bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of community-acquired lower respiratory tract infections in adults
Authors: Örtqvist Å. 
Published: January 2003

Community-acquired lower respiratory tract infection (LRTI) is a common cause of acute illness in adults. The spectrum of disease ranges from a mild mucosal colonisation or infection, acute bronchitis or acute exacerbation of chronic bronchitis/chronic obstructive pulmonary disease (AE-CB/COPD), to an overwhelming parenchymal infection with the patient presenting with severe community-acquired pneumonia (CAP).Although the great majority of LRTIs are self-limiting viral infections, CAP is most often a bacterial disease with a substantial mortality. Thus, antibiotic treatment is rarely indicated for acute bronchitis and is only indicated for the more severe cases of AE-CB/COPD, but it is nearly always indicated for CAP, for which a delay in treatment may increase the risk of a fatal outcome. It may be difficult to differentiate between a viral and a bacterial LRTI, or between bronchitis/AE-CB/COPD and CAP. This may be one reason why antibiotics are prescribed to more than two-thirds of patients with LRTIs in Europe and the USA. Considering the worldwide development of antibiotic resistance, this is not an acceptable situation.Since an empirical approach is nearly always necessary in the management of LRTI, greater emphasis must be placed on the decision of whether or not to prescribe an antibiotic at all. This decision should be based on an assessment of the severity of the disease, including underlying risk factors, and on markers for bacterial/parenchymal/invasive LRTI. The choice of empirical therapy must be based on the same data together with epidemiological information. The choice of antibiotic must always coverStreptococcus pneumoniae, which remains the main pathogen of morbidity and mortality in CAP. In hospital, attempts should be made to obtain an aetiological diagnosis in order to be able to switch to a specific treatment or to evaluate a failure of empirical therapy.Several guidelines for the management of community-acquired pneumonia have been published during the last 10 yrs. Some reports indicate that the implementation of such guidelines has resulted in lowered costs, length of stay in hospital and mortality. However, the results from these studies are not consistent and the evidence is still weak.
Tuberculosis therapy: past, present and future
Authors: Iseman M.D. 
Published: January 2003

The major historical landmarks of tuberculosis (TB) therapy include: the discovery of effective medications (streptomycin and para-aminosalicylic acid) in 1944; the revelation of “triple therapy” (streptomycin, para-aminosalicylic acid and isoniazid) in 1952, which assured cure; recognition in the 1970s that isoniazid and rifampin could reduce the duration of treatment from 18 to 9 months; and the observation in the 1980s that adding pyrazinamide to these drugs allowed cures in only 6 months.To combat noncompliance, intermittent regimens, twice or thrice weekly, have been proven to cure even far-advanced TB in as few as 62–78 encounters over 26 weeks.However, these regimens are not sufficiently short or convenient to facilitate effective treatment in resource-poor countries. Therefore, drug-resistant strains have emerged to threaten TB control in various areas of the world, including India, China, Russia and the former Soviet Union. For these reasons, it is vital that new medications are developed to shorten the duration of therapy, increase the dosing interval of intermittent regimens and replace agents lost to resistance. Other special considerations include identifying optimal therapy for persons with acquired immune deficiency syndrome, particularly noting the problems of drug/drug interactions for those receiving antiretroviral treatment.Finally, the Alchemist's Dream of tuberculosis should be pursued: modulating the immune response to shorten treatment and/or overcome drug resistance.
Comparative mycobacterial genomics as a tool for drug target and antigen discovery
Authors: Cole S.T. 
Published: January 2003

Genomics and the associated downstream technologies are generating vast data sets that provide new opportunities for understanding and combating both infectious and genetic diseases in humans.The genomic approach has been applied to tuberculosis, a major cause of transmissible morbidity and mortality, with notable success. Complete genome sequences are now available for three members of theMycobacterium tuberculosiscomplex and the related intracellular pathogenM. leprae.Many of the predictions generatedin silicoby genomics have been validated through functional analysis, including studies of the transcriptome and proteome, and led to the identification of essential genes. Knowledge of the latter defines potential targets for new and existing drugs and their specificity can be assessed by comparative genomics with the host or other pathogens. Genomics is also furthering tuberculosis vaccine development by pinpointing potentially antigenic proteins as well as providing better diagnostic tools to detect infection.
Exacerbations of chronic obstructive pulmonary disease: when are bacteria important?
Authors: Miravitlles M. 
Published: January 2003

The progressive course of chronic obstructive pulmonary disease (COPD) is often aggravated by exacerbations, the majority of them produced by bronchial infection. Frequent exacerbations have been demonstrated to have a negative impact on quality of life and pulmonary function in patients with COPD, particularly in active smokers. Furthermore, acute exacerbations are the most frequent cause of medical visits, hospital admissions and death among patients with chronic lung disease.Evidence indicates that the number of patients with pathogenic bacteria in respiratory secretions and the bronchial bacterial load increase during exacerbations. Furthermore, the local inflammatory response of the host parallels the increase in bacterial load. From these observations, it can be speculated that, for symptoms of acute exacerbation to appear, there must be a minimum bacterial load in the airways,i.e.a threshold above which the inflammatory reaction is severe enough to elicit clinical symptoms of exacerbation. This threshold may vary from patient to patient owing to different modifying factors. Some of these factors may be the recognised risk factors for relapse, such as increasing age, impairment of lung function, comorbid conditions or frequent exacerbations in the past.Relapse rates after ambulatory treatment of acute exacerbation of COPD may be as high as 20–25% of cases. Relapses are associated with significant mordibity and increased costs.A number of unanswered questions remain regarding exacerbations of chronic obstructive pulmonary disease. These include the role of viral infection, the importance of residual bacterial colonisation and the impact of new antibiotics on the treatment of exacerbations.
Bacteriological evidence of antibiotic failure in pneumococcal lower respiratory tract infections
Authors: Klugman K.P. 
Published: January 2003

The global pandemic of antimicrobial resistance, particularly in the pneumococcus, has had a major impact on the management of community-acquired pneumonia.A number of prospective and retrospective studies have analysed the impact of penicillin resistance on clinical outcome in pneumonia. Pharmacodynamic principles predicting success when the antibiotic dose exceeds the minimum inhibitory concentration (MIC) for 40–50% of the dosing interval have proved remarkably accurate. There is no evidence of bacteriological failure of penicillins active against resistant strains. There is a single report of the failure of the less active agent, ticarcillin. High dose oral and intravenous amoxicillin should treat strains with MICs ≤4 µg·mL−1, as should high doses of intravenous penicillin, ceftriaxone and cefotaxime. Strains of pneumococci resistant to these agents at an MIC ≥8 µg·mL−1are rare at the present time. Most other cephalosporins are less active and should not be used empirically for drug-resistantStreptococcus pneumoniae. Bacteriological failures of cefazolin, cefuroxime and ceftazidime have been reported.There is increasing evidence of bacteriologically confirmed macrolide failure of pneumonia therapy at MICs ≥4 µg·mL−1. The molecular basis of the resistance is irrelevant if the MIC is in that range or higher. Double mutants in theparCandgyrAgenes lead to fluoroquinolone resistance that has been found to cause bacteriological failure of the fluoroquinolones, particularly levofloxacin and ciprofloxacin, in the management of pneumonia and exacerbations of chronic bronchitis. Two mutations in these genes can greatly increase the MICs of all the marketed fluoroquinolones, and raise the prospect of failure of therapy even with the more active ones. However, demonstration of bacteriological failure of gatifloxacin or moxifloxicin has not yet been reported.High dose, active β‐lactams or fluoroquinolones with enhanced activity against Gram positive pathogens remain the drugs of choice for the management of community-acquired pneumonia caused by the drug-resistant pneumococcus.
Pyogenic bacterial lower respiratory tract infection in human immunodeficiency virus-infected patients
Authors: Mayaud C. , Parrot A. , Cadranel J. 
Published: January 2003

In human immunodeficiency virus (HIV)-infected patients, bacterial lower respiratory tract infections are the most frequent respiratory diseases. They are frequently the first clinical manifestation of HIV infection.The incidence and severity of bacterial lower respiratory tract infections increase with the degree of immunosuppression. At the acquired immune deficiency syndrome (AIDS) stage, the responsible bacteria and clinical presentation may be atypical. Bacterial pneumonia may be fatal, particularly in AIDS patients, and its occurrence is predictive of a reduced survival time.Pneumococcal vaccine is recommended in patients with a CD4 T‐lymphocyte count of >200 cells·mm−3and cotrimoxazole (trimethoprim/sulfamethoxazole) in patients with a CD4 T‐lymphocyte count of <200 cells·mm−3. Unfortunately, such prophylaxis remains insufficiently prescribed and its protective effect is limited.Highly active antiretroviral treatment has dramatically reduced the incidence of lower respiratory tract infection due toPseudomonasaeruginosaand opportunistic bacteria. In contrast, successful highly active antiretroviral therapy slightly decreased the risk of bacterial pneumonia due to usual bacteria, even in patients on successful highly active antiretroviral therapy.
Molecular epidemiology of tuberculosis
Authors: Burgos M.V. , Pym A.S. 
Published: January 2003

Despite the almost 50 yrs since the introduction of curative antituberculosis drugs,Mycobacterium tuberculosiscontinues to exert an enormous toll on world health, and tuberculosis remains the world's leading cause of death due to a single infectious agent. This has stimulated research efforts into finding new tools to tackle the continuing tuberculosis pandemic.One of the few successes to date has been the development of a new discipline, molecular epidemiology. This has added a further dimension to the classical epidemiology of tuberculosis and enhanced understanding of howM. tuberculosiscontinues to be successfully transmitted within populations. In the process, inadequacies in tuberculosis control programmes have been identified, helping accumulate resources for their improvement.Other technologies, based on knowledge of the complete genome sequence ofM. tuberculosis, which will provide newer tools for probing the epidemiology of tuberculosis, are now emerging. In spite of these advances, tuberculosis continues to remain a devastating infectious disease, disproportionately impacting on the world's poorest countries.The future challenge for molecular epidemiology is to provide better understanding of the transmission dynamics of tuberculosis in these settings and to stimulate the implementation of control measures on a more global scale.
Strategies against multidrug-resistant tuberculosis
Authors: Loddenkemper R. , Sagebiel D. , Brendel A. 
Published: January 2003

The rise of multidrug-resistant tuberculosis (MDR-TB), defined as tuberculosis showing resistance to at least isoniazid and rifampicin, is a serious threat to tuberculosis control in some high prevalence countries and may have some impact on low prevalence regions as well.The World Health Organization estimates that 50 million people worldwide are infected with MDR-TB, and that, in the year 2000, 273,000 (3.1%) MDR-TB cases were among the 8.7 million new tuberculosis cases. In 1998, the highest MDR-TB rates among new cases and the highest combined (new and previously treated cases) MDR-TB rates were found in Estonia (14.1 and 18.1%), Henan province in China (10.8 and 15.1%), Latvia (9.0 and 12.0%), and Ivanovo Oblast (9.0 and 12.3%) and Tomsk Oblast (6.5 and 13.7%) in the Russian Federation. The risk factors for MDR-TB are previous treatment or relapse, originating from “hot spot” areas, a history of imprisonment, homelessness and possibly also human immunodeficiency virus.The treatment of multidrug-resistant tuberculosis is difficult due to side-effects and a treatment duration of up to 3 yrs, which is expensive and often unsuccessful. Therefore, strategies for the treatment and prevention of multidrug-resistant tuberculosis are urgently required. This requires functioning tuberculosis control programmes (directly observed treatment short course), and, in some high prevalence countries, the introduction of second-line drugs on the basis of appropriate susceptibility testing (directly observed treatment short course-Plus). Only the future will show whether this “ticking time bomb” can be defused.
Community-acquired pneumonia in Europe: causative pathogens and resistance patterns
Authors: Woodhead M. 
Published: January 2003

Community-acquired pneumonia (CAP) is a common condition affecting about 1/1,000 of the adult population per year. It occurs when bacteria enter the alveolar spaces of the lung initiating an inflammatory response which leads to the clinical features of cough, sputum production, breathlessness and sometimes chest pain and haemoptysis.At the end of the last century the causal relationship between bacteria and pneumonia was established and many of the early discoveries about the causes of CAP were made in Europe. Some 41 different prospective studies have established that ∼10 different microbial pathogens regularly cause CAP with occasional cases due to other rarer causes. The frequency of these organisms in Europe is similar in most countries, but there are some geographic differences. Differences in frequency are also apparent according to illness severity. It is generally recognised thatStreptococcus pneumoniaeis the most important causal bacterium in all countries.A relatively recent development has been the appearance and spread, in some of the common causative bacteria, of resistance to commonly used antibiotics to which they were once sensitive. The frequency of such resistance does vary markedly between European countries.However, published data is often difficult to interpret. The reasons for this are that the frequency of resistance varies according to the age of the patient, the site of the sample, the clinical diagnosis, the use of prior antibiotics and the influence of special groupse.g.those with cystic fibrosis. The impact ofin vitroantibiotic resistance on clinical outcome is still poorly understood, but recent studies are helping to clarify this issue and will be discussed.
Usefulness of procalcitonin for diagnosis of sepsis in the intensive care unit
Authors: Balci Canan , Sungurtekin Hülya , Gürses Ercan , Sungurtekin Uğur , Kaptanoğlu Bünyamin 
Published: January 2003

Abstract
Introduction
The diagnosis of sepsis in critically ill patients is challenging because traditional markers of infection are often misleading. The present study was conducted to determine the procalcitonin level at early diagnosis (and differentiation) in patients with systemic inflammatory response syndrome (SIRS) and sepsis, in comparison with C-reactive protein, IL-2, IL-6, IL-8 and tumour necrosis factor-α.

Method
Thirty-three intensive care unit patients were diagnosed with SIRS, sepsis or septic shock, in accordance with the American College of Chest Physicians/Society of Critical Care Medicine consensus criteria. Blood samples were taken at the first and second day of hospitalization, and on the day of discharge or on the day of death. For multiple group comparisons one-way analysis of variance was applied, with post hoc comparison. Sensitivity, specificity and predictive values of PCT and each cytokine studied were calculated.

Results
PCT, IL-2 and IL-8 levels increased in parallel with the severity of the clinical condition of the patient. PCT exhibited a greatest sensitivity (85%) and specificity (91%) in differentiating patients with SIRS from those with sepsis. With respect to positive and negative predictive values, PCT markedly exceeded other variables.

Discussion
In the present study PCT was found to be a more accurate diagnostic parameter for differentiating SIRS and sepsis, and therefore daily determinations of PCT may be helpful in the follow up of critically ill patients.
Lung recruitment manoeuvres are effective in regaining lung volume and oxygenation after open endotracheal suctioning in acute respiratory distress syndrome
Authors: Dyhr Thomas , Bonde Jan , Larsson Anders 
Published: January 2003

Abstract
Introduction
Lung collapse is a contributory factor in the hypoxaemia that is observed after open endotracheal suctioning (ETS) in patients with acute lung injury and acute respiratory distress syndrome. Lung recruitment (LR) manoeuvres may be effective in rapidly regaining lung volume and improving oxygenation after ETS.

Materials and method
A prospective, randomized, controlled study was conducted in a 15-bed general intensive care unit at a university hospital. Eight consecutive mechanically ventilated patients with acute lung injury or acute respiratory distress syndrome were included. One of two suctioning procedures was performed in each patient. In the first procedure, ETS was performed followed by LR manoeuvre and reconnection to the ventilator with positive end-expiratory pressure set at 1 cmH2O above the lower inflexion point, and after 60 min another ETS (but without LR manoeuvre) was performed followed by reconnection to the ventilator with similar positive end-expiratory pressure; the second procedure was the same as the first but conducted in reverse order. Before (baseline) and over 25 min following each ETS procedure, partial arterial oxygen tension (PaO2) and end-expiratory lung volume were measured.

Results
After ETS, PaO2 decreased by 4.3(0.9–9.7)kPa (median and range; P < 0.005). After LR manoeuvre, PaO2 recovered to baseline. Without LR manoeuvre, PaO2 was reduced (P = 0.05) until 7 min after ETS. With LR manoeuvre end-expiratory lung volume was unchanged after ETS, whereas without LR manoeuvre end-expiratory lung volume was still reduced (approximately 10%) at 5 and 15 min after ETS (P = 0.01).

Discussion
A LR manoeuvre immediately following ETS was, as an adjunct to positive end-expiratory pressure, effective in rapidly counteracting the deterioration in PaO2 and lung volume caused by open ETS in ventilator-treated patients with acute lung injury or acute respiratory distress syndrome.
Cost of intensive care in a Norwegian University hospital 1997–1999
Authors: Flaatten Hans , Kvåle Reidar 
Published: January 2003

Abstract
Aim
The present study was performed in order to document costs of intensive care in a Norwegian university hospital and to perform an average cost-effectiveness study using the expected remaining life-years in survivors after 18 months.

Materials and methods
Patients admitted to the general intensive care unit (ICU) at Haukeland University Hospital from 1997 to 1999 were followed up to 18 months post ICU using data from the Norwegian Peoples' registry. Our ICU patients have a further mortality equal to the average population in Norway from that time. By creating an age-matched and sex-matched sample of the general Norwegian population equal to survivors 18 months after ICU treatment, we could find the expected further survival time for each ICU survivor. Direct and indirect ICU expenses in the study period were retrieved using a 'top-down' method. Outcome assessment was performed using the total ICU expenses in the period divided by the sum of the life expectancy (years) in survivors after 18 months.

Results
The total ICU costs (converted to 2001 values) were € 16,697,415, excluding the costs of radiology and the use of operating theatres, which were both impossible to retrieve. A total of 1051 patients were treated, of whom 60.9% survived up to 18 months. Further total life expectancies were 24,428 years. The average costs of an ICU day and stay per patient were € 2601 and € 14,223, respectively, and the average cost per year of survival per patient was € 684.

Discussion
The absolute costs were found to be higher than recent European ICU studies reporting on the cost of ICU treatment. However, the price of a further life-year in survivors was lower and was comparable with other medical treatment.
Systematic analysis of sequences of anti-DNA antibodies—relevance to theories of origin and pathogenicity
Authors: Rahman A , Giles I , Haley J , Isenberg D 
Published: January 2003

Sequence analysis of anti-DNA antibodies is important in determining the molecular features which distinguish potentially pathogenic antibodies from those which are less likely to be pathogenic. Previous analysis of murine anti-DNA antibody sequences suggested that particular murine immunoglobulin genes are used preferentiallyto encode such antibodies and that somatic mutations to arginine, asparagine and lysine may be important in the creation of DNA binding sites. In this paper, a systematic analysis of published human anti-DNA sequences shows no strong evidence for preferential usage of particular human VH or VL genes in anti-DNA antibodies. Somatic mutations in IgG and IgA antibodies are clustered in the complementarity determining regions (CDRs) due to the effect of antigen drive. This pocess contributes to an excess of arginine, asparagine and lysine residues in these CDRs, some of which are likely to play an important role in binding to DNA. Computer modeling and in-vitro expression experiments are likely to help define the roles played by these residues in antigen binding and pathogenicity more clearly.
Anti-DNA antibodies - overview of assays and clinical correlations
Authors: Rahman A , Hiepe F 
Published: January 2003

Many authors have studied the links between levels of anti-dsDNA antibodies and disease activity in patients with SLE. Interpretationof these studies must take into account the facts that there are a range of possible assays for anti-dsDNA and a number of indices available for assessing disease activity. A recent study compared levels of various autoantibodies with organ specific disease activity assessed during the British Isles Lupus Assessment Group (BILAG) index. Amti-dsDNA and anti-heparan sulphate levels were more likely to be raised in patients with renal than non-renal disease. Some anti-DNA antibodies are actually anti-nucleosome antibodies, which lose DNA reactivity when purified under dissociating conditions. Patients with SLE have significantly increased levels of nucleosomes in their sera compared with healthy controls. In patients with SLE, reduced clearance of nucleosomes released from apoptotic cells may induce the formation of antinucleosome antibodies.