International Journal of Medical Sciences http://www.medsci.org International Journal of Medical Sciences RSS feed -- Volume 6 en-us Sat, 13 Jun 2009 04:00:00 GMT Sat, 13 Jun 2009 04:00:00 GMT http://www.medsci.org/v06p0168.htm Elevated Serum Levels of Arachidonoyl-lysophosphatidic Acid and Sphingosine 1-Phosphate in Systemic Sclerosis http://www.medsci.org/v06p0168.htm Systemic sclerosis (SSc) is an often fatal disease characterized by autoimmunity and inflammation, leading to widespread vasculopathy and fibrosis. Lysophosphatidic acid (LPA), a bioactive phospholipid in serum, is generated from lysophospholipids secreted from activated platelets in part by the action of lysophospholipase D (lysoPLD). Sphingosine 1-phosphate (S1P), a member of the bioactive lysophospholipid family, is also released from activated platelets. Because activated platelets are a hallmark of SSc, we wanted to determine whether subjects with SSc have altered serum lysophospholipid levels or lysoPLD activity. Lysophospholipid levels were measured using mass spectrometric analysis. LysoPLD activity was determined by quantifying choline released from exogenous lysophosphatidylcholine (LPC). The major results were that serum levels of arachidonoyl (20:4)-LPA and S1P were significantly higher in SSc subjects versus controls. Furthermore, serum LPA:LPC ratios of two different polyunsaturated phospholipid molecular species, and also the ratio of all species combined, were significantly higher in SSc subjects versus controls. No significant differences were found between other lysophospholipid levels or lysoPLD activities. Elevated 20:4 LPA, S1P levels and polyunsaturated LPA:LPC ratios may be markers for and/or play a significant role in the etiology of SSc and may be future pharmacological targets for SSc treatment.

]]> Akira Tokumura, Laura D. Carbone, Yasuko Yoshioka, Junichi Morishige, Masaki Kikuchi, Arnold Postlethwaite, Mitchell A. Watsky Ivyspring International Publisher 6 4 168 176 2009-6-5 Research Paper http://www.medsci.org/v06p0160.htm Determinants of improvement in quality of life of alcohol-dependent patients during an inpatient withdrawal programme http://www.medsci.org/v06p0160.htm Background: To investigate the improvement in quality of life (QoL) of alcohol-dependent patients during a 3-week inpatient withdrawal programme, and to identify the sociodemographic, clinical and alcohol-related variables associated with baseline QoL on admission and with improvement of QoL during residential treatment.

Methods: This prospective, observational study included 414 alcohol-dependent patients, hospitalised for a period of 3 weeks. QoL was measured on admission and at discharge using the French version of the Medical Outcome Study SF-36. The mean scores for each dimension and for the Physical and Mental Component Summary scores were calculated.

Results: The mean scores per dimension and the mean Physical and Mental Component Summary scores were significantly lower on admission than at discharge; the lowest scores being observed for social functioning and role limitations due to emotional problems. At discharge, the mean scores per dimension were similar to those observed in the French general population. Female gender, age >45 years, living alone, working as a labourer or employee, somatic comorbidity, and the existence of at least five criteria for alcohol dependence according to the DSM-IV classification were associated with a low Physical Component Summary score on admission; psychiatric comorbidity, the presence of at least five DSM-IV dependence criteria, smoking and suicidality were associated with a low Mental Component Summary score on admission. The increase in Physical and Mental Component Summary scores during hospitalisation was more marked when the initial scores were low. Apart from the initial score, the greatest improvement in Physical Component Summary score was seen in patients with a high alcohol intake and in those without a somatic comorbidity; the increase in Mental Component Summary score was greatest in patients without psychotic symptoms and in those who abused or were dependent on illegal drugs.

Conclusion: QoL improvement after a residential treatment was related to low QoL scores at admission. Improvement in physical component of QoL was related to baseline alcohol intake and good somatic status. Improvement in mental component of QoL was related to other drugs abuse/dependence.

]]> Pierre Lahmek, Ivan Berlin, Laurent Michel, Chafia Berghout, Nadine Meunier, Henri-Jean Aubin Ivyspring International Publisher 6 4 160 167 2009-5-18 Research Paper http://www.medsci.org/v06p0156.htm Gene expression analysis of human red blood cells http://www.medsci.org/v06p0156.htm Understanding of molecular mechanisms governing the enucleating phenomena of human erythrocytes is of major importance in both fundamental and applied studies. Total RNA (n=7) from human RBCs (purity of erythrocyte preparation >99,99%) was tested using 2100 Bioanalyzer (Agilent, USA), and transcribed to cDNA. Microarray analysis was performed with the Human Genome Focus GeneChip (Affymetrix, USA), containing 8500 transcripts corresponding to 8400 human genes. Here we report that human RBCs contain typical eukaryotic RNA with 28S- and18S-rRNA standard bands. Microarray studies revealed the presence of transcripts of 1019 different genes in erythrocytic RNA. Gene Ontology analysis recognized 859 genes involved in general biological processes: 529 genes for cellular metabolism, 228 genes for signal transduction, 104 genes for development, 107 genes for immune response, 62 genes for protein localization, 53 genes for programmed cell death, and 5 genes for autophagy. A number of genes responsible for transcription, translation, RNA-stabilisation as well as for apoptosis and anti-apoptosis have been identified for the first time in circulating human RBCs. The presented data shed new light on the genetic determination of erythropoiesis, apoptosis and may have implications on the pathophysiology and diagnosis of various diseases involving red blood cells.

]]> Sveta Kabanova, Petra Kleinbongard, Jens Volkmer, Birgit Andrée, Malte Kelm, Thomas W. Jax Ivyspring International Publisher 6 4 156 159 2009-4-28 Research Paper http://www.medsci.org/v06p0143.htm Comparison of a Two-Lead, Computerized, Resting ECG Signal Analysis Device, the MultiFunction-CardioGramsm or MCG (a.k.a. 3DMP), to Quantitative Coronary Angiography for the Detection of Relevant Coronary Artery Stenosis (>70%) - A Meta-Analysis of all Published Trials Performed and Analyzed in the US http://www.medsci.org/v06p0143.htm Background: Accurate, non-invasive diagnosis of, and screening for, coronary artery disease (CAD) and restenosis after coronary revascularization has been a challenge due to either low sensitivity/specificity or relevant morbidity associated with current diagnostic modalities.

Methods: To assess sensitivity and specificity of a new computerized, multiphase, resting electrocardiogram analysis device (MultiFunction-CardioGramsm or MCG a.k.a. 3DMP) for the detection of relevant coronary stenosis (>70%), a meta-analysis of three published prospective trials performed in the US on patient data collected using the US manufactured device and analyzed using the US-based software and New York data analysis center from patients in the US, Germany, and Asia was completed. A total of 1076 patients from the three trials (US - 136; Germany - 751; Asia - 189) (average age 62 ± 11.5, 65 for women, 60 for men) scheduled for coronary angiography, were included in the analysis. Patients enrolled in the trials may or may not have had prior angiography and/or coronary intervention. Angiographic results in all studies were classified for hemodynamically relevant stenosis (> 70%) by two US based angiographers independently.

Results: Hemodynamically relevant stenosis was diagnosed in 467 patients (43.4%). The device, after performing a frequency-domain, computational analysis of the resting ECG leads and computer-database comparison, calculated a coronary ischemia “severity” score from 0 to 20 for each patient. The severity score was significantly higher for patients with relevant coronary stenosis (5.4 ± 1.8 vs. 1.7 ± 2.1). The study device (using a cut-off score for relevant stenosis of 4.0) correctly classified 941 of the 1076 patients with or without relevant stenosis (sensitivity-91.2%; specificity-84.6%; NPV 0.942, PPV 0.777). Adjusted positive and negative predictive values (PPV and NPV) were 81.9% and 92.6%, respectively (ROC AUC = 0.881 [95% CI: 0.860-0.903]). Subgroup analysis showed no significant influence of sex, age, race/nationality, previous revascularization procedures, resting ECG morphology, or participating center on the device's diagnostic performance.

Conclusions: The new computerized, multiphase, resting ECG analysis device (MultiFunction-CardioGramsm) has been shown in this meta-analysis to safely and accurately identify patients with relevant coronary stenosis (>70%) with high sensitivity and specificity and high negative predictive value. Its potential use in the evaluation of symptomatic patients suspected to suffer from coronary disease/ischemia is discussed.

]]> John E. Strobeck, Joseph T. Shen, Binoy Singh, Kotaro Obunai, Charles Miceli, Howard Sacher, Franz Ritucci, Michael Imhoff Ivyspring International Publisher 6 4 143 155 2009-4-7 Research Paper http://www.medsci.org/v06p0140.htm Update on the treatment of ocular toxoplasmosis http://www.medsci.org/v06p0140.htm Yan Guex-Crosier Ivyspring International Publisher 6 3 140 142 2009-3-19 Short Communication http://www.medsci.org/v06p0139.htm Usefulness of vitrectomy in the treatment of ocular toxoplasmosis http://www.medsci.org/v06p0139.htm Etienne H. Bovey Ivyspring International Publisher 6 3 139 139 2009-3-19 Short Communication http://www.medsci.org/v06p0137.htm Optical Coherence Tomography in ocular toxoplasmosis http://www.medsci.org/v06p0137.htm Dominique Monnet, Kristel Averous, Emmanuelle Delair, Antoine P. Brézin Ivyspring International Publisher 6 3 137 138 2009-3-19 Short Communication http://www.medsci.org/v06p0135.htm Laboratory diagnosis of Toxoplasma gondii infection http://www.medsci.org/v06p0135.htm A. Calderaro, S. Peruzzi, G. Piccolo, C. Gorrini, S. Montecchini, S. Rossi, C. Chezzi, G. Dettori Ivyspring International Publisher 6 3 135 136 2009-3-19 Short Communication http://www.medsci.org/v06p0133.htm Human toxoplasmosis and the role of veterinary clinicians http://www.medsci.org/v06p0133.htm Laura Kramer Ivyspring International Publisher 6 3 133 134 2009-3-19 Short Communication http://www.medsci.org/v06p0131.htm Ocular Bartonellosis http://www.medsci.org/v06p0131.htm Massimo Accorinti Ivyspring International Publisher 6 3 131 132 2009-3-19 Short Communication http://www.medsci.org/v06p0129.htm Ocular Toxocariasis http://www.medsci.org/v06p0129.htm Paola Pivetti-Pezzi Ivyspring International Publisher 6 3 129 130 2009-3-19 Short Communication http://www.medsci.org/v06p0128.htm Ocular manifestations of Rickettsiosis: 2. Retinal involvement and treatment http://www.medsci.org/v06p0128.htm Leila El Matri Ivyspring International Publisher 6 3 128 128 2009-3-19 Short Communication http://www.medsci.org/v06p0126.htm Ocular Manifestations of Rickettsiosis: 1. Mediterranean Spotted Fever: laboratory analysis and case reports http://www.medsci.org/v06p0126.htm Antonio Pinna Ivyspring International Publisher 6 3 126 127 2009-3-19 Short Communication http://www.medsci.org/v06p0124.htm Ocular manifestations of Lyme borreliosis in Europe http://www.medsci.org/v06p0124.htm Paolo Mora, Arturo Carta Ivyspring International Publisher 6 3 124 125 2009-3-19 Short Communication http://www.medsci.org/v06p0123.htm Local epidemiology and clinical manifestations of Lyme disease http://www.medsci.org/v06p0123.htm Walter O. Pavan Ivyspring International Publisher 6 3 123 123 2009-3-19 Short Communication http://www.medsci.org/v06p0120.htm Introduction into Pathology of Ocular Zoonoses http://www.medsci.org/v06p0120.htm Hans E. Schaefer Ivyspring International Publisher 6 3 120 122 2009-3-19 Short Communication http://www.medsci.org/v06p0118.htm Incidence of Ocular Zoonoses referred to the Inflammatory and Autoimmune Ocular Diseases Service of the University of Parma - Italy http://www.medsci.org/v06p0118.htm Stefania Gonzales, Alessandro Giannone, Pierangela Rubino, Francesca Manzotti, Isabella Pellistri, Paolo Mora, Jelka G. Orsoni Ivyspring International Publisher 6 3 118 119 2009-3-19 Short Communication http://www.medsci.org/v06p0116.htm Introduction to special issue on Eye and Zoonosis - from the guest editors http://www.medsci.org/v06p0116.htm Papers of this special issue are based on the presentations given in the Congress “Eye and Zoonosis” - October 10-11th 2008, Parma (Italy). This issue aims to provide researchers with timely update on a number of important topics on Zoonosis in Ophthalmology.

]]> Jelka G. ORSONI, Paolo MORA Ivyspring International Publisher 6 3 116 117 2009-3-19 Editorial http://www.medsci.org/v06p0114.htm Ocular Manifestations of West Nile Virus Infection http://www.medsci.org/v06p0114.htm Salim Ben Yahia, Moncef Khairallah Ivyspring International Publisher 6 3 114 115 2009-5-26 Short Communication http://www.medsci.org/v06p0106.htm Clinical Symptoms Associated with Asystolic or Bradycardic Responses on Implantable Loop Recorder Monitoring in Patients with Recurrent Syncope http://www.medsci.org/v06p0106.htm Background: Implantable loop recorders (ILR) have been found to be useful in the diagnosis and management of syncope of unclear etiology. The clinical symptoms of abnormalities seen during ILR monitoring have not been adequately studied.

Aim: The aim of this retrospective study was to determine the clinical symptoms which were the best predictors of asystolic or bradycardic responses during ILR monitoring.

Methods: Patients with either asystole or bradycardia recorded during ILR monitoring were analyzed from our database. The clinical characteristics of these patients were compared to the patients with ILR's who did not have recorded bradycardic episodes. The episodes were characterized as being convulsive or nonconvulsive, brief (<5 minutes) or prolonged (> 5 minutes), and having had a prodrome or no prodrome.

Results: Eleven patients (4 males and 7 females; age 39 ±11years) had asystole or bradycardia on ILR monitoring. Eleven patients (2 males and 9 females; age 46±23) had no bradycardiac events. Palpitations, convulsive syncope, prolonged episode, and prodrome were present in 37% vs. 74% (P = 0.125), 62% vs. 0% (P = 0.002), 87% vs. 0% (P=0), and 73% vs. 13% (P=0.009) patients, respectively, in the asystole/bradycardia and non-bradycardia groups. In the asystole/bradycardia group eight patients had bradycardia (HR < 20) for > 10 seconds and three patients had asystole >10 seconds.

Conclusion: Convulsive syncope, prolonged loss of consciousness during syncopal episode, and absence of prodrome or aura are clinical predictors of asystole or bradycardia on ILR monitoring.

]]> Khalil Kanjwal, Yousuf Kanjwal, Beverly Karabin, Blair P. Grubb Ivyspring International Publisher 6 2 106 110 2009-4-9 Research Paper http://www.medsci.org/v06p0102.htm Endoscopic laminoforaminoplasty success rates for treatment of foraminal spinal stenosis: report on sixty-four cases http://www.medsci.org/v06p0102.htm Background: Foraminal stenosis is an important cause of radicular and generalized back pain. In patients who do not respond to conservative interventions, endoscopic spinal surgery provides similar results to open surgical approaches with lower rates of complication, postoperative pain, and shorter duration of hospital stay.

Methods: We performed a prospective, open, uncontrolled trial of 64 patients to evaluate endoscopic laminoforaminoplasty for the treatment of refractory foraminal stenosis.

Results: Fifty-nine percent of patients had at least 75% improvement in Oswestry Disability Index (Oswestry) and Visual Analog Scale (VAS) scores. All patients were discharged the day of surgery. Dural leaks occurred in two patients, which were repaired intraoperatively. No other adverse events occurred.

Conclusions: Endoscopic laminoforaminoplasty appears to be a safe alternative to open decompression in patients with spinal foraminal stenosis; additional controlled trials are warranted.

]]> Scott M.W. Haufe, Anthony R. Mork, Morgan A. Pyne, Ryan A. Baker Ivyspring International Publisher 6 2 102 105 2009-3-22 Research Paper http://www.medsci.org/v06p0093.htm PKC and PKA Phosphorylation Affect the Subcellular Localization of Claudin-1 in Melanoma Cells http://www.medsci.org/v06p0093.htm Cytoplasmic expression of claudin-1 in metastatic melanoma cells correlates to increased migration, and increased secretion of MMP-2 in a PKC dependent manner, whereas claudin-1 nuclear expression is found in benign nevi. Melanoma cells were transfected with a vector expressing CLDN-1 fused to a nuclear localization signal (NLS). Despite significant nuclear localization of claudin-1, there was still transport of claudin-1 to the cytoplasm. Phorbol ester treatment of cells transfected with NLS-claudin-1 resulted in an exclusion of claudin-1 from the nucleus, despite the NLS. To ascertain whether PKC or PKA were involved in this translocation, we mutated the putative phosphorylation sites within the protein. We found that mutating the PKC phosphorylation sites to mimic a non-phosphorylated state did not cause a shift of claudin-1 to the nucleus of the cells, but mutating the PKA sites did. Mutations of either site to mimic constitutive phosphorylation resulted in cytoplasmic claudin-1 expression. Stable claudin-1 transfectants containing non-phosphorylatable PKA sites exhibited decreased motility. These data imply that subcellular localization of claudin-1 can be controlled by phosphorylation, dicating effects on metastatic capacity.

]]> Amanda D. French, Jennifer L. Fiori, Tura C. Camilli, Poloko D. Leotlela, Michael P. O'Connell, Brittany P. Frank, Sarah Subaran, Fred. E. Indig, Dennis D. Taub, Ashani T. Weeraratna Ivyspring International Publisher 6 2 93 101 2009-3-12 Research Paper http://www.medsci.org/v06p0085.htm Induction and effector phase of allergic lung inflammation is independent of CCL21/CCL19 and LT-beta http://www.medsci.org/v06p0085.htm The chemokines CCL21 and CCL19, and cell bound TNF family ligand lymphotoxin beta (LTβ), have been associated with numerous chronic inflammatory diseases. A general role in chronic inflammatory diseases cannot be assumed however; in the case of allergic inflammatory disease, CCL21/CCL19 and LTβ have not been associated with the induction, recruitment, or effector function of Th2 cells nor dendritic cells to the lung. We have examined the induction of allergic inflammatory lung disease in mice deficient in CCL21/CCL19 or LTβ and found that both kinds of mice can develop allergic lung inflammation. To control for effects of priming differences in knockout mice, adoptive transfers of Th2 cells were also performed, and they showed that such effector cells had equivalent effects on airway hyper-responsiveness in both knockout background recipients. Moreover, class II positive antigen presenting cells (B cells and CD11c+ dendritic cells) showed normal recruitment to the peribronchial spaces along with CD4 T cells. Thus, the induction of allergic responses and recruitment of both effector Th2 cells and antigen presenting cells to lung peribronchial spaces can develop independently of CCL21/CCL19 and LTβ.

]]> Corinne Ploix, Riaz I. Zuberi, Fu-Tong Liu, Monica J. Carson, David D. Lo Ivyspring International Publisher 6 2 85 92 2009-3-10 Research Paper http://www.medsci.org/v06p0077.htm Relationship between anal symptoms and anal findings http://www.medsci.org/v06p0077.htm Background: The frequencies and types of anal symptoms were compared with the frequencies and types of benign anal diseases (BAD).

Methods: Patients transferred from GPs, physicians or gynaecologists for anal and/or abdominal complaints/signs were enrolled and asked to complete a questionnaire about their symptoms. Proctologic assessment was performed in the knee-chest position. Definitions of BAD were tested in a two year pilot study. Findings were entered into a PC immediately after the assessment of each individual.

Results: Eight hundred seven individuals, 539 (66.8%) with and 268 without BAD were analysed. Almost one third (31.2%) of patients with BAD had more than one BAD. Concomitant anal findings such as skin tags were more frequently seen in patients with than without BAD (<0.01). After haemorrhoids (401 patients), pruritus ani (317 patients) was the second most frequently found BAD. The distribution of stages in 317 pruritus ani patients was: mild (91), moderate (178), severe (29), and chronic (19). Anal symptoms in patients with BAD included: bleeding (58.6%), itch (53.7%), pain (33.7%), burning (32.9%), and soreness (26.6%). Anal lesions could be predicted according to patients' answers in the questionnaire: haemorrhoids by anal bleeding (p=0.032), weeping (p=0.017), and non-existence of anal pain (p=0.005); anal fissures by anal pain (p=0.001) and anal bleeding (p=0.006); pruritus ani by anal pain (p=0.001), itching (p=0.001), and soreness (p=0.006).

Conclusions: The knee-chest position may allow for the accumulation of more detailed information about BAD than the left lateral Sims' position, thus enabling physicians to make more reliable anal diagnoses and provide better differentiated therapies.

]]> Hans Georg Kuehn, Ole Gebbensleben, York Hilger, Henning Rohde Ivyspring International Publisher 6 2 77 84 2009-3-6 Research Paper http://www.medsci.org/v06p0072.htm High-intensity non-invasive positive pressure ventilation for stable hypercapnic COPD http://www.medsci.org/v06p0072.htm Background: The objective of the present analysis is to describe the outcomes of high-intensity non-invasive positive pressure ventilation (NPPV) aimed at maximally decreasing PaCO2 as an alternative to conventional NPPV with lower ventilator settings in stable hypercapnic COPD patients.

Methods: Physiological parameters, exacerbation rates and long-term survival were assessed in 73 COPD patients (mean FEV1 30±12 %predicted) who were established on high-intensity NPPV due to chronic hypercapnic respiratory failure between March 1997 and May 2006.

Results: Controlled NPPV with breathing frequencies of 21±3 breath/min and mean inspiratory/expiratory positive airway pressures of 28±5/5±1 cmH2O led to significant improvements in blood gases, lung function and hematocrit after two months. Only sixteen patients (22%) required hospitalisation due to exacerbation during the first year, with anaemia increasing the risk for exacerbation. Two- and five-year survival rates of all patients were 82% and 58%, respectively. The five year survival rate was 32% and 83% in patients with low (≤39%) and high (≥55%) hematocrit, respectively.

Conclusion: High-intensity NPPV improves blood gases, lung function and hematocrit, and is also associated with low exacerbation rates and a favourable long-term outcome. The current report strongly emphasises the need for randomised controlled trials evaluating the role of high-intensity NPPV in stable hypercapnic COPD patients.

]]> Wolfram Windisch, Moritz Haenel, Jan H Storre, Michael Dreher Ivyspring International Publisher 6 2 72 76 2009-2-27 Research Paper http://www.medsci.org/v06p0065.htm Esterified Hyaluronic Acid and Autologous Bone in the Surgical Correction of the Infra-Bone Defects http://www.medsci.org/v06p0065.htm We study the osteoinductive effect of the hyaluronic acid (HA) by using an esterified low-molecular HA preparation (EHA) as a coadjuvant in the grafting processes to produce bone-like tissue in the presence of employing autologous bone obtained from intra-oral sites, to treat infra-bone defects without covering membrane.

We report on 9 patients with periodontal defects treated by EHA and autologous grafting (4 males and 5 females, all non smokers, with a mean age of 43,8 years for females, 40,0 years for males and 42 years for all the group, in good health) with a mean depth of 8.3 mm of the infra-bone defects, as revealed by intra-operative probes. Data were obtained at baseline before treatment and after 10 days, and subsequently at 6,9, and 24 months after treatment.

Clinical results showed a mean gain hi clinical attachment (gCAL) of 2.6mm of the treated sites, confirmed by radiographic evaluation. Such results suggest that autologous bone combined with EHA seems to have good capabilities in accelerating new bone formation in the infra-bone defects.

]]> Andrea BALLINI, Stefania CANTORE, Saverio CAPODIFERRO, Felice Roberto GRASSI Ivyspring International Publisher 6 2 65 71 2009-2-26 Research Paper http://www.medsci.org/v06p0051.htm Transcriptome analysis of murine thymocytes reveals age-associated changes in thymic gene expression http://www.medsci.org/v06p0051.htm The decline in adaptive immunity, naïve T-cell output and a contraction in the peripheral T cell receptor (TCR) repertoire with age are largely attributable to thymic involution and the loss of critical cytokines and hormones within the thymic microenvironment. To assess the molecular changes associated with this loss of thymic function, we used cDNA microarray analyses to examine the transcriptomes of thymocytes from mice of various ages ranging from very young (1 month) to very old (24 months). Genes associated with various biological and molecular processes including oxidative phosphorylation, T- and B- cell receptor signaling and antigen presentation were observed to significantly change with thymocyte age. These include several immunoglobulin chains, chemokine and ribosomal proteins, annexin A2, vav 1 and several S100 signaling proteins. The increased expression of immunoglobulin genes in aged thymocytes could be attributed to the thymic B cells which were found to be actively producing IgG and IgM antibodies. Upon further examination, we found that purified thymic T cells derived from aged but not young thymi also exhibited IgM on their cell surface suggesting the possible presence of auto-antibodies on the surface thymocytes with advancing age. These studies provide valuable insight into the cellular and molecular mechanisms associated with thymic aging.

]]> Ana Lustig, Arnell Carter, Dorothy Bertak, Divya Enika, Bolormaa Vandanmagsar, William Wood, Kevin G. Becker, Ashani T. Weeraratna, Dennis D. Taub Ivyspring International Publisher 6 1 51 64 2009-2-9 Research Paper http://www.medsci.org/v06p0043.htm Multivariate explanatory model for sporadic carcinoma of the colon in Dukes' stages I and IIa http://www.medsci.org/v06p0043.htm Objective: We obtained before an explanatory model with six dependant variables: age of the patient, total cholesterol (TC), HDL cholesterol (HDL-C), VLDL cholesterol (VLDL-C), alkaline phosphatase (AP) and the CA 19.9 tumour marker. Our objective in this study was to validate the model by means of the acquisition of new records for an additional analysis.

Design: Non-paired case control study.

Setting: Urban and rural hospitals and primary health facilities in Western Andalusia and Extremadura (Spain).

Patients: At both the primary care facilities and hospital level, controls were gathered in a prospective manner (n= 275). Cases were prospective and retrospective manner collected on (n=126).

Main outcome measures: Descriptive statistics, logistic regression and bootstrap analysis.

Results: The AGE (odds ratio 1.02; 95% CI 1.003-1.037) (p= 0.01), the TC (odds ratio 0.986; 95% C.I. 0.980-0.992) (p< 0.001) and the CA 19.9 (odds ratio 1.023; 95% C.I. 1.012- 1.034) (p<0.001) were the variables that showed significant values at logistic regression analysis and bootstrap. Berkson's bias was statistically assessed.

Conclusions: The model, validated by means of logistic regression and bootstrap analysis, contains the variables AGE, TC, and CA 19.9 (three of the original six) and has a level 4 over 5 according to the criteria of Justice et al. (multiple independent validations) [Ann. Intern. Med.1999; 130: 515].

]]> J.M. Villadiego-Sánchez, M. Ortega-Calvo, R. Pino-Mejías, A. Cayuela, P. Iglesias-Bonilla, F. García-de la Corte, J.M. Santos-Lozano, José Lapetra-Peralta Ivyspring International Publisher 6 1 43 50 2009-1-30 Research Paper http://www.medsci.org/v06p0037.htm Continuous Non-Invasive Arterial Pressure Technique Improves Patient Monitoring during Interventional Endoscopy http://www.medsci.org/v06p0037.htm Introduction: Close monitoring of arterial blood pressure (BP) is a central part of cardiovascular surveillance of patients at risk for hypotension. Therefore, patients undergoing diagnostic and therapeutic procedures with the use of sedating agents are monitored by discontinuous non-invasive BP measurement (NIBP). Continuous non-invasive BP monitoring based on vascular unloading technique (CNAP®, CN Systems, Graz) may improve patient safety in those settings. We investigated if this new technique improved monitoring of patients undergoing interventional endoscopy.

Methods: 40 patients undergoing interventional endoscopy between April and December 2007 were prospectively studied with CNAP® in addition to standard monitoring (NIBP, ECG and oxygen saturation). All monitoring values were extracted from the surveillance network at one-second intervals, and clinical parameters were documented. The variance of CNAP® values were calculated for every interval between two NIBP measurements.

Results: 2660 minutes of monitoring were recorded (mean 60.1±34.4 min/patient). All patients were analgosedated with midazolam and pethidine, and 24/40 had propofol infusion (mean 90.9±70.3 mg). The mean arterial pressure for CNAP® was 102.4±21.2 mmHg and 106.8±24.8 mmHg for NIBP. Based on the first NIBP value in an interval between two NIBP measurements, BP values determined by CNAP® showed a maximum increase of 30.8±21.7% and a maximum decrease of 22.4±28.3% (mean of all intervals).

Discussion: Conventional intermittent blood pressure monitoring of patients receiving sedating agents failed to detect fast changes in BP. The new technique CNAP® improved the detection of rapid BP changes, and may contribute to a better patient safety for those undergoing interventional procedures.

]]> Sylvia Siebig, Felix Rockmann, Karl Sabel, Ina Zuber-Jerger, Christine Dierkes, Tanja Brünnler, Christian E. Wrede Ivyspring International Publisher 6 1 37 42 2009-1-20 Research Paper http://www.medsci.org/v06p0028.htm Sustained High Quality of Life in a 5-Year Long Term Follow-up after Successful Ablation for Supra-Ventricular Tachycardia. Results from a large Retrospective Patient Cohort http://www.medsci.org/v06p0028.htm Introduction: The ablation of supraventricular tachycardias (SVT) using radiofrequency energy (RF) is a procedure with a high primary success rate. However, there is a scarcity of data regarding the long term outcome, particularly with respect to quality of life (QoL).

Methods and Results: In this retrospective single-center study, 454 patients who underwent ablation of SVT between 2002 and 2007 received a detailed questionnaire addressing matters of QoL. The questionnaire was a modified version of the SF-36 Health Survey questionnaire and the Symptom Checklist – Frequency and Severity Scale.

After a mean follow up of 4.5±1.3 years, 309 (68.1%) of the contacted 454 patients (269 female, 59.2%, mean age 58+/-6.5) completed the questionnaire. Despite of 27% of relapses in the study group, 91.7% considered the procedure a long-term success. The remainder of patients experienced no change in (3.7%) or worsening of (4.7%) symptoms. There were no significant differences between the various types of SVT (p=1). QoL in patients with Atrio-Ventricular Nodal Reentry Tachycardia (AVNRT) and Atrio-Ventricular Reentry Tachycardia (AVRT) improved significantly (p<0.0005 respectively p<0.043), whereas QoL in patients with Ectopic Atrial Tachycardia (EAT) showed a non-significant trend towards improvement. Main symptoms before ablation, such as tachycardia (91.5%), increased incidence of tachycardia episodes over time (78.1%), anxiety (55.5%) and reduced physical capacity in daily life (52%) were significantly improved after ablation (p<0.0001).

Conclusion: The high acute ablation success of SVT persists for years in long term follow up and translates into a significant improvement of QoL in most patients.

]]> Axel Meissner, Irini Stifoudi, Peter Weismüller, Max-Olav Schrage, Petra Maagh, Martin Christ, Thomas Butz, Hans-Joachim Trappe, Gunnar Plehn Ivyspring International Publisher 6 1 28 36 2009-1-11 Research Paper http://www.medsci.org/v06p0018.htm Transporter Molecules influence the Gene Expression in HeLa Cells http://www.medsci.org/v06p0018.htm Progresses in biology and pharmacology led to highly specific bioactive substances, but their poor bioavailability at the site of action is a result of their physico-chemical properties. Various design approaches for transport carrier molecules facilitating the cellular entry of bioactive substances could help to reach their molecular target in cells and tissues. The transfer efficacy and the subsequent pharmacological effects of the cargo molecules are well investigated, but the investigations of effects of the carrier molecules themselves on the target cells or tissues remain necessary. A special attention should be paid to the differential gene expression, particularly in the interpretation of the data achieved by highly specific active pharmaceutical products. After application of transmembrane transport peptides, particularly the pAnt and also the HIV-1 Tat, cells respond with a conspicuous altered gene expression of at least three genes. The PKN1 gene was induced and two genes (ZCD1 and BSG) were slightly repressed. The genes and the chromosomes are described, the moderate differential gene expression graphed, and the ontology is listed.

]]> Waldemar Waldeck, Ruediger Pipkorn, Bernhard Korn, Gabriele Mueller, Matthias Schick, Katalin Tóth, Manfred Wiessler, Bernd Didinger, Klaus Braun Ivyspring International Publisher 6 1 18 27 2008-12-18 Research Paper http://www.medsci.org/v06p0009.htm Matrix Metalloproteinase Activity in Pediatric Acute Lung Injury http://www.medsci.org/v06p0009.htm Pediatric Acute Lung Injury (ALI) is associated with a high mortality and morbidity, and dysregulation of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis and evolution of ALI. Here we examined MMP expression and activity in pediatric ALI compared with controls. MMP-8, -9, and to a lesser extent, MMP-2, -3, -11 and -12 were identified at higher levels in lung secretions of pediatric ALI patients compared with controls. Tissue Inhibitor of Matrix metalloproteinase-1 (TIMP-1), a natural inhibitor of MMPs was detected in most ALI samples, but MMP-9:TIMP-1 ratios were high relative to controls. In subjects who remained intubated for ≥10 days, MMP-9 activity decreased, with > 80% found in the latent form. In contrast, almost all MMP-8 detected at later disease course was constitutively active. Discriminating MMP-9:TIMP-1 ratios were found in those who had a prolonged ALI course. These results identify a specific repertoire of MMP isoforms in the lung secretions of pediatric ALI patients, and demonstrate inverse changes in MMPs -8 and -9 with protracted disease.

]]> Michele YF Kong, Amit Gaggar, Yao Li, Margaret Winkler, J Edwin Blalock, JP Clancy Ivyspring International Publisher 6 1 9 17 2008-12-16 Research Paper http://www.medsci.org/v06p0001.htm Evaluation of Fractional Analysis of Bronchoalveolar Lavage Combined with Cellular Morphological Features http://www.medsci.org/v06p0001.htm Background. The value of bronchoalveolar lavage (BAL) still remains controversial, prompting a need for further improvement. The purpose of this study was to develop and evaluate a sequential analysis of cell content in fractional BAL (FBAL) from the airways and alveolar sacs with incorporation of the cellular morphologic features. Methods. Initially, 30 ml saline was infused into a subsegmental lobe of the lung and the recovered fluid was assigned as FBAL-I being mainly originated from whole airways. The second and third lavages (FBAL-II and FBAL-III) each were performed using 50 ml saline being from more distal portions of airways and alveolar sacs respectively in the same lobe. Total cell number/ml and percentages of macrophages, lymphocytes, neutrophils, and eosinophils in each fraction together with their morphological alterations and mast cells, basophils and Masson bodies were assessed. Results. In the 12 controls, percentage of neutrophils was high and lymphocytes and macrophages were low in FBAL-I while in FBAL-III, neutrophils decreased to nearly nil and lymphocytes and macrophages were increased. Analysis of FBAL from 76 patients with sarcoidosis and 14 with hypersensitivity pneumonitis (HP) revealed that a predominance of small, round and well-differentiated lymphocytes with relative absence of neutrophils, basophils and Masson bodies correlated best with sarcoidosis. In contrast, neutrophil predominance and presence of lymphocytes having deep nuclear indentations and abundant cytoplasm with a process resembling a “hand-mirror” correlated well with HP. Conclusions. Evaluation of FBAL together with cellular morphological features especially characteristics of lymphocytes provides valuable information for establishing the diagnosis in interstitial lung diseases.

]]> Namiko Taniuchi, Mohammad Ghazizadeh, Tatsuji Enomoto, Kiyoshi Matsuda, Masashi Sato, Yuko Takizawa, Enjing Jin, Seiko Egawa, Arata Azuma, Akihiko Gemma, Shoji Kudoh, Oichi Kawanami Ivyspring International Publisher 6 1 1 8 2008-12-1 Research Paper