent acquired (antiphospholipid antibodies), 2.64 (95% CI 1.23–5.66) for male gender and 2.27(1.00–5.15) for body mass index >30 kg/m2. In the multivariate analysis, male gender [hazard ratio (HR) 4.23, 95% CI 1.88–9.77) the presence of congenital factors (HR 3.28, 95% CI 1.25–8.63) and acquired persistent factors (HR 8.50, 95% CI 2.84–25.50) were independent risk factors for recurrent VTE. In patients under 50 years of age without malignancy or underlying chronic disease, hospitalized for an acute thromboembolic event, the presence of antiphospholipid antibodies, congenital defects of coagulation, male sex, and obesity were risk factors for recurrent VTE. These data raise the possibility that selected patients with VTE may require prolonged anticoagulation to prevent recurrent disease.
Association of Leukocyte Activation, but Not the Common Cold, with Restenosis after Percutaneous Coronary Intervention in Patients with Angina Pectoris
Authors: Inami N. , Nomura S. , Kimura Y. , Sutani Y. , Yamada K. , Nakamori H. , Takahashi N. , Tsuda N. , Fukuhara S. , Iwasaka T.
Published: February 2006

We investigated the relationship between the common cold and restenosis after percutaneous coronary intervention (PCI) in Japanese patients with angina pectoris, because suffering from a common cold during the follow-up period after PCI may be involved in the development of restenosis. In addition, we measured the soluble (s) L-selectin level early after PCI in patients with and without restenosis. The study group included 104 effort angina pectoris patients. We examined whether or not they had had a common cold in the 6 months following angioplasty. Finally, 88 patients, whose common cold status was known, were selected as the study subjects. Twelve patients caught a common cold after PCI. All of these patients were given antibiotics and/or anti-inflammatory agents and recovered within 2 weeks. None had clinically detectable influenza infection. Thirty-three patients suffered from restenosis and 55 did not. There was no significant difference in the restenosis frequency between effort angina pectoris patients with and without a common cold. The sL-selectin level was significantly increased in patients with restenosis early after PCI, whereas in patients without restenosis, sL-selectin remained unchanged. These findings suggest that restenosis development after PCI in patients with effort angina pectoris may involve leukocyte activation early after PCI, while suffering from a common cold during the follow-up period after PCI has no effect.
Preexisting Antibodies to Platelet Factor 4-Heparin Complexes in Patients with Acute Coronary Syndrome Who Have No History of Heparin Exposure
Authors: Matsuo Takefumi , Suzuki Shunji , Matsuo Miyako , Kobayasi Hiroko
Published: February 2006

Preexisting heparin-induced thrombocytopenia (HIT) antibodies are detected in some patients who have not previously been exposed to any kind of heparin. However, the role of preexisting HIT antibodies in acute coronary syndrome (ACS) is still unknown. This study was carried out to clarify the role of preexisting HIT antibodies in patients with ACS. Forty patients with ACS who had not been exposed to any kind of heparin via the venous or subcutaneous route or heparin-coated materials and had undergone percutaneous coronary intervention (PCI) under heparin anticoagulation within 6 h from the onset of ACS were chosen from the medical records in the cardiac emergency department. As a control of the ACS patients, 51 patients with angina pectoris who underwent elective PCI under heparin anticoagulation were chosen in the same manner as the ACS patients. Preexisting HIT antibodies were detected by ELISA in 6 patients. Two of the 6 patients developed HIT and 1 patient experienced thrombosis requiring intracoronary thrombolytic therapy. Thrombotic complications during and immediately after PCI in the very early stage after heparin administration were found in 4 of 6 patients with preexisting HIT antibodies. The frequency of preexisting HIT antibodies in ACS patients was significantly increased in comparison with that in non-ACS patients. The odds ratio of the risk of thrombotic complication between ACS and non-ACS patients was estimated at 8.82 (95% CI: 1.3–63). Also, preexisting HIT antibodies in ACS patients significantly increased the risk of thrombotic complications compared with ACS without preexisting HIT antibodies. In conclusion, ACS patients with positive HIT antibodies have an increased risk of thrombotic complications during PCI performed under anticoagulation with heparin.
Evaluation of Urokinase-Type Plasminogen Activator and Its Receptor in Neointima of Polyester Vascular Grafts
Authors: Kowalewski Radoslaw , Zimnoch Lech , Wojtukiewicz Marek Z. , Glowinski Jerzy , Glowinski Stanislaw
Published: February 2006

The aim of the study was to assess the expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in neointima of polyester vascular grafts. Anastomotic areas were examined at 1, 4 and 12 months after prosthesis implantation in dogs, as well as in human vascular grafts. Immunohistochemistry was performed for uPA and uPAR. Graft neointima in dogs was positively stained for uPA with increased intensity at 4 and 12 months, whereas uPAR expression appeared at 4 and its intensity was increased at 12 months. Intensive uPA and positive uPAR labeling was shown in human grafts. The results demonstrated that in the early period of the healing process of polyester vascular grafts only uPA is present in the neointima in the region of the graft to adjacent artery anastomosis, whereas in healed grafts in dogs and humans uPAR is found as well.
Platelet Aggregation in Portal Hypertension and Its Modification by Ultra-Low Doses of Aspirin
Authors: Eizayaga Francisco X. , Aguejouf Omar , Belon Philippe , Doutremepuich Christian
Published: February 2006

Aspirin (ASA) is widely accepted as antithrombotic drug, but several reports point out that its use in ultra-low doses (ULD) has prothrombotic properties. In this study, we evaluate the effect of portal hypertension in rats on platelet aggregation in an in vivo arterial thrombosis model induced by a laser beam. Portal hypertension was produced by calibrated stenosis of the portal vein. ASA in ULD was injected to both control and portal hypertensive groups. Platelet aggregation induced by ADP, prothrombin time, activated partial thromboplastin time, fibrinogen and induced hemorrhagic time test were also performed. Portal hypertensive rats showed a diminished number of emboli and duration of embolization in the laser procedure and an increase in induced hemorrhagic time. These changes were reverted by one injection of ASA at ULD. This observation could be of importance for primary prevention or the treatment of recurrence in upper digestive tract hemorrhage in portal hypertensive patients.
Platelets Treated with Ticlopidine Are Less Reactive to Unusually Large von Willebrand Factor Multimers than Are Those Treated with Aspirin under High Shear Stress
Authors: Matsumoto M. , Kawaguchi S. , Ishizashi H. , Yagi H. , Iida J. , Sakaki T. , Fujimura Y.
Published: February 2006

Much attention has recently been focused on the interaction between unusually large von Willebrand factor multimers (UL-VWFM) and platelets under high shear stress in pathological thrombus formation. The antiplatelet drugs acetylsalicylic acid (aspirin) and a thienopyridine derivative (ticlopidine) are commonly used to treat cerebral ischemia but exert different effects on high-shear-stress-induced platelet aggregation (H-SIPA) in the plasma. To examine the effects of these drugs in the absence of plasma factors, we studied H-SIPA using washed platelets (WPs) and purified UL-VWFM. WPs were prepared from the blood of 9 aspirin-treated and 11 ticlopidine-treated patients with cerebral ischemia, and H-SIPA in the presence of UL-VWFM was measured using a cone plate aggregometer. Plasma levels of VWF antigen with its multimer analysis, ristocetin cofactor and VWF-cleaving protease (ADAMTS13) activity were also measured. Forty-six healthy volunteers from 2 age groups, 20–40 years (n = 20) and 41–60 years old (n = 26), were also tested as controls. H-SIPA was significantly inhibited for ticlopidine-treated platelets, but it was observed to a lesser extent for aspirin-treated platelets. For both groups, no difference in the plasma levels of VWF antigen, ristocetin cofactor and ADAMTS13 activity was noted. All patients possessed UL-VWFM, and it was detected in healthy volunteers with increasing frequency with increasing age. Under plasma-free conditions, platelets from aspirin-treated patients exhibit marginal but significant inhibition of H-SIPA. Furthermore, the presence of UL-VWFM in the plasma of patients and normal volunteers is directly related to their age rather than being a consequence of underlying disease.
Inhibition of Thrombin-Induced Vascular Endothelial Growth Factor Production in Human Neuroblastoma (NB-1) Cells by Argatroban
Authors: Sarker Krishna Pada , Biswas Kamal Krishna , Yamaji Kazuyo , Yamakuchi Munekazu , Hashiguchi Teruto , Lee Ki-Young , Maruyama Ikuro
Published: February 2006

Thrombin, a serine protease that plays a pivotal role in blood coagulation, wound healing, and angiogenesis, has also been implicated in the mitogenesis of various cell types. Previously, we showed that thrombin and the thrombin receptor agonist peptide (TRAP-14; SFLLRNPNDKYEPF) for protease-activated receptor 1 (PAR1) induce vascular endothelial growth factor (VEGF) secretion in PC-12 cells. In this study, we show that thrombin and TRAP-14 also stimulate VEGF secretion in the human NB-1 neuroblastoma cells. In these cells, we further show that thrombin-induced VEGF secretion was blocked by cycloheximide and actinomycin D, indicating that de novo protein synthesis is essential for this process. Reduced thrombin-induced VEGF secretion upon treatment with LY294002, calphostin C, or BAPTA, further suggests that the process is dependent on phosphatidyl-inositol-3-kinase, protein kinase C, and calcium. However, the complete loss of thrombin-induced VEGF production upon treatment with argatroban, a derivative of arginine and a potent anticoagulant/antithrombin agent, supports the notion that argatroban serves as a useful therapeutic tool for thrombin-associated pathologic conditions. Here, it appears that argatroban may be effective in controlling disorders linked to thrombin-induced VEGF production in neuronal cells.
Effects of Corneal Thickness, Curvature, Astigmatism and Direction of Gaze on Goldmann Applanation Tonometry Readings
Authors: Rask Gunilla , Behndig Anders
Published: February 2006

Background: The aim of this study was to evaluate the impact of various sources of error in Goldmann applanation tonometry (GAT). Objectives: We evaluated the effect of corneal thickness, curvature, astigmatism and direction of gaze as sources of error in GAT. Methods: Orbscan-II® (Bausch & Lomb, Inc., Rochester, N.Y., USA) examinations were made on 30 healthy subjects and 9 keratoconus patients, and the intraocular pressure (IOP) was measured with GAT centrally, temporally and inferiorly, with the tonometer prism set horizontally and vertically. Orbscan-II images from 50 younger subjects and 49 older subjects were analysed retrospectively. Results: IOP was lower on nasal gaze (p = 0.009) but higher on upward gaze (p < 0.001) compared with forward gaze. IOP and the corneal thickness were independently correlated (R2 = 0.04; p = 0.003), as were the difference in astigmatic vector in the horizontal and vertical meridians and the difference in IOP measured with a horizontal and vertical prism (R2 = 0.17; p < 0.001). No correlation between IOP and corneal curvature was found. In the keratoconus patients, IOPs were generally low, with large astigmatic differences. Conclusions: Corneal thickness, astigmatism and direction of gaze are clinically important sources of error in GAT. IOP should preferably be measured with the prism both horizontally and vertically. If only one direction is chosen, a vertical prism is less sensitive to different directions of gaze. Direction of gaze should be carefully monitored, especially in an irregular cornea.
An Examination of Characteristics of Lung and Colon Cancer Patients Participating in a Web-Based Decision Support Program
Authors: Markman Maurie , Petersen Judith , Montgomery Robert
Published: February 2006

Objectives: Little is known about the characteristics of cancer patients who employ the Internet as a technique to gather information to assist them in their management. Methods: To address this issue, aggregate data from individuals with colon (n = 7,543), non-small cell lung (n = 24,778) and small cell lung (n = 13,817) cancers who provided personal clinical information through participation in a proprietary Web-based decision support program (NexProfilerTM Treatment Option Tools for Cancer; NexCura®, Inc., Seattle, Wash., USA) were evaluated for potential differences between specific patient subgroups. Results: Examination of a number of objective (e.g., prior therapy) and subjective (e.g., overall health, activity level) parameters failed to reveal any major differences based on sex, geographical location (US vs. non-US) or newly diagnosed versus recurrent disease (non-small cell lung cancer patients). Several notable findings included: (1) overall >65% of colon cancer patients and >70% of lung cancer patients stated that they ‘were interested in learning about clinical trials’; (2) 65–70% of patients with recurrent non-small cell lung cancer stated that their ‘general health was good’, while >60% noted they had symptoms and >50% declared their activity level to be essentially ‘normal’; (3) while almost 80% of small cell lung cancer patients noted symptoms, >60% stated their activity level was ‘normal’. Conclusion: These data suggest that the population of patients who seek information from Web-based decision support programs share a number of relevant clinical features, yet they appear to represent a unique subset among all individuals with malignant disease. It will be important for oncologists to more fully understand the objectives of this population in order to assist such patients (and their families) in their use of this remarkably powerful, but essentially unregulated, technology.
Allelic Loss at TP53 Is Not Related to p53 Protein Overexpression in Primary Human Endometrial Carcinomas
Authors: Semczuk Andrzej , Marzec Barbara , Skomra Danuta , Roessner Albert , Cybulski Marek , Rechberger Tomasz , Schneider-Stock Regine
Published: February 2006

We examined loss of heterozygosity (LOH) at the TP53 gene in primary human endometrial carcinomas (EC), and investigated the relationship between allelic loss, p53 protein overexpression, pRb-1 pathway alterations and MIB-1 proliferative activity. Applying the non-isotopic PCR-RFLP/VNTR-silver staining techniques, we investigated TP53 LOH in 46 tumors at four polymorphic loci. Out of 42 informative carcinomas, LOH was found in 19% of the cases studied. In general, there was no significant relationship between LOH and the clinical and pathological variables of cancer, including patient age, clinical stage, histological grade or depth of myometrial invasion. Interestingly, none of 7 tumors associated with hyperplasia revealed allelic imbalance, whereas 8 of 27 (30%) tumors without hyperplasia exhibited LOH (p = 0.312; Fisher’s exact test). Overexpression of nuclear p53 was not correlated with allelic loss at TP53 (p = 0.336, Fisher’s exact test). It is worth pointing out that p53 immunoreactivity was significantly related to proliferative activity of cancer (R = 0.42, p = 0.0037; Spearman’s rank correlation test). A tendency towards a poorer outcome was reported in EC patients displaying TP53 LOH during short-time follow-up (p = 0.093; log-rank test). None of the tumors simultaneously showed LOH at TP53 and RB1 genes(R = –0.211, p = 0.16; Spearman’s rank correlation test). p16INK4A alterations (LOH and gene deletion) occurred concomitantly, with 3 tumors showing the TP53 allelic loss, whereas the cyclin D1/cdk4 complex was overexpressed in a case with TP53 LOH. Altogether, losses at TP53 were not associated with p53 nuclear overexpression, but may affect a subset of EC patients characterized by an unfavorable prognosis at short-time follow-up. Allelic loss at TP53 seems to arise independently of LOH at the RB1 gene in carcinomas of the uterine corpus in humans. Disruptions at p16INK4A and/or cdk4/cyclin D1 concomitantly occurring with TP53 LOH may participate in the development of a subset of endometrioid-type ECs.
Gastrointestinal Stromal Tumours: Correlation of 18F-FDG Gamma Camera-Based Coincidence Positron Emission Tomography with CT for the Assessment of Treatment Response – An AGITG Study
Authors: Goldstein David , Tan Beng S. , Rossleigh Monica , Haindl Walter , Walker Brenda , Dixon Jenny
Published: February 2006

Background: Malignant gastrointestinal stromal tumours (GISTs) are a rare subset of aggressive mesenchymal tumours specific to the gastrointestinal system. They are both locally aggressive and can metastasize. The aim of this analysis was to report on our experience of the utility of coincidence positron emission tomography (co-PET) based on an 18F-FDG gamma camera in assessing treatment response to imatinib using CT as the comparator and the final clinical outcome as the end point. Methods: We compared the results of CT and PET scans as predictors of outcome in a consecutive series of patients treated at the Prince of Wales hospital. All patients had biopsy-proven malignant GIST and were on treatment with the targeted pharmacotherapeutic agent imatinib. The majority of the patients were receiving treatment as part of the randomized trial of the European Organization for Research and Treatment of Cancer, the Australian Gastrointestinal Trials Group and the Italian Sarcoma Group, comparing 400 with 800 mg (400 mg b.i.d.). The monitoring of tumour response was achieved by serial CT measurements according to the RECIST criteria. Concurrent 18F-FDG co-PET studies were performed within a mean of 2.8 days from the CT scan and were interpreted by a consensus panel of 2 nuclear medicine physicians. Results: A total of 18 patients were recruited into the study, with a total of 74 lesions. There were 47 liver lesions, 31 of which were identified on the initial 18F-FDG co-PET scans (63%). There were 10 primary lesions (4 stomach, 4 duodenal, 2 small bowel), 9 of which were demonstrated on initial 18F-FDG co-PET examinations (90%). There were 17 extrahepatic metastatic sites, 15 of which were visualized on the initial 18F-FDG study (88%). Of the 18 patients, 8 showed concordant improvement on both CT and 18F-FDG co-PET criteria. One patient showed concordant worsening and 1 was not FDG avid. Eight patients initially showed discordance. 18F-FDG co-PET studies demonstrated changes preceding CT findings in all 8 patients with subsequent concordant improvement. Conclusion:18F-FDG co-PET is a useful modality to monitor treatment response to imatinib in patients with malignant GIST. Although there is a relatively reduced sensitivity when compared with CT for the detection of lesions especially in the liver, co-PET changes in several instances precede the changes on CT scanning. This modality has the potential to influence clinical decision making and should be considered as part of the standard care of patients on imatinib.
Suppressed MKP-1 Is an Independent Predictor of Outcome in Patients with Hepatocellular Carcinoma
Authors: Tsujita Eiji , Taketomi Akinobu , Gion Tomonobu , Kuroda Yousuke , Endo Kazuya , Watanabe Akihiro , Nakashima Hideaki , Aishima Shin-ichi , Kohnoe Shunji , Maehara Yoshihiko
Published: February 2006

Objective: An increase in the activity of mitogen-activated protein kinases (MAPKs) has been correlated with a more malignant phenotype in several tumor models in vivo. This study was designed to clarify the expression of MKP-1 in surgically resected hepatocellular carcinoma (HCC). Methods: We reviewed the cases of 77 patients who had undergone initial liver resection for HCC without preoperative treatment. Immunohistochemical analysis of MKP-1 was performed on paraffin-embedded tissues. The correlation between MKP-1 expression and clinical outcome was investigated. Results: Tumor cells were immunohistochemically stained for MKP-1 expression, and the same levels as in normal hepatocytes were detected in 66 (85%) of 77 HCC patients, being decreased in 11 (15%) HCCs. Decreased MKP-1 expression significantly correlated with serum α-fetoprotein levels and tumor size (p < 0.05). The disease-free survival rates in MKP-1-negative and -positive patients were 0 and 31.0% at 5 years, respectively (p < 0.01). The survival rates after a surgical resection in MKP-1-negative and -positive patients were 18.2 and 65.5% at 5 years, respectively (p < 0.01). Conclusions: The MKP-1 expression in HCC was an independent prognostic factor for outcome in HCC patients. In the future, it will be useful to explore whether the phosphatase expression might account for the response to HCC treatments targeting at MAPK activation.
Sequential Combination of Paclitaxel-Carboplatin and Paclitaxel-Liposomal Doxorubicin as a First-Line Treatment in Patients with Ovarian Cancer
Authors: Potamianou Anna , Androulakis Nikolaos , Papakotoulas Pavlos , Toufexi Helen , Latoufis Christos , Kouroussis Charalambos , Christofilakis Charalambos , Xenidis Nikolaos , Georgoulias Vassilios , Polyzos Aristidis
Published: February 2006

Cisplatin or carboplatin plus paclitaxel is considered the standard first-line treatment in ovarian cancer. Attempts to maximize tumor cytoreduction with first-line chemotherapy by incorporating new promising agents led to sequential drug administration with two or three doublets. In the present study, we aimed to evaluate the activity and the tolerance of two sequential doublets (paclitaxel/carboplatin and liposomal doxorubicin/carboplatin) administered as first-line treatment in patients with FIGO III/IV ovarian cancer. Treatment consisted of four cycles of carboplatin (6 AUC) plus paclitaxel (175 mg/m2; PC regimen) followed by four cycles with carboplatin (6 AUC) plus liposomal doxorubicin (40 mg/m2; LD/C regimen) every 3 weeks. Forty-one patients in FIGO III or IV were enrolled. In an intention-to-treat analysis, 20 (49%) complete (CR) and 12 (29%) partial (PR) responses were achieved (overall response rate, ORR: 78%; 95% confidence interval, CI: 64.1–91.9%); with the PC regimen (164 cycles); 7 (17%) patients have stable (SD) and 2 (5%) progressive (PD) disease. The LD/C regimen (124 cycles) was administered in 36 (88%) patients because of 2 early deaths and 3 patient withdrawals. Three additional patients, 2 with PR and 1 with SD after PC chemotherapy) achieved a CR. Upon completion of the LD/C chemotherapy there were 18 (44%) patients with CR and 9 (22%) with PR (ORR = 66%; 95% CI: 64–92%). The median duration of response was 27 months and the median time to progression 20 months. The probability of 2-year survival was 67%. Grade 3 and 4 neutropenia was observed in 34 and 14.6% of the patients, respectively, during the PC regimen, while during the treatment with LD/C the percentages for grade 3 and 4 neutropenia were 44.4 and 19.4%, respectively. Febrile neutropenia occurred only in patients treated with the PC regimen (4.9%). The incorporation of liposomal doxorubicin in this sequential doublet schedule of first-line treatment of ovarian carcinoma created a feasible and active regimen. Prospective randomized studies are required to assess its efficacy on patient survival.
Microsatellite Instability Caused by hMLH1 Promoter Methylation Increases with Tumor Progression in Right-Sided Sporadic Colorectal Cancer
Authors: Noda Hiroshi , Kato Yo , Yoshikawa Hirohide , Arai Masami , Togashi Kazutomo , Nagai Hideo , Konishi Fumio , Miki Yoshio
Published: February 2006

Objective: A subset of sporadic colorectal cancers (SCRCs) exhibits microsatellite instability (MSI). Most MSI in SCRCs is caused by hMLH1 inactivation due to promoter methylation. However, the role of MSI in the progression of SCRCs remains unclear. Methods: Thirty-two intramucosal cancers and 63 cancers with submucosal invasion were assigned to group 1 (early-stage cancer), and 30 Dukes’ B and 26 Dukes’ C cancers to group 2 (advanced-stage cancer). hMLH1 promoter methylation status was determined by methylation-specific PCR. MSI was determined using five markers. hMLH1 expression was determined immunohistochemically. Results: MSI was found in 1 of 95 (1.1%) tumors in group 1, compared with 4 of 56 (7.1%) tumors in group 2. In right-sided tumors, the overall frequency of hMLH1-methylation-positive tumors in group 1 was not significantly different from that in group 2 (17 of 43, 39.5%, vs. 9 of 23, 39.1%). In right-sided tumors with hMLH1 promoter methylation, the frequency of MSI-positive tumors in group 1 was significantly lower than that in group 2 (1 of 17, 5.9%, vs. 4 of 9, 44.4%, p = 0.0081). Conclusion: The frequency of MSI caused by hMLH1 promoter methylation increases with tumor progression in right-sided SCRCs.
Pseudocyst Treatment in Chronic Pancreatitis – Surgical Treatment of the Underlying Disease Increases the Long-Term Success
Authors: Schlosser Wolfgang , Siech Marco , Beger Hans G.
Published: February 2006

Background: For reasons of persisting controversies concerning indications for surgery, we evaluated chronic pancreatitis patients following pancreatic head resection or drainage procedure for pseudocysts located in the pancreatic head. Material and Methods: 206 patients (166 male, 40 female) with chronic pancreatitis and pseudocysts in the pancreatic head were operated between April 1982 and July 2001. 169 patients (82%) were treated with the duodenum-preserving pancreatic head resection, a pseudocyst-jejunostomy was performed in 37 patients (18%). Results: The hospital mortality was 0.4%. The late mortality was 19% in a median follow-up of 7.3 years. The rate of patients with complete relief of pain was significantly higher after resection compared to drainage procedure in the long-term follow-up (94 vs. 75%; p = 0.003). With regard to recurrence of pseudocysts, patients had an elevated rate of reoperations following drainage procedure (13 vs. 1%; p = 0.008). The endocrine function was significantly better preserved in patients of the drainage group compared to the resection group (no diabetes 67 vs. 35%, p < 0.01). Conclusion: The resection has, compared to drainage procedures alone, the advantage of low recurrence rate of pseudocysts and a high rate of pain-free patients in the long-term follow-up. However, the risk of diabetes is increased in the resection group.
Nutritional Support and Oral Intake after Gastric Resection in Five Northern European Countries
Authors: Lassen Kristoffer , Dejong Cornelis H.C. , Ljungqvist Olle , Fearon Ken , Andersen Jens , Hannemann Pascal , von Meyenfeldt Maarten F. , Hausel Jonatan , Nygren Jonas , Revhaug Arthur
Published: February 2006

Background: A comprehensive evidence base for perioperative care in upper gastrointestinal (GI) surgery is lacking. Little is known about the routines currently practiced in the absence of such evidence. We describe postoperative practice after gastric resections in five northern European countries. Method and Setting: Questionnaire survey in all major digestive surgical centres in Scotland, the Netherlands, Denmark, Sweden and Norway. Results: 76% of all centres (n = 200/263) responded. Routines varied extensively both nationally and between countries. No uniformity was traced although a conservative trend was noticeable in the use of nasogastric decompression tubes and ‘nil-by-mouth’ regimens. Nutritional support during the first 5 days is generally offered in Denmark, but not in Scotland. Drinking at will is generally allowed in Denmark and Norway by the first postoperative day. Eating at will is uniformly restricted. Conclusion: The paucity of evidence is reflected by the marked heterogeneity in practice. Large groups of patients may be treated suboptimally. Best perioperative care for these patients must be defined and documented. Especially, the role of early oral intake at will in upper GI surgery needs to be clarified by sufficiently powered trials.
Influence of Surgical Resection and Post-Operative Complications on Survival following Adjuvant Treatment for Pancreatic Cancer in the ESPAC-1 Randomized Controlled Trial
Authors: Bassi C. , Stocken D.D. , Olah A. , Friess H. , Buckels J. , Hickey H. , Dervenis C. , Dunn J.A. , Deakin M. , Carter R. , Ghaneh P. , Neoptolemos J.P. , Büchler M.W.
Published: February 2006

Background/Aims: The influence of type of surgery and occurrence of post-operative complications on survival following adjuvant therapy for pancreatic cancer are uncertain. Methods: Cox proportional hazard modelling was used to investigate the influence of type of surgery and the presence of complications on survival in conjunction with clinico-pathological variables in the 550 patients of the ESPAC-1 adjuvant randomized controlled trial. Results: Standard Kausch-Whipple (KW) was performed in 282 (54%) patients, 186 (35%) had a pylorus-preserving (PP) KW, 39 (7%) had a distal pancreatectomy and 21 (4%) had a total pancreatectomy. Post-operative complications were reported in 140 (27%) patients. PP-KW patients survived longer with a median (95% CI) survival of 19.9 (17.3, 23.1) months compared to 14.8 (13.0, 16.7) for KW patients (χ2LR = 15.1, p < 0.001). KW patients were more likely however to have R1 margins (67 (24%) vs. 29 (16%), χ2 = 4.59, p = 0.032), poorly differentiated tumours (70 (26%) vs. 19 (10%), χ2 = 18.65, p < 0.001) and positive lymph nodes (165 (60%) vs. 81 (44%), χ2 = 11.32, p < 0.001). Post-operative complications did not significantly affect survival. Independent prognostic factors were tumour grade, nodal status and tumour size but not type of surgery or post-operative complications. There was a survival benefit for chemotherapy irrespective of the type of surgery or post-operative complications. Conclusions: The KW and PP-KW procedures did not significantly influence the hazard of death in the presence of tumour staging, demonstrating that ESPAC-1 surgeons showed good judgement in their choice of operation. Post-operative complications did not adversely affect the survival benefit from adjuvant chemotherapy.
Evaluation of Enzymes Involved in Proteoglycan Degradation in the Wall of Abdominal Aortic Aneurysms
Authors: Kowalewski Radosław , Sobolewski Krzysztof , Małkowski Andrzej , Wolańska Małgorzata , Gacko Marek
Published: February 2006

The abdominal aortic aneurysm (AAA) wall represents an extreme example of arterial remodeling with disturbed elastin, collagen and proteoglycan metabolism. The aim of this study was to evaluate enzymes involved in the degradation of glycosaminoglycan chains and core proteins of proteoglycans in the AAA wall. The study material consisted of wall samples from 10 AAA. Fragments of 5 normal abdominal aortas from organ donors were used as a control. The activity of endoglycosidases, exoglycosidases and sulfatases was measured using colorimetric methods. To assess matrix metalloproteinases (MMPs), Western blot and zymography were performed. The activity of endoglycosidase degrading chondroitin-4-sulfate was lower in the AAA wall. Endoglycosidase degrading heparan sulfate and dermatan sulfate, arylosulfatase B, as well as all the exoglycosidases assessed demonstrated higher activities in the AAA wall. Furthermore, increased expression of MMP1, MMP2 and MMP9 was also shown in the AAA wall. Zymography revealed decreased activity of pro-MMP2 and presence of pro-MMP9 in the AAA wall compared to the wall of normal aorta. Extensive changes in the activity of glycosaminoglycan-degrading enzymes and MMPs may influence the organization of the extracellular matrix network and lead to previously demonstrated changes in the proteoglycan and glycosaminoglycan content in the AAA wall.
Orchidectomy Modulates α2-Adrenoceptor Reactivity in Rat Mesenteric Artery through Increased Thromboxane A2 Formation
Authors: Blanco-Rivero Javier , Balfagón Gloria , Ferrer Mercedes
Published: February 2006

The present study evaluates the effect of endogenous male sex hormones on the reactivity to α2-adrenoceptor activation, and to analyze the role of the endothelium in this response in intact and endothelially denuded superior mesenteric arteries from control and orchidectomized male Sprague-Dawley rats. The concentration-dependent constriction induced by clonidine was analyzed in the absence and presence of the nitric oxide synthase (NOS) inhibitor, Nω-nitro-L-arginine (L-NAME), cyclooxygenase (COX-1 and COX-2) inhibitors, indomethacin, the specific COX-2 inhibitor NS-398, the thromboxane-prostanoid receptor antagonist SQ29,548 and the thromboxane A2 (TXA2) synthase inhibitor, furegrelate. Endothelial NOS (eNOS), COX-2 and TXA2 synthase protein expression was studied by Western blot analysis. In addition, the basal and clonidine-stimulated production of TXB2, the stable TXA2 metabolite, was also measured. In intact vessels from control male rats, the concentration-dependent constriction induced by clonidine was increased by both L-NAME or endothelial removal, unaltered by indomethacin and decreased by NS-398; in denuded vessels, the clonidine response was decreased by NS-398 and unaltered by L-NAME, indomethacin, SQ29,548 or furegrelate. In intact vessels from orchidectomized rats, the constriction induced by clonidine was increased by L-NAME but practically abolished by indomethacin or NS-398; in endothelially denuded segments the clonidine response was unaltered by L-NAME, but was decreased by indomethacin, NS-398, SQ29,548 or furegrelate. Orchidectomy failed to modify eNOS,COX-2 and TXA2 synthase expression, and increased basal and clonidine-stimulated TXB2 release. These results show that TXA2 produced in smooth muscle cells is increased in mesenteric arteries from orchidectomized rats compared to their controls, and that this prostanoid is functionally involved in the vasoconstrictor response to clonidine only in arteries from the orchidectomized rats.
Cardiac Troponin I in Asphyxiated Neonates
Authors: Trevisanuto Daniele , Picco Giorgio , Golin Rosanna , Doglioni Nicoletta , Altinier Sara , Zaninotto Martina , Zanardo Vincenzo
Published: February 2006

Background: Cardiac troponins T (cTnT) and I (cTnI) are well-established markers in detecting myocardial ischemic damage in adults. Perinatal asphyxia is associated with cardiac dysfunction. Objectives: To evaluate serum concentrations of cTnI in asphyxiated neonates and to investigate whether cTnI is correlated with the traditional markers of asphyxia. Methods: Blood samples were collected from 13 asphyxiated neonates (umbilical artery pH <7.18 and either a 1-min Apgar score <4 or a 5-min Apgar score <7) and 39 controls. Data on gestation, birth weight, sex, Apgar scores, mode of delivery, umbilical pH, creatinine, serum activity of aspartate and alanine aminotransferase, and QTc interval were investigated. Results: Median (range) cTnI concentrations were significantly higher in asphyxiated neonates with respect to healthy infants: 0.36 µg/l (0.05–11) versus 0.04 µg/l (0.04–0.06); p < 0.01. In asphyxiated babies, no statistically significant correlations were found between concentrations of cTnI and the other markers of asphyxia. Conclusions: In asphyxiated neonates, cTnI concentrations are higher with respect to healthy infants, suggesting the presence of myocardial damage in this group of high-risk patients. cTnI does not correlate with the traditional markers of asphyxia.
Effects of Oral Administration of Insulin-Like Growth Factor-I on Circulating Concentration of Insulin-Like Growth Factor-I and Growth of Internal Organs in Weanling Mice
Authors: Kim W.K. , Ryu Y.H. , Seo D.S. , Lee C.Y. , Ko Y.
Published: February 2006

Insulin-like growth factor (IGF)-I is a polypeptide that mediates the growth-promoting action of growth hormone in postnatal animals. The present study was conducted to examine whether orally administered IGF-I would be absorbed into the general circulation and also whether ingested IGF-I would enhance the growth of whole body as well as internal organs, and tissues in 3-week-old ICR-strain female weanling mice. In experiment (Exp) 1, a total of 70 mice received IGF-I orally at 1 µg·g–1 in 0.2-ml PBS or the vehicle alone. Concentrations of IGF-I and glucose in heart blood were measured after killing 5 animals in each group every fourth hour during a 24-hour period. In Exp 2, a total of 40 mice received oral IGF-I administration at 1 µg·g–1 or vehicle every third day beginning from day 0 for a 13-day period. Half the animals were killed at day 7 and the other half at day 13. Weights of whole body and organs/tissues (small intestine, liver, thigh muscle, and brain) were measured every day and at slaughter, respectively. In Exp 1, following the oral IGF-I administration, serum IGF-I concentration increased at hour 4 (p < 0.01) and returned to the hour 0 level by hour 8, whereas glucose concentration was lowest at hour 4 and returned to the hour 0 level by hour 16. In the PBS-fed group, neither IGF-I nor glucose concentration changed during the 24-hour period. In Exp 2, weight of small intestine increased (p < 0.05) in response to the oral IGF-I, whereas weights of liver and thigh muscle of the IGF-I-fed group were greater (p < 0.01) and tended to be greater (p = 0.06), respectively, than those of the PBS-fed only at day 13. However, brain weight and serum concentrations of IGF-I and IGF-II were not affected by oral IGF-I administration. Results suggest that although orally administered IGF-I mainly acts at the intestine, a portion of ingested IGF-I is absorbed into the general circulation to enhance the growth of selective organs/tissues in weanling mice.
Spontaneous Contraction of Pseudoglandular-Stage Human Airspaces Is Associated with the Presence of Smooth Muscle-α-Actin and Smooth Muscle-Specific Myosin Heavy Chain in Recently Differentiated Fetal Human Airway Smooth Muscle
Authors: Pandya Hitesh C. , Innes Jennifer , Hodge Rachel , Bustani Porus , Silverman Michael , Kotecha Sailesh
Published: February 2006

Background: Recent investigations demonstrating that pseudoglandular-stage airspaces contract spontaneously suggest that the production of contractile proteins by airway wall smooth muscle (ASM) is an important factor in the functional and structural differentiation of ASM. Aims: Ouraim was to determine if smooth muscle (SM)-myosin heavy chain (MHC) myofilaments, the ‘motor’ underlying SM contraction, and SM-α-actin myofilaments were distributed simultaneously in pseudoglandular-stage human lungs and to further define the nature of fetal airway contractions. Methods: Immunohistochemically stained sections of fetal lung (14 fetuses, 10.1–17 weeks gestation) were analysed by computer-assisted morphometry to determine airspace dimensions and detect SM-MHC- and SM-α-actin-ASM. Lung tissue from the same fetuses was also placed in explant culture to observe airway contractions using videomicroscopy. We found that the smallest airspaces were just as likely to be invested by a layer of SM-MHC-positive ASM as by a layer of SM-α-actin-positive ASM. In addition, larger airways or airways from more mature fetal lungs were more likely to be invested by either SM-MHC- or SM-α-actin-positive ASM. Spontaneous airspace contractions were peristalsis-like and variable in amplitude. The time interval between contractions was temperature dependent (mean ± SEM, 44 ± 7.5 s at 37°C), shortened by carbachol and increased by nitric oxide (NO)-donating drugs. Conclusions: These observations suggest that ASM differentiation is characterised by the simultaneous production of SM-α-actin and SM-MHC myofilaments and that the presence of these proteins is likely to be responsible for cholinergic- and NO-sensitive spontaneous contractions of fetal human airspaces.
Effects of Cyclooxygenase-1 and -2 Inhibition on Gastric Acid Secretion and Cardiovascular Functions in Rats
Authors: Adami Maristella , Coppelli Gabriella , Guaita Elena , Pozzoli Cristina , Menozzi Alessandro , Giovannini Elena , Coruzzi Gabriella
Published: February 2006

The discovery of a second isoform of cyclooxygenase has led to a re-evaluation of the mechanisms underlying the adverse effects of nonsteroidal anti-inflammatory drugs, focusing in particular on the gastrointestinal system. We investigated the involvement of cyclooxygenase-1 and -2 in the regulation of gastric acid secretion and cardiovascular functions in anesthetized rats, after acute intravenous administration of the selective cyclooxygenase-1 inhibitor SC-560, the selective cyclooxygenase-2 inhibitor celecoxib and the nonselective inhibitor indomethacin. Indomethacin, celecoxib and SC-560 did not significantly modify basal acid secretion. Indomethacin and celecoxib were also ineffective on the acid secretion stimulated by pentagastrin; by contrast, SC-560 significantly enhanced the acid secretion stimulated by pentagastrin, electrical vagal stimulation or histamine. The stimulatory effects of SC-560 were prevented by cervical vagotomy, atropine and famotidine. Indomethacin caused either no change, increasing or decreasing effects on mean arterial pressure and heart rate. By contrast, SC-560 was unable to change cardiovascular parameters at 5 mg/kg, while inducing a marked bradycardia at 10 mg/kg. Celecoxib was ineffective. Our findings indicate that cyclooxygenase-1-derived prostaglandins are involved in the regulation of stimulated acid secretion and of basal heart rate; the role of prostaglandins in the acute control of systemic blood pressure under resting conditions seems to be negligible.
Hysteroscopy and Ultrasonography in the Diagnosis of Endometrial Cancer
Authors: Clark T. Justin
Published: February 2006

The main aim of investigating women with abnormal uterine bleeding is to exclude serious intrauterine pathology, particularly endometrial cancer. Endometrial assessment has traditionally been achieved by obtaining tissue for histological analysis utilising blind in-patient dilatation of the cervix and curettage of the endometrium under general anaesthesia. This procedure is now generally accepted as outmoded practice associated with unnecessary morbidity and cost and has been largely replaced by minimally invasive out-patient or ‘ambulatory’ diagnostic modalities. These modalities include transvaginal ultrasonography, out-patient hysteroscopy and miniature endometrial biopsy. The most controversial debate has centred on how best to image the uterine cavity with advocates of hysteroscopy and ultrasonography holding apparently implacable views. However, the concept of hysteroscopy and ultrasonography as competing tests may be misplaced, and perhaps they should be viewed as complementary diagnostic tools. To help us answer such questions requires an appraisal of the available evidence. In this way, a more rational approach to investigating women for endometrial cancer is possible based on the clinical and economic performance of hysteroscopy and ultrasonography. This review assesses the evidence and suggests approaches available to gynaecologists for the diagnostic work-up of women suspected to have endometrial cancer utilising hysteroscopy and ultrasonography.
Die Rolle der Laparoskopie in der Behandlung von Frauen mit Endometriumkarzinom
Authors: Grund Dorothee , Köhler Christhardt , Schneider Achim , Marnitz Simone
Published: February 2006

Die laparoskopische oder laparoskopisch-assistierte vaginale Hysterektomie mit beidseitiger Adnexektomie ist der abdominalen Hysterektomie beim Endometriumkarzinom in den Stadien I und II in onkologischer Hinsicht äquivalent. Mit der sicheren Durchführung der laparoskopischen Lymphonodekto- mie pelvin und paraaortal kann die Entscheidung zur adjuvanten perkutanen Radiatio eindeutig gestellt werden. Die Entfernung tumorbefallener Lymphknoten scheint einen signifikanten İberlebensvorteil zu erbringen.
Fertility-Preserving Treatment in Young Women with Endometrial Cancer
Authors: Böing Carsten , Kimmig Rainer
Published: February 2006

Nonsurgical fertility-preserving treatment of well-differentiated endometrial cancer with systemic progestins has been described for young women who desire to preserve their fertility. The overall response to progestin treatment in 9 retrospective studies is 79% with 79 subsequent live births. Recurrence can be expected in approximately 36–40% of conservatively treated patients who initially responded. Synchronous ovarian cancer has been reported in approximately 9%. However, amongst 162 receiving systemic, continuous treatment with progestins no death caused by cancer has been reported. We review guidelines for diagnosis, treatment and follow-up in young women undergoing conservative treatment for endometrial cancer.