bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Ethanol Exposure on Extraembryonic Vascular Development in the Chick Area Vasculosa
Authors: Tufan A. Cevik , Satiroglu-Tufan N. Lale
Published: November 2003

The effect of ethanol (EtOH) exposure on extraembryonic vascular development was examined using the chick embryo area vasculosa (AV) in shell-less culture. Embryos were placed in cultures at Hamburger Hamilton (HH) stage 11/12 and a single dose of EtOH (10, 30 or 50%) was applied to the center of the blastodisc. Untreated/sodium-chloride-treated controls showed normal embryonic growth and well-developed extraembryonic vessels at 24/48 h of treatment. At doses of 30 and 50%, the mortality rate was significantly increased, and survivors demonstrated significant growth retardation and inhibition of normal vascular development in a dose-dependent manner. Immunostaining for vascular endothelial growth factor (VEGF) showed that mesenchymal cells continued to differentiate into angioblasts to form blood islands, but their assembly into primitive vessels was perturbed in a dose-dependent manner. Northern blot analyses of basic fibroblast growth factor, VEGF, Flt-1 and Flk-1 mRNA expression supported these findings and showed a dose-dependent decrease in EtOH-treated cultures compared to controls. Co-treatment with α-tocopherol (0.05 M) or all-trans-retinoic acid (10–8M) significantly decreased the mortality rate and improved both embryonic growth and extraembryonic vascular development in the cultures. On the other hand, almost all embryos treated with 10% EtOH survived the first 48 h after treatment. However, the complexity of the vascular tree measured as the relative vasculogenesis index, the surface area of the AV and the mRNA expression of vasculogenic molecules were increased during the first 24 h. This acute effect disappeared 48 h after treatment and the vascular tree continued to develop parallel to the controls. No significant growth retardation was observed in this group. These results suggest that, in terms of extraembryonic vascular development, an early, single, low-dose EtOH exposure may have an acute, short-term positive effect, whereas moderate- or high-dose EtOH exposure may severely perturb this process disabling the necessary absorption of the nutrients for the embryo to develop properly. The mechanisms of action of EtOH on extraembryonic vascular development may involve the establishment of reactive oxygen species, resulting in the initiation of oxidative stress and perturbation of retinoic acid signaling and alterations in the expression of growth-regulatory vasculogenic factors and their receptors.
The Pattern of Distribution of Selected ATP-Sensitive P2 Receptor Subtypes in Normal Rat Kidney: An Immunohistological Study
Authors: Turner C.M. , Vonend O. , Chan C. , Burnstock G. , Unwin R.J.
Published: November 2003

Using immunohistological techniques and available polyclonal antibodies, we have identified several ATP-sensitive P2 receptor subtypes in specific structures of the normal rat kidney. Of the P2 receptor subtypes examined, P2X1, P2X2 and P2Y1 receptors were found in the smooth muscle layer of intrarenal vessels. The P2Y1 receptor was also found on glomerular mesangial cells, the brush border membrane of the proximal straight tubule and on peritubular fibroblasts. In the cortex, P2Y4 receptors were found on the tubule epithelium of the proximal convoluted tubule, and P2Y2 receptors on glomerular epithelial cells (podocytes). P2X4 and P2X6 receptors were present throughout the renal tubule epithelium from the proximal tubule to the collecting duct. P2X5 receptors were expressed on medullary collecting duct cells and the apical membrane of the S3 segment of the proximal tubule. Possible functions of these receptor subtypes in normal rat kidney are discussed.
Early Drug Therapy and In-Hospital Mortality following Acute Myocardial Infarction
Authors: Erne Paul , Radovanovic Dragana , Urban Philip , Stauffer Jean-Christophe , Bertel Osmund , Gutzwiller Felix
Published: November 2003

Background: Early drug therapy in patients with ST-elevation infarction is essential for improved short- and long-term outcomes. Most of the drugs used currently have been extensively studied in the era prior to reperfusion therapies, and thus it is important to assess the value of these drugs in today’s clinical practice and compare the results with those of randomized trials. Objectives: The study assessed the effects of age, gender, risk factors, reperfusion therapy and early drug therapy in patients with acute myocardial infarction with ST elevation or new left bundle-branch block on in-hospital mortality. Methods: The analysis of drug administration and in-hospital mortality is based on the AMIS Plus project, a registry of acute coronary syndromes in Switzerland since 1997. Data from 7,279 patients admitted to participating hospitals between 1997 and 2002 were analyzed, and the effect of factors and drug therapies on in-hospital mortality was assessed by logistic regression analysis. Results: Age and diabetes were identified as factors associated with a higher likelihood of in-hospital mortality, while a significant and important reduction of in-hospital mortality was due to the use of thrombolytic therapy or primary percutaneous coronary intervention (PCI) [relative risk reduction (RRR) of 31%, odds ratio (OR) and 95% confidence interval: 0.69; 0.54–0.87; p = 0.002 for thrombolysis, RRR of 34%; OR 0.66; 0.44–0.99; p = 0.044 for PCI]. Early administration of aspirin or ADP antagonists is associated with a risk reduction of in-hospital mortality by 36% (OR 0.63; 0.45–0.89; p = 0.009) and 50% (OR 0.49; 0.35–0.70; p < 0.001), respectively. The use of unfractionated heparin did not reduce in-hospital mortality. Administration of ACE inhibitors, nitrates or beta-blockers reduced the relative risk of in-hospital death by 40% (OR 0.60; 0.49–0.75; p = 0.009), 42% (OR 0.58; 0.46–0.72; p < 0.001) and 54% (OR 0.46; 0.37–0.57; p < 0.001), respectively. Less frequent use of reperfusion therapies and beta-blockers was documented for older patients. Gender was not a determining factor for in-hospital survival. Conclusion: Early administration of aspirin or ADP inhibition with ticlopidine or clopidogrel as well as the early use of beta-blockers, nitrates and ACE inhibitors had a beneficial effect on in-hospital mortality in the reperfusion era with either thrombolytics or PCI. The association of a beneficial effect of ADP inhibition was more pronounced than that found in randomized trials for non-ST-elevation infarction. However, it cannot be excluded that patients with a lower risk for in-hospital death who were selected for early invasive assessment received more frequently ADP inhibitors and that this influenced this beneficial effect. Diabetes and age had negative effects on in-hospital mortality, and both reperfusion therapy and beta-blockers were much less frequently used in elderly patients.
Value of N-Terminal proBNP in the Diagnosis of Left Ventricular Systolic Dysfunction in Primary Care Patients Referred for Echocardiography
Authors: Gustafsson Finn , Badskjær Jørn , Stensgaard Hansen Frank , Poulsen Allan H. , Hildebrandt Per
Published: November 2003

Background: Echocardiography is the method of choice to detect left ventricular systolic dysfunction (LVSD), but access to this examination is limited. Therefore, simpler diagnostic tests would be of clinical importance. Objectives: We sought to evaluate the performance of a new N-terminal pro-brain natriuretic peptide (NT-proBNP) analysis in diagnosing LVSD in primary care patients with a provisional diagnosis of heart failure referred for echocardiography. Methods: Serum levels of NT-proBNP were measured with an immunoassay and left ventricular ejection fraction (LVEF) was assessed by echocardiography in 367 patients. Results: Mean age of the patients was 68.8 years (39.0–84.0 years), and 54% were female. Ten percent of the patients had LVEF <0.40. Depending on which cutoff values were used, NT-proBNP analysis detected patients with LVEF <0.40 with a sensitivity of 91–100% and specificity of 46–60%. If the limit for LVSD was set to 0.30, the sensitivity was 100% and the specificity ranged from 44 to 58%. The area under the receiver operating characteristics curves for detecting LVEF ≤0.30 and LVEF ≤0.40 was 0.93 and 0.87, respectively. Conclusion: Irrespective of which cut off value is used, normal NT-proBNP levels effectively rule out LVSD in primary care patients referred for echocardiographic evaluation of possible heart failure.
Changes in Bone Density during Long-Term Administration of Low-Molecular-Weight Heparins or Acenocoumarol for Secondary Prophylaxis of Venous Thromboembolism
Authors: Wawrzyńska L. , Tomkowski W.Z. , Przedlacki J. , Hajduk B. , Torbicki A.
Published: November 2003

Background: Indications for long-term anticoagulation are expanding. Osteoporosis is a complication which can develop after prolonged treatment with unfractionated heparin and is probably multifactorial. Data on osteoporosis associated with low-molecular-weight heparins (LMWH) are contradictory. Vitamin K participates in bone metabolism and since oral anticoagulants antagonize vitamin K, their use may also increase the risk of osteoporosis. Aim: To assess and compare the effects of long-term secondary venous thromboembolic prophylaxis with LMWH or acenocoumarol on bone structure. Methods: We assessed bone mineral density (BMD) by densitometry in 86 patients receiving LMWH or acenocoumarol for 3–24 months. The initial BMD was compared to the final result expressed as the percentage difference. The Z-score was also assessed and defined for individual patients as the number of standard deviations of BMD from its ideal value calculated for age and sex groups. Results: Excessive decrease in BMD was evidenced, which seemed to relate to the duration as well as type of treatment. At 1 and 2 years of follow-up, the mean decrease in BMD of the femur was 1.8% and 2.6% in patients on acenocoumarol and 3.1 and 4.8% in patients on enoxaparin, respectively. Conclusions: Long-term exposure to treatment and prophylaxis of venous thromboembolism cause a modest but progressive decrease in BMD, more evident in patients on LMWH than on acenocoumarol. It might be advisable to perform densitometry before starting long-term anticoagulation and to repeat it every 12 months, especially in patients with concomitant risk factors for osteoporosis in order to identify patients in need of its prophylaxis.
Coagulation and Fibrinolysis in Inflammatory Bowel Disease and in Giant Cell Arteritis
Authors: Vrij Anton A. , Rijken Joop , van Wersch Jan W.J. , Stockbrügger Reinhold W.
Published: November 2003

Background: In inflammatory bowel disease (IBD), gut microvascular thrombosis as well as thromboembolic complications have repeatedly been observed. We examined the long-term course of markers of coagulation and fibrinolysis in relation to clinical disease activity. Materials and Methods: In a prospective study, prothrombin fragment 1 and 2 (F1.2), thrombin-antithrombin complex (TAT), antithrombin, D-dimer, plasmin-α2-antiplasmin complex (PAP) and plasminogen activator inhibitor-1 (PAI-1) were measured in 20 patients with Crohn’s disease (CD), 18 with ulcerative colitis (UC), and 19 with giant cell arteritis during active and inactive disease, as well as in 51 controls without inflammation. Results: Levels of F1.2, TAT, D-dimer, PAP and PAI-1 were significantly higher in active versus inactive CD and UC. However, even after 12 months of follow-up, in CD and UC the mean levels of F1.2, D-dimer and PAP were significantly higher than the levels of the controls. Conclusions: Levels of F1.2, D-dimer and PAP were markedly raised for a long time in clinically inactive IBD, underlining a chronic state of hypercoagulation and enhanced fibrinolysis.
Indices of Thrombogenesis, Endothelial Damage and Platelet Function following Percutaneous Peripheral Artery Angiography and Angioplasty for Peripheral Vascular Disease
Authors: Makin Andrew J. , Chung Natali A.Y. , Silverman Stanley H. , Moss Mark S. , Lip Gregory Y.H.
Published: November 2003

We hypothesised that there would be alterations in markers of endothelial damage/dysfunction, platelet activation and thrombogenesis in patients with peripheral vascular disease (PVD) as a result of undergoing diagnostic angiography and therapeutic angioplasty. To test this hypothesis, we measured sequential changes in von Willebrand factor (vWf, an index of endothelial damage/dysfunction), tissue factor (TF, an index of thrombogenesis) and soluble P-selectin (sP-sel, an index of platelet activation) in 52 consecutive patients (32 male; mean age 69 years, SD 10) who were undergoing elective angiography and angioplasty for PVD. Patients with PVD had significantly higher vWf and sP-sel levels compared to healthy controls (both p < 0.001), but median TF levels were not significantly different (p = 0.344). In the whole group, there was a significant reduction in sP-sel levels (p < 0.001, paired t test) post-angiography/angioplasty, but no significant change in vWf and TF levels. In patients undergoing angiography only, there was a significant drop in mean sP-sel (p < 0.001, paired t test) and vWf (p = 0.044) values after the procedure, whilst TF levels were not significantly changed (p = 0.370, Mann-Whitney U test). In patients undergoing angioplasty and stent, mean sP-sel levels fell immediately after the procedure (p = 0.001, paired t test), but there were no statistically significant changes in vWf and TF-levels. In conclusion, there appears to be a reduction in plasma sP-sel levels following angioplasty and stenting for PVD, suggesting alterations in platelet physiology, which may be accompanied by some alterations in the endothelium. The possibility that these changes may have pathophysiological implications for understanding platelet and endothelial reactions to angiography and associated interventions (that is, angioplasty and stent) needs to be explored.
Laparoscopic Splenectomy for Immune Thrombocytopenic Purpura in Patients with Severe Refractory Thrombocytopenia
Authors: Keidar Andrei , Sagi Boaz , Szold Amir
Published: November 2003

Laparoscopic splenectomy (LS) for immune thrombocytopenic purpura has a success rate of 70–90%. This invasive procedure is sometimes required for patients with refractory thombocytopenia. However, no data on their outcome are available. If the hematologic response is inadequate, its value vis-à-vis the risk associated with major surgery is open to question. Twelve of 110 patients who underwent LS in our institution had a platelet count lower than 20 × 109/l (mean 6.6 × 109/l). Nine patients (75%) had a good-to-excellent hematologic response. The complication rate was 33%. LS in patients with very low platelet counts is feasible and yields a response rate similar to the average of patients with immune thrombocytopenic purpura. However, it bears a higher perioperative morbidity compared with LS in patients with higher counts.
Antioxidants: A Possible Role in Kidney Protection
Authors: Tylicki Leszek , Rutkowski Boleslaw , Hörl Walter H.
Published: November 2003

Oxidative stress contributes to the pathophysiology of kidney injury. Beneficial renal effects of some medications, such as angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor antagonists, calcium channel blockers, β-blockers and lipid lowering agents depend at least partially on the ability to alleviate oxidative stress. The administration of various natural or synthetic antioxidants has been shown to be of benefit in prevention and attenuation of renal scaring in numerous animal models of kidney diseases. These include vitamins, N-acetylcysteine, α-lipoic acid, melatonin, dietary flavonoids and phytoestrogens, and many others. Human studies are limited in this regard. Under certain conditions, surprisingly, the antioxidant supplements may exhibit pro-oxidant properties and even worsen renal damage. To date, the evidence is insufficient to recommend antioxidant supplements in patients with kidney disease. Prospective, controlled clinical trials on safety and effectiveness of different therapeutic antioxidant strategies are indispensable.
Effect of Epidermal Growth Factor on Phosphate Uptake in Renal Proximal Tubule Cells: Involvement of PKC, MAPK, and cPLA2
Authors: Han Ho Jae , Park Ji Yeong , Lee Yun Jung , Park Soo Hyun
Published: November 2003

Objective: The present study was conducted to examine the effect of epidermal growth factor (EGF) on Pi uptake and its related signal pathways in the primary cultured renal proximal tubule cells (PTCs). Results: EGF (50 ng/ml) inhibited Pi uptake, a typical marker of Na+/phosphate cotransporter, in a time- and dose-dependent manner. EGF-induced inhibition of Pi uptake was blocked by AG1478 (an EGF receptor antagonist), genistein or herbimycin A (tyrosine kinase inhibitors) and also blocked by mepacrine (a phospholipase A2 (PLA2) inhibitor) and AACOCF3 (a cPLA2 inhibitor). EGF increased [3H]-arachidonic acid (AA) release, which was also blocked by AG1478, genistein or herbimycin. Furthermore, EGF-induced inhibition of Pi uptake was blocked by indomethacin (a cyclooxygenase inhibitor) and econazole (a cytochrome P-450 epoxygenase inhibitor), but not by NDGA (a lipoxygenase inhibitor). On the other hand, EGF-induced inhibition of Pi uptake was blocked by staurosporine, H-7, or bisindolylmaleimide I (PKC inhibitors), PD 98059 (a p44/42 MAPK inhibitor), but not by SB 203580 (a p38 MAPK inhibitor). EGF-induced increase of [3H]-AA release was blocked by PKC inhibitors and a p44/42 mitogen-activated protein kinase (MAPK) inhibitor, but not by a p38 MAPK inhibitor. In addition, a PKC inhibitor blocked EGF-induced phosphorylation of p44/42 MAPK. Conclusion: EGF inhibits Pi uptake via PKC-p44/42 MAPK-cPLA2 pathway in the PTCs.
Vascular Endothelial Growth Factor in Diabetic Nephropathy
Authors: Lenz Tomas , Haak Thomas , Malek Joanna , Gröne Hermann-Josef , Geiger Helmut , Gossmann Jan
Published: November 2003

Background: Vascular endothelial growth factor (VEGF) increases endothelial permeability. VEGF is produced in podocytes and functional receptors are located on endothelial glomerular cells. The aim of the current study in diabetic patients with normal renal function to various degrees of proteinuric nephropathy was therefore to unravel a possible role of the most important isoform VEGF165 for albuminuria and to investigate the impact of therapy with an inhibitor of the renin-angiotensin system on VEGF165 secretion. Subjects and Methods: A cross-sectional study in 72 patients (41 female, 31 male) with long-standing type 1 (n = 35, mean age 43.3 years, range 22–67) or type 2 (n = 37, mean age 66 years, range 53–83) diabetes mellitus was performed; in 19 patients the serum creatinine value was >1.5 mg/dl. Twenty-six healthy volunteers (17 female, 9 male, mean age 34.8 years, range 19–58) with normal renal function served as controls. Serum and urinary VEGF165 was measured by ELISA. Urinary albumin was measured nephelometrically. Mann Whitney U tests were used for comparisons. Results: In type 1 and type 2 diabetics mean urinary VEGF165 concentration amounted to 112 ± 88 (mean ± SD) and 88 ± 85 ng/l, respectively, compared to 101 ± 60 ng/l in the normal volunteers (NS vs. diabetics). The respective mean urinary albumin concentrations were 443 ± 1029, 394 ± 749 and 20 ± 33 mg/l (p < 0.01 vs. diabetics type 2). There was a correlation between urinary VEGF and albumin, but only in patients with type 2 diabetes (R = 0.497; n = 36; p = 0.002). Urinary VEGF165 was similar in patients with (n = 40) and without ACE inhibitor/AT1 antagonist therapy (n = 32) and in normal volunteers, whereas serum VEGF165 was higher in the treated type 1 diabetics. Conclusions: These results may suggest that VEGF165 plays some role in the development of albuminuria in diabetic nephropathy due to type 2 but not type 1 diabetes.
Nephropathy in a Hypercholesterolemic Mouse Model with Streptozotocin-Induced Diabetes
Authors: Hammad Samar M. , Hazen-Martin Debra J. , Sohn Mimi , Eldridge Leslie , Powell-Braxton Lyn , Won Wesley , Lyons Timothy J.
Published: November 2003

Background/Aims: The contribution of preexisting hypercholesterolemia to diabetic nephropathy remains unclear. We assessed the impact of hypercholesterolemia on diabetic nephropathy using a double knockout (DKO) mouse, null for the low-density lipoprotein receptor (Ldlr–/–) and the apoB mRNA editing catalytic polypeptide 1 (Apobec1–/–). Methods: Wild-type (WT) and DKO mice received sham or streptozotocin injections at age 7 weeks, yielding control (WT-C, DKO-C) and diabetic (WT-D, DKO-D) groups. At sacrifice (age 40 weeks), albuminuria was determined by ELISA, and kidney sections were examined by light and electron microscopy. Results: Albuminuria increased in diabetic mice (WT-D: 82.4 ± 37.2 µg/18 h; DKO-D: 58.0 ± 45.7 µg/18 h) versusnondiabetic controls (WT-C: 10.2 ± 7.2 µg/18 h; DKO-C: 8.6 ± 5.3 µg/18 h) (p < 0.0001), but was unaffected by hypercholesterolemia. Light microscopy of kidney sections demonstrated increased collagen levels in glomeruli in WT-D mice, but not in DKO-D mice or either control group. Electron microscopy showed a thickened glomerular basement membrane in WT-D mice only. The proximal tubular basement membrane thickness was increased in both diabetic groups versusnondiabetic controls (p < 0.01); in WT-D mice this was attributable to collagen accumulation, but in DKO-D mice it was mainly caused by lipid vacuoles. Conclusions: In this animal model, preexisting hypercholesterolemia did not exacerbate either glomerular lesions of diabetes (collagen accumulation, basement membrane thickening) or albuminuria, but appeared to mitigate these effects. Furthermore, the combination of hypercholesterolemia and diabetes resulted in a significant lipid accumulation in the tubular basement membrane.
Primary Failure of Arteriovenous Fistulae in Auto-Immune Disease
Authors: Baumann Marcus , Niebel Wolfgang , Kribben Andreas , Philipp Thomas , Heemann Uwe
Published: November 2003

Background/Aim: Chronic haemodialysis depends on an arteriovenous fistula. Primary failure of vascular access is a common problem which is mainly related to thrombosis. As ambulatory surgery is common, it is mandatory to identify patients with a high thrombophilic risk to allow better prevention (anticoagulation) and direct re-intervention after thrombosis. The purpose of this study was to determine thrombophilic risk factors for primary access failure in order to identify patients at risk before the operation. Methods: We performed a retrospective study on 62 chronic haemodialysis patients who received permanent vascular access. We evaluated established risk factors for chronic access failure as well as the number of earlier shunt operations in these patients. Results: The patients predominantly suffered from auto-immune diseases. The frequency of a successful first vascular access was above average (92.5%). We identified four major risk factors for primary access failure: number of previous vascular access thromboses (p < 0.01; R = 0.96), pre-existing thrombophilic risk factors (p < 0.01), pre-operative fibrinogen (p < 0.02), and vasculitis (p < 0.01). Conclusions: We identified four risk factors which allowed an individual risk evaluation. Among the factors investigated, the activity of the auto-immune disease was the most striking. Our data suggest not to perform a vascular access during an active period of vasculitis.
Leptin Levels Increase during Flutamide Therapy in Women with Polycystic Ovary Syndrome
Authors: Sahin Ibrahim , Serter Rustu , Karakurt Feridun , Demirbas Berrin , Guler Serdar , Culha Cavit , Taskapan Cagatay , Aral Yalcin
Published: November 2003

Aim: To evaluate the serum leptin levels and the effects of flutamide treatment on the leptin levels in women with polycystic ovary syndrome (PCOS). Methods: 20 women with PCOS and 20 controls were enrolled in the study. Leptin levels and leptin response to an oral glucose tolerance test were assessed in both groups before and after a 4-week flutamide therapy period. Results: The leptin levels were similar in both groups at baseline. In the PCOS group, leptin levels and area under curve for leptin levels increased significantly after flutamide treatment. Conclusions: Women with PCOS had similar leptin levels to those of controls with similar age and body mass index. Flutamide treatment led to increased leptin levels and leptin responses to oral glucose tolerance tests in PCOS patients. Further studies are needed to gain insights into the clinical consequences of these effects of flutamide.
Aneuploidy in carcinomas may be initiated by the acquisition of a single trisomy
Authors: Atkin N.B.
Published: November 2003

Karyotypic studies of eight endometrioid carcinomas of the endometrium in this laboratory, four colorectal polyps (from this laboratory or reported in the literature), and four early carcinomas of the ovary (from the literature), provide evidence that clonal evolution leading to malignant neoplasms at these sites originates when a cell acquires a single additional chromosome. In different tumors, different chromosomes may be involved in this change from euploidy to aneuploidy. Since the resultant clones of trisomic cells occur at an early stage of tumor development, their presence is only likely to be determined when they are at a location that is accessible for study. As aneuploidy is a virtually constant feature of malignancy, the possibility that the concept of a single trisomy as the initial event in the development of all malignant solid neoplasias should be addressed.
Supernumerary small marker chromosome (SMC) and uniparental disomy 22 in a child with confined placental mosaicism of trisomy 22: Trisomy rescue due to marker chromosome formation
Authors: Bartels I. , Schlueter G. , Liehr T. , von Eggeling F. , Starke H. , Glaubitz R. , Burfeind P.
Published: November 2003

Trisomy rescue is one of various proposed mechanisms in formation of supernumerary small marker chromosomes (SMC) and uniparental disomy (UPD). In the present report a small de novo marker chromosome derived from chromosome 14 or 22 was diagnosed at prenatal diagnosis due to maternal age. Follow up investigations at birth revealed mosaicism 47,XX,+mar/46,XX. Using FISH, the marker was positive for the probe D14/22Z1, but negative for the probes midi 54 and D22Z4. Using three informative markers both chromosomes 22 were shown to be inherited from the mother (UPDmat). The results are consistent with nondisjunction at maternal meiosis I. The girl is 18 months old now and phenotypically normal. Cardiac and abdominal malformations were excluded by sonographic examinations. Motor and mental development is according to or ahead of developmental milestones (free walking with 10 months, first words at 12 months). The case confirms that maternal UPD 22 most likely is not associated with clinical abnormalities. According to FISH results, UPD 22, and 47,XX,+22 in the placenta, we conclude that the SMC was derived from alpha satellite sequences of chromosome 22. This case for the first time gives evidence that early postzygotic reduction of a chromosome to a small marker chromosome is a real existing mechanism to rescue a conceptus with trisomy.
Loss of 9p21 is embedded in a complex but consistent pattern of genomic imbalances in oral squamous cell carcinomas
Authors: Gebhart E. , Liehr T. , Wolff E. , Wiltfang J. , Koscielny S. , Ries J.
Published: November 2003

35 oral squamous cell carcinomas examined previously by comparative genomic hybridization (CGH) exhibited 5 up to 47 copy number alterations (CNAs). 13 of those cases showed a loss of parts of the short arm of chromosome 9, band p21 being affected in all of these cases. A highly complex but strikingly consistent pattern of genomic imbalances with an average 31.5 CNAs per tumor was associated with this deletion, and gains clearly dominated over losses of genomic material. Comparable patterns, however, could also be found in tumors with a high number of CNAs (24 CNAs) but without the deletion. Low numbers of imbalances were accompanied by low consistency of the CNA patterns. None of these latter cases showed the deletion 9p21. 66.7% of the dim(9p21)-positive tumors were of class pT4 (vs. 22% in dim(9p21)-negative cases), 77% of stage III or IV (vs. 47% in the group without the deletion), but only 8% of the dim(9p21)-positive tumors were classified as grade 3 (vs. 41% in the negative group). Other clinicopathologic features like prevalence of relapse, or survival time could not be as clearly associated with the deletion. For instance, short relapse-free survival was clearly associated with a high number of CNAs, rather independent of presence or absence of dim(9p21) in the affected tumor. From these findings it is concluded that previously found associations of 9p21 deletion with clinical parameters can reasonably be estimated only in the context of the pattern and complexity of the genomic imbalances accompanying this chromosomal loss in the examined tumors.
A 3.4-kbp transcript of ZNF331 is solely expressed in follicular thyroid adenomas
Authors: Meiboom M. , Murua Escobar H. , Pentimalli F. , Fusco A. , Belge G. , Bullerdiek J.
Published: November 2003

Translocations involving chromosomal region 19q13 are a frequent finding in follicular adenomas of the thyroid and might represent the most frequent type of structural aberration in human epithelial tumors. By positional cloning, a putative candidate gene, ZNF331 (formerly RITA) located close to the breakpoint was identified. Recently, aberrant expression of ZNF331 has been described in two cell lines of follicular thyroid adenomas with aberrations in 19q13 indicating an involvement of ZNF331 in tumorigenesis. Nevertheless, knowledge about structure and expression of ZNF331 is limited. We performed RACE-PCR and genomic sequence analyses to gain a deeper insight into its molecular structure. To elucidate ZNF331 expression patterns we performed Northern blot analyses on various normal tissues as well as on thyroid carcinoma and adenoma cell lines. Herein, unique expression of a 3.4-kbp transcript is described in thyroid adenoma cell lines with 19q13 aberrations, which was not detected either in normal tissues or in thyroid carcinoma cell lines.
Cosegregation of Robertsonian metacentric chromosomes in the first meiotic division of multiple heterozygous male mice as revealed by FISH analysis of spermatocyte II metaphases
Authors: Scascitelli M. , Pacchierotti F. , Rizzoni M. , Gustavino B. , Spirito F.
Published: November 2003

Contrasting results (random segregation or cosegregation of isomorphic chromosomes) have been reported up to now on the segregation pattern of Robertsonian metacentric chromosomes of Mus musculus domesticus in multiple heterozygotes, using different approaches (karyotypical analysis of the progeny or of second meiotic metaphases). In the present contribution data are presented based on FISH (Fluorescence In Situ Hybridisation) analysis with telomeric probes, which allowed us to distinguish metacentric chromosomes from pairs of acrocentric chromosomes with their centromeric regions close to each other. Probes were hybridized to DAPI stained metaphases of spermatocytes II of mice heterozygous for two, three or four Robertsonian metacentrics in an all-acrocentric background, the karyotype of which has been reconstructed starting from laboratory strains. Isomorphic chromosomes tend to cosegregate (metacentrics with metacentrics, acrocentrics with acrocentrics); the values found for cosegregation have a clear even if moderate effect on the reproductive isolation caused by underdominant chromosomal rearrangements.
Gene arrangement at the Rhesus blood group locus of chimpanzees detected by fiber-FISH
Authors: Suto Y. , Ishikawa Y. , Hyodo H. , Ishida T. , Kasai F. , Tanoue T. , Hayasaka I. , Uchikawa M. , Juji T. , Hirai M.
Published: November 2003

The Rhesus (Rh) blood group system in humans is encoded by two genes with high sequence homology. These two genes, namely, RHCE and RHD, have been implied to be duplicated during evolution. However, the genomic organization of Rh genes in chimpanzees and other nonhuman primates has not been precisely studied. We analyzed the arrangement of the Rh genes of chimpanzees (Pan troglodytes) by two-color fluorescence in situ hybridization on chromatin DNA fibers (fiber-FISH) using two genomic DNA probes that respectively contain introns 3 and 7 of human RH genes. Among the five chimpanzees studied, three were found to be homozygous for the two-Rh-gene type, in an arrangement of Rh (5′→3′) – Rh (3′←5′). Although a similar gene arrangement can be detected in the RH gene locus of typical Rh-positive humans, the distance between the two genes in chimpanzees was about 50 kb longer than that in humans. The remaining two chimpanzees were homozygous for a four-Rh-gene type, in an arrangement of Rh (5′→3′) – Rh (3′←5′) – Rh (3′←5′) – Rh (3′←5′) within a region spanning about 300 kb. This four-Rh-gene type has not been detected in humans. Further analysis of other great apes showed different gene arrangements: a bonobo was homozygous for the three-Rh-gene type; a gorilla was heterozygous for the one-Rh- and two-Rh-gene types; an orangutan was homozygous for the one-Rh-gene type. Our findings on the intra- and interspecific genomic variations in the Rh gene locus in Hominoids would shed further light on reconstructing the genomic pathways of Rh gene duplication during evolution.
Glucose-Induced Changes in the Phenotype of Human Peritoneal Mesothelial Cells: Effect of L-2-Oxothiazolidine Carboxylic Acid
Authors: Bręborowicz Andrzej , Bręborowicz Maciej , Oreopoulos Dimitrios G.
Published: November 2003

Background: During peritoneal dialysis, mesothelial cells are chronically exposed to high concentrations of glucose. Therefore, the cytotoxic effect of glucose may alter the function and reactivity of these cells. Methods: For 4 weeks, human peritoneal mesothelial cells were cultured in vitroin medium supplemented with 45 mM glucose or 45 mM mannitol or with 45 mM glucose and 1 mM L-2-oxothiazolidine-4-carboxylic acid (OTZ), the latter being a precursor for glutathione synthesis. Peroxidation of the mesothelial cell lipids, synthetic activity and reaction of these cells to peritoneal dialysis fluids were studied. Results: In contrast to mannitol, glucose enhanced the peroxidation of the cellular lipids (+65%, p < 0.01) an effect that was prevented by OTZ. Synthesis of hyaluronan and vascular endothelial growth factor was reduced in mesothelial cells treated with glucose by 36% (p < 0.01) and 44% (p < 0.05), respectively; both glucose effects were reversed when cells were incubated with glucose plus OTZ. Monocyte chemoattractant protein-1 synthesis by cells exposed to glucose was increased by 31% (p < 001), and again that effect was prevented by OTZ. Glucose and mannitol stimulated synthesis of fibronectin (+32%, p < 0.05). Mesothelial cells chronically exposed to glucose became activated after subsequent exposure to the dialysis fluid, as reflected by the increased release of interleukin (IL)-6, in contrast to control mesothelial cells, in which IL-6 synthesis was suppressed. Conclusions: Chronic exposure of mesothelial cells to glucose changes their synthetic activity and their reaction after exposure to dialysis fluids. Some of these effects are prevented by OTZ, which suggests that glucose-induced free radicals are responsible for a change in mesothelial cell phenotype under the conditions of peritoneal dialysis.
Morphological Features of Rat Gastric Mucosa after Acute and Chronic Treatment with Amtolmetin Guacyl: Comparison with Non-Selective and COX-2-Selective NSAIDs
Authors: Morini Giuseppina , Guaita Elena , Lazzaretti Mirka , Grandi Daniela , Coruzzi Gabriella
Published: November 2003

Background/Aims: The compound amtolmetin guacyl (AMG) has been characterized in both animal and human studies as a novel non-selective non-steroidal anti-inflammatory drug (NSAID) endowed with lower ulcerogenicity in comparison with traditional NSAIDs due to a unique mechanism of action, namely the increase in endogenous production of gastric nitric oxide. Methods: Conscious rats were treated either acutely (4 h) or chronically (3 and 14 days) with intragastric AMG (50 and 150 mg/kg), the non-selective NSAID tolmetin (TOL, 30 and 100 mg/kg) or the COX-2-selective NSAID celecoxib (CXIB, 20 and 60 mg/kg). Macroscopically visible and histologic lesions were evaluated. The ultrastructure of mucosal microvasculature was assessed. Results: (1) TOL and CXIB caused quantitatively greater endothelial damage and inflammatory cell infiltration than that induced by AMG; (2) AMG and CXIB, unlike TOL, did not cause epithelial damage after acute or chronic treatment, and (3) gastric lesions induced by TOL underwent adaptation during chronic treatment. Conclusion: Endothelial cell damage in the gastric microvasculature is an early event following both non-selective and COX-2-selective inhibitors. The low gastric mucosal toxicity of AMG is confirmed after acute and chronic treatment.
Obstetric Outcome in Women with Endometriosis – A Matched Case-Control Study
Authors: Kortelahti Minna , Anttila Maarit A. , Hippeläinen Maritta I. , Heinonen Seppo T.
Published: November 2003

Background: Immunological deficiencies, altered angiogenic activity, infiltrative potential and growth factors are plausible factors behind endometriosis. The aim of this study was to determine whether endometriosis interferes with the course or outcome of pregnancy. Study Design: In this matched case-control study, we analyzed obstetric outcome among 137 women with endometriosis and 137 controls matched as regards IVF procedures and parity who gave singleton births at Kuopio University Hospital between January 1994 and December 2000. In affected women, the diagnosis was histologically verified, whereas the controls were eligible for the study only if they had undergone laparoscopy/tomy in connection with tubal sterilization, or infertility unrelated to endometriosis. Results: No statistically significant differences were detected in reproductive risk factors in women with endometriosis, with the exception of mean maternal age (31.2 years in the cases vs. 34 years in the controls). The mean birth weight (±SD) among those delivering at term (>37 completed weeks) was 3,600 (±542) g in the control group and 3,547 (±456) g in the study group. Placental weight was comparable in both groups. Overall pregnancy characteristics and pregnancy outcome measures were similar in women affected by endometriosis when compared with the control group. Conclusions: Any potential negative effect of endometriosis on obstetric outcome was undetectable.
Endothelial Dysfunction in Preeclampsia
Authors: Var Ahmet , Yildirim Yasemin , Onur Ece , Kuscu N. Kemal , Uyanik B. Sami , Goktalay Kayhan , Guvenc Yesim
Published: November 2003

Endothelial dysfunction underlies the pathogenesis of preeclampsia, but its mechanism has not yet been completely understood. Elevated oxygen free radicals may partially explain the endothelial cell damage. In this study, we have aimed to measure homocysteine (Hcy) and nitric oxide (NO) levels as endothelial dysfunction markers in preeclamptic women. Nineteen preeclamptic (33.9 ± 1.4 weeks) and 15 gestational-age-matched normal pregnant women (35.5 ± 0.7 weeks) were included in the study. Mean NO level was significantly lower (p < 0.001) and mean Hcy level was significantly higher (p < 0.001) in the preeclamptic group. Elevated Hcy and oxygen free radical levels could decrease NO levels due to the reaction with each other and reduced NO may increase blood pressure and ischemia in preeclamptic patients. We have concluded that increased Hcy and oxygen free radical levels, and decreased NO levels are closely associated with preeclampsia-related endothelial dysfunction.
Current Developments; Procedural Developments at the International Court of Justice
Authors:   Prager
Published: November 2003

No Abstract
World Court Decisions at the Turn of the Millennium (1997–2001) by Pieter H.F. Bekker
Authors:   Meadows
Published: November 2003

No Abstract
U.S.-Canada Negotiating Situations
Authors: Williamson
Published: November 2003

No Abstract
American Strengths and Weaknesses
Authors: Koh
Published: November 2003

No Abstract
A Third World Perspective
Authors: Wills
Published: November 2003

No Abstract
U.S.-Canada Free Trade Agreement, 1986-1987
Authors: Merkin  , Katz  , Hughes  , Johnson
Published: November 2003

No Abstract
Bilateral Relations between Mexico and the U.S.
Authors: Pinto-Mazal
Published: November 2003

No Abstract
The Teaching of International Negotiation – Editor's Introduction
Authors: Kaufman
Published: November 2003

No Abstract
Negotiating the European Union: Conclusions
Authors: Pfetsch
Published: November 2003

No Abstract
Success and Failure in Saudi-American Negotiations: American Views
Authors: Al-Ghamdi
Published: November 2003

This article draws on prior research studies and comparable measures to empirically investigate American views on what constitutes critical success and failure factors in negotiating with the Saudis. The findings from this new venue of research indicate that the Americans consider non-personal factors, such as technical expertise and financing terms, as more important than personal factors in successful negotiations with the Saudis. Moreover, among the failure factors studied, none were rated high in importance. Yet, from a Saudi viewpoint, Americans should not necessarily ignore these factors in their negotiations with the Saudis. Personal relationships may be important in generating pre-negotiation contacts, and cultural factors, linked to patience, language, and social customs, may help to prevent breakdowns in the negotiation process. Based on these conclusions, the study provides implications and draws some parallels with previous research on American perceptions.
Examining International Business Negotiations and Directions for the Future
Authors: Weiss  , Tinsley
Published: November 2003

No Abstract
Approaches to Water Dispute Resolution: Applications to Arab-Israeli Negotiations
Authors: Shmueli
Published: November 2003

Increasing and competing demands among countries for water is a major cause of international disputes. This article builds on research of negotiation processes and institutional frameworks of international river basin management. Its focus is the search for effective approaches that can be applied to the resolution of Arab-Israeli water disputes. While every dispute is unique, the Arab-Israeli situation is not the only case with stubborn and long-standing enmities, shortages of water resources, political and economic power imbalances, absences from negotiations of vital riparians, and rapidly changing political climates. In the Arab-Israeli water dispute, there are both parallels and lessons to be learned from the situations in other river basins.The treaties that have thus far emerged from Arab-Israeli negotiations are briefly reviewed, as is the potential for future regional agreements. The history of other river basin negotiations is useful in charting the future directions of the Arab-Israeli water conflict. Issues include options and modes of negotiation, information and technology sharing, the importance of the geopolitical climate, comprehensive versus incremental agreements, linkage of water agreements to environmental and other issues, the power balance among participants, cost-sharing strategies, and institutions, and the capacity for implementation.Although the strained political relations between Arabs and Israelis have worsened in the past year and one-half, the water treaties do not seem endangered for the most part. Indeed, water negotiations may again become one of the confidence-building measures that can facilitate other more general negotiations, after the current stalemate is broken.
Patients' Rights in Europe: Where Do We Stand and Where Do We Go?
Authors: Fallberg
Published: November 2003

No Abstract
Internet, the Patient and the Right to Care for Health
Authors: Roscam Abbing
Published: November 2003

No Abstract
Book Review
Authors: Birmontiene
Published: November 2003

No Abstract
The Development of Euthanasia in the Netherlands
Authors: Leenen
Published: November 2003

No Abstract
Wrongful Life: The Recent French Cour de Cassation Decisions
Authors: Duguet
Published: November 2003

No Abstract
The Kuhse-Singer Euthanasia Survey: Why it Fails to Undermine the Slippery Slope Argument — Comparing Apples and Apples
Authors: Bagaric
Published: November 2003

A survey published in the Medical Journal of Australia in 1997 showed that the incidence of non-voluntary euthanasia in Australia was higher than in the Netherlands. Euthanasia is illegal in Australia, while it is openly practiced in the Netherlands. It has been suggested that the results of the survey undermine the slippery slope argument against legalising euthanasia. This is wrong. Although at the time of the survey, euthanasia was formally prohibited by the law in Australia, the medical and legal culture was such that doctors could practice euthanasia with impunity — in certain circumstances euthanasia by doctors was effectively condoned. This is in fact supported by the findings of the survey. The survey suggests that there were approximately 6,700 cases of euthanasia in Australia in the year from July 1994 to June 1995 — not one of which was prosecuted, let alone resulted in a conviction. Ultimately the survey merely shows that in a climate where voluntary euthanasia is tolerated, wide scale abuses (in the form of non-voluntary euthanasia) occur. Paradoxically the results of the survey give further support to the slippery slope argument.
Private Health Insurance in Ireland
Authors:   Kennedy
Published: November 2003

No Abstract
Health Care and Positive State Obligations
Authors: Hendriks
Published: November 2003

No Abstract
Prospects for the Development of Medical Negligence Litigation in the UK
Authors: Hughes
Published: November 2003

The system of compensation for medical negligence in the UK is under substantial strain. Government response to this reflects the quintessential role of mediating and harmonising between conflicting rights and competing goods. The increasing tide of consumer pressure in society at and on providers of healthcare has resulted in a rapid growth of claims and complaints. Government responsibility for the administration of justice, the provision of legal aid and the funding of healthcare presents a related net of policy choices to government seeking to reflect and shape public attitudes and public services.
Development of Patients' Rights Legislation
Authors: Merakou  , Tragakes
Published: November 2003

In the period up to 1992, patients' rights in Greece were indirectly addressed through relevant provisions in Civil, Penal, Administrative and Disciplinary Law, as well as in the Code on the Practice of Medicine and the Regulation of Medical Deontology. In 1992, broader health care reform legislation contained provisions directly addressing the rights of hospital patients. In 1997, again as part of broader health care reform legislation, further provisions extended the rights of patients granted in 1992 to the entire population, and in addition provided for the implementation of the legislative provisions. The immediate implementation of the patients' rights provisions of the 1997 legislation represents a major step forward with respect to improving the quality of health care services provided.
Clinical Practice Guidelines: Which Objectives? Whose Responsibilities?
Authors: Gevers
Published: November 2003

No Abstract
Kohll and Decker, or That is Somebody Else's Problem. The Challenge Facing Spain
Authors: de Cortazar
Published: November 2003

No Abstract
Linos-Alexandre Sicilianos, L'ONU et la démocratisation de l'état, systèmes régionaux et ordre juridique universel
Authors:   Søndergaard
Published: November 2003

No Abstract
Elements of Nordic Practice 1999: Denmark
Authors:   Klingenberg
Published: November 2003

No Abstract