bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Polymorphisms at the Adiponectin Gene Locus in Association with Type 2 Diabetes, Body Mass Index and Cardiovascular Traits in Latvian Population
Authors: Kalniņa Ineta , Latkovskis Gustavs , Ņkitina-Zaķe Liene , Mackevičs Vitolds , Pečulis Raitis , Kāpa Ivo , Fridmanis Dāvids , Ērglis Andrejs , Pīrāgs Valdis , Kloviņš Jānis 
Published: November 2009

Analysis of Polymorphisms at the Adiponectin Gene Locus in Association with Type 2 Diabetes, Body Mass Index and Cardiovascular Traits in Latvian PopulationDespite the number of recently conducted studies seeking to determine the association between genetic variants of adiponectin gene and susceptibility to type 2 diabetes (T2D) and increased body mass index (BMI), the results obtained are often inconsistent. To determine the impact of common polymorphisms in promoter and coding regions of adiponectin gene on these conditions in Latvian population, we selected ten SNPs (rs2241767, rs1501299, rs3777261, rs16861210, rs2241766, rs822396, rs182052, rs17300539, rs16861194, rs266729) based on haploblock structure and previously reported association studies. The selected SNPs were screened in a study group of 835 participants from the Genome Data Base of Latvian Population and mainly consisted of patients with T2D and coronary heart disease. None of the individual polymorphisms were significantly associated with T2D status or BMI when analysed using logistic or linear regression and adjusted for gender, age and other significant covariates. Frequency of rs2241766 T allele homozygotes however was significantly increased in T2D patients compared to controls (uncorrected P = 0.007). When analysed with other traits, the rs182052 G allele was found to be less frequent in patients suffering from myocardial infarction (P = 0.02; OR = 0.76, CI95% [0.61-0.92]) compared to others. Haplotype analysis revealed significant association of one haplotype with atrial fibrillation (uncorrected P = 0.01). In summary, we conclude that SNPs in adiponectin gene are unlikely to represent the risk for T2D, but may be involved in pathogenesis of CHD in the Latvian population.
Assessment of Tissue Perfusion During Cardiopulmonary Bypass
Authors: Porīte Nora , Striķe Eva , Bekers-Ančipolovskis Mihails , Semčenko Larisa , Krustiņa Inguna , Stradiņš Pēteris 
Published: November 2009

Assessment of Tissue Perfusion During Cardiopulmonary Bypass
Cardiopulmonary bypass (CPB) remains essential for all valvular operations and the vast majority of coronary bypass surgeries. Inadequate CPB results in tissue underperfusion, activation of anaerobic metabolism and increased lactate production. The goal of the study was to determine the factors influencing oxygen delivery to and consumption in tissue. Fifty-six patients (41 male and 14 female patients of 27 to 84 years of age) scheduled to undergo cardiac surgery with CPB were enrolled in this prospective study. No operation-based selection was applied. The following data have been collected and analysed: demographics, preoperative cardiovascular profile. Arterial and venous blood gas tests, including blood glucose and lactate concentrations were obtained. We have assessed DO2 (mL/min/m2) and VO2 (mL/min/m2), venous oxygen content (CvO2) (mL/dL), arterial oxygen content (CaO2) (mL/dL) calculated according to standard equations based on haemoglobin concentration and saturation in arterial blood, cardiac output or pump flow. The main factors of organ dysoxia during CPB are the haemodilution degree and low peripheral oxygen delivery (DO2). Our study confirmed that hematocrit on pump and systemic flow rate determine the amount of oxygen delivery to the body, i.e. DO2 decrease is correlated with decrease of both hematocrit (Ht) and pump flow.
Diagnostic Markers for Early Sepsis Diagnosis in Children With Systemic Inflammatory Response Syndrome
Authors: Pavāre Jana , Grope Ilze , Kalniņš Imants , Gardovska Dace 
Published: November 2009

Diagnostic Markers for Early Sepsis Diagnosis in Children With Systemic Inflammatory Response Syndrome
Sepsis caused by infection remains a major cause of mortality among children. One of the main reasons for high sepsis mortality rates is the inability to obtain early diagnosis. Sensitive and specific biomarkers are greatly needed in rapid diagnosis of sepsis. The main aim of study was to investigate the ability of high-mobility group box-1 protein (HMGB1), lipopolysaccharide-binding protein (LBP), Interleukin-6 (IL-6), procalcitonin (PCT) and C reactive protein (CRP) to differentiate sepsis patients. Eighty-four children with Systemic Inflammatory Response Syndrome (SIRS) were included in the prospective study. Sepsis was recognised in 23% (n = 19) of them. LBP, IL-6, CRP and PCT levels were significantly higher among the sepsis group (P < 0.05). HMGB1 levels in the sepsis patients did not significantly differ from SIRS patients. In ROC analysis in sepsis patients, identification markers LBP, IL6 and CRP performed quite similarly (P < 0.001), with the best result being for IL6. Our data suggest that in early sepsis diagnosis in children, LBP, IL-6, PCT and CRP are probably the superior diagnostic markers, with the best performance by IL6. LBP and IL-6 are superior markers for sepsis patients' disease process monitoring. HMGB1 does not have a diagnostic value for sepsis patient identification.
Glucose Metabolism Disorders and Risk Factors of Type 2 Diabetes in 45-74-Years-old Population in Rīga, Latvia
Authors: Barengo Noël , Misiņa Dana , Zariņa Lauma , Kloviņš Jānis , Ozola Dita , Dērveniece Andra , Tarāsova Linda , Pīrāgs Valdis 
Published: November 2009

Glucose Metabolism Disorders and Risk Factors of Type 2 Diabetes in 45-74-Years-old Population in Rīga, Latvia
The aims of this study were to investigate the current prevalence of abnormal glucose tolerance (AGT), compare the risk factor profile between persons with and without AGT among 45-74 years-old Latvian men and women, and to validate the Finnish diabetes risk score (FINDRISC) questionnaire in detecting AGT in the middle-aged Latvian population. A cross-sectional survey among the 45-74-years old population randomly selected from the registers of general practitioners in Rīga, Latvia was carried out between April 2008 and March 2009. The survey consisted of a questionnaire, measurements such as height, weight, waist circumference, and blood pressure as well as blood oral glucose tolerance test (OGTT), cholesterol and its fractions. Prevalence of obesity, central obesity and physical inactivity were high in the Latvian population. Women with AGT had a worse risk factor profile for T2D and cardiovascular diseases compared to those with normal glucose tolerance. No differences were found in the risk factor profile between men with and without AGT. A high proportion of men and women with more than 11 FINDRISC points had undetected AGT. The FINDRISC questionnaire can be used in clinical practice to detect persons with AGT in the Latvian population.
Sensitivity and Reproducibility of Polymerase Chain Reaction Assays for Detection of Human Herpesviruses 6 and 7
Authors: Kozireva Svetlana , Užameckis Dmitrijs , Bariševs Mihails , Murovska Modra 
Published: November 2009

Sensitivity and Reproducibility of Polymerase Chain Reaction Assays for Detection of Human Herpesviruses 6 and 7
Human herpesvirus 6 (HHV-6) and 7 (HHV-7) are ubiquitous viruses that undergo latency and may become reactivated leading to cytomegalovirus reactivation, bone marrow suppression, nervous system dysfunction, graft-versus-host disease and increased mortality. The aim of this study was to identify the most sensitive and reproducible nPCR for detection of HHV-6 and HHV-7 infection and to evaluate the reproducibility of these assays in different laboratories. The sensitivity of the six previously published HHV-6 (one targeting hypothetical protein Bgp009 gene, two — large tegument protein gene, one — major binding protein gene and two targeting hypothetical Bgp071 protein gene) and four HHV-7 (targeting nuclear phosphoprotein, tegument phosphoprotein, large tegument protein and immediately early A transactivator gene) nPCRs was determined. The most sensitive HHV-6 nPCR was targeted Bgp071 protein gene, which could detect 5 genomic copies of HHV-6. The most sensitive and reproducible HHV-7 nPCR assay, targeting nuclear phosphoprotein gene, could detect 1 genomic copy of HHV-7. The reproducibility of the selected HHV-6 and HHV-7 nPCRs was evaluated in five different laboratories. The results obtained in all laboratories were identical to our results, confirming that these nPCRs are useful as assays for molecular diagnostics of HHV-6 and HHV-7 infection.
Relation of Endothelial Dysfunction and Adipokines Levels to Insulin Resistance in Metabolic Syndrome Patients
Authors: Tretjakovs Pēteris , Jurka Antra , Bormane Inga , Miķelsone Indra , Reihmane Dace , Balode Līga , Jaunalksne Inta , Mackēvičs Vitolds , Stuķēna Inga , Bahs Guntis , Lejnieks Aivars , Aivars Juris , Pīrāgs Valdis 
Published: November 2009

Relation of Endothelial Dysfunction and Adipokines Levels to Insulin Resistance in Metabolic Syndrome Patients
Obese metabolic syndrome (MS) patients were categorised into three groups: 44 with type 2 diabetes mellitus (T2DM)(D); 20 with T2DM and coronary artery disease (CAD) (DC), and 26 with MS alone (M). Eighteen healthy subjects were selected as controls (C). Insulin resistance (IR) was assessed by HOMA-IR. Adiponectin, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) concentrations were measured by xMAP technology. Endothelin-1 (ET-1) was determined by ELISA. We used laser Doppler imaging for evaluating cutaneous endothelium-dependent vasodilatation in the hand. D and DC groups had significantly elevated IR compared with M or C group (P < 0.01). TNF-α, IL-6, IL-8, MCP-1 and ET-1 levels in DC were significantly elevated compared with other groups (P < 0.001). IL-6, IL-8, MCP-1 and ET-1 in D group were higher than those in C group (P < 0.05). TNF-α, IL-6, IL-8, MCP-1 and ET-1 concentrations were correlated with HOMA-IR indexes and adiponectin levels. All patients had lower adiponectin concentrations than controls (P < 0.001), but there were no differences between the patient groups. Only D and DC groups demonstrated a significant and similar decrease in LDI-Ach marker compared to C group (P < 0.001). LDI-Ach values were significantly correlated with HOMA-IR indexes and adiponectin levels (P < 0.001). Our findings show that obese MS patients have significantly increased HOMA-IR, TNF-α, IL-6, MCP-1 and IL-8 levels, decreased adiponectin concentration, and endothelial dysfunction, but the presence of T2DM and CAD in these patients is associated with more pronounced endothelial dysfunction and increased production of inflammatory cytokines and chemokines.
Importance of the Exercise Test Follow-up Programme for Patients with Coronary Artery Disease who Underwent Percutaneous Coronary Intervention
Authors: Mintāle Iveta , Narbute Inga , Jēgere Sanda , Zabunova Milāna , Lūriņa Dace , Zakke Iļja , Dzērve Vilnis , Ērglis Andrejs 
Published: November 2009

Importance of the Exercise Test Follow-up Programme for Patients with Coronary Artery Disease who Underwent Percutaneous Coronary Intervention
The clinical course and prognosis of coronary heart disease (CHD) can be modified favourably with percutaneous coronary intervention (PCI) in combination with medication. A follow-up programme was developed in the Latvian Centre of Cardiology, which included a stress electrocardiogram for patients after PCI. This is the first study in Latvia, and provides wide opportunities to evaluate functional status of patients, treatment effectiveness, possible risks and prognosis after PCI. Exercise tests are widely used for the evaluation and diagnostics of CHD. This method has been successfully implemented in diagnostics of restenosis in coronary arteries, a process which pathophysiologically differs from primary atherosclerosis. A total of 7,300 patients with CHD were followed-up in one year after PCI. An exercise test was conducted one, three, six and twelve months after PCI. Clinical and functional status of patients and risk of restenosis were evaluated and corrections in medications were made. Seventeen percent of patients had chest pain and 13% had significant ST-segment changes in electrocardiogram. Restenosis of coronary arteries in angiography were established in 6.4%. In half of those patients above restenosis was diagnosed early — three to six months after PCI. We established a patient subgroup (22%) with "silent" ischemia (positive exercise test without chest pain), out of whom 41% had restenosis. For left main (LM) disease patients 50% of all restenosis diagnoses also were diagnosed early (three to six month after PCI). Restenosis was associated with ST-segment deviation in the exercise electrocardiogram. A lower Robinson index (RI) was registered in the same group of patients. A focussed follow-up programme performing exercise test allows to determine timely possible risk of restenosis, to adapt medication doses, to reduce risk factors and to influence positively patients' compliance.
The Incidence Rate of HIV Type-1 drug Resistance in Patients on Antiretroviral Therapy: A Nationwide Population-Based Danish Cohort Study 1999–2005
Authors: Audelin Anne Margrethe , Lohse Nicolai , Obel Niels , Gerstoft Jan , Jørgensen Louise Bruun 
Published: November 2009

Background Newer antiretroviral treatment regimens for HIV carry a lower risk of inducing drug resistance mutations. We estimated changes in incidence rates (IRs) of new mutations in HIV-infected individuals receiving highly active antiretroviral therapy (HAART). Methods Population-based data were obtained from the Danish HIV Cohort Study and the Danish HIV Sequence Database. We included treatment-naive patients initiating HAART after December 1997 and computed time to first drug resistance mutation, identified as new mutations detected within 1 year after a 60-day period of treatment failure (HIV RNA>1,000 copies/ml). We estimated annual IRs of new resistance mutations towards nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs) and protease inhibitors (PI), and of new specific resistance mutations. Results A total of 1,829 individuals were observed for 7,294 person-years at risk (PYR). The IR of NRTI resistance decreased from 13.1 per 1,000 PYR (95% confidence interval [CI] 4.9–35.0) in 1999 to 3.7 (1.9–7.2) in 2004–2005 (test for trend P=0.024). The IR of NNRTI resistance decreased from 15.4 (2.2–109.6) in 1999 to 7.9 (4.6–13.6) in 2004–2005 ( P=0.077). The IR of PI resistance decreased from 7.5 (1.4–21.8) in 1999 to 2.9 (0.7–11.4) in 2002–2003 ( P=0.148). The IRs were low for specific resistance mutations, except for M184V (IR 5.6 [4.0–7.9]) and K103N (IR 8.2 [5.6–12.0]). Conclusions The incidence of acquired drug resistance has decreased among HIV-infected patients treated with HAART in Denmark during 1999–2005.
Prophylactic and therapeutic efficacy of a chimeric monoclonal antibody specific for H5 haemagglutinin against lethal H5N1 influenza
Authors: Prabhu Nayana , Prabakaran Mookkan , Hongliang Qian , He Fang , Ho Hui-Ting , Qiang Jia , Goutama Michael , Lim Angeline Pei-Chiew , Hanson Brendon J , Kwang Jimmy 
Published: November 2009

Background Recent outbreaks of highly pathogenic H5N1 viruses in humans indicate that no endogenous protection exists in the general population. Vaccination programmes against this new pathogen require synthesis of endogenous antibodies and cannot provide any immediate protection in the event of a pandemic. Passive immunization with humanized neutralizing monoclonal antibodies can prove to be promising in preventing a catastrophic pandemic. Methods A murine monoclonal antibody (mAb) 3B1 of immunoglobulin M isotype was switched to a chimeric immunoglobulin G1. BALB/c mice were used to study the protective efficacy of the chimeric mAbs against a lethal H5N1 virus challenge with strains from clades 1 and 2.1. Kinetics of the viral load were determined during the course of the treatment. Results The chimeric mAb, in passive administration, was able to protect 100% of the mice when challenged with H5N1 strains from clades 1 or 2.1. Prophylaxis at 1 day prior to challenge and treatment at 1 day after challenge with this mAb resulted in the clearance of the virus from the lungs of the infected mice within 6 days post-viral challenge. Conclusions Passive immunotherapy using chimeric mAb 3B1 can be an effective tool in both the prophylaxis and treatment of highly pathogenic H5N1 infection, providing the immediate immunity needed to contain a future influenza pandemic.
A population analysis of weight-related differences in lopinavir pharmacokinetics and possible consequences for protease inhibitor-naive and -experienced patients
Authors: Bouillon-Pichault Marion , Jullien Vincent , Piketty Christophe , Viard Jean-Paul , Morini Jean-Pierre , Chhun Stéphanie , Krivine Anne , Salmon Dominique , Dupin Nicolas , Weiss Laurence , Lortholary Olivier , Pons Gérard , Launay Odile , Treluyer Jean-Marc 
Published: November 2009

Background Lopinavir is a potent protease inhibitor (PI) used for the treatment of HIV infection. Different lopinavir target trough concentrations (Ctroughs) were previously determined according to patient treatment histories: 1 mg/l for PI-naive patients, and 4 and 5.7 mg/l for PI-experienced patients. However, the probability to achieve these target Ctroughs with the current 400 mg twice-daily or 800 mg once-daily doses of the new tablet form, and the influence of body weight on this probability are unknown. Methods A population pharmacokinetic model for lopinavir was developed using data from 424 HIV type-1-infected patients, and the final model was used to estimate the probability to achieve target Ctroughs via Monte Carlo simulations. Results A one-compartment model adequately described the data. Mean population estimates (percentage inter-individual variability) were 4.61 l/h (36%) for apparent clearance (CL/F) and 63.2 l (70%) for apparent distribution volume. Body weight was found to explain the interindividual variability of lopinavir CL/F. Probability to achieve the 1 mg/l target Ctrough was >96% for the twice-daily dose and comprised between 80% and 90% for the once-daily dose. The probability to achieve the 4 and 5.7 mg/l target Ctroughs with the twice-daily dose significantly decreased when body weight increased (from 76% to 61% and from 56% to 37% respectively, for body weights increasing from 50 to 90 kg). Conclusions These results support lopinavir therapeutic drug monitoring and the use of higher lopinavir doses for PI-pretreated patients.
Prevalence of HIV type-1 drug-associated mutations in pre-therapy patients in the Free State, South Africa
Authors: Huang Kuan-Hsiang Gary , Goedhals Dominique , Fryer Helen , van Vuuren Cloete , Katzourakis Aris , Oliveira Tulio De , Brown Helen , Cassol Sharon , Seebregts Chris , McLean Angela , Klenerman Paul , Phillips Rodney , Frater John ,   the Bloemfontein-Oxford Collaborative Group
Published: November 2009

Background We aimed to characterize the molecular epidemiology of HIV type-1 (HIV-1) and the prevalence of drug- associated mutations prior to initiating highly active antiretroviral therapy (HAART) in the Free State province, South Africa. The Free State has a population of 3 million, an antenatal HIV prevalence of approximately 34% and a well established infrastucture for antiretroviral (ARV) provision. Methods HIV-1 polymerase genes were sequenced from 425 HAART-naive HIV-1-positive patients at voluntary primary healthcare HIV testing centres, who were subsequently attending district centres for assessment for commencing ARVs. Patients (>18 years) were sampled randomly with no exclusion for gender or clinical criteria. Sequences were analysed according to phylogeny and drug resistance. Results Phylogenetic clustering within the cohort was suggestive of multiple introductions of subtype C virus into the region. Drug resistance mutations (according to the International AIDS Society-USA classification) were distributed randomly across the cohort phylogeny with an overall prevalence of 2.3% in the sampled patients. When stratified according to CD4+ T-cell count, the prevalence of resistance was 3.6%, 0.9% and 1.2% for CD4+ T-cell counts <100, 200-350 and >500 cells/μ l, respectively, and was most common for non-nucleoside reverse transcriptase inhibitor resistance (3.1% in patients with CD4+ T-cell count <100 cells/μ l). We surveyed all drug-selected mutations and found further significant clustering among patients with low CD4+ T-cell counts ( P=0.003), suggesting unrecognized exposure to ARVs. Conclusions In the Free State population, there was a statistical association between low CD4+ T-cell counts and drug-associated viral polymorphisms. Our data advocate the benefit of detailed history taking from patients starting HAART at low CD4+ T-cell counts with close follow-up of the virological response.
Evolution of hepatitis B virus mutation during entecavir rescue therapy in patients with antiviral resistance to lamivudine and adefovir
Authors: Choe Won Hyeok , Hong Sun Pyo , Kim Byung Kook , Ko Soon Young , Jung Young Kul , Kim Ji Hoon , Yeon Jong Eun , Byun Kwan Soo , Kim Kyun-Hwan , Ji Seung Il , Kim Soo-Ok , Lee Chang Hong , Kwon So Young 
Published: November 2009

Background The efficacy of entecavir (ETV) monotherapy in treatment-experienced patients with chronic hepatitis B (CHB) is debatable. Methods A total of 22 hepatitis B e antigen (HBeAg)-positive CHB patients who had shown viral breakthrough or suboptimal response with lamivudine (3TC) and adefovir disoproxil (ADV) therapy were treated with 1.0 mg of ETV. Clinical and virological parameters were monitored every 3 months. Restriction fragment mass polymorphism assays were used to detect antiviral resistance. Results During 3TC and ADV therapy, 11 patients had rtM204V/I mutations, 2 had rtA181V/T or rtN236T, 7 had both and 2 had no 3TC- or ADV-related mutations. After switching to ETV monotherapy, the median change in serum hepatitis B virus (HBV) DNA level was -2.1 log10 copies/ml. Virological response (HBV DNA<300 copies/ml) was achieved in 1 of 18 patients with pre-existing rt204 mutations, whereas it was achieved in all 4 patients without pre-existing rt204 mutations regardless of the presence of rt181 or rt236 mutations. Changes in mutational patterns during ETV therapy showed that rt204 mutations persisted or re-emerged. Relative abundances of rtM204V/I mutations in total viral populations gradually increased under ETV rescue, whereas those with rtA181V/T and rtN236T mutations decreased. ETV resistance mutations (rtL180M+rtT184I/L[rtS202G]+rtM204V) were detected in five patients with pre-existing rt204 mutations. Conclusions ETV monotherapy resulted in a limited virological response in patients who had previously failed 3TC and ADV rescue therapy. The limited efficacy might be associated with residual or reselected rtM204V/I mutations leading to ETV resistance. Combination treatment including potent antiviral agents should be recommended for patients with pre-existing rtM204V/I mutations.