bluuebunny/crossref_metadata_2025 huggingface dataset:
A Perspective on Regulation of Cell-Cell Adhesion and Epithelial-Mesenchymal Transition: Known and Novel
Authors: Khew-Goodall Yeesim , Wadham Carol
Published: June 2005

A number of recent reviews in the field have described many of the known growth factors and signalling pathways that may be involved in regulating epithelial-mesenchymal transitions. This perspective will focus on some aspects of posttranslational regulation of cell-cell adhesion that are less well understood and their potential role in initiating epithelial-mesenchymal transitions. In addition, a potential novel intermediate in the signalling pathway of epithelial-mesenchymal transition will also be described.
Effect of School-Based Fluoride Varnish Programmes on Approximal Caries in Adolescents from Different Caries Risk Areas
Authors: Moberg Sköld Ulla , Petersson Lars G. , Lith Agneta , Birkhed Dowen
Published: June 2005

The aim was to evaluate, in a 3-year RCT study, school-based fluoride varnish programme on approximal caries incidence and approximal caries progression in 13- to 16-year-olds in high, medium and low caries risk areas on the Swedish west coast. Seven hundred and fifty-eight (89%) fulfilled the trial. Using a simple mobile unit, 2 dental nurses treated the adolescents with F varnish: (1) twice a year at 6-month intervals, (2) 3 times a year within 1 week, (3) 8 times per year during the semesters with 1-month intervals, and (4) no treatment (control). Radiographic caries recording was performed blindly by one of the authors. Concerning total approximal caries incidence, control groups in all areas developed more caries than F varnish groups, with the largest difference in the high risk area: 3.05 ± 3.37 new approximal caries lesions (mean ± SD) compared to 0.54 ± 1.26 for group 3, 0.95 ± 1.67 for group 1 and 1.40 ± 1.89 for group 2 (p < 0.001). More than 90% of the new approximal lesions in all the groups and in all areas consisted of new enamel lesions. Regarding progression of enamel lesions, there were only significant differences between groups 1–3 and group 4 in the high caries risk area. Prevented fraction for fluoride varnish treatment twice a year at 6-month intervals was 69% in high, 66% in medium and 20% in low risk areas. To conclude, school-based F varnish treatment every 6 months in 13- to 16-year-olds is excellent to prevent approximal caries in medium and high caries risk areas.
Milieu-Adopted in vitro and in vivo Differentiation of Mesenchymal Tissues Derived from Different Adult Human CD34-Negative Progenitor Cell Clones
Authors: Moosmann Sabine , Hutter Jörg , Moser Christian , Krombach Fritz , Huss Ralf
Published: June 2005

Adult mesenchymal stem cells with multilineage differentiation potentially exist in the bone marrow, but have also been isolated from the peripheral blood. The differentiation of stem cells after leaving their niches depends predominately on the local milieu and its new microenvironment, and is facilitated by soluble factors but also by the close cell-cell interaction in a three-dimensional tissue or organ system. We have isolated CD34-negative, mesenchymal stem cell lines from human bone marrow and peripheral blood and generated monoclonal cell populations after immortalization with the SV40 large T-antigen. The cultivation of those adult stem cell clones in an especially designed in vitro environment, including self-constructed glass capillaries with defined growth conditions, leads to the spontaneous establishment of pleomorphic three-dimensional cell aggregates (spheroids) from the monoclonal cell population, which consist of cells with an osteoblast phenotype and areas of mineralization along with well-vascularized tissue areas. Modifications of the culture conditions favored areas of bone-like calcifications. After the transplantation of the at least partly mineralized human spheroids into different murine soft tissue sites but also a dorsal skinfold chamber, no further bone formation could be observed, but angiogenesis and neovessel formation prevailed instead, enabling the transplanted cells and cell aggregates to survive. This study provides evidence that even monoclonal adult human CD34-negative stem cells from the bone marrow as well as peripheral blood can potentially differentiate into different mesenchymal tissues depending on the local milieu and responding to the needs within the microenvironment.
Hypothalamic Hamartoma in Association with a Suprasellar Arachnoid Cyst: A Case Report
Authors: Mocco J. , Lozier Alan P. , Komotar Ricardo J. , Silver A.John , Feldstein Neil A.
Published: June 2005

A 5-year-old female presented with a history of precocious puberty and increased height. MRI of the brain revealed a nonenhancing hypothalamic mass and associated suprasellar arachnoid cyst. The patient underwent a right frontal craniotomy with orbital osteotomy for wide fenestration of the cyst. Intraoperatively, it was clear the mass represented a hamartoma with a very smooth glistening surface. For this reason, no biopsy of the wall was performed. Postoperatively, the patient remains neurologically intact and without any medication dependence. This case highlights the occurrence of a suprasellar arachnoid cyst in association with a hypothalamic hamartoma.
Bronchiolitis obliterans Organizing Pneumonia
Authors: Oymak F. Sema , Demirbaş H. Murat , Mavili Ertugrul , Akgun Hulya , Gulmez Inci , Demir Ramazan , Ozesmi Mustafa
Published: June 2005

Background: Bronchiolitis obliterans organizing pneumonia (BOOP) may be classified as cryptogenic (idiopathic) and secondary. There are no clear clinical and radiological features distinguishing between idiopathic and secondary BOOP. Objectives: To analyze the etiologic factors, clinical and radiological features, diagnostic approach and response to therapy at onset and outcome in subjects with BOOP. Methods: The medical files of Erciyes University Hospital from 1995 to 2003 were retrospectively reviewed. Patients with biopsy-proven BOOP were selected for evaluation. The etiology and initial features of BOOP, treatment, resolution, relapse, and survival were obtained from medical records, and a follow-up patient questionnaire. Results: We have diagnosed 26 cases (13 males /13 females) with BOOP syndrome (mean age 54 ± 15 years, range 14–93). More than half the patients (58%) were classified as idiopathic BOOP. Patients presented with cough (92%), dyspnea (70%), pleuritic chest pain, hemoptysis and fever (50%). The biopsy specimens had been obtained by transbronchial and/or transthoracic lung biopsy in 18 cases (69%). At radiological evaluation, there were bilateral patchy alveolar and/or interstitial infiltrates in 16 patients (62%), and solitary pneumonic involvement in 10 patients (38%). Three patients recovered spontaneously, 5 remained cured after resection of the focal lesion. Corticosteroid therapy was given in 17 patients (65%). Apart from four patients who died (death was attributable to BOOP in only 1 patient) and three patients who relapsed, the prognosis was good in all patients. Conclusions: The etiology of BOOP is usually idiopathic. We observed that hemoptysis and pleuritic chest pain were a relatively frequent symptom in BOOP in the present series, in contrast to previous observations. The diversity of radiological and clinical presentations including hemotysis and pleuritic chest pain should prompt consideration of the diagnosis in patients with persisting pulmonary symptoms and radiological findings.
Prevalence of Chronic Obstructive Pulmonary Disease and Rhinitis in Northern Greece
Authors: Sichletidis L. , Tsiotsios I. , Gavriilidis A. , Chloros D. , Kottakis I. , Daskalopoulou E. , Konstantinidis T.
Published: June 2005

Background: Chronic obstructive pulmonary disease (COPD) constitutes one of the main factors responsible for morbidity and mortality worldwide. Rhinitis has a high prevalence, but its relationship to COPD has not been determined. Objectives: To estimate the prevalence of COPD and rhinitis in northern Greece and to examine their correlation. Patients andMethods: Of a total of 8,151 subjects (aged 21–80 years, from three regions of northern Greece) invited to participate in the study, 6,112 (75%) were included. The regions studied were: (a) Thessaloniki (1,733 study participants, 52.7 ± 18.6 years old), an urban area with particulate air pollution frequently exceeding the acceptable limit, (b) Eordea (3,537 study participants, 51.4 ± 15.5 years old), a typical industrial area with particulate air pollution with daily values exceeding the acceptable limit and (c) Grevena (842 study participants, 55.6 ± 15.4 years old), a mountainous area without pollution. The study participants filled in the questionnaire on respiratory symptoms of the Committee on Environmental and Occupational Health of the Medical Research Council and underwent spirometry and rhinomanometry tests. Results: The prevalence of COPD was 5.6% (8.2% in men and 2.5% in women) and that of rhinitis 24.7% (27.4% in men and 21.4% in women). COPD and rhinitis are related to common predisposing factors (smoking, age and sex). Moreover, rhinitis is related to particulate air pollution levels. Conclusions: The prevalence of COPD and rhinitis in northern Greece does not differentiate from that found in other industrial countries. A functional relationship between upper and lower airways is speculated.
Mycobacterium kansasii Endobronchial Ulcer in a Nonimmunocompromised Patient
Authors: Manali E.D. , Tomford W.J. , Liao D.W. , Farver C. , Mehta A.C.
Published: June 2005

In this report we describe the case of an immunocompetent patient found to have an endobronchial, ulcerated lesion due to Mycobacterium kansasii. Predisposing factors could have been severe endobronchial stenosis of the main stem bronchi and distortion of the carina, due to healed endobronchial tuberculosis. Diagnosis was set through fiberoptic bronchoscopy and the patient responded well to treatment. Endobronchial non tuberculous mycobacterial infection should be considered in both HIV seropositive and seronegative patients, especially in endemic areas and in the proper clinical setting. Prompt recognition is important for the effective control and prevention of an unfavorable outcome in an otherwise easily treatable disease.
Molecular Pathology of Non-Small-Cell Lung Cancer
Authors: Breuer R.H.J. , Postmus P.E. , Smit E.F.
Published: June 2005

The molecular basis of lung carcinogenesis must be understood more fully and exploited to enhance survival rates of patients suffering from lung cancer. In this review we will discuss the major molecular alterations that occur in lung cancer. Emphasis is placed on alterations that occur early during carcinogenesis since they might be relevant for future screening programs. Finally we will shortly review new approaches that are used to study the molecular pathology of lung cancer and how they can be applied in a clinical setting.
Differential Localization of Metabotropic Glutamate Receptors 1α and 2/3 in the Rat Striatum during Early Postnatal Development
Authors: Lam R.W.C. , Chan Y.S. , Yung K.K.L.
Published: June 2005

Metabotropic glutamate receptors (mGluRs) are a group of G-protein-coupled receptors that play important roles in mediation of glutamatergic transmission in the rat striatum. mGluR1α and mGluR2/3 are major mGluRs found in the striatum. The present study investigated the changes in expression of mGluR1α and mGluR2/3 during postnatal development. Rats at postnatal day (PND) 1, PND 7, PND 14 and adult stage were employed. Results of the immunofluorescence showed that mGluR1α immunoreactivity was primarily found in the neuropil, and an increasing trend was observed. An intense level of mGluR2/3 immunoreactivity was observed in the fiber bundles of the striatum of PND 1 rats but not in rats of other ages. A large proportion of mGluR2/3 but not mGluR1α immunoreactivities were found to be colocalized with synaptic vesicle protein two immunoreactive glutamatergic terminals. The present results demonstrate that mGluR2/3 is primarily expressed in glutamatergic axonal terminals in the striatum, but mGluR1α is expressed in postsynaptic elements in the striatum. There is a differential expression of mGluR1α and mGluR2/3 in rat striatum during postnatal developmental stages.
Effect of the Cysteinyl Leukotriene Antagonist Pranlukast on Transendothelial Migration of Eosinophils
Authors: Nagata Makoto , Saito Keiko , Kikuchi Izumi , Hagiwara Koichi , Kanazawa Minoru
Published: June 2005

Background:Evidence shows that leukotriene receptor antagonist (LTRA) can cause a partial reduction of eosinophils in the asthmatic airway. Although cysteinyl leukotrienes (CysLTs) can regulate the development of eosinophilic inflammation, LTRA might modulate the eosinophilic response to other inflammatory molecules involved in allergic inflammation. Montelukast is an LTRA that inhibits eosinophil transendothelial migration (TEM) in response to platelet-activating factor (PAF). The present study evaluates whether pranlukast (an LTRA) modifies eosinophil TEM in response to chemoattractants including PAF and C-C chemokines. Methods: Eosinophils isolated from the blood of healthy individuals were incubated with or without pranlukast. We then evaluated eosinophil transmigration across human umbilical vein endothelial cells in response to LTD4, eotaxin, RANTES and PAF. Results: Pranlukast did not modify the spontaneous transmigration of eosinophils (n = 5). As reported, eosinophil TEM was significantly augmented by 0.1 µM LTD4 and this enhancement was blocked by 1 µM pranlukast (p < 0.001; n = 6). On the other hand, pranlukast did not modify eosinophil transmigration in response to eotaxin, RANTES, or PAF (p > 0.1; n = 5). Conclusion: The inhibitory effect of pranlukast on eosinophil transmigration is highly specific for the CysLT1-dependent pathway.
Role of GATA-3 in IL-5 Gene Transcription by CD4+ T Cells of Asthmatic Patients
Authors: Kaminuma Osamu , Mori Akio , Kitamura Noriko , Hashimoto Tomomi , Kitamura Fujiko , Inokuma Shigeko , Miyatake Shoichiro
Published: June 2005

Background: Helper T cells and T cell cytokines play central roles in allergic disorders including bronchial asthma. We reported enhanced IL-5 production by peripheral blood T cells of asthmatic patients. A transcription factor, GATA-3, has been implicated in IL-5 gene expression. This study was undertaken to clarify the role of GATA-3 in the upregulation of IL-5 synthesis in asthmatic patients. Method: Peripheral CD4+ T cells were transfected with an IL-5 promoter reporter construct as well as its mutants in the presence or absence of a GATA-3 expression vector. Messenger RNA expression level of GATA-3 in CD4+ T cells of asthmatic subjects was compared to that of healthy donors. Results: IL-5 promoter activity in CD4+ T cells was enhanced by overexpression of GATA-3, whereas it was diminished by the introduction of mutations in the putative GATA-3 binding sites. The GATA-3 expression level in CD4+ T cells of asthmatic patients was equivalent to that of healthy controls. Conclusion: The expression level of GATA-3 may not be an essential factor to cause IL-5 hyperproduction in bronchial asthma, though GATA-3 is crucially involved in IL-5 gene transcription in human peripheral CD4+ T cells.
Mechanism of the Eosinophilic Differentiation of HL-60 Clone 15 Cells Induced by n-Butyrate
Authors: Ishihara Kenji , Hong JangJa , Zee OkPyo , Ohuchi Kazuo
Published: June 2005

n-Butyrate is one of the most powerful chemical inducers of the differentiation of human eosinophilic leukemia HL-60 clone 15 cells into mature eosinophils. We have recently reported that the mechanism by which HL-60 clone 15 cells differentiate into eosinophils by n-butyrate is that n-butyrate continuously inhibits histone deacetylase activity as a histone deacetylase inhibitor, resulting in continuous acetylation of histones. In this review, we discuss roles of histone acetyltransferase, histone deacetylase and histone deacetylase inhibitors in the differentiation of HL-60 clone 15 cells into eosinophils.
Pathogenesis and Prevention of Pontosubicular Necrosis
Authors: Takashima Sachio , Ichinohe Akiko , Itoh Masayuki
Published: June 2005

Perinatal pontosubicular neuron necrosis (PSN) has similar characteristics to apoptosis, such as karyorrhexis, cellular atrophy and little glial reaction. In PSN pathogenesis, the developmental discrepancy between neurons exhibiting late maturation and vessels showing an early increase in the basis pontis and subiculum may predispose fetuses and neonates to PSN. Ischemia, hyperoxygenemia, hypocarbia and hypoglycemia have been reported to be causal factors. Apoptotic neurons are associated with activation of caspase-3, and remaining neurons are accompanied by growth factors in glial cells. Nestin, which is abundant in multipotential stem cells, is reactivated in cells surrounding the subacute and chronic lesions. Thus, local plasticity may be activated both in necrotic and apoptotic cell death, and the period of regeneration is important for the treatment of PSN.
Ghrelin Plasma Levels during Psychopharmacological Treatment
Authors: Himmerich Hubertus , Fulda Stephany , Künzel Heike E. , Pfennig Andrea , Dzaja Andrea , Cummings David E. , Pollmächer Thomas
Published: June 2005

The mechanisms underlying weight gain induced by psychopharmacological agents are poorly understood. Because the recently discovered enteric hormone, ghrelin, stimulates food intake, we hypothesized that increases in circulating ghrelin levels might mediate the weight gain caused by certain antidepressants and atypical antipsychotic drugs. Fifty-two patients receiving psychopharmacological treatments were included in the study: 16 patients received antidepressants that are not known to induce weight gain, and 13 patients received mirtazapine or trimipramine, which are antidepressants known to lead to weight gain; 6 patients received clozapine and olanzapine, which have the highest liability among the antipsychotics to cause weight gain, and 17 patients received other antipsychotics. Fasting venous blood samples for the measurement of ghrelin were drawn in the morning between 06:00 and 08:00 a.m. in the second week of treatment. Although psychopharmacological treatment induced significant weight changes in the expected directions (most prominent in the clozapine or olanzapine treatment group), ghrelin levels did not differ significantly between groups. Psychotropic drugs with different propensities to induce body weight gain are associated with similar concentrations of plasma ghrelin in psychiatric patients after a short period of treatment.
On the Waveform of the Acoustic Startle Blink in the Paradigm of Prepulse Inhibition – Methodological and Physiological Aspects
Authors: Meincke Ulrich , Light Gregory A. , Geyer Mark A. , Braff David L.
Published: June 2005

Recent studies suggest that the eye blink response to intense acoustic stimuli consists of two components that may occasionally result in waveforms with two peaks. In the present study, the prevalence, peak latencies, and peak magnitudes in responses exhibiting one or two peaks were investigated in healthy subjects in 25 pulse-alone and 25 prepulse-pulse trials using an interstimulus interval of 60 ms. Electromyographic activity was recorded simultaneously from the orbicularis oculi muscle (OOM) and from the sternocleidomastoid muscle (SCM) to explore the temporal relationship of the peaks to the generalized startle reaction. Responses in the OOM occurred with shorter onset and peak latencies than the responses in the SCM. In about 30% of pulse-alone trials, OOM responses exhibited two peaks that showed similar prepulse inhibition. These findings support the view that both components of the acoustically evoked OOM response exhibit similar plasticity in the paradigm of prepulse inhibition.
Anhedonia and Substance-Related Symptoms in Detoxified Substance-Dependent Subjects: A Correlation Study
Authors: Janiri L. , Martinotti G. , Dario T. , Reina D. , Paparello F. , Pozzi G. , Addolorato G. , Di Giannantonio M. , De Risio S.
Published: June 2005

Anhedonia is a condition in which the capacity of experiencing pleasure is totally or partially lost, frequently occurring in mood disorders, as a negative symptom in schizophrenia, and in substance use disorders. In order to test a set of instruments for anhedonia in a population of detoxified opiate, alcohol and multiple substance-dependent subjects, 70 individuals were recruited from three different clinical settings. The following scales were applied: Snaith-Hamilton Pleasure Scale (SHAPS), Bech-Rafaelsen Melancholia Scale (BRMS), Scale for the Assessment of Negative Symptoms (SANS), specific withdrawal scales, and visual analogue scales (VAS) for hedonic capability and substance craving. The scales measuring anhedonia either directly (SHAPS, VAS for hedonic capability) or in some key items (SANS, BRMS) were significantly correlated with each other. The period of time since detoxification was inversely correlated with anhedonia and withdrawal symptomatology. Craving was positively correlated with anhedonia. Out of the total sample, only 18.5% could be defined as psychometrically anhedonic. The same correlations were found in this subsample. The composite instrument employed for assessing anhedonia and hedonic capability was found to be sensitive enough to detect such a dimension in the population considered, with the single scales significantly interrelated. In conclusion, we found interrelations between hedonic capability, craving and protracted withdrawal, particularly in opiate-dependent subjects. The strongest association occurred between hedonic capability and craving.
Cardiopulmonary Effects of Chronic Administration of the NO Synthase Inhibitor L-NAME in the Chick Embryo
Authors: Villamor Eduardo , Kessels Carolina G.A. , van Suylen Robert J. , De Mey Jo G.R. , Blanco Carlos E.
Published: June 2005

Background: Experimental observations in mammalian models suggest that endothelial nitric oxide (NO) synthase (NOS) content and activity are decreased in persistent pulmonary hypertension of the newborn. Objectives: To test the hypothesis that disruption of NO signaling in the developing chick embryo lung may contribute to pulmonary hypertension. Methods: We analyzed pulmonary arterial reactivity and structure and heart morphology of 19-day chick embryos (incubation time 21 days) that received a daily injection of the NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 20 µg per gram egg) or vehicle from day 12 until day 18. Results: Exposure to L-NAME did not affect embryonic survival or body mass of the embryos. The contractile responses to KCl, endothelin-1, the thromboxane A2 mimetic U46619, noradrenaline, and electrical-field stimulation were not affected by exposure to L-NAME. In contrast, in ovo L-NAME exposure reduced the sensitivity of pulmonary arteries to acetylcholine (pD2: 6.53 ± 0.14 vs. 6.96 ± 0.13; p < 0.05) and this effect was reversed by the NOS substrate L-arginine. Relaxations induced by sodium nitroprusside or forskolin were not altered by chronic L-NAME. Pulmonary vessel density was not different, but the percentage medial wall area of small pulmonary arteries (external diameter 10–50 µm) was slightly but significantly increased in the embryos exposed to L-NAME. In addition, hearts of L-NAME-exposed embryos showed an increase in right and left ventricular wall area. Conclusions: Chronic inhibition of NOS produced, in the chick embryo, impairment of endothelium-dependent relaxation, structural remodeling of the pulmonary vascular bed and biventricular cardiac enlargement.
Preliminary Evidence for Ethnic Differences in Primary Hyperoxaluria Type 1 Genotype
Authors: Coulter-Mackie Marion B.
Published: June 2005

Background: Primary hyperoxaluria type 1 (PH1) is caused by a deficiency of peroxisomal alanine:glyoxylate aminotransferase (AGT). In about one third of patients, enzymatically active AGT is synthesized but is mistargeted to mitochondria. There are more than 50 mutations identified in the gene for AGT. Four mutations, G170R, 33_34insC, F152I and I244T account for more than 50% of PH1 alleles. The question arose whether there are ethnic differences in PH1 genotype. Methods: The published data on mutations in the AGT gene were examined with respect to recurrences and geographic or ethnic association. The mutations that have been found in at least 2 unrelated individuals were considered. Results: Two common mutations, G170R and 33_34insC showed no obvious ethnic associations and have been found in a variety of populations. A third common PH1 mutation, I244T, has a strong association with people from a Spanish or North African background. A particularly high frequency among Canary Islands PH1 patients suggests a probable founder effect. Between these two extremes are a number of mutations that recur at low frequency within certain ethnic groups. Conclusions: Ethnic associations of PH1 genotypes span a spectrum ranging from limited recurrences confined to a population group, to a probable founder effect.
Primary Hyperoxaluria – The German Experience
Authors: Hoppe Bernd , Latta Kay , von Schnakenburg Christian , Kemper Markus J.
Published: June 2005

Background: Primary hyperoxaluria (PH) is a heterogeneous disease with variable age of onset and inconsistent progression into renal failure (ESRF). Aims: In 1994 we initiated a survey within our Pediatric Nephrology working group to ascertain epidemiologic data and current practices. Updates were performed in 2000 and 2004. Results: Diagnosis of PH was made in 65 patients (42 with PH type I, 3 with PH type II, 12 unclassified and 8 reported dead), which suggests a minimum prevalence of 0.7 per 1 million of the population. First symptoms were urolithiasis, nephrocalcinosis, urinary tract infection or hematuria. Diagnosis was often delayed and was made only in ESRF in 11% of patients. Measurement of urine metabolites or plasma oxalate in ESRF was performed in 76 and 57%, respectively. Determination of enzyme activity in liver biopsy (55% overall) and mutation analysis have increasingly been performed since 2000 (84.2 and 51%). Treatment included high fluid intake, pyridoxine, citrate and magnesium preparations. Pyridoxine response was reported in 21% of patients. No genotype/phenotype correlation was seen. Most patients (39) do not require renal replacement therapy, 5 patients receive chronic hemodialysis. Preemptive liver (n = 5) and combined liver-kidney transplantation (n = 9) were the preferred transplantation procedures. Conclusion: Despite increasing knowledge and awareness, diagnosis of PH is still too often delayed and diagnosis only made in ESRF. Most German patients, however, do currently not require renal replacement therapy. Genotype/phenotype correlations were not found. Combined liver kidney transplantation is the preferred procedure, but has its specific risks. Additional treatment options are clearly needed.
Left Ventricular Hypertrophy Is More Prevalent in Blacks Than Whites in the General Population
Authors: Drazner Mark H. , Dries Daniel L. , Peshock Ronald M. , Cooper Richard S. , Klassen Chris , Kazi Farhana , Willett DuWayne , Victor Ronald G.
Published: June 2005

Although recent studies have suggested that blacks compared with whites have an increased prevalence of left ventricular hypertrophy, it remains uncertain whether this is true despite adjustment for body composition (fat mass and fat-free mass) and when assessed by cardiac MRI in the general population. The Dallas Heart Study is a population-based study of Dallas County in which 1335 black and 858 white participants 30 to 67 years of age underwent detailed assessment including dual-energy x-ray absorptiometry scan to measure body composition and cardiac MRI. Left ventricular hypertrophy, whether defined by indexation to body surface area (
P
<0.001), fat-free mass (
P
=0.002), or height
2.7
(
P
<0.001) was 2- to 3-fold more common in black versus white women. Similar results were seen when comparing black and white men (
P
<0.001 when left ventricular hypertrophy was indexed to body surface area or height
2.7
and
P
=0.05 when indexed to fat-free mass). Ethnic disparities in left ventricular mass persisted in multivariable models despite adjustment for fat mass, fat-free mass, systolic blood pressure, age, gender, and measures of socioeconomic status. We conclude that blacks compared with whites have increased left ventricular mass and a 2- to 3-fold higher prevalence of left ventricular hypertrophy in the general population, as assessed by cardiac MRI. The ethnic differences in left ventricular mass are independent of differences in body composition.
Superiority of Ambulatory Over Clinic Blood Pressure Measurement in Predicting Mortality
Authors: Dolan Eamon , Stanton Alice , Thijs Lut , Hinedi Kareem , Atkins Neil , McClory Sean , Hond Elly Den , McCormack Patricia , Staessen Jan A. , O’Brien Eoin
Published: June 2005

The purpose of this study was to determine if ambulatory blood pressure measurement predicted total and cardiovascular mortality over and beyond clinic blood pressure measurement and other cardiovascular risk factors; 5292 untreated hypertensive patients referred to a single blood pressure clinic who had clinic and ambulatory blood pressure measurement at baseline were followed up in a prospective study of mortality outcome. Multiple Cox regression was used to model time to total and cause-specific mortality for ambulatory blood pressure measurement while adjusting for clinic blood pressure measurement and other risk factors at baseline. There were 646 deaths (of which 389 were cardiovascular) during a median follow-up period of 8.4 years. With adjustment for gender, age, risk indices, and clinic blood pressure, higher mean values of ambulatory blood pressure were independent predictors for cardiovascular mortality. The relative hazard ratio for each 10-mm Hg increase in systolic blood pressure was 1.12 (1.06 to 1.18;
P
<0.001) for daytime and 1.21 (1.15 to 1.27;
P
<0.001) for nighttime systolic blood pressure. The hazard ratios for each 5-mm Hg increase in diastolic blood pressure were 1.02 (0.99 to 1.07;
P
=NS) for daytime and 1.09 (1.04 to 1.13;
P
<0.01) for nighttime diastolic pressures. The hazard ratios for nighttime ambulatory blood pressure remained significant after adjustment for daytime ambulatory blood pressure. These results have 2 important clinical messages: ambulatory measurement of blood pressure is superior to clinic measurement in predicting cardiovascular mortality, and nighttime blood pressure is the most potent predictor of outcome.
Effect of Compensated Renal Dysfunction on Approved Heart Failure Markers
Authors: Luchner Andreas , Hengstenberg Christian , Löwel Hannelore , Riegger Günter A.J. , Schunkert Heribert , Holmer Stephan
Published: June 2005

Brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) are markers of heart failure. Although renal dysfunction may increase plasma concentrations, the magnitude of this effect has not been assessed in a head-to-head comparison between the clinically approved tests. We assessed the effect of compensated renal dysfunction on BNP (Triage BNP; Biosite) and NT-proBNP (elecsys proBNP; Roche) in 469 randomly selected stable outpatients after myocardial infarction (MI; Monitoring Trends and Determinants in Cardiovascular Diseases [MONICA] register Augsburg) who were characterized with respect to renal function (glomerular filtration rate [GFR]; Cockroft method) and left ventricular (LV) ejection fraction (EF) and mass (2D echocardiography). BNP and NT-proBNP were elevated in MI patients with LV dysfunction (LVD; EF <35%) compared with MI patients with preserved EF (>45%; BNP 139±27 pg/mL versus 75±6; NT-proBNP 816±237 pg/mL versus 243±20; both
P
<0.03). Among all MI patients, the prevalence of renal dysfunction (GFR <85 mL/min) was 24%. BNP and NT-proBNP were significantly elevated in MI patients with renal dysfunction (BNP 132±17 pg/mL versus 68±4 without renal dysfunction; NT-proBNP 535±80 pg/mL versus 232±19; both
P
<0.05), and both markers were correlated with GFR in univariate and multivariate analyses (all
P
<0.01). When binary cut-off values were stratified according to the absence or presence of renal dysfunction (BNP 75 pg/mL and 125 pg/mL, respectively; NT-proBNP 100 pg/mL and 350pg/mL, respectively), the predictive power of both markers for the detection of LVD increased substantially. BNP and NT-proBNP are almost similarly influenced by mild-to-moderate renal dysfunction. Renal dysfunction is a potential cause of elevated marker concentrations in the absence of LVD, and cut-off concentrations should be stratified according to renal function.
Safety and Efficacy of Mechanical Embolectomy in Acute Ischemic Stroke
Authors: Smith Wade S. , Sung Gene , Starkman Sidney , Saver Jeffrey L. , Kidwell Chelsea S. , Gobin Y.Pierre , Lutsep Helmi L. , Nesbit Gary M. , Grobelny Thomas , Rymer Marilyn M. , Silverman Isaac E. , Higashida Randall T. , Budzik Ronald F. , Marks Michael P.
Published: June 2005

Background and Purpose—

The only Food and Drug Administration (FDA)-approved treatment for acute ischemic stroke is tissue plasminogen activator (tPA) given intravenously within 3 hours of symptom onset. An alternative strategy for opening intracranial vessels during stroke is mechanical embolectomy, especially for patients ineligible for intravenous tPA.

Methods—

We investigated the safety and efficacy of a novel embolectomy device (Merci Retriever) to open occluded intracranial large vessels within 8 hours of the onset of stroke symptoms in a prospective, nonrandomized, multicenter trial. All patients were ineligible for intravenous tPA. Primary outcomes were recanalization and safety, and secondary outcomes were neurological outcome at 90 days in recanalized versus nonrecanalized patients.

Results—

Recanalization was achieved in 46% (69/151) of patients on intention to treat analysis, and in 48% (68/141) of patients in whom the device was deployed. This rate is significantly higher than that expected using an historical control of 18% (
P
<0.0001). Clinically significant procedural complications occurred in 10 of 141 (7.1%) patients. Symptomatic intracranial hemorrhages was observed in 11 of 141 (7.8%) patients. Good neurological outcomes (modified Rankin score ≤2) were more frequent at 90 days in patients with successful recanalization compared with patients with unsuccessful recanalization (46% versus 10%; relative risk [RR], 4.4; 95% CI, 2.1 to 9.3;
P
<0.0001), and mortality was less (32% versus 54%; RR, 0.59; 95% CI, 0.39 to 0.89;
P
=0.01).

Conclusions—

A novel endovascular embolectomy device can significantly restore vascular patency during acute ischemic stroke within 8 hours of stroke symptom onset and provides an alternative intervention for patients who are otherwise ineligible for thrombolytics.
Association of Osteoprotegerin With Human Abdominal Aortic Aneurysm Progression
Authors: Moran Corey S. , McCann Moira , Karan Mirko , Norman Paul , Ketheesan Natkunam , Golledge Jonathan
Published: June 2005

Background—

Abdominal aortic aneurysm (AAA) is characterized by destruction of the arterial media associated with loss of vascular smooth muscle cells, infiltration of mononuclear cells, and high concentration of metalloproteinases (MMPs) and cytokines. Osteoprotegerin (OPG) has recently been identified in atherosclerosis. The presence and functional importance of OPG in human AAA was investigated.

Methods and Results—

In 146 men with small AAA followed up by ultrasound for 3 years, serum OPG was weakly correlated with aneurysm growth rate. Western analysis showed 3-, 8-, and 12-fold-greater OPG concentrations in human AAA biopsies compared with biopsies of atherosclerotic narrowed aorta (1.4±0.1 versus 0.5±0.1 ng/mg tissue;
P
=0.002), postmortem nondiseased abdominal aorta (1.4±0.1 versus 0.2±0.1 ng/mg tissue;
P
<0.001), and nondiseased thoracic aorta (1.4±0.1 versus 0.1±0.06 ng/mg tissue;
P
<0.001). Healthy human aortic vascular smooth muscle cells incubated with recombinant human (rh)OPG (0 to 20 ng rhOPG/10
5
cells per 1 mL per 24 hours) developed an aneurysmal phenotype defined by impaired cell proliferation (
P
<0.001), increased apoptosis (
P
<0.01), and increased MMP-9 (92 kDa) expression (
P
<0.001). Incubation of monocytic THP-1 cells with 1 ng rhOPG/10
5
cells per 1 mL per 24 hours induced a 2-fold increase in MMP-9 expression (
P
<0.001), a 1.5-fold increase in MMP-2 activity (
P
=0.005), and a 2-fold stimulation of IL-6 production in these cells (
P
=0.02). Finally, secretion of OPG from human AAA explant was abrogated by treatment with the angiotensin II blocker irbesartan, with the reduction in secreted levels averaging 63.0±0.9 ng/mg tissue per 48-hour period.

Conclusions—

These findings support a role for OPG in the growth of human AAA and suggest a potential benefit for angiotensin II blockade in slowing aneurysm expansion.
Long-Term Response to Calcium Channel Blockers in Idiopathic Pulmonary Arterial Hypertension
Authors: Sitbon Olivier , Humbert Marc , Jaïs Xavier , Ioos Vincent , Hamid Abdul M. , Provencher Steeve , Garcia Gilles , Parent Florence , Hervé Philippe , Simonneau Gérald
Published: June 2005

Background—

Characteristics of patients with idiopathic pulmonary arterial hypertension (IPAH) who benefit from long-term calcium channel blockers (CCB) are unknown.

Methods and Results—

Acute pulmonary vasodilator testing with epoprostenol or nitric oxide was performed in 557 IPAH patients. Acute responders, defined by a fall in both mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) >20%, received long-term oral CCB. Patients who benefit from long-term CCB were defined as those being in New York Heart Association (NYHA) functional class I or II after at least 1 year on CCB monotherapy. Among the 70 patients who displayed acute pulmonary vasoreactivity (12.6%; 95% CI, 9.8% to 15.3%) and received CCB therapy, only 38 showed long-term improvement (6.8%; 95% CI, 4.7% to 8.9%). Long-term CCB responders had less severe disease at baseline than patients who failed. During acute vasodilator testing, long-term CCB responders displayed a more pronounced fall in mean PAP (−39±11% versus −26±7%;
P
<0.0001), reaching an absolute value of mean PAP lower than that measured in patients who failed (33±8 versus 46±10 mm Hg;
P
<0.0001). After 7.0±4.1 years, all but 1 long-term CCB responders were alive in NYHA class I or II, with a sustained hemodynamic improvement. In the group of patients who failed on CCB, the 5-year survival rate was 48%.

Conclusions—

Long-term CCB responders represent <10% of IPAH patients evaluated in a pulmonary vascular referral center. During acute vasodilator testing, these patients showed significantly lower levels of both mean PAP and PVR, which reached near-normal values.
Long-Term Survival After Acute Myocardial Infarction Is Lower in More Deprived Neighborhoods
Authors: Tonne Cathryn , Schwartz Joel , Mittleman Murray , Melly Steve , Suh Helen , Goldberg Robert
Published: June 2005

Background—

As part of the Worcester Heart Attack Study, a community-wide study examining changes over time in the incidence and long-term case-fatality rates of greater Worcester, Mass, residents hospitalized with confirmed acute myocardial infarction (AMI), we investigated the hypothesis that census tract–level socioeconomic position is an important predictor of survival after hospital discharge for AMI, after adjusting for demographic and clinical characteristics.

Methods and Results—

Data were available for 3423 confirmed cases of AMI among metropolitan Worcester residents during the 4 study years of 1995, 1997, 1999, and 2001 who were followed up through the end of 2002. The mean age among patients was 69 years, and 58% were men. Using a multilevel Cox proportional hazards regression model, we estimated a 30% higher death rate after AMI for patients living in census tracts with the most residents living below the poverty line compared with patients living in the wealthiest census tracts (relative risk=1.30; 95% CI, 1.08 to 1.56). Similarly, patients living in census tracts with the highest proportion of residents with less than a high school education experienced a 47% higher death rate than patients living in census tracts with the lowest proportion of residents with less than a high school education (relative risk=1.47; 95% CI, 1.15 to 1.88).

Conclusions—

Within a medium-sized urban area, there are important variations in survival after hospital discharge for AMI that are associated with socioeconomic position. These associations persist after adjustment for demographic and clinical characteristics. Reasons for these differences warrant further investigation.
Apolipoprotein E Mimetic Peptide Dramatically Lowers Plasma Cholesterol and Restores Endothelial Function in Watanabe Heritable Hyperlipidemic Rabbits
Authors: Gupta Himanshu , White C. Roger , Handattu Shaila , Garber David W. , Datta Geeta , Chaddha Manjula , Dai Lijun , Gianturco Sandra H. , Bradley William A. , Anantharamaiah G.M.
Published: June 2005

Background—

These studies were designed to determine whether the dual-domain peptide with a class A amphipathic helix linked to the receptor-binding domain of apolipoprotein (apo) E (Ac-hE-18A-NH
2
) possesses both antidyslipidemic and antiinflammatory properties.

Methods and Results—

A single bolus (15 mg/kg IV) of Ac-hE-18A-NH
2
that contains LRKLRKRLLR (141- to 150-residue region of apo E) covalently linked to apo A-I mimetic peptide 18A not only reduced plasma cholesterol levels (baseline, 562±29.0 mg/dL versus 287.7±22.0 mg/dL at 18 hours,
P
<0.001) in the Watanabe heritable hyperlipidemic rabbit model but also significantly improved arterial endothelial function. This improvement was associated with a reduction in 2 markers of oxidative stress. First, the plasma lipid hydroperoxide content was reduced significantly, an effect associated with a 5-fold increase in HDL paraoxonase activity. Second, the formation of superoxide anion, a scavenger of nitric oxide, was also significantly reduced in arteries of these animals.

Conclusions—

Because dyslipidemia and endothelial dysfunction are common features of the atherosclerotic disease process, this unique dual-domain peptide has ideal composite properties that ameliorate key contributory factors to atherosclerosis.
D-4F Induces Heme Oxygenase-1 and Extracellular Superoxide Dismutase, Decreases Endothelial Cell Sloughing, and Improves Vascular Reactivity in Rat Model of Diabetes
Authors: Kruger Adam L. , Peterson Stephen , Turkseven Saadet , Kaminski Pawel M. , Zhang Frank Fan , Quan Shuo , Wolin Michael S. , Abraham Nader G.
Published: June 2005

Background—

Apolipoprotein A1 mimetic peptide, synthesized from D-amino acid (D-4F), enhances the ability of HDL to protect LDL against oxidation in atherosclerotic animals.

Methods and Results—

We investigated the mechanisms by which D-4F provides antioxidant effects in a diabetic model. Sprague-Dawley rats developed diabetes with administration of streptozotocin (STZ). We examined the effects of daily D-4F (100 μg/100 g of body weight, intraperitoneal injection) on superoxide (O
2
−
), extracellular superoxide dismutase (EC-SOD), vascular heme oxygenase (HO-1 and HO-2) levels, and circulating endothelial cells in diabetic rats. In response to D-4F, both the quantity and activity of HO-1 were increased. O
2
−
levels were elevated in diabetic rats (74.8±8×10
3
cpm/10 mg protein) compared with controls (38.1±8×10
3
cpm/10 mg protein;
P
<0.01). D-4F decreased O
2
−
levels to 13.23±1×10
3
(
P
<0.05 compared with untreated diabetics). The average number of circulating endothelial cells was higher in diabetics (50±6 cells/mL) than in controls (5±1 cells/mL) and was significantly decreased in diabetics treated with D-4F (20±3 cells/mL;
P
<0.005). D-4F also decreased endothelial cell fragmentation in diabetic rats. The impaired relaxation typical of blood vessels in diabetic rats was prevented by administration of D-4F (85.0±2.0% relaxation). Western blot analysis showed decreased EC-SOD in the diabetic rats, whereas D-4F restored the EC-SOD level.

Conclusions—

We conclude that an increase in circulating endothelial cell sloughing, superoxide anion, and vasoconstriction in diabetic rats can be prevented by administration of D-4F, which is associated with an increase in 2 antioxidant proteins, HO-1 and EC-SOD.
Elastic-Vessel Arteritis in Interleukin-1 Receptor Antagonist–Deficient Mice Involves Effector Th1 Cells and Requires Interleukin-1 Receptor
Authors: Shepherd Joanna , Nicklin Martin J.H.
Published: June 2005

Background—

In mice that lack interleukin-1 receptor antagonist (IL-1ra), transmural inflammation of the elastic arteries develops at sites of turbulent flow. We described late histopathology previously. Here, we investigate the cellular events in nonlethal arteritis at the aortic root and compare them with Takayasu’s arteritis and giant cell arteritis.

Methods and Results—

IL-1ra–deficient mice were inbred from the original stocks and from BALB/c backcrosses. Disease was ascertained histologically and immunohistologically postmortem at the aortic root. Onset appeared to be stochastic and was not detectably age dependent; in our local Sf3 strain, the half-time of onset was ≈52 days. Loss of the type I IL-1 receptor suppressed the arteritis. Microvascular activation, as determined by absence of strong E-selectin expression, was absent from preaffected vessels. In mildly affected cases, infiltration was adventitial. In severely affected animals, infiltrates appeared to be active in destroying elastin, but resynthesis of disorganized elastin occurred at closely adjacent sites. Infiltrates consisted predominantly of macrophages but were rich in CD4
+
–interferon-γ
+
cells, which are likely to represent Th1 cells. Dendritic cells accumulated in lesional areas.

Conclusions—

The arteritic phenotype of IL-1ra deficiency is mediated by the interleukin-1 receptor and involves effector Th1 cells. The destructive pattern and many of the cellular features of arteritis in IL-1ra–deficient mice resemble the human elastic-vessel arteritides, for which these mice may be a useful animal model.
Maslaha in Contemporary Islamic Legal Theory
Authors: Opwis Felicitas
Published: June 2005

This article investigates the concept of maslaha in contemporary Islamic legal theory. After presenting models of maslaha developed by al-Ghazālī, Fakhr al-Dīn al-Rāzī, al-Qarāfī, al-Tūfī, and al-Shātibī, I analyze writings on maslaha by leading jurists from the late 13th/19th century to the 1380s/1960s, namely al-Qāsimī, Rashīd Ridā, Mahmasānī, 'Allāl al-Fāsī, Khallāf, and al-Būtī. The findings show that the early reformers tended towards al-Tūfī's expansive understanding of the principle of maslaha in the law-finding process. Later jurisprudents, in contrast, either advocated a holistic approach similar to that of al-Shātibī or espoused a more restrictive use of maslaha like that of al-Ghazālī and al-Rāzī. The way in which jurists employ the principle of maslaha is not random but rather is influenced by education, personal position, and historical environment.
The Minor Compendium of Ibn 'Abd al-Hakam (d. 214/829) and its reception in the early Mālikī school
Authors: Brockopp Jonathan
Published: June 2005

Ibn 'Abd al-Hakam's Minor Compendium may be the earliest known handbook of Islamic law. Remarkably compact and comprehensive, it challenges depictions of the pre-classical period as a time of unsystematic legal scholarship, consisting of only "organic" texts and student notebooks. In this article, I argue for an early date for this text, based on analysis of the manuscript witnesses. I then compare the Minor Compendium with several contemporary texts to highlight its unique characteristics; in the process I discover, and seek to explain, several discrepancies in the descriptions of this text that are found in the biographical dictionaries. In my reading, the Minor Compendium is part of a nascent Mālikī tradition and demonstrates a close affinity to Mālik's Muwatta'. Yet it is also a highly creative and independent work, and its method of making legal arguments is quite different than that found in the Muwatta' and other early legal texts.