bluuebunny/crossref_metadata_2025 huggingface dataset:
Leptin and TNF-Alpha Levels in Patients with Chronic Obstructive Pulmonary Disease and Their Relationship to Nutritional Parameters
Authors: Çalıkoglu Mukadder , Şahin Gulsah , Unlu Ali , Ozturk Candan , Tamer Lülüfer , Ercan Bahadir , Kanik Arzu , Atik Uğur
Published: February 2004

Background: Leptin is a protein mainly secreted by adipocytes, and the major function of leptin was its role in body weight regulation. In humans, there was a strong correlation between leptin and nutritional parameters, such as body mass index (BMI) and fat mass (FM). Administration of recombinant leptin to ob/ob mice, which have a genetic defect in leptin production, reduces food intake, increases energy expenditure, and decreases body weight. It is suggested that increased levels of circulating leptin levels may contribute to anorexia and weight loss in pathologic conditions including chronic obstructive pulmonary disease (COPD). Recent studies have provided evidence for a link between leptin and proinflammatory cytokines such as TNF-α. Objective: This study aimed to detect serum leptin and TNF-α levels in COPD patients without weight loss during stable disease and acute exacerbation, and to investigate relationships between leptin, TNF-α and nutritional parameters at different stages of the disease. Material and Methods: 26 stable COPD patients, 16 COPD patients with acute exacerbation and 15 control subjects participated in this study. To eliminate the effects of sex differences, all patients and controls were male. BMI, percent ideal body weight, percent FM, sum of skinfold tickness and serum leptin and TNF-α levels were measured in all participants. Leptin and TNF-α levels were measured by ELISA. Results: Serum leptin and TNF-α levels were significantly higher in the patients experiencing exacerbation than in the stable patients and controls. Although leptin levels were lower and TNF-α levels were higher in the stable patient group than in the controls, these differences were not statistically different. Leptin levels were significantly correlated with the nutritional parameters in both control and stable groups. However, in patients with acute exacerbation, a correlation between leptin and nutritional parameters was not found. There was no significant relationship between TNF-α and nutritional parameters in the three groups. In addition, while there was no correlation between leptin and TNF-α levels in the stable and control groups, a significant positive correlation was observed in patients with exacerbation. Conclusion: In conclusion (1) elevated TNF-α levels may be related to increased inflammation in patients, (2) circulating TNF-α levels were associated with increased leptin levels and (3) although leptin and nutritional parameters were correlated in the stable COPD patients, the correlation was weaker compared to controls, and during an exacerbation it disappeared completely. Therefore, inappropriately increased levels of leptin and TNF-α noted during recurrent acute exacerbations in patients with COPD may lead to changes in nutritional parameters and body weight in the course of the disease.
Lung Function and Methacholine Responsiveness among Adolescents in an Air-Polluted Area
Authors: Longhini Erminio , Fanari Paolo , Giacomotti Emanuela , Palmulli Patrizia , Gabrione Marina , Gori Daniela , Barlera Simona , Tognoni Gianni , Salvadori Alberto
Published: February 2004

Background: Outdoor air pollution is hazardous to human pulmonary health. Airway inflammation is an important cause of bronchial hyperresponsiveness. Information is not univocal about the potential effects of prolonged exposure to environmental air pollutants on lung function. Objectives: A cross-sectional study was performed to assess bronchial responsiveness to methacholine in children living in an air-polluted area. Afterwards, the same study protocol was repeated in children of similar age living in mountain valleys with virtually no air pollution. Methods: Every child underwent a lung function test, skin tests to common allergens, total serum levels of IgE, and a challenge to methacholine at increasing doses (PD20 FEV1). Subjects were 246 children 11–12 years old living in an air-polluted area, and 285 children 11–13 years old living in mountain valleys. Respectively, 156 and 161 were negative to skin tests and had serum total IgE <100 IU/ml, and had no asthma or other recurrent or ongoing respiratory symptoms. Results: Lung function data, adjusted for the effect of potential confounders showed significantly lower FVC, and even more so FEV1, in the children from the polluted area. After the exclusion of subjects with positive skin tests and serum total IgE >100 IU/ml and those with history of asthma or respiratory disorders, there were higher percentages of positive responses in the challenge to methacholine in children from the polluted area (28.9 vs. 15.5%, p < 0.001). Conclusions: These data may corroborate the possible importance of long exposure to air pollutants on the prevalence of bronchial aspecific hyperresponsiveness in otherwise normal children.
Effects of Respiratory Therapist-Directed Protocol on Prescription and Outcomes of Pulmonary Rehabilitation in COPD Inpatients
Authors: Tramacere Antonio , Rizzardi Roberta , Cilione Carmela , Serri Barbara , Florini Fabio , Lorenzi Maria Cristina , Clini Enrico
Published: February 2004

Background: The use of respiratory therapist-directed (RD) protocols in non-ICU hospitalized patients decreases respiratory care charges as compared with physician-directed (PD) protocols. Objectives: To determine whether RD or PD protocol assessments in COPD patients may impact: (1) prescription of respiratory treatments, and (2) outcomes of pulmonary rehabilitation program (PRP). Methods: In a retrospective observational case-control study, 73 cases (RD) were compared with controls (PD) matched for age, sex, FEV1 and diagnosis of either chronic airflow obstruction (CAO), pulmonary emphysema (PE) or chronic respiratory insufficiency (CRI). PRP programs were specifically tailored and assessed for inpatients with moderate to severe COPD. Type of PRP protocol (P), number of respiratory treatments (RT), number of exercise training prescription (EXP) and failure (EXF), time to start PRP (T) and length of hospital stay (LOS) were recorded. Perceived breathlessness (B) as assessed by MRC scale, 6-min walk meters (6MWD), and BORG-dyspnea at rest (D-rest) and end of effort (D-effort) were also assessed as outcome measures before (T0) and after (T1) the PRP. Results: Frequency distribution of P, EXP and EXF was similar in the two groups. However, prescription of additional RT (1.9 ± 0.8 and 2.5 ± 1.1 days, p < 0.01), T (1.2 ± 0.4 and 1.8 ± 1.2 days, p < 0.001) and LOS (17.2 ± 2.0 and 18.2 ± 1.8 days, p < 0.05) were lower in cases than in controls. Both cases and controls similarly improved (p < 0.0001) B, 6MWD, D-rest and D-effort at T1. Conclusions: RT-directed assessment results in less respiratory treatments prescription than PD-directed protocol and it does not affect the outcomes of in-hospital pulmonary rehabilitation of COPD patients.
Gut Decontamination Prevents Bronchoscopy-Induced Bacterial Translocation
Authors: Nayci Ali , Atis Sibel , Ersoz Gulden , Polat Ayse
Published: February 2004

Background: Selective gut decontamination is suggested to suppress the gram-negative bacterial overgrowth in the intestine and consequently to reduce bacterial translocation. Objective: The purpose of the present study is to examine the effects of gut decontamination on bronchoscopy-induced bacterial translocation, and intestinal mucosal injury. Methods: Forty-five rats were assigned into three groups. Group 1 served as control (n = 15). Group 2 (n = 15) and group 3 (n = 15) underwent bronchoscopy. In addition, group 3 underwent gut decontamination. Gut decontamination was performed two days prior to bronchoscopy with erythromycin and neomycin. Twenty-four hours after bronchoscopy, blood, mesenteric lymph nodes, spleen, liver, ileum and cecum were harvested for bacterial determination. The ileum was also assessed and graded histologically according to Chiu’s injury scale. Results: In the bronchoscopy group, bacterial translocation to the mesenteric lymph nodes was found in 7/15 rats (46.7%), compared to none of the controls (p = 0.01). These rats also showed significant evidence of intestinal injury, compared to the controls (mean ranks, 32.7 or 8.5, p < 0.0001). On the other hand, gut decontamination prevented bacterial translocation, compared to the bronchoscopy group (p = 0.011). However, gut decontamination provided no beneficial effect on the intestinal mucosal injury, compared to the bronchoscopy group. These animals also revealed significant intestinal injury, compared to the controls (mean ranks, 27.8 or 8.5, p < 0.0001). Conclusions: Our data shows that despite no amelioration in bronchoscopy-induced intestinal mucosal injury, gut decontamination has a preventive role for bronchoscopy-induced bacterial translocation.
The Yield of Endobronchial Biopsy in Pulmonary Sarcoidosis: Connection between Spirometric Impairment and Lymphocyte Subpopulations in Bronchoalveolar Lavage Fluid
Authors: Kieszko Robert , Krawczyk Paweł , Michnar Marek , Chocholska Sylwia , Milanowski Janusz
Published: February 2004

Background: Sarcoidosis is a multi-organ granulomatous disorder of undetermined aetiology with 90% of patients exhibiting some degree of pulmonary involvement. Transbronchial biopsy and endobronchial biopsy (EBB) with a fiber-optic bronchoscope, which demonstrate giant or epithelial cells of granuloma formation, have been established as standard methods for histological confirmation of sarcoidosis. Objectives: The analysis of EBB and bronchoalveolar lavage (BAL) specimens was used to assess the frequency of positive EBB findings in patients with pulmonary sarcoidosis. The influence of spirometric abnormalities and BAL findings on EBB-based diagnosis was also evaluated. Methods: The examined group of patients comprised 60 subjects mean age 39.4 ± 9.65 years). The results of pulmonary function tests, EBB and BAL were analysed. Results: EBB was performed on 52 patients. Positive histological results were found in 40% of subjects; 12 of them were affected by spirometry impairment. All patients with restriction and almost half of the subjects with obstruction disorders had positive EBB findings. In the BAL fluid, the percentage of CD3+ and CD4+ cells was significantly lower and the percentage of CD19+ and CD8+ lymphocytes was significantly higher in patients with positive biopsies in comparison with the subjects with negative EBB findings. Conclusions: Positive biopsies are related to the intensity of abnormalities in the pulmonary function tests and BAL, and may reflect an advanced stage of sarcoidosis.
Interferon gamma-1b as Therapy for Idiopathic Pulmonary Fibrosis
Authors: Nathan Steven D. , Barnett Scott D. , Moran Brian , Helman Donald L. , Nicholson Karin , Ahmad Shahzad , Shorr Andrew F.
Published: February 2004

Background: The only proven therapeutic option for idiopathic pulmonary fibrosis (IPF) is lung transplantation. It is biologically plausible that interferon gamma-1b (G-IFN) may halt or even reverse the disease process and therefore prove to be an effective medical therapy. We report our results using this medication in a cohort of patients with a wide range of severity of IPF. Objectives: To determine the impact of G-IFN therapy on the progression of disease in patients with IPF. Methods: We performed a retrospective analysis of patients’ pulmonary function tests (PFTs), specifically the forced vital capacity (FVC) and the single breath diffusing capacity for carbon dioxide (DLCO). Comparisons of these parameters prior to and after the implementation of therapy were made by generating regression slopes by least-squares equations. Results: Twenty-two patients qualified for the analysis. For the FVC, comparison of pre- and post-therapy best-fit regression lines demonstrated a significant difference in favor of G-IFN (p < 0.015). For the DLCO, a significant difference in favor of gamma interferon therapy was detected in the advanced group (p < 0.03). Seventy percent of the patients showed either stabilization or regression of disease in both their FVCs and their DLCO. Conclusion: G-IFN appears to be an effective new therapy for patients with IPF. Salutary effects on the rate of change in the FVC and DLCO were most apparent in patients with advanced disease. With slowing or reversal in loss of lung function, G-IFN may improve longevity and may have utility as a bridge to lung transplantation in those patients who are appropriate candidates.
Use of Studded Polyflex™ Stents in Patients with Neoplastic Obstructions of the Central Airways
Authors: Bolliger Chris T. , Breitenbuecher Albrecht , Brutsche Martin , Heitz Markus , Stanzel Franz
Published: February 2004

Background: The Polyflex™ is a commercially available silastic airway stent with proven efficacy. Due to a smooth outer surface its anchorage in the airway wall is superficial which may lead to stent migration. Objective: To study the performance of an newer version of the Polyflex stent with a studded outer surface, which should improve anchorage. Methods: In a 5-centre international study the new stent was prospectively tested in symptomatic patients with neoplastic central airway stenosis of more that 50% of normal diameter. Insertion technique, efficacy of stent placement and stent-related complications were recorded before, 1 month and 3 months post stent placement. Results: Under general anaesthesia and rigid bronchoscopy 27 stents were inserted in 26 patients, mean age: 62 years (range: 37–83), 16 men. Diagnoses were 18 bronchogenic carcinoma, 4 oesophageal carcinoma, 2 metastases, 1 tracheal carcinoma, and 1 schwannoma. The stents were inserted in the following locations: 10 right main bronchus, 8 left main bronchus, 7 trachea, and 2 tracheo-bronchial. There was significant improvement in all functional parameters assessed from before (A), to 1 month (B) and 3 months (C) after stent placement. The measured values (mean ± SD) were for the WHO scale: A: 2.7 (0.8), B: 1.5 (0.9), C: 1.6 (1.0); for the Karnofsky scale: A: 44 (19), B: 72 (18), C: 71 (21); for the Dyspnoea Index: A: 3.3 (0.7), B: 1.5 (0.8), C: 1.9 (1.2); for FEV1: A: 1.2 (0.5), B: 1.9 (0.6), C: 1.5 (0.5), and for FVC: A: 2.1 (0.7), B: 2.8 (0.7), C: 2.5 (1.0). Stent-related complications were 4 reversible stent obstructions by secretions, 1 migration. The observation period was mean 4.3 months (range 2 days to 23 months). Conclusion: The studded Polyflex showed excellent efficacy, was very well tolerated, and had a very low migration rate. It presents an improvement over the older smooth model and can be considered a true alternative to the most widely used silastic stent, the Dumon stent.
Detection and Typing of Human Papillomavirus in Non-Small Cell Lung Cancer
Authors: Zafer Emre , Ergun Mehmet Ali , Alver Goknur , Sahin Feride I. , Yavuzer Sinasi , Ekmekci Abdullah
Published: February 2004

Background: Lung cancer is the most frequent cause of death in both men and women. Smoking is the greatest risk factor for lung cancer and the relation of human papillomavirus (HPV) infection with lung cancer has been reported. HPV can be detected in small cell lung cancer samples with the methods like in situ hybridization, polymerase chain reaction (PCR), Southern blotting, dot blotting. Objective: We aimed to detect and type HPV infection in non-small cell lung carcinoma tissue samples. Methods: Tumor samples from 40 patients were collected during surgery and PCR and restriction fragment length polymorphism (RFLP) were used in order to detect HPV infection in the samples. Results: Two HPV DNA were detected among 40 of the patients, revealing a low frequency of HPV in the samples. Conclusions: HPV can be regarded as an environmental factor in tumor development. There might be a relationship between HPV infection and some non-small cell lung cancers, especially in the smoking group.
A Case of Congenital Pulmonary Vein Stenosis in an Adult
Authors: Omasa Mitsugu , Hasegawa Seiki , Bando Toru , Okano Yoshiaki , Otani Hideo , Nakashima Yasuaki , Wada Hiromi
Published: February 2004

A 35-year-old Japanese woman, complaining of dyspnea after her first delivery, was diagnosed as having primary pulmonary hypertension. Continuous intravenous prostacyclin resulted in an improvement in her cardiac function, 6-min walk and New York Heart Association class, before she died of pulmonary hypertension crisis during further evaluation for pulmonary transplantation. Since the autopsy findings revealed that all 4 pulmonary veins were extremely stenotic due to hypoplasia, she was diagnosed as having had congenital pulmonary vein hypoplasia with stenosis.
An Unusual Case of Bronchiolitis obliterans Organizing Pneumonia Concomitant with Bronchioloalveolar Carcinoma
Authors: Song Jungsik , Gorgan Lucian , Corkey Richard , Kwa Sew-Leong C.
Published: February 2004

Although bronchiolitis obliterans organizing pneumonia (BOOP) has been associated with a variety of underlying disorders, the majority of cases of BOOP are idiopathic. We present the case of a 61-year-old patient with fever, dry cough, bilateral patchy consolidation and high erythrocyte sedimentation rate. Open lung biopsy shows coexistence of BOOP and bronchioloalveolar carcinoma. It is interesting that both diseases are predominantly air space diseases and present similar radiologic features making the diagnosis and follow-up of treatment more difficult.
Cystic Fibrosis Diagnosed in an Elderly Man
Authors: Gilljam Marita , Björck Eva
Published: February 2004

Although most patients with cystic fibrosis (CF) are diagnosed in early childhood, the diagnosis may be delayed for patients with mild symptoms or single-organ disease. We describe a man with known infertility and a history of productive cough diagnosed with CF at 61 years of age. The patient carries two mutations and one variant in the CF transmembrane conductance regulator gene: 394delTT, P99L and R75Q. During a 15-year follow-up time he has developed significant pulmonary disease.
Nuclear Hormone and Orphan Receptors: Their Role in Neuronal Differentiation and Cytoprotection and in the Pathogenesis of Parkinson’s Disease
Authors: Malaspina A. , Pearce R.K.B. , Graeber M.B.
Published: February 2004

Human nuclear hormone receptors (NHR) and orphan receptors (NOR) act as transcription factors in response to a wide range of circulating hormones and unknown ligands. A role for NHR and NOR in disorders of the subcortical dopaminergic pathways such as Parkinson’s disease (PD) is suggested by a wealth of recent data including experimental observations. Both classes of receptors promote the formation of specific neuronal identities, tissue patterning during embryonic development and the maturation of vulnerable monoaminergic and cholinergic neurons. NHR and NOR are also known to exert a neuroprotective function on adult neurons. The scope of this review is to revisit the functional profile of these receptors with particular reference to their activity in the development of selected neuronal populations relevant to the pathophysiology of PD and to discuss how they may relate to the neuropathological and clinical expression of the disease.
Ionotropic Glutamate Receptor Expression and Dopaminergic Modulation in the Developing Subthalamic Nucleus of the Rat: An Immunohistochemical and Electrophysiological Analysis
Authors: Lobo M.K. , Itri J.N. , Cepeda C. , Chavira C.A. , Levine M.S.
Published: February 2004

Using standard immunohistochemical procedures, we investigated the changes in the expression of ionotropic glutamate receptor (GluR) subunits, GluRl, GluR5/6/7, and NMDAR1, in the subthalamic nucleus of developing rats. The general sequence of development for each subunit was the same. At early postnatal ages, there was dense neuropil staining and cellular clustering which progressed to decreased neuropil staining and an even distribution of conspicuous cells in the later postnatal ages and in the adult. GluR5/6/7 displayed the earliest maturation, while GluR1 exhibited the slowest maturation. These morphological changes suggest a different time course for the functionality of GluR subtypes in the developing subthalamic nucleus. Correlative electrophysiological studies demonstrated functional GluRs as early as 16 days of age. All neurons tested displayed robust responses to kainate and N-methyl-D-aspartate, and these responses were modulated by dopamine.
Can Lateralizing Sensorimotor Deficits Be Identified after Neonatal Cerebral Hypoxia-Ischemia in Rats?
Authors: Grow Jennifer L. , Liu Yi Qing , Barks John D.E.
Published: February 2004

The neonatal rat model of unilateral cerebral hypoxia-ischemia (HI) is commonly used to test the efficacy of therapeutic strategies for prevention or treatment of stroke in the immature brain. Traditionally neuroprotection has been defined as reduction in tissue injury; there is growing interest in complementary functional assessment. Our objectives were to determine whether lateralizing performance deficits could be detected in two sensorimotor tests not previously used after neonatal HI, and to determine whether performance reflected the extent of tissue damage. Seven-day-old rats that underwent right carotid ligation followed by 1.5 h in 8% O2 and age-matched controls were tested for sensorimotor performance on postnatal day 35 (P35). We evaluated initial forepaw placement on the wall of a cylinder, and time taken to contact and remove adhesive stickers from the dorsum of each forepaw. Cortical, striatal and hippocampal damage severity was evaluated on P36 by calculating the contralateral-ipsilateral percent difference in regional areas. There was an inverse relationship between cortical and striatal damage severity and percent contralateral forepaw initiation in the cylinder. There was a direct linear relationship between damage severity and the delay from contact to removal of the contralateral sticker. These two tests revealed quantifiable contralateral sensorimotor deficits 4 weeks after unilateral neonatal cerebral HI in animals with cortical and striatal damage.
Expression of c-fos in the Brain after Activation of L-Type Calcium Channels
Authors: Jinnah H.A. , Egami Kiyoshi , Rao Lekha , Shin MeYeon , Kasim Suhail , Hess Ellen J.
Published: February 2004

In rodents, administration of the L-type calcium channel activators, ±Bay K 8644 and FPL 64176, causes an unusual neurobehavioral syndrome that includes dystonia and self-injurious biting. To determine the regional influence of these drugs in the brain, the induction of c-fos was mapped after administration of these drugs to mice. In situ hybridization with an antisense riboprobe directed to c-fos mRNA revealed widespread induction, with the highest levels in the striatum, cortex, hippocampus, locus coeruleus, and cerebellum. The induction of c-fos mRNA was dose dependent, reached maximal expression approximately 60 min after drug treatment, and could be blocked by pretreatment with the L-type calcium channel antagonist, nifedipine. Immunohistochemical stains with an antibody directed to c-fos protein revealed a pattern of induction similar to that obtained with in situ hybridization in most brain regions. These results demonstrate a very heterogeneous influence of L-type calcium channel activation in different brain regions, despite the nearly universal expression of these channels implied by more classical anatomical methods.
Perinatal Iron Deficiency Alters Apical Dendritic Growth in Hippocampal CA1 Pyramidal Neurons
Authors: Jorgenson Lyric A. , Wobken Jane D. , Georgieff Michael K.
Published: February 2004

Iron deficiency early in life is associated with cognitive disturbances that persist beyond the period of iron deficiency. Within cognitive processing circuitry, the hippocampus is particularly susceptible to insults during the perinatal period. During the hippocampal growth spurt, which is predominantly postnatal in rodents, iron transport proteins and their messenger RNA stabilizing proteins are upregulated, suggesting an increased demand for iron import during this developmental period. Rat pups deprived of iron during the perinatal period show a 30–40% decrease in hippocampal metabolic activity during postnatal hippocampal development. We hypothesized that this reduced hippocampal neuronal metabolism impedes developmental processes such as neurite outgrowth. The goals of the current study were to investigate the effects of perinatal iron deficiency on apical dendritic segment growth in the postnatal day (P) 15 hippocampus and to determine if structural abnormalities persist into adulthood (P65) following iron treatment. Qualitative and quantitative immunohistochemical analyses of dendritic structure and growth using microtubule-associated protein-2 as an index showed that iron-deficient P15 pups have truncated apical dendritic morphology in CA1 and a persistence of an immature apical dendritic pattern at P65. These results demonstrate that perinatal iron deficiency disrupts developmental processes in the hippocampal subarea CA1 and that these changes persist despite iron repletion. These structural abnormalities may contribute to the learning and memory deficits that occur during and following early iron deficiency.
Expression of Creatine Kinase Isoenzyme Genes during Postnatal Development of Rat Brain Cerebrum: Evidence for Posttranscriptional Regulation
Authors: Shen Wei , Willis Dianna , Zhang Yanping , Molloy George R.
Published: February 2004

Brain creatine kinase (CKB) has a central role in the regeneration of ATP in the brain. During postnatal development of rat brain cerebrum, the CKB protein level was very low at postnatal day 1 and week 1 but by week 4 had increased 6- to 7-fold and remained constant through week 10. Surprisingly, CKB mRNA levels were already maximal at postnatal day 1 and week 1, indicating that CKB protein expression does not simply reflect the levels of CKB mRNA and is likely regulated posttranscriptionally during early postnatal times. Interestingly, the majority of cytoplasmic CKB mRNA was found to be associated with polyribosomes both at postnatal day 3 and week 6. Therefore, low CKB protein levels at early postnatal times could either be due to (1) normal translation initiation of CKB mRNA followed by a subsequent arrest during elongation or termination and/or (2) normal translation of CKB mRNA followed by rapid degradation of CKB protein. However, CKB protein increased coincidently with ubiquitous mitochondrial CK protein, suggesting that a functional phosphocreatine energy shuttle is formed in the cerebrum during postnatal development. The apparent posttranscriptional regulation of CKB in early postnatal cerebrum contrasts with the transcriptional regulation controlling accumulation of CKB protein in postnatal developing cerebellum.
Glucocorticoid-Induced Apoptosis in CNS Microvascular Pericytes
Authors: Katychev Andre , Wang Xueqain , Duffy Alexandra , Dore-Duffy Paula
Published: February 2004

Pericyte loss or migration from its vascular location may be an important step in microvascular remodeling. Decreased pericyte to endothelial ratios are characteristics of newly formed vessels as well as microvessels undergoing regression, and may be due to selective degeneration via necrotic cell death or via programmed cell death. In this study, we have examined glucocorticoid-induced apoptosis in primary rat CNS pericytes. Characterization of apoptosis was determined using five independent criteria: (1) the translocation of receptors for annexin V from the inner to the outer surface of the plasma membrane, (2) the translocation of cytochrome C from the mitochondria to the cytosol, (3) the induction of DNA fragmentation, (4) the induction of classic changes in cell morphology, and (5) the appearance of TUNEL-positive cells. Incubation of CNS pericytes with dexamethasone induced the appearance of apoptotic cells in a time- and dose-dependent manner. Pericytes express immunologically detectable glucocorticoid receptors, and addition of the glucocorticoid receptor antagonist mifepristone inhibited dexamethasone-induced pericyte apoptosis. That pericytes undergo apoptosis in response to dexamethasone suggests that the regulatory function of this steroid may be important in vascular development and that pericyte apoptotic cell death may accompany vascular regression. Deregulation of pericyte involvement in vascular homeostasis and hemostasis may result in clinical disease.
Effect of Pulmonary Vein Isolation on Quality of Life in Patients with Paroxysmal Atrial Fibrillation
Authors: Nilsson Brian , Chen Xu , Svendsen Jesper Hastrup
Published: February 2004

Background: Recent studies have demonstrated that delivering radiofrequency energy to isolate the pulmonary veins (PVs) can cure patients with paroxysmal atrial fibrillation (PAF). Objective: To quantify the effects of radiofrequency catheter isolation of PVs on quality of life (QoL), symptom burden and non-scheduled visiting to physicians in patients with PAF. Methods: Thirty consecutive patients referred for radiofrequency ablation of PAF were included. Questionnaires were administered retrospectively, 6.3 months after the ablation procedure. QoL was measured by the SF-36 (a measure of general health status) and symptoms and health care utilization by a locally constructed questionnaire. Results: Before ablation, patients with PAF had significantly lower scores on all SF-36 subscales with the exception of the pain subscale, compared with a healthy control group. Apart from bodily pain all subscales significantly improved after PV isolation. Twenty patients had an improvement in their total health perception. PV isolation significantly reduced the frequency of episodes of atrial fibrillation (AF) and the proportion of nonscheduled contacts to physicians for AF. Conclusion: QoL in patients with PAF is significantly impaired. PV isolation improves the QoL and reduces the frequency and severity of symptoms and non-scheduled contacts to physicians.
Review of Cardiovascular Disease in Women: Awareness, Prevention, and Psychosocial Characteristics
Authors: Mobasseri Sara , Liebson Philip R. , Klein Lloyd W.
Published: February 2004

In the United States, cardiovascular disease remains the leading cause of death in postmenopausal women. Despite these alarming trends in the prevalence, the magnitude of the problem is still underappreciated. Women traditionally have been underrepresented in clinical trials with poor enrollment, and information for prevention and treatment of coronary heart disease (CHD) is extrapolated from populations of men. In addition to biologic risk factors for CHD, psychosocial risk factors have also been studied more in men than women. Both traditional coronary and psychosocial risk factors are reviewed as to how they uniquely affect women. A comprehensive approach, encompassing life-style changes, coping strategies and pharmacologic interventions for both prevention and treatment of CHD in women is emphasized.
Drug-Eluting Stents
Authors: Liistro Francesco , Bolognese Leonardo
Published: February 2004

Although coronary stenting improves angiographic and clinical outcome of patients with coronary stenosis compared to balloon angioplasty, in-stent restenosis (ISR) still represents a major limitation of this approach. In the last decades several attempts have been made to lower ISR occurrence but most of the strategies adopted failed to demonstrate any benefit. Recently, the concept of using stents coated with agents that could potentially inhibit restenosis has emerged and drug-eluting stents (DES) represent one of the fastest growing fields in interventional cardiology today. The article reviews the progress of the DES concept and the results of the major clinical trials evaluating the impact of DES on restenosis.
A New Class of Lipid-Lowering Drugs: Ezetimibe
Authors: Keller Ulrich
Published: February 2004

Ezetrol® (Ezetimibe) is the first substance of a new class of selective cholesterol absorption inhibitors; it was registered in Switzerland in 2002. Ezetimibe is glucuronidised and recirculated in the enterohepatic circulation. It acts exclusively in the intestinal lumen, but has no effect on the absorption of bile acids and liposoluble vitamins. When given as monotherapy, the standard dose of 10 mg/day lowers the serum LDL cholesterol by about 15–20%. Combined therapy with statins is particularly useful, because in this way the adaptive increase in cholesterol synthesis is prevented; with this combination, the LDL cholesterol level can be lowered by up to 58%. The effect of ezetimibe is also pronounced in combination with low doses of statins. In contrast to the bile acid binders, ezetimibe slightly lowers the triglycerides and slightly raises the HDL cholesterol level. Other combinations have not been investigated in detail; up till now, side effects and drug interactions have scarcely been observed. Ezetimibe is suitable for use in the treatment of primary hypercholesterolaemia, in which monotherapy with statins has an inadequate effect on the target LDL cholesterol values. This is the case especially with severe familial (genetic) hypercholesterolaemia and/or hypercholesterolaemia in which treatment with statins has led to side effects or intolerance. Long-term studies with ezetimibe, investigating the cardiovascular morbidity or other long-term effects, have not been carried out to date.
Polymorphisms in the Apolipoprotein(a) Gene, Plasma Lp(a) and Cardiovascular Risk
Authors: Beneš Petr
Published: February 2004

Increased plasma concentration of lipoprotein(a) [Lp(a)] represents an established risk factor for coronary artery disease (CAD). The plasma Lp(a) level is relatively stable during life and it is more than 90% genetically determined by the apolipoprotein(a) [apo(a)] gene. Numerous polymorphisms have been identified in the apo(a) gene. The extreme apo(a) protein size polymorphism, based on the variable number of so-called kringle IV type 2 repeats (KIV-2), accounts for a large portion of variability of plasma Lp(a) levels. Moreover, it has been shown that several other apo(a) sequence changes, both in the coding and regulatory sequences, influence plasma Lp(a) levels and/or Lp(a) prothrombogenic properties. Associations between some of them and the increased risk of CAD have also been reported. However, the existence of strong linkage disequilibria in the apo(a) locus represents a serious problem to identify a real effect of single polymorphism on Lp(a) phenotype. Large and complex association and family studies in different populations, together with in vitro expression and functional studies, should clarify the importance of so far identified positive apo(a) polymorphism-plasma Lp(a) associations in the future. In addition, standardization of measurement of Lp(a) is necessary to allow comparison of results obtained with different immunoassays.
Right Heart Catheterization: Indications, Technique, Safety, Measurements, and Alternatives
Authors: Kaluski Edo , Shah Monika , Kobrin Isaac , Vered Zvi , Cotter Gad
Published: February 2004

For over three decades, balloon-tipped right heart catheterization (RHCn) has been employed to assist in the diagnosis, assessment, and management of high-risk patients and interventions. There has been a considerable debate regarding the safety and efficacy of this clinical tool, and even moratorium has been suggested. Currently, even in the face of contemporary noninvasive methods to obtain hemodynamic data, RHCn is still utilized. However, quality randomized clinical trials, assessing the effects RHCn on outcome of well-defined patient’s subsets, are clearly lacking. The contemporary indications, technique, and safety issues are discussed. Accurate data acquisition and interpretation are emphasized. Finally, RHC data are compared with hemodynamic information obtained noninvasively by impedance cardiography (ICG), and echocardiograpy and Doppler analysis. Recently, modern pump-function descriptor (cardiac power) derived from cardiac output measurements have emerged. The important interplay between the systemic and pulmonary circulation became increasingly acknowledged. Although modern right heart catheters (RHCs) are able to provide comprehensive, continuous, real-time, and effort-free hemodynamic data, they did not replace the 30-year-old inexpensive RHCs. Regrettably, no noninvasive alternatives can provide all these features. Our educational goals should include more appropriate case selection, along with safer insertion and reliable data acquisition and interpretation. The industry should attempt to incorporate into the monitored intensive care bed, safer systems and devices that provide continuous, ‘hands-off’, low maintenance, comprehensive and accurate hemodynamic data. RHCn is still an excellent and most comprehensive clinical and research method for hemodynamic assessment and monitoring. It is likely to continue to play a pivotal role in modern intensive care as well as contemporary research. In clinical practice, case selection for RHCn should be based on the clinical questions and dilemmas the patient is presenting. In research, RHCn should be employed whenever noninvasive methods could not reliably obtain data that are required to answer the scientific question.
Mapping of 195 genes in cattle and updated comparative map with man, mouse, rat and pig
Authors: Hayes H. , Elduque C. , Gautier M. , Schibler L. , Cribiu E. , Eggen A.
Published: February 2004

Our on-going goal is to improve and update the comparative genome organization between cattle and man but also among the most detailed mammalian species genomes i.e. cattle, mouse, rat and pig. In this work, we localized 195 genes in cattle and checked all human/bovine non-concordant localizations found in the literature. Next, we compiled all the genes mapped in cattle, goat, sheep and pig (2,166) for which the human ortholog with its chromosomal position is known, added corresponding data in mouse and rat, and ordered the genes relatively to the human genome sequence. We estimate that our compilation provides bovine mapping information for about 89% of the human autosomes. Thus, a near complete, overall and detailed picture of the number, distribution and extent of bovine conserved syntenies (regardless of gene order) on human R-banded autosomes is proposed as well as a comparison with mouse, rat and pig genomes.
Development of a comprehensive comparative radiation hybrid map of bovine chromosome 7 (BTA7) versus human chromosomes 1 (HSA1), 5 (HSA5) and 19 (HSA19)
Authors: Gautier M. , Hayes H. , Bønsdorff T. , Eggen A.
Published: February 2004

In this study, we present a comprehensive 3,000-rad radiation hybrid (RH) map of bovine chromosome 7 (BTA7) with 108 markers including 54 genes or ESTs. For 52 of them, a human ortholog sequence was found either on HSA1 (one gene), HSA5 (31 genes) or HSA19 (19 genes and one non-annotated sequence) confirming previously described syntenies. Moreover, in order to refine boundaries of blocks of conserved synteny, nine new genes were mapped to the bovine genome on the basis of their localization on the human genome: six on BTA7 and originating from HSA1 (TRIM17), HSA5 (MAN2A1, LMNB1, SIAT8D and FLJ1159) and HSA19 (VAV1), and the three others (AP3B1, APC and CCNG1) on BTA10. The available draft of the human genome sequence allowed us to present a detailed picture of the distribution of conserved synteny segments between man and cattle. Finally, the INRA bovine BAC library was screened for most of the BTA7 markers considered in this study to provide anchors for the bovine physical map.
A comparative map of bovine chromosome 19 based on a combination of mapping on a bacterial artificial chromosome scaffold map, a whole genome radiation hybrid panel and the human draft sequence
Authors: Moore S.S. , Hansen C. , Williams J.L. , Fu A. , Meng Y. , Li C. , Zhang Y. , Urquhart B.S.D. , Marra M. , Schein J. , Benkel B. , de Jong P.J. , Osoegawa K. , Kirkpatrick B.W. , Gill C.A.
Published: February 2004

We have constructed a medium density physical map of bovine chromosome 19 using a combination of mapping loci on both a bovine bacterial artificial chromosome (BAC) scaffold map and a whole genome radiation hybrid (WGRH) panel. The resulting map contains 70 loci spanning the length of bovine chromosome 19. Three contiguous groups of BACs were identified on the basis of multiple loci mapping to individual BAC clones. Bovine chromosome 19 was found in this study to be comprised almost entirely from regions of human chromosome 17, with a small region putatively assigned to human chromosome 10. Fourteen breakpoints between the bovine and human chromosomes were detected, with a possibility of five more based on ordering of the WGRH map.
Comparative FISH-mapping of the survival of motor neuron gene (SMN) in domestic bovids
Authors: Iannuzzi L. , Di Meo G.P. , Perucatti A. , Rullo R. , Incarnato D. , Longeri M. , Bongioni G. , Molteni L. , Galli A. , Zanotti M. , Eggen A.
Published: February 2004

A comparative fluorescence in situ mapping of the SMN gene was performed on R-banded chromosome preparations of cattle (Bos taurus, BTA, 2n = 60), river buffalo (Bubalus bubalis, BBU, 2n = 50), sheep (Ovis aries, OAR, 2n = 54) and goat (Capra hircus, CHI, 2n = 60), as well as on those of a calf from Piedmont breed affected by arthrogryposis. SMN was located on BTA20q13.1, OAR16q13.1, CHI20q13.1 and BBU19q13. These chromosomes and chromosome bands are believed to be homeologous, confirming the high degree of chromosome homeologies among bovids. The position of SMN was refined in cattle, compared to the two previous localizations, while it is a new gene assignment in the other three bovids. A comparative fiber-FISH performed on extended chromatin of both normal cattle and calf affected by arthrogryposis revealed more extended FITC signals in the calf, compared to the normal cattle (control), suggesting a possible duplication of the SMN gene in the calf affected by arthrogryposis.
Genomic organization of the DGAT2/MOGAT gene family in cattle (Bos taurus) and other mammals
Authors: Winter A. , van Eckeveld M. , Bininda-Emonds O.R.P. , Habermann F.A. , Fries R.
Published: February 2004

We report the cloning and initial characterization of the genes encoding DGAT2 (diacylglycerol transferase 2), MOGAT1 and MOGAT2 (monoacylglycerol transferases 1 and 2) in domestic cattle (Bos taurus). The three closely related genes belong to a gene family with at least eight members in mammals and are candidate genes for quantitative traits related to dietary fat uptake, lipid synthesis and storage. MOGAT2 and DGAT2 form a tandem and were mapped to bovine chromosome (BTA) 15q25→q26 by fluorescence in situ hybridization. MOGAT1 was localized to BTA 2q43→q44. The three genes were investigated for polymorphisms that might be associated with breeding values for milk fat percentage in the dairy breeds German Holstein, German Simmental and German Brown. All the detected polymorphisms were located outside exons or, with one exception, were silent. In MOGAT1, a missense mutation in exon 4 was found that causes a non-conservative substitution of cysteine170 (uncharged, hydrophobic) by lysine (positively charged, hydrophilic). However, allele frequency estimates from pooled DNA samples revealed no significant association of the observed polymorphisms with breeding values for milk fat percentage. A comparative analysis of chromosomal locations and exon-intron structure of the known members of the DGAT2/MOGAT gene family in humans, rodents and cattle indicates an ancient tandem duplication of the ancestor gene combined with an intron gain (or loss) in one copy. Further members of the family may have arisen by duplications of this gene tandem via two rounds of interchromosomal or genome duplications as well as further local (single) gene duplication and loss events.
Bovine Y chromosome microsatellite polymorphisms
Authors: Liu W.-S. , Beattie C.W. , Ponce de León F.A.
Published: February 2004

Thirty-eight bovine Y chromosome (BTAY) microsatellites (MS) were assessed for polymorphisms in DNA samples obtained from 17 unrelated bulls. Thirty-three of these microsatellites are new and were used for the construction of a first generation radiation hybrid map for BTAY (Liu et al., 2002). Five MS had been previously reported and were used as positive controls. Fourteen out of 38 MS were found to be polymorphic; the remaining 24 were uninformative among the animals tested. The number of hemizygous loci per MS within individual ranged from two to over 20. Seven MS presented smear- or ladder-like bands, a unique feature for Y chromosome multi-copy hemizygous MS loci. The locus length variance, within individual, ranged from 2 to 42 bp corresponding to the MS with the minimum and maximum number of loci observed, respectively. Within the 14 polymorphic MS, the five pseudoautosomal MS, on average, were more polymorphic (35.3%) than the nine Y-specific MS (19.6%). Haplotypes resulting from combinations of these polymorphic loci will provide a powerful tool for future studies on the origin of domestic cattle and the evolution of bovid species.
Development of a linkage map and QTL scan for growth traits in North American bison
Authors: Schnabel R.D. , Taylor J.F. , Derr J.N.
Published: February 2004

PCR protocols incorporating fluorescently labeled multiplexed primer combinations were developed to produce a linkage map for bison. Three hundred fifty eight microsatellite loci spanning all 29 autosomes were genotyped via 83 PCR multiplexes and nine individual amplifications. A total of 292 markers were integrated into an autosomal linkage map for bison. The sex averaged bison map (2,647 cM) was approximately 9% longer than the corresponding USDA MARC map, which covered 2,415 cM. Utilizing weaning, yearling and 17-month weights from two private bison herds, a QTL scan was conducted using the developed linkage map. LOD peaks suggestive of QTL were identified on chromosomes 2, 7, 15, and 24 for weaning weight, chromosomes 4, 14, and 15 for yearling weight and chromosomes 8, 14, and 25 for 17-month weight. Four of the identified chromosomes have conserved synteny with regions harboring growth QTL in cattle.
Current status of the ovine genome map
Authors: Cockett N.E.
Published: February 2004

Genome maps in livestock species have been under development for the last decade. While the sheep map is one of the least advanced for livestock, the amount of available information is noteworthy, in light of the paucity of funding and personnel devoted to this project. These limited resources have been strategically aligned to take advantage of information from the human, mouse and bovine mapping and sequencing efforts. The resulting ovine linkage and physical maps have greatly enhanced the search for genes controlling important traits in sheep. In order to improve the efficiency of these investigations, it is imperative that efforts on the sheep comparative map be continued.
Systematic screening of sheep skin cDNA libraries for microsatellite sequences
Authors: DeSilva U. , Franklin I.R. , Maddox J.F. , van Hest B. , Adelson D.L.
Published: February 2004

65,000 sheep skin cDNA clones were gridded in high density on to nylon membranes and screened for (CA)n and (GA)n repeat containing clones. 296 dinucleotide repeat-containing clones were identified with ∼85% non-redundancy. Clones were single-pass 5′ sequenced and we compared the Expressed Sequence Tag (EST) sequences to the Swiss-Prot database to ascertain their identity and/or putative function. We then aligned the ESTs against the human genomic sequence to determine the locations of human orthologous sequences. Finally, we developed a subset of polymorphic microsatellite markers and positioned them on the ovine linkage map.