bluuebunny/crossref_metadata_2025_split huggingface dataset:
An evaluation of data for 10 children born to mothers who attempted suicide by taking large doses of alprazolam during pregnancy
Authors: Gidai J , Ács N , Bánhidy F , Czeizel AE 
Published: September 2008

FDA has identified alprazolam, a new type of benzodiazepine, as pregnancy category D. The objective of this study was to evaluate the effects on fetal development of very large doses of alprazolam that were used for suicide attempts during pregnancy. Pregnant women were identified among the patients of the Department of Toxicology Internal Medicine, Korányi Hospital, Budapest, who were admitted as self-poisoned subjects from a total population of the three million people of Budapest and its surrounding region. Rates of congenital abnormalities, intrauterine fetal development, and cognitive-behavioral status were compared between children born to mothers who attempted suicide during pregnancy using alprazolam alone or in combination with other drugs and in their sib controls. Between 1984 and 1993, 559 pregnant women attempted suicide during pregnancy with drugs: 30 of these women self-poisoned with alprazolam, 10 delivered live-born infants who were examined. Doses of alprazolam used were between 7.5 and 100 mg, with a mean of 30 mg. Six of the 10 exposed children were born to mothers who attempted suicide between the 6th and 12th postconceptional weeks. Of the 10 exposed children, two had congenital abnormalities. One had a multiple congenital abnormality that included atypical gastroschisis and minor anomalies; an association of this defect and the 30 mg alprazolam used for self-poisoning in the 14th postconceptional week cannot be excluded. Another exposed child had mild pectus excavatum, but the times of the suicide attempt and the critical period for producing this defect did not overlap. Of 12 sibs, one had a multiple congenital abnormality. Thus, the rate of congenital abnormalities did not significantly differ between exposed children and their sibs. Mean birth weight was higher for babies born to mothers who attempted suicide by alprazolam during pregnancy than in their sib controls. Cognitive status and behavioral scale of the exposed children did not indicate fetotoxic effects, including neurotoxic effects, of large doses of alprazolam. The large doses of alprazolam used for self-poisoning during pregnancy did not result in a significantly higher rate of congenital abnormalities; however, there were only 10 self-poisoned pregnant women, and an association of one multiple congenital abnormality with a large dose of alprazolam cannot be excluded. The findings in this study did not identify fetotoxicity, including neurotoxicity, of very large doses of alprazolam. Our study shows that the self-poisoning model is feasible and provides beneficial information for use in estimating human teratogenic and fetotoxic risks of drugs.
Self-poisoning during pregnancy as a model for teratogenic risk estimation of drugs
Authors: Czeizel AE , Gidai J , Petik D , Timmermann G , Puhó EH 
Published: September 2008

The results of animal investigations cannot be directly extrapolated to pregnant women. Clinical and analytical epidemiological studies for human teratogenic risks have many inherent methodological problems and their predictions must be regarded with caution. Evaluation of the potential teratogenicity of extremely large doses of drugs in self-poisoned pregnant women who attempted suicide offers a unique model for finding associations between congenital abnormalities and different drugs. All self-poisoned patients were cared for at a toxicological inpatient clinic in Budapest, between 1960 and 1993. Out of 1044 pregnant women identified from three different periods of the project, 19 died. Women who survived were visited at home to reveal birth outcomes, and their children were evaluated medically to identify congenital abnormalities and to estimate cognitive–behavioral status. The previous or subsequent children of these pregnant women were used as controls. In general, self-poisoned pregnant women were young (peak age was 18 to 20 years) and primiparous; 55% were unmarried and of lower socioeconomic status. Suicide attempts with drugs were most frequent in the fourth postconceptional week and second pregnancy month. Of 1044 self-poisoned pregnant women, 411 delivered live-born babies, of which 367 children (89.3%) were evaluated. The self-poisoning model appears to have several benefits (e.g., dose-response estimation) in comparison with other methods. It is suggested that an international monitoring system of self-poisoned pregnant women should be established to provide a larger database.
Opinion Leadership in Indian Villages and Diffusion of E-Choupal
Authors: Kim Do Kyun , Chitnis Ketan , Vasanti P.N. , Singhal Arvind 
Published: September 2008

e-Choupal was initially set up by the Indian Tobacco Company (ITC) in 2000, providing farmers with information about latest market prices of crops, a provision to sell crops directly to buyers and up-todate information on weather and farming practices through its Internet networks. This article analyzes the role of opinion leadership in farmers’ communication networks of farmers in Madhya Pradesh, India, and its strategic use to diffuse a source of innovative-framing information source, e-Choupal. The specific purposes of this study are to identify opinion leaders by using social network analysis and to analyze the attributes of the opinion leaders in the diffusion of e-Choupal in Indian villages. Our research site was the State of Madhya Pradesh in India where e-Choupal centres were first set up. Our data was collected in 14 villages covered by three e-Choupal centers. Using a sociometric method of social network analysis, 225 Indian farmers’ communication networks were analyzed. As a result, we revealed four network groups and identified opinion leaders in the groups. The identified opinion leaders were Sanchalaks, who were selected and trained by ITC, and who lived in and owned the house where the e-Choupal system was installed. In terms of diffusion, the Sanchalaks were both, that is, information sources about e-Choupal and key influentials on farmers’ decisions to adopt the innovation. This study also discusses some important social network attributes among Indian farmers, grounded in the diffusion of innovation theory.
New approaches to COPD
Authors: Barnes P. J. 
Published: September 2008

No currently available treatments reduce the progression or suppress the inflammation of chronic obstructive pulmonary disease (COPD). However, with a better understanding of the inflammatory and destructive process, several targets have been identified, and new treatments are now in clinical development.Several specific therapies are directed against the influx of inflammatory cells into the airways and lung parenchyma that occurs in COPD, including adhesion molecule and chemokine-directed therapy, as well as therapies to inhibit tumour necrosis factor-α. Broad spectrum anti-inflammatory drugs are also in development, and include inhibitors of phosphodiesterase-4, p38 mitogen-activated protein kinase, nuclear factor-κB and phosphoinositide-3 kinase-γ. More specific approaches include antioxidants, inhibitors of inducible nitric oxide synthase, and leukotriene B4receptor antagonists. Inhibitors of epidermal growth factor receptor kinase and calcium-activated chloride channel inhibitors have the potential to inhibit mucus hypersecretion. Other therapies are targeted at the structural changes of COPD. Therapy to inhibit fibrosis is being developed against transforming growth factor-β1and protease activated receptor-2. There is also a search for serine proteinase and matrix metalloproteinase inhibitors to prevent lung destruction and the development of emphysema, as well as drugs such as retinoids that may even reverse this process.There is the need for validated biomarkers and monitoring techniques in early clinical studies with new therapies for chronic obstructive pulmonary disease.
Treatment of stable COPD: antioxidants
Authors: MacNee W. 
Published: September 2008

There is considerable evidence that an increased oxidative burden occurs in the lungs of patients with chronic obstructive pulmonary disease (COPD) and this results in an imbalance between oxidants/antioxidants or oxidative stress, which may play a role in many of the processes involved in the pathogenesis of COPD. These include enhanced proteolytic activity, mucus hypersecretion and the enhanced inflammatory response in the lungs to inhaling tobacco smoke, which is characteristic of COPD. COPD is now recognised to have multiple systemic consequences, such as weight loss and skeletal muscle dysfunction. It is now thought that oxidative stress may extend beyond the lungs and is involved in these systemic effects.Antioxidant therapy therefore would seem to be a logical therapeutic approach in chronic obstructive pulmonary disease. There is a need for more potent antioxidant therapies to test the hypothesis that antioxidant drugs may be a new therapeutic strategy for the prevention and treatment of chronic obstructive pulmonary disease.
Bronchodilator treatment of stable COPD: long-acting anticholinergics
Authors: Vincken W. 
Published: September 2008

Since airflow obstruction in chronic obstructive pulmonary disease (COPD) is to some extent reversible, bronchodilators play an important role in the maintenance treatment of COPD the more they reduce hyperinflation and, as a result, improve dyspnoea and exercise capacity. Since parasympathetic activity is the dominant reversible component of airflow obstruction in COPD, inhaled short-acting anticholinergic agents (SAAC), in particular ipratropium, became an efficient and safe first-line treatment, especially when combined with a short-acting β2-adrenergic receptor agonist. Even better results were obtained when combining the SAAC ipratropium to a long-acting β2-adrenergic receptor agonist (LABA), once they became available.Recently, tiotropium bromide, the first of a new class of selective and long-acting anticholinergic agents was introduced for once-daily maintenance treatment of COPD patients. Several large long-term randomised clinical trials comparing tiotropium to placebo as well as to the SAAC ipratropium and the LABA salmeterol, have confirmed the long-acting and superior bronchodilator effect of tiotropium without any evidence of drug tolerance developing. These studies also have clearly demonstrated that tiotropium positively affects several other important health outcomes, such as dyspnoea sensation, exercise capacity, utilisation of rescue bronchodilators, health-related quality of life, COPD exacerbations and hospitalisations because of exacerbations. The improvement in these real-life outcomes appears related to the reduction in both static and dynamic hyperinflation. In all these studies, tiotropium was well tolerated and safe; the only relevant side-effect encountered being dry mouth, usually mild and often transitory. Finally, it has been shown that the combination of tiotropium with a LABA affords superior bronchodilatation than both agents alone, indicating that both classes of long-acting bronchodilators should be regarded as complements rather than opponents.In conclusion, a sufficiently large and convincing database now exists to propose the once-daily long-acting anticholinergic tiotropium as first-line maintenance treatment for all chronic obstructive pulmonary disease patients in global initiative for chronic obstructive lung disease (GOLD)-class II and above, with a step-up to its combination with a long-acting β2-adrenergic receptor agonist in case of suboptimal clinical effect.
Treatment of COPD exacerbations: antibiotics
Authors: Wilson R. 
Published: September 2008

The debate about the importance of bacterial infection in chronic obstructive pulmonary disease will continue. About half of exacerbations yield positive sputum bacteriology, and the isolation rate can be increased by selection of purulent samples.However, bacteria are also isolated in the stable state. The presence of bacteria in sputum alone during an exacerbation does not prove causation. Bacteria have been associated with airway inflammation both in the stable state, when the level of inflammation is related to the size of the bacterial load, and during exacerbations, when resolution of the inflammation is related to bacterial eradication.New evidence has been obtained from epidemiological, immunological and antibiotic studies that supports a role for bacterial infection in causing neutrophilic airway inflammation in chronic obstructive pulmonary disease, and if accepted should lead to new research in the use of antibiotics.
Reducing cholinergic constriction: the major reversible mechanism in COPD
Authors: Brusasco V. 
Published: September 2008

The airway narrowing in chronic obstructive pulmonary disease (COPD) has often been misunderstood as being irreversible. However, a large proportion of patients with COPD do respond to bronchodilator agents with significant changes in lung function.Unlike in asthma, abnormalities in airway smooth muscle structure or function are not believed to play a key role in COPD airway narrowing. Although there are only limited data suggesting that cholinergic tone may be increased in COPD, the well-documented efficacy of antimuscarinic agents in increasing airway calibre suggests that cholinergic tone represents the major reversible component of airflow obstruction in these patients. Airway wall thickening and loss of airway-to-parenchyma interdependence are nonreversible components of airflow obstruction in COPD that may amplify the effect of changes in airway smooth muscle tone. Thus, keeping airway smooth muscle tone to a minimum might offer patients long-lasting airway patency and protection against breathlessness, which is the major complaint of patients with COPD.Receptor antagonism by anticholinergic agents can achieve effective relaxation of airway smooth muscle in COPD. According to a classical view of cholinergic receptor function and distribution, the ideal anticholinergic bronchodilator would be one that blocks both M1and M3receptors, which mediate airway smooth muscle contraction, but not the M2receptor, stimulation of which reduces acetylcholine release from vagus nerve endings and prevents the airway smooth muscle from contracting by excessive increments.Agents with such pharmacodynamic selectivity are not available, but effective and prolonged inhibition of airway smooth muscle tone has been obtained with tiotropium, which binds to all three major muscarinic receptor subtypes, but for much longer to M3than to M2receptors. Recent data show that long-term treatment with tiotropium for 1 yr helps sustain 24-h airway patency. This sustained effect may help to explain the improvements in both exacerbation rate and lung function observed in chronic obstructive pulmonary disease patients treated with tiotropium.
Impacting patient-centred outcomes in COPD: deconditioning
Authors: Casaburi R. 
Published: September 2008

Patients with chronic obstructive pulmonary disease (COPD) frequently suffer from exercise intolerance, leading to a reduced ability to participate in activities of daily life and, therefore, to a reduced health-related quality of life (HRQoL). An important determinant of exercise intolerance is the loss of muscle mass.Although the mechanism for loss of muscle function is multi-factorial, deconditioning appears to play a primary role in many patients. COPD patients often have decreased fat-free mass compared with healthy counterparts and reduced muscle cross-sectional area. It seems, then, that a cycle of decline often characterises COPD, in which inactivity results in muscle weakness, which in turn acts as a further deterrent to exercise. Such deconditioning can be reversed by pulmonary rehabilitation, leading to significant improvements in exercise tolerance and HRQoL.Recent research suggests that the effectiveness of pulmonary rehabilitation can be amplified with concomitant administration of tiotropium (a long-acting bronchodilator) or supplemental oxygen. This suggests that facilitating higher training work-rates can enhance the anabolic effects of training.Patients should be encouraged to maintain activity levels in the follow-up period after training, in order to retain the benefits of rehabilitation.
Tiotropium as essential maintenance therapy in COPD
Authors: Decramer M. 
Published: September 2008

Over the past decade, several large-scale clinical trials have been performed to assess the impact of pharmacological treatments on patient-centred outcomes such as dyspnoea, exercise tolerance, exacerbations and health-related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD).Tiotropium, a once-daily inhaled anticholinergic agent that works through prolonged muscarinic M3receptor blockade, has consistently been shown to provide sustained improvements in lung function parameters. Furthermore, several prospective trials have shown that tiotropium improves exercise tolerance and augments the beneficial effects of pulmonary rehabilitation. Beyond these important physiological outcomes, tiotropium has been shown to reduce dyspnoea, decrease the frequency of exacerbations and improve HRQoL in studies of ≤1 yr in duration. Such improvements in patient-centred outcomes may allow patients to increase their activity levels, thereby interrupting the downward spiral of chronic inactivity that leads to physical deconditioning and further reductions in exercise tolerance.Recently, combination therapies of two long-acting bronchodilators have been examined more closely regarding their potential to provide patients with superior symptom relief compared with that provided by single-agent therapy.Because maintenance treatment with tiotropium provides consistent and sustained improvements in many relevant clinical outcomes of chronic obstructive pulmonary disease, it may reduce the progression of the disease. This hypothesis is being tested in the ongoing Understanding the Potential Long-term Impacts on Function with Tiotropium (UPLIFT) trial.
Circulatory effects of expiratory flow-limited exercise, dynamic hyperinflation and expiratory muscle pressure
Authors: Macklem P. T. 
Published: September 2008

This article reviews recent research in normal subjects exercising with and without expiratory flow limitation at ∼1 L·s−1imposed by a Starling resistor in the expiratory line, and in patients with chronic obstructive pulmonary disease (COPD), using optoelectronic plethysmography to measure respiratory kinematics, combined with mouth, pleural and abdominal pressure measurements, to assess work of breathing and respiratory muscle performance.In normal subjects, flow-limited exercise resulted in the following: 1) Impaired exercise performance due to intolerable dyspnoea; 2) hypercapnia; 3) excessive respiratory muscle recruitment; 4) blood shifts from trunk to extremities; 5) a 10% reduction in cardiac output and a 5% reduction in arterial oxygen saturation, decreasing energy supplies to working respiratory and locomotor muscles. In both normal subjects and in COPD patients, dynamic hyperinflation did not always occur. Those patients that hyperinflated had worse lung function and less work of breathing, but better exercise performance than the others, in whom expiratory muscle recruitment prevented dynamic hyperinflation at the cost of increased work of breathing and excessive oxygen cost of breathing. This established an early competition between respiratory and locomotor muscles for available energy supplies.Dynamic hyperinflation is a better exercise strategy in chronic obstructive pulmonary disease than expiratory muscle recruitment, but the benefit it confers is small.
Sampling for stereology in lungs
Authors: Nyengaard J. R. , Gundersen H. J. G. 
Published: September 2008

The present article reviews the relevant stereological estimators for obtaining reliable quantitative structural data from the lungs. Stereological sampling achieves reliable, quantitative information either about the whole lung or complete lobes, whilst minimising the workload. Studies have used systematic random sampling, which has fixed and constant sampling probabilities on all blocks, sections and fields of view. For an estimation of total lung or lobe volume, the Cavalieri principle can be used, but it is not useful in estimating individual cell volume due to various effects from over- or underprojection. If the number of certain structures is required, two methods can be used: the disector and the fractionator.The disector method is a three-dimensional stereological probe for sampling objects according to their number. However, it may be affected on tissue deformation and, therefore, the fractionator method is often the preferred sampling principle. In this method, a known and predetermined fraction of an object is sampled in one or more steps, with the final step estimating the number. Both methods can be performed in a physical and optical manner, therefore enabling cells and larger lung structure numbers (e.g.number of alveoli) to be estimated. Some estimators also require randomisation of orientation, so that all directions have an equal chance of being chosen. Using such isotropic sections, surface area, length, and diameter can be estimated on a Cavalieri set of sections.Stereology can also illustrate the potential for transport between two compartments by analysing the barrier width. Estimating the individual volume of cells can be achieved by local stereology using a two-step procedure that first samples lung cells using the disector and then introduces individual volume estimation of the sampled cells.The coefficient of error of most unbiased stereological estimators is a combination of variance from blocks, sections, fields of view, and noise due to random positioning of the probes. This can be decreased by increasing the number of units from the element causing the most variance. Overall, stereology provides lung scientists with efficient tools for estimating structural components correctly.