bluuebunny/crossref_metadata_2025_split huggingface dataset:
A study of the potential teratogenic effect of large doses of promethazine used for a suicide attempt by 32 pregnant women
Authors: Petik D , Ács N , Bánhidy F , Czeizel AE 
Published: September 2008

In Hungary, promethazine, a phenothiazine antihistamine, is the second most frequently used drug during pregnancy. The purpose of this study was to examine the effects of very large doses of promethazine that were used for a suicide attempt during pregnancy on embryo-fetal development. Self-poisoned pregnant women were identified from patients of the Department of Toxicology Internal Medicine, Korányi Hospital, Budapest, who were admitted from the three million people of Budapest and surrounding region. The rate of congenital abnormalities, intrauterine development (based on pregnancy age at delivery and birth weight), and cognitive-behavioral status of exposed children born to mothers who attempted suicide with promethazine alone or in combination with other drugs during pregnancy was compared with their sib controls. In all, 89 of the 1044 women with self-poisoning during pregnancy between 1960 and 1993 used promethazine for a suicide attempt. Of these 89 women, 32 delivered newborn babies. The dose of promethazine taken by these women for self-poisoning ranged between 125 mg and 1750 mg (mean of 544 mg, i.e., 21.8 tablets). Of the 32 promethazine-exposed children, nine (28.1 %) were affected with congenital abnormalities. However, of 11 pregnant women who attempted suicide with promethazine between the 3rd and 12th postconceptional week, that is, the critical period for production of most major congenital abnormalities, only three were affected with defects, and the critical periods for producing these defects did not overlap with the time of the suicide attempt during pregnancy. Of 34 unexposed sibs, five (14.7%) had congenital abnormalities; the difference in the total rate of congenital abnormalities between the exposed children and their sib controls was not significant. There also was no difference in pregnancy age-specific birth weight between exposed children and their sibs. Mean intelligence quotient was not reduced, and the incidence of behavioral deviation was not increased in the exposed children. The findings of this study did not indicate teratogenic or fetotoxic (including neurotoxic) effects of large doses of promethazine in children born to mothers who self-poisoned during pregnancy, although the total rate of congenital abnormalities was very high. Our experience shows the feasibility and benefits of using the self-poisoning model in estimating human teratogenic/fetotoxic risks of exposure to drugs.
A study of the effects of large doses of medazepam used for self-poisoning in 10 pregnant women on fetal development
Authors: Gidai J , Ács N , Bánhidy F , Czeizel AE 
Published: September 2008

The purpose of this article is to report an evaluation of the teratogenic and fetotoxic potential of medezepam in humans based on pregnant women who used very large doses of medazepam for a suicide attempt. All self-poisoned patients were cared for at the Department of Toxicology Internal Medicine, Koranyi Hospital, a toxicological inpatients clinic in Budapest, Hungary, between 1960 and 1993. Pregnant women were identified from self-poisoned subjects admitted from a population base of three million people of Budapest and the surrounding region. The rates of congenital abnormalities (CAs), intrauterine fetal development, cognitive and behavioral status in children born to mothers who attempted suicide with medazepam alone or in combination with other drugs during pregnancy was compared in their sib controls. Between 1980 and 1993, 835 pregnant women in our study attempted suicide during pregnancy with drugs. Of these, 314 delivered live-born infants and 283 were examined and/or evaluated. Thirty-two (3.8%) of these 835 pregnant women used medazepam with or without other drugs for self-poisoning; 10 of these women delivered live-born babies. The dose of medazepam used for the suicide attempt ranged between 60 and 500 mg, with a mean of 276 mg. Eight of the 32 suicide attempts involving medazepam occurred between the 4th and 12th postconceptional weeks. Of the 10 live-born exposed children, one was affected with congenital inguinal hernia; one of the 13 sib controls had a lethal hydronephrosis. No adverse effects were observed on intrauterine growth, cognitive status, or behavioral deviations in the 10 children born to mothers who attempted suicide with medazepam during pregnancy. Very large doses of medazepam were used for self-poisoning during pregnancy. These doses did not increase the rate of CAs even though eight mothers attempted suicide during the most critical period for production of CAs. No fetotoxic, including neurotoxic, effects of exposure of live-born children to a very large dose of medazepam were observed. Our experiences show the feasibility and benefits of use of the self-poisoning model in estimating human teratogenic and fetotoxic risks of drugs.
A study of the teratogenic and fetotoxic effects of large doses of chlordiazepoxide used for self-poisoning by 35 pregnant women
Authors: Gidai J , Ács N , Bánhidy F , Czeizel AE 
Published: September 2008

The human teratogenic potential of chlordiazepoxide is debated. To study the effects on the fetal development of very large doses of chlordiazepoxide that were used for a suicide attempt during pregnancy, self-poisoned pregnant women were identified from patients in a toxicological inpatient clinic in Budapest, Hungary. Comparisons were made between congenital abnormalities, intrauterine fetal development, and cognitive–behavioral status of the exposed children born to mothers who attempted suicide with chlordiazepoxide alone or in combination with other drugs during pregnancy and their sib controls. Of 1044 women with self-poisoning during pregnancy between 1960 and 1993, 88 (8.4%) used chlordiazepoxide with or without other drugs for suicide attempt; 35 of these women delivered live-born infants. Doses of chlordiazepoxide taken ranged between 20 and 300 mg, with a mean of 117 ± 86 mg. Of 35 exposed children, six (17.1 %) were affected with congenital abnormalities compared with three (13.6%) of their 22 sibs (OR with 95% CI: 1.3 (0.3–4.4). Of 18 pregnant women who attempted suicide between the 4th and 12th postconceptional week, the period most sensitive to congenital malformation, four delivered live-born children affected with a congenital abnormality (atrial septal defect type II, complex defect of respiratory system, mild pyelectasis because of the stenosis of ureteropelvic junction, congenital inguinal hernia). Two other children had fetal alcohol syndrome and unrecognized multiple congenital abnormality including talipes equinovarus, deformation type, and four minor anomalies. The pregnancy age–specific mean birth weight indicated intrauterine fetal growth retardation, which was confirmed by a dose–response relationship and by the higher rate of low birth–weight newborns. Cognitive status and behavioral scale of exposed children did not indicate neurotoxic effects. Very large doses of chlordiazepoxide used for suicide attempts during pregnancy did not induce a higher rate of congenital abnormalities but were associated with dose-dependent intrauterine growth retardation.
No association found between use of very large doses of diazepam by 112 pregnant women for a suicide attempt and congenital abnormalities in their offspring
Authors: Gidai J , Ács N , Bánhidy F , Czeizel AE 
Published: September 2008

The teratogenic potential of diazepam is debated. The objective of this study was to examine the effects of extremely high doses of diazepam used for attempted suicide during pregnancy on embryo-fetal development. Pregnant women were identified from the female patients of the Department of Toxicology Internal Medicine, Korányi Hospital, Budapest, who had been admitted as self-poisoned subjects from the three million people of Budapest and the surrounding region. This evaluation compares the incidences and types of congenital abnormalities observed in exposed children born to mothers who attempted suicide with diazepam alone or in combination with other drugs during pregnancy with their sib controls. The database consists of a total of 1044 women with self-poisoning during pregnancy between 1960 and 1993. Of these 1044 self-poisoned pregnant women, 229 (21.9%) used diazepam with or without other drugs for a suicide attempt; 112 of these women delivered live-born infants. Doses of diazepam taken ranged between 25 and 800 mg. Of 112 exposed children, 15 (13.4%) had congenital abnormalities, whereas of their 112 matched sibs, eight (7.1%) had congenital abnormalities (odds ratios with 95% confidence intervals: 2.0, 0.8–5.0). Of 37 pregnant women who attempted suicide between the 4th and 12th postconceptional weeks, five (13.5%) delivered live-born babies with a congenital abnormality (undescended testis in two exposed children; congenital dysplasia of the hip, talipes equinovarus deformation type, congenital inguinal hernia—each in one exposed child). The suicide attempts of the mothers of these children did not occur during the critical periods for induction of these defects, indicating that the observations were unrelated to diazepam. The very large doses of diazepam used for self-poisoning during pregnancy did not increase the rate of congenital abnormalities in the offspring.
Introduction and history of the Hungarian project for monitoring suicide attempts in pregnant women
Authors: Christian MS , Czeizel AE 
Published: September 2008

The introduction describes the series of manuscripts resulting from the Hungarian Project for monitoring suicide attempts in pregnant women, as well as a history of the project, its various phases and participating individuals. This unique database contains information on all patients who attempted suicide by “self-poisoning” and were cared for at central toxicological inpatient clinic in Budapest, between 1960 and 1993. A total of 1044 patients were pregnant women, of which 19 died and 411 delivered live-born babies. Of these 411 live-born children, 367 exposed children were examined and/or evaluated. This is the first report of data on the human teratogenic potential of 93 medicinal products separately used for a suicide attempt during pregnancy. Each manuscript presents results for drugs used by at least 10 pregnant women for a suicide attempt, whereas the final paper summarizes the data of drugs used rarely for suicide attempt by pregnant women. Each patient consented to participate in the study. Critical information collected under medical supervision included examination of the patients upon admittance, stage of pregnancy at suicide attempt, blood levels of the drug(s) taken for the suicide attempt (at admittance), evaluation of the infant at birth for gestational age, weight and congenital abnormalities, and follow-up studies for 2 years after a child’s birth. These studies provide insight into the potential effects of a high dose of a drug or drugs taken during pregnancy because it is well accepted that “pulse high doses” of a drug during the initial susceptible period of pregnancy are those most likely to result in congenital abnormality. Although it is obvious that these data are not sufficient to ensure safety, and that it is necessary to have a larger population of exposed children, to achieve better statistical power, as well as to include data on other populations, this collection of papers provides an important introduction of the so-called disaster epidemiological approach in human teratology. It shows the feasibility of such studies and suggests that an international surveillance system of self-poisoned pregnant women would be useful to better estimate risk and benefit of drug use during pregnancy. It is envisioned that the information provided will assist physicians and mothers in making better decisions regarding drug exposure during pregnancy.
A study of the teratogenic and fetotoxic effects of large doses of amobarbital used for a suicide attempt by 14 pregnant women
Authors: Petik D , Timmermann G , Czeizel AE , Ács N , Bánhidy F 
Published: September 2008

The teratogenic effect of barbitals is debated, and this study was performed to identify the effects of very large doses of amobarbital used for suicide attempts during pregnancy on embryo–fetal development. Self-poisoned pregnant women were identified from patients of the Department of Toxicology Internal Medicine, Korányi Hospital, Budapest, Hungary, who were admitted from the 3 million people of Budapest and its surrounding region. A comparison was made between outcomes of pregnancies of women who attempted suicide with amobarbital alone or in combination with other drugs during pregnancy with sib controls. Of 1044 women with self-poisoning during pregnancy between 1960 and 1993, 33 used amobarbital for a suicide attempt. Of these 33 women, 14 delivered live-born babies. The dose of amobarbital taken by these women ranged between 600 and 10,000 mg, with a mean of 3886 mg. Of the 14 amobarbital-exposed children, 9 had mothers who attempted suicide between the 3rd and 12th post-conceptional weeks. None of these children had a congenital abnormality, and there was no evidence of fetal growth retardation. The distribution of cognitive status and behavioral scale of the exposed children were comparable with those of their sibs although one exposed child had a very low (about 75) IQ, whereas another one was treated because of a very severe aggressive behavioral deviation. Exposure to very large doses of amobarbital that were used for self-poisoning during pregnancy did not produce teratogenic effects in this study.
Perceived control moderated the self-efficacy-enhancing effects of a chronic illness self-management intervention
Authors: Jerant Anthony , Moore Monique , Lorig Kate , Franks Peter 
Published: September 2008

Objective: Identifying moderators of the effects of self-efficacy-enhancing interventions could improve their efficiency. We examined the effects of a home-based variant of the Chronic Disease Self-Management Program on self-efficacy, and explored the moderating effects of perceived control over self-management (PCSM). Methods: In a randomized controlled trial, patients ( N= 415) aged>40 years with various chronic conditions plus basic activity impairment and/or significant depressive symptoms were randomized to one of three groups: intervention provided in homes or by telephone, v. usual care control. We used mixed effects linear models for repeated measures to examine effects on self-management self-efficacy at 6-month follow-up and explore moderation by PCSM. Results: Only the home intervention had a significant self-efficacy-enhancing effect (Wald test, χ 2 = 13.8, p = 0.008; effect size = 0.3). The effect was moderated by PCSM, considered as a continuous [effective in subjects with lower PCSM (Wald test, χ2 = 13.4, p = 0.009)] or categorical (effective only for subjects in the lowest tercile) variable. Conclusions: People with lower PCSM appear more likely to experience enhanced self-efficacy from chronic illness self-management training than those with higher PCSM. These findings, although preliminary, suggest that office-based measurement of PCSM might identify those chronically ill patients likely to benefit most from self-management training.
Limited stair-climbing ability and weight control in family medicine patients
Authors: Rohrer James E. , Barnes Darryl E. , Adamson Steven C. , Altrichter Paul M. , Yapuncich Victor P. 
Published: September 2008

Objective: To assess the association between self-assessed stair-climbing limitation and weight control among family medicine patients, after adjustment for age, gender, marital status, body mass index (BMI), and co-morbidity. Methods: This study was a retrospective analysis of a cohort of 840 adult family medicine patient records drawn from a large family medicine department in Rochester, Minnesota. Weight control was measured as no change or decline in BMI over approximately 1 year. Results: Adjusting for co-morbidity and other confounders using multiple logistic regression analysis revealed that limited stair-climbing ability was unrelated to weight control over approximately 1 year. Instead, patients with BMI ≥ 30 were more likely to control their weight (p<0.01), and age exhibited a non-linear relationship with weight control. The odds of weight control were lower for patients between the ages of 36 and 45 years than for those aged 18—35 years (p<0.01). Conclusions: In our sample of family medicine patients, self-assessed stair-climbing limitations did not preclude weight control. Weight gain prevention programmes might be targeted at patients who are entering middle age.
Adaptive coping with rheumatoid arthritis: the transforming nature of response shift
Authors: Sinclair Vaughn G. , Blackburn Donna S. 
Published: September 2008

Objective: Qualitative investigations of patients' perspectives of coping can offer insights into a wide array of adaptive coping patterns selectively used to deal with illness-related challenges. The purpose of this qualitative study was to examine adaptive coping patterns reported by a sample of women with rheumatoid arthritis (RA). Methods: Using thematic analysis, interviews from 19 participants were analysed until theoretical saturation was achieved. The interviews were coded, with narrative excerpts collated within each code, sorted by codes into potential themes, and then collated within identified themes. These themes were then further defined, providing specific adaptive coping strategies for each major theme. Results: Major themes included accepting role limitations, reclaiming control, reframing their situation, and bolstering courage. Women described accepting more realistic performance standards, accepting their limitations and dependence on others, and altering their basis of self-worth. They reclaimed control of their lives by changing priorities, pacing themselves, being flexible, delegating to others, and setting appropriate boundaries. Reframing their situation enabled them to change their perspective, minimize threats from RA, re-prioritize their values, and find meaning and positive changes associated with their suffering. To bolster courage, they turned to a variety of sources for encouragement, including confidence from past successes, inspiring role models, and social support. Conclusions: The data reflect adaptive strategies similar to response shift processes. A link between response shift processes and higher levels of perceived control is discussed.
Cell functions impaired by frataxin deficiency are restored by drug-mediated iron relocation
Authors: Kakhlon Or , Manning Hila , Breuer William , Melamed-Book Naomi , Lu Chunye , Cortopassi Gino , Munnich Arnold , Cabantchik Z. Ioav 
Published: September 2008

Abstract
Various human disorders are associated with misdistribution of iron within or across cells. Friedreich ataxia (FRDA), a deficiency in the mitochondrial iron-chaperone frataxin, results in defective use of iron and its misdistribution between mitochondria and cytosol. We assessed the possibility of functionally correcting the cellular properties affected by frataxin deficiency with a siderophore capable of relocating iron and facilitating its metabolic use. Adding the chelator deferiprone at clinical concentrations to inducibly frataxin-deficient HEK-293 cells resulted in chelation of mitochondrial labile iron involved in oxidative stress and in reactivation of iron-depleted aconitase. These led to (1) restoration of impaired mitochondrial membrane and redox potentials, (2) increased adenosine triphosphate production and oxygen consumption, and (3) attenuation of mitochondrial DNA damage and reversal of hypersensitivity to staurosporine-induced apoptosis. Permeant chelators of higher affinity than deferiprone were not as efficient in restoring affected functions. Thus, although iron chelation might protect cells from iron toxicity, rendering the chelated iron bioavailable might underlie the capacity of deferiprone to restore cell functions affected by frataxin deficiency, as also observed in FRDA patients. The siderophore-like properties of deferiprone provide a rational basis for treating diseases of iron misdistribution, such as FRDA, anemia of chronic disease, and X-linked sideroblastic anemia with ataxia.
Impacting patient-centred outcomes in COPD: breathlessness and exercise tolerance
Authors: O'Donnell D. E. 
Published: September 2008

The physiological hallmark of chronic obstructive pulmonary disease (COPD) is expiratory flow limitation. However, it is the resultant air trapping and associated increases in lung volume (hyperinflation) that provide a mechanistic link between the physiological impairment and the characteristic symptoms of COPD, such as dyspnoea (breathlessness), exercise intolerance and reduced health-related quality of life (HRQoL).During exercise, the negative consequences of hyperinflation are particularly apparent. Delayed lung emptying and increased end-expiratory lung volume are aggravated, and tidal volume cannot rise to meet the increased ventilatory demands. Dyspnoea intensity rises abruptly to intolerable levels, and further increases in ventilation can only be achieved by rapid breathing. This rebounds to cause greater hyperinflation in a vicious cycle. As a result, patients with COPD often prematurely stop or avoid activity, leading to deconditioning, increased dyspnoea, worsening of disease and, ultimately, reduced HRQoL.The Global Initiative for Chronic Obstructive Lung Disease guidelines recommend long-acting bronchodilators as first-line maintenance treatment in COPD.Once-daily tiotropium 18 µg, a long-acting anticholinergic agent with 24-h efficacy, has been consistently shown to relieve dyspnoea and improve exercise tolerance and health status. These improvements may allow patients with chronic obstructive pulmonary disease to increase their daily activities, thereby reversing the cycle of chronic inactivity and muscle deconditioning.
Impacting patient-centred outcomes in COPD: exacerbations and hospitalisations
Authors: Rodríguez-Roisin R. 
Published: September 2008

Patients with chronic obstructive pulmonary disease (COPD) frequently develop exacerbations, leading to major clinical and healthcare utilisation ramifications. Exacerbations, especially those that result in hospitalisation, are the main cost driver in COPD and frequent exacerbations are associated with increased mortality, impaired health-related quality of life (HRQoL) and perhaps a more rapid decline in lung function over time. Prevention and treatment of exacerbations is, therefore, an important goal of maintenance therapy in COPD.The impact of tiotropium, a long-acting anticholinergic agent, on exacerbations and associated healthcare utilisation has been studied in five randomised, controlled clinical trials of ≥6 months' duration involving >5,000 patients.Analyses of adverse events reports submitted during three long-term efficacy and safety trials showed that tiotropium significantly reduced the incidence of exacerbations and delayed the time to first exacerbation, compared with either placebo or the short-acting anticholinergic agent, ipratropium. More recent prospective data confirmed previous findings.Collectively, the results of these studies support the role of tiotropium as maintenance therapy in chronic obstructive pulmonary disease, demonstrating that this agent can provide significant reductions in the incidence of exacerbations and associated healthcare utilisation.