bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of in vivo effects of nitroglycerin and insulin on the aortic pressure waveform
Authors: Westerbacka J. , Tamminen M. , Cockcroft J. , Yki‐Järvinen H. 
Published: January 2004

AbstractBackground  Individuals whose platelets are resistant to the antiaggregatory effects of insulin in vitro are also resistant to the antiaggregatory effects of nitroglycerin (GTN). We have previously shown that insulin acutely diminishes central wave reflection in large arteries and that this action of insulin is blunted in insulin‐resistant subjects. However, as yet, no studies have compared the haemodynamic effects of insulin and GTN on large arterial function in the same group of subjects. The aim of this study was to determine whether resistance to the haemodynamic effects of insulin is a defect specific to insulin or whether individuals resistant to the vascular actions of insulin are also resistant to GTN.Design and results  Dose–response characteristics of insulin and GTN on the aortic waveform were determined using applanation tonometry and pulse wave analysis (PWA) in seven healthy men (age 26 ± 1 year, BMI 25 ± 2 kg m−2). Three doses of sublingual GTN (500 µg for 1, 3 or 5 min) and insulin (0·5, 1 or 2 mU kg−1 min−1 for 120 min) were administered on three separate occasions. Both agents dose‐dependently decreased central pulse pressure and the augmentation index (AIx) without changing brachial artery blood pressure. We next compared responses to insulin (2 mU kg−1 min−1 for 120 min) and sublingual GTN (500 µg for 5 min) in 20 nondiabetic subjects (age 50 ± 2 year, BMI 21·0–36·3 kg m−2). Again, both agents significantly decreased AIx. Although the vascular effects of insulin and GTN vascular were positively correlated [Spearman's r = 0·92 (95% confidence interval 0·81–0·97), P < 0·0001], the time‐course for the action GTN was faster than that of insulin. Brachial systolic blood pressure remained unchanged during the insulin infusion (122 ± 3 vs. 121 ± 3 mmHg, 0 vs. 120 min) but aortic systolic blood pressure decreased significantly by 30 min (111 ± 3 vs. 107 ± 3 mmHg, 0 vs. 30 min, P < 0·01). Similarly, GTN decreased aortic systolic blood pressure from 119 ± 4 to maximally 112 ± 3 mmHg (P < 0·001) without significantly decreasing systolic blood pressure in the brachial artery.Conclusions  The effects of insulin and GTN on large arterial haemodynamics are dose‐dependent and significantly correlated. The exact mechanisms and sites of action of insulin and GTN in subjects with insulin resistance remain to be established.
Angiopoietin/tie‐2 as mediators of angiogenesis: a role in congestive heart failure?
Authors: Chong A. Y. , Caine G. J. , Lip G. Y. H. 
Published: January 2004

AbstractAngiogenic factors, in particular vascular endothelial growth factor (VEGF) and the angiopoietins, Ang‐1 and ‐2, have recently generated significant interest, especially in oncology. The process of angiogenesis is also thought to occur in response to ischaemic conditions, which lie at the core of cardiovascular disease states such as coronary artery disease and congestive heart failure. However, current data do not conclusively show evidence of angiogenesis per se in these conditions, despite (for example) the presence of high levels of VEGF and Ang‐2. High levels of these angiogenic factors in heart disease also have not translated into clinically significant new vessel formation, as in accelerated cancer growth or proliferative retinopathy. Indeed, we would hypothesize that these angiogenic markers – especially the angiopoietins – do not necessarily translate into new vessel formation in congestive heart failure (CHF), but may well reflect disturbances of endothelial integrity in CHF.
Impaired neutrophil store‐mediated calcium entry in Type 2 diabetes
Authors: Advani A. , Marshall S. M. , Thomas T. H. 
Published: January 2004

AbstractBackground  In Type 2 diabetes impaired neutrophil function leads to increased bacterial infection and cardiovascular disease. Many neutrophil functions depend on calcium signalling, which involves release of calcium from intracellular stores and subsequently translocation of stores via the cytoskeleton to the plasma membrane, causing store‐mediated calcium entry (SMCE) into the cell. We hypothesized that in Type 2 diabetes there would be a defect in SMCE.Materials and methods  Neutrophils were prepared from patients with Type 2 diabetes (DM, n = 15) and controls (NC, n = 15). Free cytosolic calcium [Ca2+]i was measured with Fura‐2 in resting cells and after stimulation of calcium release with fMLP and thapsigargin.Results  Baseline [Ca2+]i was higher in neutrophils from the patients than the controls (NC 65 ± 5 nm, DM 80 ± 4 nm, P < 0·05). However, after fMLP‐treatment [Ca2+]i was significantly lower in the patients (NC 301 ± 28 nm, DM 210 ± 20 nm, P < 0·01). The greater increase in controls was not observed when cells were treated with fMLP in the absence of extracellular calcium (– fold increase NC 2·9 ± 0·5, DM 2·7 ± 0·3). Treatment of cells with thapsigargin caused a similar greater increase in [Ca2+]i in the controls than in the patients that was not seen in the absence of extracellular calcium (– fold increase with Ca2+ NC 5·2 ± 1·0, DM 3·0 ± 0·4, P < 0·05; fold increase without Ca2+ NC 2·5 ± 0·4, DM 2·2 ± 0·2).Conclusions In Type 2 diabetes there is a defect in neutrophil calcium signalling which results in a lesser increase in free cytosolic calcium owing to impaired influx across the plasma membrane. Abnormal calcium signalling is likely to be important in the pathogenesis of diabetic complications.
Interaction between smoking and PON2 Ser311Cys polymorphism as a determinant of the risk of myocardial infarction
Authors: Martinelli N. , Girelli D. , Olivieri O. , Stranieri C. , Trabetti E. , Pizzolo F. , Friso S. , Tenuti I. , Cheng S. , Grow M. A. , Pignatti P. F. , Corrocher R. 
Published: January 2004

AbstractBackground  Increased oxidative stress is thought to play a role in the pathogenesis of the atherothrombotic process. Paraoxonases (PONs) are closely related antioxidant enzymes encoded by clustered genes on chromosome 7q. We evaluated three PON polymorphisms (PON1 Leu55Met and Gln192Arg; PON2 Ser311Cys) as possible risk factors for coronary atherosclerotic disease (CAD) and/or its main thrombotic complication, myocardial infarction (MI).Materials and methods  We studied 890 subjects with angiographic documentation of coronary vessels (272 = CAD‐free; 618 = CAD). In the CAD group, 341 subjects had a previous MI.Results  Frequencies of various genotypes were not significantly different between CAD‐free subjects and the entire CAD population. In the latter group, there were more carriers of the PON2 311Cys variation among those who had suffered a MI than among those who had not (P < 0·01 by χ2). The adjusted OR for MI among PON2 311Cys carriers was 1·5 (95%CI, 1·03–2·19). A gene–environmental interaction was found between PON2 Ser311Cys and smoking. Smoking by itself was associated with an increased MI risk. Among smokers, however, the MI risk was related to PON2 genotype: Cys/Cys homozygotes (OR = 5·3; 95%CI, 1·7–16·4) and Ser/Cys heterozygotes (OR = 2·1; 95%CI, 1·3–3·6) were at greater risk than Ser/Ser subjects (OR = 1·2; 95%CI, 0·8–1·8). The PON2 polymorphism did not influence the MI risk among nonsmokers.Conclusions  In CAD subjects, a proportion of the risk of MI may be influenced by the interaction between smoking and a polymorphism in the antioxidant enzyme PON2.
Delayed genomic and acute nongenomic action of glucocorticosteroids in seasonal allergic rhinitis
Authors: Tillmann H.‐C. , Stuck B. A. , Feuring M. , Rossol‐Haseroth K. , Tran B. M. , Lösel R. , Schmidt B. M. , Hörmann K. , Wehling M. , Schultz A. 
Published: January 2004

AbstractBackground  Glucocorticosteroids are effective in the treatment of allergic rhinitis, a disease characterized by a variety of symptoms, e.g. rhinorrhea and itching. The time course of symptomatic relief for allergic rhinitis by steroids has not been examined in detail to date, although the onset of steroid action is one of the main discriminations between genomic and nongenomic actions of steroids. We therefore investigated the time course of subjective and objective measures of nasal affection after steroid administration in patients with allergic rhinitis following specific allergen challenge.Methods  Six female and 18 male volunteers (median age 26 years) with a history of allergic rhinitis but currently free of symptoms were included in this randomized, placebo‐controlled, double‐blind, three‐period crossover study. A single dose of either betamethasone (60 mg), methylprednisolone (400 mg) or placebo was given intravenously, 5 min after intranasal allergen provocation. After 10, 20, 60, 150 and 240 min, nasal itching and nasal obstruction were assessed using a standardized visual analogue scale. In addition, nasal airflow was measured by anterior rhinomanometry.Results  Nasal itching was markedly reduced following either of the two steroids within 10 min after administration of study drug. Itching was depressed by 38% following betamethasone (P < 0·05) and by 18% following methylprednisolone (P = 0·07) compared with placebo. Nasal airflow and nasal obstruction were not significantly altered by steroids during the first 2 h of the study. However, after 150 min, nasal airflow was 21% rsp. 19% higher after methylprednisolone and betamethasone (P < 0·05) compared with placebo. After 240 min, nasal airflow was increased by 20% following betamethasone (P < 0·05) and by 19% following methylprednisolone. Nasal obstruction was also beneficially affected by both steroids 150 and 240 min after administration compared with placebo (P < 0·05 for both time points following betamethasone).Conclusion  This study for the first time shows rapid in vivo effects of external glucocorticosteroids in humans. Itching, a pathophysiologically complex sensation, is favourably influenced by steroids within 10 min, therefore presumably via nongenomic mechanisms. Though no detailed mechanisms can be derived from this study, steroid interaction with receptors in the central nervous system may play an important role in mediating this effect.
Extensive vascular invasion is a marker of risk of relapse in encapsulated non‐Hürthle cell follicular carcinoma of the thyroid gland: a clinicopathological study of 18 consecutive cases from a single institution with a 11‐year median follow‐up
Authors: Collini P , Sampietro G , Pilotti S 
Published: January 2004

Aims : To determine the prognostic value of certain clinicopathological features in a series of 18 consecutive cases of encapsulated follicular carcinoma (EFC) of the thyroid gland with long follow‐up.Methods and results : Eighteen consecutive cases of EFC were retrieved from 1975 to 1993. Gender, age at onset, type of surgery, presence of capsular and/or vascular invasion, number of involved vessels, tumour size, and TNM/pTNM classification were evaluated and correlated with disease outcome. None of the cases presented with distant metastases. Extensive vascular invasion (defined as more than four capsular vessels involved) was present in two cases. After a median follow‐up of 133 months, all patients were alive. Three cases had relapsed in lung and bone. In two out of these three cases, extensive vascular invasion was present. Radioiodine therapy was curative in two of three of the relapsed cases.Conclusions : EFC is a low‐risk carcinoma, with no patients' deaths after a median follow‐up of 11 years. Extensive vascular invasion should be considered as a risk factor for relapse. A conservative surgical approach is recommended. Since relapses may occur up to 14 years after the initial surgery, life‐long follow‐up is advisable.
Pyothorax‐associated lymphoma (PAL): a western case with marked angiocentricity and review of the literature
Authors: Androulaki A , Drakos E , Hatzianastassiou D , Vgenopoulou S , Gazouli M , Korkolopoulou P , Patsouris E , Dosios T 
Published: January 2004

Aims : To report a case of pyothorax‐associated lymphoma in a non‐immunocompromised 78‐year‐old man with a 45‐year history of tuberculous pleuritis and left pleural effusion. Pyothorax‐associated lymphoma is a high‐grade non‐Hodgkin's lymphoma occurring in 2% of patients with long‐standing tuberculous pleuritis and pyothorax. Pyothorax‐associated lymphoma is frequently Epstein–Barr virus (EBV)‐associated, mainly reported in Japan but exceedingly rare in western countries.Methods and results : Histology revealed a high‐grade, diffuse large B‐cell lymphoma with immunoblastic and plasmacytoid features and marked angiocentricity with focal destruction of the vessel walls. Immunohistochemistry revealed a post germinal B‐cell phenotype. RNA in‐situ hybridization and molecular analysis showed a latent EBV infection and absence of human herpes virus‐8 (HHV‐8).Conclusions : Pyothorax‐associated lymphoma represents a rare but distinctive type of diffuse large B‐cell lymphoma, with characteristic clinico‐epidemiological, immunohistological, and biological features.
Assessment of apoptosis by M30 immunoreactivity and the correlation with morphological criteria in normal colorectal mucosa, adenomas and carcinomas
Authors: Koornstra J J , Rijcken F E M , De Jong S , Hollema H , De Vries E G E , Kleibeuker J H 
Published: January 2004

Aims : To investigate the monoclonal antibody M30 for the assessment of apoptosis in colorectal tissues. Although Terminal deoxyribonucleotidyl transferase mediated nick end labelling (TUNEL) and in‐situ end labelling (ISEL) are the methods most often used to demonstrate and quantify apoptosis in histological tissue sections, the interpretation and specificity of these techniques have been controversial. Immunohistochemistry using the monoclonal antibody M30 that recognizes caspase‐cleaved cytokeratin 18 is considered to be a promising alternative but has yet to be validated against a generally accepted standard.Methods and results : Paraffin sections of normal colonic mucosa (n = 30), normal mucosa obtained from resection margins from carcinomas (n = 30), colorectal adenomas (n = 84) and carcinomas (n = 40) were studied. Apoptosis of epithelial cells was assessed by M30 immunoreactivity and morphological criteria and expressed as a proportion of the total number of cells counted (apoptotic index). Mean apoptotic indices using M30 were 0.18 ± 0.04% in normal mucosa, 0.42 ± 0.04% in adenomas and 1.97 ± 0.24% in carcinomas. Using morphological criteria, these indices were 0.23 ± 0.03%, 0.62 ± 0.06% and 1.78 ± 0.19%, respectively. Apoptotic counts were higher in normal mucosa obtained from resection margins than in genuinely normal mucosa using the M30 antibody. Apoptotic indices obtained by M30 immunoreactivity and morphological criteria were positively correlated (r = 0.71, P < 0.01).Conclusion : Assessment of apoptotic cells by M30 immunoreactivity correlates well with morphological criteria. Apoptotic indices increase in the course of the adenoma–carcinoma sequence. Apoptosis in normal mucosa obtained from resection margins differs from genuinely normal mucosa necessitating caution when interpreting studies of apoptosis in normal colonic mucosa. Our findings support the use of the M30 method in the study of apoptosis in colorectal tissues.
Towards reasonable workload in diagnosis of sentinel lymph nodes: comparison of two frozen section methods
Authors: Krogerus L A , Leidenius M H K , Toivonen T S , Von Smitten K J A 
Published: January 2004

Aims : To compare two methods of histological assessment with intraoperative diagnosis of sentinel node metastases in breast cancer.Methods and results : A total of 204 consecutive breast cancer cases with lymphatic mapping, sentinel node biopsy and intraoperative diagnosis were included. The sentinel nodes in the first 102 cases (method A) were bisected and serially sectioned. In the other 102 cases (method B) the nodes were sliced thinly with a razor blade. All 1–1.5 mm thick slices were mounted on prechilled mounting medium on frozen section buttons. Cytological imprints were also made of the attached tissue slices. Postoperative diagnosis of sentinel lymph node metatases was taken as gold standard. Sentinel node metastases were found in 28 (27%) cases in group A and in 42 (40%) cases in group B (P = 0.05). The median size of the sentinel node metastases was 4.3 mm in group A and 3.3 mm in group B (P < 0.05).Conclusion : Method B finds more and smaller metastases and takes less time and effort in the laboratory. When using method A, many small metastases are not detected at all.
Ki67 expression in bronchial preneoplastic lesions and carcinoma in situ defined according to the new 1999 WHO/IASLC criteria: a preliminary study
Authors: Meert A‐P , Feoli F , Martin B , Verdebout J‐M , Mascaux C , Verhest A , Ninane V , Sculier J‐P 
Published: January 2004

Aims : The World Health Organization classification of bronchial intraepithelial neoplastic lesions has been shown to be reproducible. However little is known about its biological value. The aim of this study was to assess the proliferative activity of mild (MiD), moderate (MoD), severe (SD) dysplasia and carcinoma in situ (CIS) by the expression of Ki67 on biopsy specimens obtained during fluorescence bronchoscopy.Methods and results : The percentage of Ki67+ lesional nuclei was calculated in each lesion. In addition, the presence of Ki67 clusters (defined as a group of at least two strongly Ki67+ nuclei located in the upper third of the epithelium) and a Ki67 score were evaluated. The Ki67 score depended on the proportion of the stained nuclei and on the intensity of staining. MiD, MoD, SD and CIS showed increased Ki67 staining (respectively, 10%, 20%, 30% and 40% median values of positive cells). Thirty‐one percent MiD, 77% MoD, 91% SD and 100% CIS showed one or more positive clusters. When only multiple clusters were considered the difference between high‐ and low‐grade lesions was accentuated. Ki67+ clusters were more frequent in SD (91%) and CIS (94%) compared with MiD (15%) and MoD (22%). This difference was statistically significant (P < 0.01). Evaluation of the Ki67 score was in line with the above results: high grade lesions (SD and CIS) more often showed scores >4 (P = 0.05 between MiD plus MoD versus SD plus CIS).Conclusions : Ki67 expression increases from MiD to CIS with a statistically significant difference between MiD plus MoD and SD plus CIS. These results suggest that, in terms of Ki67 positivity, SD behaves like CIS rather than like MiD or MoD.
Prognostic value of immunohistochemical expression of p53, bax, Bcl‐2 and Bcl‐xL in resected non‐small‐cell lung cancers
Authors: Groeger A M , Esposito V , De Luca A , Cassandro R , Tonini G , Ambrogi V , Baldi F , Goldfarb R , Mineo T C , Baldi A , Wolner E 
Published: January 2004

Aims : Some experimental evidence suggests that in lung cancer, development, progression and an increased proliferation rate can be linked to apoptosis‐related factors. In this study we evaluated the possible role of p53 and Bcl‐2 gene family members as prognostic factors for non‐small‐cell lung cancer.Methods and results : We investigated the immunohistochemical expression of p53 and Bcl‐2 gene family members (bax, Bcl‐2 and Bcl‐xL) in 94 non‐small‐cell lung cancer specimens to establish the role of these genes in lung cancer pathogenesis, and to evaluate their prognostic importance. The expression of Bcl‐2 was correlated with a shorter patient survival time and with the nodal status of the neoplasm. We also found frequent over‐expression of bax and Bcl‐xL to be of no prognostic significance. Finally, we found no correlation between frequent detection of aberrant p53 protein and expression of either Bcl‐2, bax or Bcl‐xL or with patient survival time.Conclusions : This study confirms a relevant role for apoptosis‐regulatory proteins in the pathogenesis of lung cancer, and highlights the possible role of Bcl‐2 as a prognostic factor for this tumour.
Invasive micropapillary carcinoma of the breast: high incidence of lymph node metastasis with extranodal extension and its immunohistochemical profile compared with invasive ductal carcinoma
Authors: Zekioglu O , Erhan Y , Çiris M , Bayramoglu H , Özdemir N 
Published: January 2004

Aims : Invasive micropapillary carcinoma of the breast is an aggressive and distinctive variant of breast cancer. These tumours have a characteristic histological appearance and have been associated with a high incidence of axillary lymph node metastases and a poor clinical outcome. The aims of this study were to investigate the immunohistochemical profile of invasive micropapillary carcinoma of the breast, to compare it with invasive ductal carcinoma, and to identify the morphological parameters which predict its poor outcome.Methods and results : Fifty‐three (2.6%) invasive micropapillary carcinomas of the breast from 2022 cases of infiltrating breast carcinomas were identified by retrospective review. The patient age at presentation ranged from 33 to 78 years (mean 52.5 years). The tumour size ranged from 5 to 70 mm (mean 27 mm). Eighty‐two percent (43 of 53) were of high histological grade; 69% (33 of 48) of cases with axillary lymph node dissections had positive lymph nodes; and 75.5% (40 of 53) had lymphatic invasion: 46% (22 of 48) of cases had extranodal extension. Of lymph node‐positive cases, 61% had four or more metastatic lymph nodes. Of tumours with tumour size >10 mm, 77% had positive lymph nodes. The percentages of cases positive for oestrogen receptor (ER) and progesterone receptor (PR) were 68% and 61%, respectively. These values were significantly higher than the values for invasive ductal carcinomas. p53 and c‐erbB‐2 were detected in 48% and 54% of cases, respectively. The mean value of Ki67 was 26%. Follow‐up was available in 36 patients. Eight patients had local recurrences, nine patients had distant metastases, and 10 patients died of disease within a follow‐up period of 9 years.Conclusion : Lymphotropism and an unfavourable prognosis are the hallmarks of this distinct entity. Prognostic markers such as ER, PR, p53, and c‐erbB‐2 failed to provide new criteria to allow discrimination of these tumours from other breast cancers.
Carcinomas arising in multilocular thymic cysts of the neck: a clinicopathological study of three cases
Authors: Moran C A , Suster S , El‐Naggar A , Luna M A 
Published: January 2004

Aims : To report three cases of primary carcinoma of the neck arising in multilocular thymic cysts (MTC).Methods and results : The patients were three men aged 47, 50 and 52 years who presented with a painless neck mass of several weeks' duration. The patients had no history of previous surgical procedures or of malignancy elsewhere. The tumours in all three patients were located on the right lateral side of the neck; all patients underwent complete surgical resection of the mass. Grossly, the tumours were cystic and measured between 20 and 30 mm in greatest diameter. Histologically, the tumours showed cyst walls lined by squamous epithelium. The cyst walls contained prominent germinal centres with lymphoid hyperplasia, cholesterol cleft granulomas, and scattered keratinized structures reminiscent of Hassall's corpuscles. In addition, a neoplastic cellular proliferation composed of round to oval cells arranged in sheets and originating from the lining of the cystic structures was present. The neoplastic cells showed moderate amounts of eosinophilic cytoplasm, round nuclei, and, in some areas, prominent nucleoli. Mitotic figures were easily found, and cellular pleomorphism was present in several areas. In two cases the tumours showed features of basaloid carcinoma of the thymus, while in one case the pattern was that of squamous cell carcinoma. Immunohistochemical studies for keratin showed a strong positive reaction in the tumour cells, while leucocyte common antigen strongly stained the lymphoid background. Follow‐up information obtained in two patients showed them to be alive 6 months after initial diagnosis. One patient was lost to follow‐up.Conclusion : The cases described here represent an unusual variant of carcinoma arising in multilocular thymic cyst in the neck region.