ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009
U. HINDORF
Summary Background, Adverse drug reactions are a significant reason for therapeutic failure during thiopurine treatment of inflammatory bowel disease. Some smaller series in this patient population have shown that a switch to mercaptopurine may be successful in many cases of azathioprine intolerance. Aim, To assess the long-term outcome of mercaptopurine treatment in a large patient population with azathioprine intolerance. Methods, We identified 135 patients (74 women; median age 40 years) with Crohn's disease (n = 88) or ulcerative colitis (n = 47) and reviewed their medical records. Results, A total of 70 patients (52%) tolerated mercaptopurine and were followed up for 736 (362,1080) days; 65 patients discontinued mercaptopurine due to adverse events after 25 (8,92) days. Mercaptopurine was tolerated in 71% (12/17) with hepatotoxicity and in 68% (13/19) with arthralgia/myalgia during azathioprine treatment. Previous abdominal surgery was more common in mercaptopurine intolerant patients [39/65 (60%) vs. 27/70 (39%); P = 0.02] and thiopurine methyltransferase activity was higher in mercaptopurine tolerant patients than in mercaptopurine intolerant patients [13.2 (11.4,15.3) vs. 11.8 (9.6,14.2) U/mL red blood cells; P = 0.04; n = 81]. Conclusions, A trial of mercaptopurine should be considered in azathioprine intolerance, as half of the patients tolerate a switch to mercaptopurine. Patients with hepatotoxicity or arthralgia/myalgia during azathioprine treatment might benefit more often than those with other types of adverse events. [source]

Early clinical experience with adalimumab in treatment of inflammatory bowel disease with infliximab-treated and naïve patients

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009
A. SWAMINATH
Summary Background, Adalimumab, at an induction dose of 160/80 mg followed by 40 mg every other week is approved for treatment of refractory Crohn's disease (CD) and for patients with loss of response to infliximab. Aim, To evaluate the indications for adalimumab, the proportion of inflammatory bowel disease patients who require dose escalation and to identify whether this strategy is effective in inducing or maintaining remission. Methods, Patients prescribed adalimumab for CD were identified and included for analysis, if they had follow-up of at least 6 weeks. Adalimumab dose was escalated if patients had return of symptoms prior to next dose. Clinical judgment was used to determine severity of disease. A second GI physician confirmed disease severity as determined by the first physician. Results, A total of 48 out of 60 patients met inclusion criteria. Adalimumab was used to treat CD in 47/48 (98%) and ulcerative colitis in one (2%). Most patients had moderate 30/48 (63%) or severe 17/48 (35%) disease. Prior infliximab exposure was present in 42/48 (88%). Adalimumab dose escalation occurred in 14/48 (29%) within an average time of 2.2 months (s.d. 1.5 months). A majority of patients who required dose escalation, nine of 14 (64%) did not improve clinically. Steroids could be discontinued in three of 16 (18.8%). Clinical improvement was noted in 21/48 (43.8%) and one of 48 (2%) patients achieved clinical remission. Adverse drug reactions necessitated drug discontinuation in four of 48 (8%) of patients. Conclusions, This retrospective review from a single academic medical centre suggests that a minority of patients, who cannot be maintained on 40 mg every other week, of adalimumab benefit from an increased dose. This suggests the need for a treatment with an alternative mode of action in anti-TNF failures. [source]

Evaluation of Naranjo Adverse Drug Reactions Probability Scale in causality assessment of drug-induced liver injury

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2008
M. GARCÍA-CORTÉS
Summary Background, Causality assessment in hepatotoxicity is challenging. The current standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale is complex and difficult to implement in daily practice. The Naranjo Adverse Drug Reactions Probability Scale is a simple and widely used nonspecific scale, which has not been specifically evaluated in drug-induced liver injury. Aim, To compare the Naranjo method with the standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale in evaluating the accuracy and reproducibility of Naranjo Adverse Drug Reactions Probability Scale in the diagnosis of hepatotoxicity. Methods, Two hundred and twenty-five cases of suspected hepatotoxicity submitted to a national registry were evaluated by two independent observers and assessed for between-observer and between-scale differences using percentages of agreement and the weighted kappa (,w) test. Results, A total of 249 ratings were generated. Between-observer agreement was 45% with a ,w value of 0.17 for the Naranjo Adverse Drug Reactions Probability Scale, while there was a higher agreement when using the Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale (72%, ,w: 0.71). Concordance between the two scales was 24% (,w: 0.15). The Naranjo Adverse Drug Reactions Probability Scale had low sensitivity (54%) and poor negative predictive value (29%) and showed a limited capability to distinguish between adjacent categories of probability. Conclusion, The Naranjo scale lacks validity and reproducibility in the attribution of causality in hepatotoxicity. [source]

Caries and dental fluorosis in a western Saharan population of refugee children

EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 6 2008
José Manuel Almerich-Silla
The aim of this study was to investigate the relationship between dental fluorosis and dental caries among western Saharan refugee children. The western Saharan child population is characterized by adverse living conditions, an unbalanced diet, poor oral hygiene habits, and a concentration of fluoride in the drinking water of around 2 p.p.m. (2 mg l,1). A sample consisting of 360 children, 6,7 yr of age, and 212 children, 11,13 yr of age, was obtained from four refugee camps (Smara, Awsard, El-Aaiun, and 27-February) situated in the vicinity of Tindouf (southern Algeria). The children were examined using the World Health Organization criteria for caries diagnosis and Dean's index for fluorosis. The decayed, missing or filled teeth (DMFT) score was 0.48 in the 6,7-yr-old children and 1.69 in the 11,13-yr-old children, with a caries prevalence (DMFT > 0 or decayed and filled primary teeth (dft) > 0) of 47.2% and 63.2%, respectively. Among the 6,7 yr-old children examined, 36.9% were free of fluorosis, 15.6% presented moderate fluorosis, and 7.8% presented severe fluorosis. Among 11,13 yr-old children, only 4.2% were free of fluorosis, 30.2% exhibited moderate fluorosis, and 27.4% presented severe fluorosis. The mean DMFT, decayed permanent teeth (DT), and caries prevalence (DMFT > 0 and DMFT or dft > 0) scores were significantly higher among the children affected by severe fluorosis, suggesting that severe fluorosis might increase the susceptibility to dental caries. [source]

Genetic Probes of Three Theories of Maternal Adjustment: I. Recent Evidence and a Model,

FAMILY PROCESS, Issue 3 2001
David Reiss M.D.
Studies focusing on genetic and social influences on maternal adjustment will illumine mother's marriage, parenting, and the development of psychopathology in her children. Recent behavioral genetic research suggests mechanisms by which genetic and social influences determine psychological development and adjustment. First, heritable, personal attributes may influence individuals' relationships with their family members. These genetically influenced family patterns may amplify the effects of adverse, heritable personal attributes on adjustment. Second, influences unique to siblings may be the most important environmental determinants of adjustment. We derive three hypotheses on maternal adjustment from integrating these findings from genetic studies with other contemporary research on maternal adjustment. First, mother's marriage mediates the influence of her heritable, personal attributes on her adjustment. Second, mother's recall of how she was parented is partially genetically influenced, and both her relationships with her spouse and her child mediate the impact of these genetically influenced representations on her current adjustment. Third, characteristics of mother's spouse are important influences on difference between her adjustment and that of her sister's These sibling-specific influences are unrelated to mother's heritable attributes. The current article develops this model, and the companion article describes the Twin Mom Study that was designed to test it as well, as its first findings. Data from this study can illumine the role of family process in the expression of genetic influence and lead to specific family interventions designed to offset adverse genetic influences. [source]

Extended antiretroviral treatment interruption in HIV-infected patients with long-term suppression of plasma HIV RNA

HIV MEDICINE, Issue 1 2005
CJ Achenbach
Objectives Evaluation of extended treatment interruption (TI) in chronic HIV infection among patients successfully treated with antiretroviral therapy. Methods An observational analysis of 25 patients in a prospectively followed cohort with chronic HIV infection, viral loads <500 HIV-1 RNA copies/mL for at least 6 months, and an interruption in therapy of ,28 days duration was carried out. Follow up was divided into 3-month time periods for analysis. The effects of time period, stratification group and stratification group by time period interactions on CD4 counts were tested using a mixed model. Univariate comparisons among patient characteristics and responses were performed using Fisher's exact test or the Wilcoxon rank sum test. Results At initiation of TI, the median CD4 count was 799 cells/,L. TI duration was a median of 7.1 months. HIV RNA rebounded to a median maximum level of 75 000 copies/mL. Maximum viral rebound was significantly greater in patients who were male, had lipodystrophy and had zenith HIV RNA prior to TI of ,50 000 copies/mL. Lower CD4 cell counts were observed during TI in patients with lipodystrophy, zenith HIV RNA ,50 000 copies/mL, history of AIDS, HIV infection ,5 years and presuppression CD4 count ,350 cells/,L. Patients who reinitiated therapy had shorter TI duration, presuppression CD4 count ,350 cells/,L, previous AIDS diagnosis and lipodystrophy. No patients developed adverse or AIDS-defining events during TI. Conclusions Long-term TI resulted in greater immune deterioration in patients with high viral set points or low CD4 cell counts prior to initiation of suppressive antiretroviral therapy. [source]

The association between early hemodynamic variables and outcome in normothermic comatose patients following cardiac arrest

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2010
C. TORGERSEN
Background: Currently, few data exist on the association between post-cardiac arrest hemodynamic function and outcome. In this explorative, retrospective analysis, the association between hemodynamic variables during the first 24 h after intensive care unit admission and functional outcome at day 28 was evaluated in 153 normothermic comatose patients following a cardiac arrest. Methods: Medical records of a multidisciplinary intensive care unit were reviewed for comatose patients (Glasgow Coma Scale ,9) admitted to the intensive care unit after successful resuscitation from an in- or an out-of-hospital cardiac arrest. The hourly variable time integral of hemodynamic variables during the first 24 h after admission was calculated. At day 28, outcome was assessed as favorable or adverse based on a Cerebral Performance Category of 1,2 and 3,5, respectively. Bi- and multivariate regression models adjusted for relevant confounding variables were used to evaluate the association between hemodynamic variables and functional outcome. Results: One hundred and fifty-three normothermic comatose patients were admitted after a cardiac arrest, of whom 64 (42%) experienced a favorable outcome. Neither in the adjusted bivariate models (r2, 0.61,0.78) nor in the adjusted multivariate model (r2, 0.62,0.73) was the hourly variable time integral of any hemodynamic variable during the first 24 h after intensive care unit admission associated with functional patient outcome at day 28 in all patients as well as in patients after an in- or an out-of-hospital cardiac arrest. Conclusion: Commonly measured hemodynamic variables during the first 24 h following intensive care unit admission due to a cardiac arrest do not appear to be associated with the functional outcome at day 28. [source]

Association between pacifier use and breast-feeding, sudden infant death syndrome, infection and dental malocclusion

INTERNATIONAL JOURNAL OF EVIDENCE BASED HEALTHCARE, Issue 6 2005
Ann Callaghan RN RM BNurs(Hons)
Executive summary Objective, To critically review all literature related to pacifier use for full-term healthy infants and young children. The specific review questions addressed are: What is the evidence of adverse and/or positive outcomes of pacifier use in infancy and childhood in relation to each of the following subtopics: ,breast-feeding; ,sudden infant death syndrome; ,infection; ,dental malocclusion. Inclusion criteria, Specific criteria were used to determine which studies would be included in the review: (i) the types of participants; (ii) the types of research design; and (iii) the types of outcome measures. To be included a study has to meet all criteria. Types of participants,The participants included in the review were healthy term infants and healthy children up to the age of 16 years. Studies that focused on preterm infants, and infants and young children with serious illness or congenital malformations were excluded. However, some total population studies did include these children. Types of research design, It became evident early in the review process that very few randomised controlled trials had been conducted. A decision was made to include observational epidemiological designs, specifically prospective cohort studies and, in the case of sudden infant death syndrome research, case,control studies. Purely descriptive and cross-sectional studies were excluded, as were qualitative studies and all other forms of evidence. A number of criteria have been proposed to establish causation in the scientific and medical literature. These key criteria were applied in the review process and are described as follows: (i) consistency and unbiasedness of findings; (ii) strength of association; (iii) temporal sequence; (iv) dose,response relationship; (v) specificity; (vi) coherence with biological background and previous knowledge; (vii) biological plausibility; and (viii) experimental evidence. Studies that did not meet the requirement of appropriate temporal sequencing of events and studies that did not present an estimate of the strength of association were not included in the final review. Types of outcome measures,Our specific interest was pacifier use related to: ,breast-feeding; ,sudden infant death syndrome; ,infection; ,dental malocclusion. Studies that examined pacifier use related to procedural pain relief were excluded. Studies that examined the relationship between pacifier use and gastro-oesophageal reflux were also excluded as this information has been recently presented as a systematic review. Search strategy, The review comprised published and unpublished research literature. The search was restricted to reports published in English, Spanish and German. The time period covered research published from January 1960 to October 2003. A protocol developed by New Zealand Health Technology Assessment was used to guide the search process. The search comprised bibliographic databases, citation searching, other evidence-based and guidelines sites, government documents, books and reports, professional websites, national associations, hand search, contacting national/international experts and general internet searching. Assessment of quality, All studies identified during the database search were assessed for relevance to the review based on the information provided in the title, abstract and descriptor/MeSH terms, and a full report was retrieved for all studies that met the inclusion criteria. Studies identified from reference list searches were assessed for relevance based on the study title. Keywords included: dummy, dummies, pacifier(s), soother(s), comforter(s), non-nutritive sucking, infant, child, infant care. Initially, studies were reviewed for inclusion by pairs of principal investigators. Authorship of articles was not concealed from the reviewers. Next, the methodological quality of included articles was assessed independently by groups of three or more principal investigators and clinicians using a checklist. All 20 studies that were accepted met minimum set criteria, but few passed without some methodological concern. Data extraction, To meet the requirements of the Joanna Briggs Institute, reasons for acceptance and non-acceptance at each phase were clearly documented. An assessment protocol and report form was developed for each of the three phases of review. The first form was created to record investigators' evaluations of studies included in the initial review. Those studies that failed to meet strict inclusion criteria were excluded at this point. A second form was designed to facilitate an in-depth critique of epidemiological study methodology. The checklist was pilot tested and adjustments were made before reviewers were trained in its use. When reviewers could not agree on an assessment, it was passed to additional reviewers and discussed until a consensus was reached. At this stage, studies other than cohort, case,control and randomised controlled trials were excluded. Issues of clarification were also addressed at this point. The final phase was that of integration. This phase, undertaken by the principal investigators, was assisted by the production of data extraction tables. Through a process of trial and error, a framework was formulated that adequately summarised the key elements of the studies. This information was tabulated under the following headings: authors/setting, design, exposure/outcome, confounders controlled, analysis and main findings. Results, With regard to the breast-feeding outcome, 10 studies met the inclusion criteria, comprising two randomised controlled trials and eight cohort studies. The research was conducted between 1995 and 2003 in a wide variety of settings involving research participants from diverse socioeconomic and cultural backgrounds. Information regarding exposure and outcome status, and potential confounding factors was obtained from: antenatal and postnatal records; interviews before discharge from obstetric/midwifery care; post-discharge interviews; and post-discharge postal and telephone surveys. Both the level of contact and the frequency of contact with the informant, the child's mother, differed widely. Pacifier use was defined and measured inconsistently, possibly because few studies were initiated expressly to investigate its relationship with breast-feeding. Completeness of follow-up was addressed, but missing data were not uniformly identified and explained. When comparisons were made between participants and non-participants there was some evidence of differential loss and a bias towards families in higher socioeconomic groups. Multivariate analysis was undertaken in the majority of studies, with some including a large number of sociodemographic, obstetric and infant covariates and others including just maternal age and education. As might be expected given the inconsistency of definition and measurement, the relationship between pacifier use and breast-feeding was expressed in many different ways and a meta-analysis was not appropriate. In summary, only one study did not report a negative association between pacifier use and breast-feeding duration or exclusivity. Results indicate an increase in risk for a reduced overall duration of breast-feeding from 20% to almost threefold. The data suggest that very infrequent use may not have any overall negative impact on breast-feeding outcomes. Six sudden infant death syndrome case,control studies met the criteria for inclusion. The research was conducted with information gathered between 1984 and 1999 in Norway, UK, New Zealand, the Netherlands and USA. Exposure information was obtained from a variety of sources including: hospital and antenatal records, death scene investigation, and interview and questionnaire. Information for cases was sought within 2 days after death, within 2,4 weeks after death and in one study between 3 and 11 years after death. Information for controls was sought from as early as 4 days of a nominated sudden infant death syndrome case, to between 1 and 7 weeks from the case date, and again in one study some 3,11 years later. In the majority of the studies case ascertainment was determined by post-mortem. Pacifier use was again defined and measured somewhat inconsistently. All studies controlled for confounding factors by matching and/or using multivariate analysis. Generally, antenatal and postnatal factors, as well as infant care practices, and maternal, family and socioeconomic issues were considered. All five studies reporting multivariate results found significantly fewer sudden infant death syndrome cases used a pacifier compared with controls. That is, pacifier use was associated with a reduced incidence of sudden infant death syndrome. These results indicate that the risk of sudden infant death syndrome for infants who did not use a pacifier in the last or reference sleep was at least twice, and possibly five times, that of infants who did use a pacifier. Three studies reported a moderately sized positive association between pacifier use and a variety of infections. Conversely, one study found no positive association between pacifier use at 15 months of age and a range of infections experienced between the ages of 6 and 18 months. Given the limited number of studies available and the variability of results, no meaningful conclusions could be drawn. Five cohort studies and one case,control study focused on the relationship between pacifier use and dental malocclusion. Not one of these studies reported a measure of association, such as an estimate of relative risk. It was therefore not possible to include these studies in the final review. Implications for practice, It is intended that this review be used as the basis of a ,best practice guideline', to make health professionals aware of the research evidence concerning these health and developmental consequences of pacifier use, because parents need clear information on which they can base child care decisions. With regard to the association between pacifier use and infection and dental malocclusion it was found that, due to the paucity of epidemiological studies, no meaningful conclusion can be drawn. There is clearly a need for more epidemiological research with regard to these two outcomes. The evidence for a relationship between pacifier use and sudden infant death syndrome is consistent, while the exact mechanism of the effect is not well understood. As to breast-feeding, research evidence shows that pacifier use in infancy is associated with a shorter duration and non-exclusivity. It is plausible that pacifier use causes babies to breast-feed less, but a causal relationship has not been irrefutably proven. Because breast-feeding confers an important advantage on all children and the incidence of sudden infant death syndrome is very low, it is recommended that health professionals generally advise parents against pacifier use, while taking into account individual circumstances. [source]

Monetary policy's effects during the financial crises in Brazil and Korea

INTERNATIONAL JOURNAL OF FINANCE & ECONOMICS, Issue 1 2003
Charles Goodhart
This paper looks at the effect of monetary policy changes on asset prices in the foreign exchange and equity markets of Brazil and Korea. We were searching for evidence whether monetary policy tightening may have had (adverse) counterproductive effects on such asset markets. In common with other authors we find only weak or sporadic evidence for this hypothesis. Using a theoretical model of financial market imperfections, we show that the failure to find monetary policy effectiveness during a crisis can come about not only because of the endogeneity caused by a ,leaning against the wind' policy reaction but also, independently, if there are large and correlated risk premia in the financial markets in which interest rates and determined. Copyright © 2003 John Wiley & Sons, Ltd. [source]

Ameliorative potential of resveratrol on proinflammatory cytokines, hyperglycemia mediated oxidative stress, and pancreatic ,-cell dysfunction in streptozotocin-nicotinamide-induced diabetic rats

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2010
P. Palsamy
Chronic exposure of pancreatic ,-cells to supraphysiologic glucose causes adverse ,-cell dysfunction. Thus, the present study was aimed to investigate the hypothesis that oral administration of resveratrol attenuates hyperglycemia, proinflammatory cytokines and antioxidant competence and protects ,-cell ultrastructure in streptozotocin-nicotinamide-induced diabetic rats. Oral administration of resveratrol (5,mg/kg body weight) to diabetic rats for 30 days showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), TNF-,, IL-1,, IL-6, NF-,B p65 unit and nitric oxide (NO) with concomitant elevation in plasma insulin. Further, resveratrol treated diabetic rats elicited a notable attenuation in the levels of lipid peroxides, hydroperoxides and protein carbonyls in both plasma and pancreatic tissues. The diminished activities of pancreatic superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione-S-transferase (GST) as well as the decreased levels of plasma ceruloplasmin, vitamin C, vitamin E and reduced glutathione (GSH) in diabetic rats were reverted to near normalcy by resveratrol administration. Based on histological and ultrastructural observations, it is first-time reported that the oral administration of resveratrol may effectively rescue ,-cells from oxidative damage without affecting their function and structural integrity. The results of the present investigation demonstrated that resveratrol exhibits significant antidiabetic potential by attenuating hyperglycemia, enhancing insulin secretion and antioxidant competence in pancreatic ,-cells of diabetic rats. J. Cell. Physiol. 224: 423,432, 2010. © 2010 Wiley-Liss, Inc. [source]

QUALITY CHARACTERISTICS OF RAGI (ELEUSINE CORACANA)-INCORPORATED "CHAKLI", AN INDIAN DEEP-FRIED PRODUCT

JOURNAL OF FOOD PROCESSING AND PRESERVATION, Issue 5-6 2005
LEENA SEBASTIAN
ABSTRACT Ragi was incorporated at different levels (5, 15 and 25%) to a deep fat fried snack item namely "chakli" to study its effect on fat absorption, sensory and storage parameters. Three sets of products were prepared incorporating untreated, dry heat treated and gelatinized ragi flour. The control products were without ragi flour. Results indicated that the fat absorbed by the control was 19%. Ragi flour incorporation (5%) increased fat content to 24% but on further increase of ragi flour (15 and 25%), it decreased to 19.7 and 18%, respectively. Incorporation of untreated and dry heat treated ragi flour resulted in a slight decline in the sensory ratings of products. The effects were more adverse with higher level of incorporation. On incorporation of gelatinized ragi flour (5%), significantly higher ratings were obtained for texture, flavor and overall quality of products in comparison with the control. The free fatty acid content of products was very low on 0 day and increased during 4 weeks of storage. It can be concluded from the results that incorporation of higher amounts of ragi resulted in lower fat uptake but compromised the sensory quality of the product. However, incorporation at the 5% level had the opposite effect. Gelatinization as a pretreatment was found to improve the quality of the product. [source]

Low-dose azathioprine or mercaptopurine in combination with allopurinol can bypass many adverse drug reactions in patients with inflammatory bowel disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010
A. ANSARI
Aliment Pharmacol Ther,31, 640,647 Summary Background, The thiopurine drugs, azathioprine and mercaptopurine (MP), are established treatments for IBD. However, therapeutic failure caused by adverse drug reactions occurs frequently. Aim, To study combination of allopurinol with reduced-dose thiopurine in an attempt to avoid adverse drug reactions in the treatment of IBD. Methods, Patients with drug reactions to full-dose thiopurines were recruited for combination therapy in two IBD centres in this retrospective study. Dosing was guided by measuring thiopurine methyltransferase (for UK patients) or thioguanine nucleotides and methyl-6MP (Australian patients). Response was monitored by clinical activity indices. Results, Of 41 patients, 25 had non-hepatic and 16 had hepatitic reactions. Clinical remission was achieved in 32 patients (78%) with a median follow-up of 41 weeks (range 0.5,400). Patients who did not respond to combination therapy tended to fail early with the same adverse reaction. The relative risk of having an adverse reaction with methyl-6MP in the top interquartile range was 2.7 (1.3,28) times that with methyl-6MP in the lower three quartiles (95% confidence interval). Conclusion, The combined experience from our centres is the largest reported experience of this combination therapy strategy in IBD, and the first to provide evidence for benefit in thiopurine and allopurinol co-therapy to avoid non-hepatitic adverse drug reactions. [source]

Novel pharmacogenetic markers for treatment outcome in azathioprine-treated inflammatory bowel disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2009
M. A. SMITH
Summary Background, Azathioprine (AZA) pharmacogenetics are complex and much studied. Genetic polymorphism in TPMT is known to influence treatment outcome. Xanthine oxidase/dehydrogenase (XDH) and aldehyde oxidase (AO) compete with TPMT to inactivate AZA. Aim, To assess whether genetic polymorphism in AOX1, XDH and MOCOS (the product of which activates the essential cofactor for AO and XDH) is associated with AZA treatment outcome in IBD. Methods, Real-time PCR was conducted for a panel of single nucleotide polymorphism (SNPs) in AOX1, XDH and MOCOS using TaqMan SNP genotyping assays in a prospective cohort of 192 patients receiving AZA for IBD. Results, Single nucleotide polymorphism AOX1 c.3404A > G (Asn1135Ser, rs55754655) predicted lack of AZA response (P = 0.035, OR 2.54, 95%CI 1.06,6.13) and when combined with TPMT activity, this information allowed stratification of a patient's chance of AZA response, ranging from 86% in patients where both markers were favourable to 33% where they were unfavourable (P < 0.0001). We also demonstrated a weak protective effect against adverse drug reactions (ADRs) from SNPs XDH c.837C > T (P = 0.048, OR 0.23, 95% CI 0.05,1.05) and MOCOS c.2107A > C, (P = 0.058 in recessive model, OR 0.64, 95%CI 0.36,1.15), which was stronger where they coincided (P = 0.019). Conclusion, These findings have important implications for clinical practice and our understanding of AZA metabolism. [source]

Credit Market Regulation and Labor Market Performance Around the World

KYKLOS INTERNATIONAL REVIEW OF SOCIAL SCIENCES, Issue 4 2006
Horst Feldmann
SUMMARY Using data from 74 industrial, developing and transition countries for the years 2000 to 2003, this paper empirically analyzes whether and to what extent credit market regulations affect the performance of the labor market. According to the regression results, anti-competitive credit market regulations have an adverse, though generally modest, impact on the labor market. Specifically, restrictions on credit extended to the private sector, on the private ownership of banks, on competition from foreign banks, and on the free determination of interest rates appear to lower the level of employment and increase unemployment, particularly among young people. [source]

Efficacy and safety of thalidomide in children and young adults with intractable inflammatory bowel disease: long-term results

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2007
M. LAZZERINI
Summary Background Anti-tumour necrosis factor- , antibodies are useful for the treatment of refractory Crohn's disease and ulcerative colitis. Thalidomide is another agent with tumour necrosis factor- , suppressive properties. Aim To investigate the long-term efficacy and safety of thalidomide in a group of children and young adults with refractory inflammatory bowel disease. Methods Twenty-eight patients with refractory moderate-severe inflammatory bowel disease (19 Crohn's disease, 9 ulcerative colitis) received thalidomide 1.5,2.5 mg/kg/day. Patients were assessed at baseline, at weeks 2, 4, 8 and 12, and then every 12 weeks by patient's diary, physical examinations, laboratory analyses and scoring on activity indexes. Primary outcomes were: (i) efficacy in inducing remission; and (ii) efficacy in maintaining remission. Results Remission was achieved with thalidomide in 21 of 28 (75%) patients (17 with Crohn's disease, 4 with ulcerative colitis). Mean duration of remission was 34.5 months. Sixteen of 20 (80%) patients suspended steroids. Reversible neuropathy occurred in seven of 28 (25%) patients, but only with cumulative doses over 28 g. Other side effects requiring thalidomide suspension were vertigo/somnolence (one of 28), and agitation/hallucinations (one of 28). Conclusions Thalidomide seems to be effective in inducing long-term remission in children and adolescents with intractable inflammatory bowel disease. Neuropathy is the main adverse effect, but appears to be cumulative dose-dependent, thus allowing long-term remission before drug suspension. [source]

The pathophysiology of faecal spotting in obese subjects during treatment with orlistat

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2004
M. Fox
Summary Background :,The intermittent loss of oil or liquid faeces (,spotting') is an adverse effect that occurs in obese patients during treatment with the lipase inhibitor orlistat; the pathophysiology is unknown. Aim :,To investigate the effects of orlistat on anorectal sensorimotor function and continence. Methods :,Obese subjects susceptible to spotting were identified by an unblind trial of orlistat. Obese spotters (n = 15) and non-spotters (n = 16) completed a randomized, double-blind, cross-over trial of orlistat and placebo. Anorectal function was assessed by rectal barostat and anal manometry, together with a novel stool substitute retention test, a quantitative measurement of faecal continence. Results :,Orlistat increased stool volume and raised faecal fat and water. Treatment had no effect on anorectal motor function, but rectal sensation was reduced; on retention testing, the volume retained was increased. Subjects susceptible to spotting had lower rectal compliance, heightened rectal sensitivity and weaker resting sphincter pressure than non-spotters. On retention testing, gross continence was maintained; however, spotters lost small volumes of rectal contents during rectal filling. Conclusion :,Treatment with orlistat has no direct adverse effects on anorectal function or continence. Spotting occurs during treatment with orlistat when patients with sub-clinical anorectal dysfunction are exposed to increased stool volume and altered stool composition. [source]

Effect of contact configuration on the durability and friction coefficient of pressure-sprayed MoS2 coatings under fretting conditions,

LUBRICATION SCIENCE, Issue 5 2009
D. B. Luo
Abstract Fretting wear is often found at the contact surfaces of a tight assembly where small-amplitude oscillatory movement occurs, which can be the concealed origin of some enormous accidents. Employment of solid lubrication coatings, as one of effective measurements to palliate the fretting damage, has been widely acknowledged. The present work studied the fretting behaviour of a molybdenum disulphide coating on SUS 316 stainless steel substrate by a relatively cheap and easy-to-use process: pressure spraying. Two contact configurations (cylinder-on-flat and ball-on-flat) were used in the tests with different displacement amplitudes (from 5 to 75,µm) and normal loads (from 100 to 400,N for ball-on-flat and from 400 to 1000,N for cylinder-on-flat). The results showed that large displacement amplitude is adverse to friction coefficient and coating lifetime and that under a critical contact pressure, coating endurance is improved contact pressure increases. Contact configuration influences friction coefficient by changing contact area and distribution of contact pressure. One master curve of average dissipated energy per cycle in initial stable stage was obtained for two contact configurations, which can be employed to approximately predict coating lifetime. Copyright © 2009 John Wiley & Sons, Ltd. [source]

The effects of smoking and indomethacin on small intestinal permeability

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2000
Suenaert
Background: Smoking modulates inflammatory bowel disease, protecting from ulcerative colitis on the one hand and worsening the course of Crohn's disease on the other. This influence might occur through changes in intestinal permeability, because permeability is increased in most patients with Crohn's disease. Aim: To study the influence of smoking on small intestinal permeability and its increase induced by indomethacin. Methods: 50 smokers and 50 nonsmokers underwent a 51Cr-EDTA basal permeability test and the same test after challenge with indomethacin 125 mg p.o. Results: Small intestinal permeability was the same in smokers (median 1.22%; IQR 1.00,1.58) and nonsmokers (1.24%; 0.94,1.66). Basal small intestinal permeability was lower in females (1.09%; 0.87,1.33) than in males (1.48%; 1.18,1.88). Indomethacin challenge increased permeability by 110% (71,141) in smokers, vs. 156% (78,220) in the nonsmokers (P=0.04). Conclusion: Smoking reduces the effect of NSAID on small intestinal permeability. It is therefore unlikely that the adverse effect of smoking on Crohn's disease is related to its influence on intestinal permeability. [source]

The impact of concomitant rhinitis on asthma-related quality of life and asthma control

ALLERGY, Issue 10 2010
O. Vandenplas
To cite this article: Vandenplas O, Dramaix M, Joos G, Louis R, Michils A, Verleden G, Vincken W, Vints A-M, Herbots E, Bachert C. The impact of concomitant rhinitis on asthma-related quality of life and asthma control. Allergy 2010; 65: 1290,1297. Abstract Background:, Characterizing the interactions between the upper and lower airways is important for the management of asthma. This study aimed at assessing the specific impact of concomitant rhinitis on asthma-related quality of life (QOL) and asthma control. Methods:, A cross-sectional, observational survey was conducted among 1173 patients with asthma (aged 12,45) recruited by general practitioners and chest physicians. AR was defined by self-reported rhinitis symptoms and previously documented sensitization to inhalant allergens. The primary outcomes were (1) asthma control assessed by the Asthma Control Questionnaire (ACQ) and (2) asthma-specific QOL evaluated through the Mini Asthma Quality of Life Questionnaire (mAQLQ). Results:, AR was present in 73.9% of the population with asthma and nonallergic rhinitis (NAR) in 13.6%. AR and NAR were associated with an increased risk of uncontrolled asthma (i.e. ACQ score > 1.5) with adjusted odds ratios (OR) of 2.00 (95% confidence interval [CI]: 1.35,2.97) and 1.77 (95%CI: 1.09,2.89), respectively. Multivariate linear regression analysis showed that AR and NAR had a modest, although significant, negative impact on the global mAQLQ score (beta coefficient: ,0.293, standard error [SE]: 0.063 and beta coefficient: ,0.221, SE: 0.080, P < 0.001, respectively), even after adjustment for the level of asthma control and demographic characteristics. Conclusion:, This survey provides direct evidence that AR and NAR are associated with an incremental adverse impact on the disease-specific QOL of patients with asthma and the level of asthma control. Further investigations are required to determine whether appropriate treatment of rhinitis would efficiently reduce asthma morbidity. [source]

Work-related stress, inability to relax after work and risk of adult asthma: a population-based cohort study

ALLERGY, Issue 10 2010
A. Loerbroks
To cite this article: Loerbroks A, Gadinger MC, Bosch JA, Stürmer T, Amelang M. Work-related stress, inability to relax after work and risk of adult asthma: a population-based cohort study. Allergy 2010; 65: 1298,1305. Abstract Background:, There is an extensive literature linking stressful work conditions to adverse health outcomes. Notwithstanding, the relationship with asthma has not been examined, although various other measures of psychological stress have been associated with asthma. Therefore, we aimed to investigate the relation between work stress and asthma prevalence and incidence. Methods:, We used data from a population-based cohort study (n = 5114 at baseline in 1992,1995 and n = 4010 at follow-up in 2002/2003). Asthma was measured by self-reports. Two scales that assessed psychologically adverse work conditions were extracted from a list of work-condition items by factor analysis (these scales were termed ,work stress' and ,inability to relax after work'). For each scale, the derived score was employed both as continuous z -score and as categorized variable in analyses. Associations with asthma were estimated by prevalence ratios (PRs) and risk ratios (RRs) using Poisson regression with a log-link function adjusting for demographics, health-related lifestyles, body mass index and family history of asthma. Analyses were restricted to those in employment (n = 3341). Results:, Work stress and inability to relax z -scores were positively associated with asthma prevalence (PR = 1.15, 95%CI = 0.97, 1.36 and PR = 1.43, 95%CI = 1.12, 1.83, respectively). Prospective analyses using z -scores showed that for each 1 standard deviation increase in work stress and inability to relax, the risk of asthma increased by approximately 40% (RR for work stress = 1.46, 95%CI = 1.06, 2.00; RR for inability to relax = 1.39, 95%CI = 1.01, 1.91). Similar patterns of associations were observed in analyses of categorized exposures. Conclusions:, This is the first study to show a cross-sectional and longitudinal association of work stress with asthma. [source]

Programme and policy issues related to promoting positive early nutritional influences to prevent obesity, diabetes and cardiovascular disease in later life: a developing countries view,

MATERNAL & CHILD NUTRITION, Issue 3 2005
Noel W. Solomons MD
Abstract Public health policy differs from programme insofar as the former is the expression of goals at a higher decision-making level (international, regional, national or provincial) and the latter involves the execution of intervention measures at the community or individual level. It has recently become fashionable to speak of ,evidence-based' policy. There is now ample evidence to suggest that early nutritional influences on chronic disease risk in later life are contributing to the acceleration of the overall worldwide epidemic of obesity and non-transmissible diseases. In developing countries, in which 80% of the world's population resides, the opportunities for preventive policy must be balanced against needs, cost and effectiveness considerations and the intrinsic limitations of policy execution. Not everyone in the population is at risk of suffering from any given negative condition of interest, nor will everyone at risk benefit from any given intervention. Hence, decisions must be made between universal or targeted policies, seeking maximal cost-efficiency, but without sowing the seeds of either discrimination or stigmatization with a non-universal application of benefits. Moreover, although large segments of the covered population may benefit from a public health measure, it may produce adverse and harmful effects on another segment. It is ethically incumbent on policy makers to minimize unintended consequences of public health measures. With respect to the particular case of mothers, fetuses and infants and long-term health, only a limited number of processes are amenable to intervention measures that could be codified in policy and executed as programmes. [source]

Estrogen and its receptors in cancer

MEDICINAL RESEARCH REVIEWS, Issue 6 2008
George G Chen
Abstract The involvement of estrogen and its receptors in the development of cancer has been known for years. However, the exact mechanism responsible is far from clear. The estrogen-mediated carcinogenic process is complicated by recent findings, which reveal that estrogens have multiple functions in cells, which can be either adverse or beneficial, and that the effects of estrogen may be cell-type or organ dependent. The estrogenic effect may be also greatly influenced by the state of two estrogen receptors, ER, and ER,. This review will discuss the role and function of estrogens and its receptors in cancers of three categories: (1) Breast cancer and gynecologic cancers, (2) Cancers of endocrine organs, (3) Lung cancer and cancers of digestive system. We will also review some novel treatments aiming to interfere with relevant pathways mediated by estrogens and its receptors. © 2008 Wiley Periodicals, Inc. Med Res Rev, 28, No. 6, 954,974, 2008 [source]

Clinical relevance of sensitization to lupine in peanut-sensitized adults

ALLERGY, Issue 4 2009
K. A. B. M. Peeters
Background:, The use of lupine in food has been increasing during the last decade and allergic reactions to lupine have been reported, especially in peanut-allergic patients. The frequency and the degree of cross-reactivity to other legumes are not known. The aim of the study was to investigate the frequency of sensitization to lupine, and in addition to pea and soy, and its clinical relevance, in peanut-sensitized patients. Furthermore, to determine the eliciting dose (ED) for lupine using double-blind placebo-controlled food challenges (DBPCFC). Methods:, Thirty-nine unselected peanut-sensitized patients were evaluated by skin prick tests (SPT) and ImmunoCAP to lupine, pea, and soy. Clinical reactivity was measured by DBPCFC for lupine, and by history for pea and soy. Results:, Eighty-two percent of the study population was sensitized to lupine, 55% to pea, and 87% to soy. Clinically relevant sensitization to lupine, pea, or soy occurred in 35%, 29%, and 33% respectively of the study population. None of the patients was aware of the use of lupine in food. The lowest ED for lupine, inducing mild subjective symptoms, was 0.5 mg, and the no observed adverse effect level (NOAEL) was 0.1 mg. No predictive factors for lupine allergy were found. Conclusion:, In peanut-sensitized patients, clinically relevant sensitization to either lupine or to pea or soy occurs frequently. The ED for lupine is low (0.5 mg), which is only fivefold higher than for peanut. Patients are not aware of lupine allergy and the presence of lupine in food, indicating that education is important to build awareness. [source]

Is the target for thalamic deep brain stimulation the same as for thalamotomy?

MOVEMENT DISORDERS, Issue 10 2003
FRCSC, Zelma H.T. Kiss MD
Abstract Deep brain stimulation (DBS) has virtually replaced thalamotomy for the treatment of essential tremor. It is thought that the site for DBS is the same as the optimal lesion site; however, this match has not been investigated previously. We sought to determine whether the location of thalamic DBS matched the site at which thalamotomy would be performed. Eleven patients who had detailed microelectrode recording and stimulation for placement of DBS electrodes and subsequent successful tremor control were analysed. An experienced surgeon, blinded to outcome and final electrode position, selected the ideal thalamotomy site based on the reconstructed maps obtained intraoperatively. When the site of long-term clinically used DBS and theoretical thalamotomy location was calculated in three-dimensional space and compared for each of the x, y, and z axes in stereotactic space, there was no significant difference in the mediolateral location of DBS and theoretical lesion site. There was also no difference between the theoretical lesion site and the placement of the tip of the electrode; however, the active electrodes used for chronic stimulation were significantly more anterior (P = 0.005) and dorsal (P = 0.034) to the ideal thalamotomy target. This mismatch may reflect the compromise required between adverse and beneficial effects with chronic stimulation, but it also suggests different mechanisms of effect of DBS and thalamotomy. © 2003 Movement Disorder Society [source]

Weight gain profiles of new anti-psychotics: public health consequences

OBESITY REVIEWS, Issue 3 2003
S. Tardieu
Summary Anti-psychotic medications are an important therapeutic option for many individuals with schizophrenia. Recently, a growing interest has been observed on weight gain, which is now a well-known adverse effect of many anti-psychotics. As obesity is frequently a comorbid condition with schizophrenia, patients with schizophrenia are inherently at increased risk of developing obesity-related conditions such as cardiovascular disease and type 2 diabetes. The consequences of excessive weight gain (obesity) associated with anti-psychotic drugs are likely to include adverse effects on health, social burden and poor compliance or even discontinuation of therapy by the patients. In this article, we focus on different aspects of weight gain induced by anti-psychotics. This review comprises the following sections: (i) the pharmacological basis of anti-psychotic-induced weight gain and metabolic effects with a review of all anti-psychotics that can be used in patients with schizophrenia; (ii) the clinical impact of the body weight gain (morbidity, psychatric consequences, mortality); (iii) the management of obesity (identification of risk factors including pharmacogenetics, diet, behavioural therapies, pharmacological approach). An understanding of these aspects is important for those who prescribe anti-psychotics in order to provide the patient the best therapeutic management. [source]

Intensive induction chemotherapy with regimen containing intermediate dose cytarabine in the treatment of de novo acute myeloid leukemia,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2009
Jiazhuo Liu
To improve long-term outcome of de novo acute myeloid leukemia (AML) patients by intermediate dose of cytarabine integrated in induction therapy and to explore the impact of cytogenetic abnormalities on the prognosis. Eighty-seven AML patients were treated with HAD regimen containing intermediate dose cytarabine (IDAra-C) as induction therapy, 83 from which with karyotype results were divided into three cytogenetic groups according to SWOG criteria. Complete remission (CR) rate, disease-free survival (DFS), and overall survival (OS) among different groups were evaluated. The CR rate of the 87 cases was 80/87 (92%). Median DFS and OS have not reached (NR). DFS rates at 1 and 3 years were 76.3% and 63.4%, respectively. OS rates at 1 and 3 years were 86.0% and 58.7%, respectively. According to SWOG criteria, CR rate, median DFS, and OS were 100%, NR and NR for the favorable group; 88.9%, NR, and 16 months for the intermediate group; 83.3%, 4.5 months, and 7.5 months for the adverse group. The differences among the three groups were statistically significant excepting for CR rate between adverse and intermediate groups. HAD regimen containing IDAra-C as induction chemotherapy regimen is effective in de novo AML of adult patients and can achieve higher CR rate and longer survival than standard dose of cytarabine (SDAra-C) regimen. Most of the patients were able to endure the therapy. Cytogenetics is still an important prognostic factor despite of the incorporation of IDAra-C in induction chemotherapy. The differences among the three groups were statistically significant. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source]

Prevalence, incidence and persistence of antipsychotic drug prescribing in the Italian general population: retrospective database analysis, 1999,2002,

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 6 2006
Mersia Mirandola StatD
Abstract Purpose To investigate the prevalence, incidence and persistence with antipsychotic drug therapy in a large and geographically defined catchment area of Italian general population. Methods All antipsychotic drug prescriptions dispensed during 1999, 2000, 2001 and 2002 were extracted from an administrative prescription database covering a population of 2,640,379 individuals. Antipsychotic drug users were defined as patients who had at least one recorded prescription in the current year. New users were defined as patients receiving a first prescription without any recorded antipsychotic drug treatment in the previous 12 months. Prevalence data were calculated by dividing users by the total number of male and female residents in each age group. Incidence data were calculated as the number of new users divided by the person-time free from antipsychotic drugs in the current year. The cumulative persistence of each medication was calculated by dividing the total prescribed amount of antipsychotic drug by the recommended daily dose, according to each agent's defined daily dose (DDD). Results A progressive rise in prevalence and incidence rates was observed during the 4-year period. In each census year, the prevalence and incidence of prescribing was higher in females than males, and progressively rose with age, with the highest rates in old and very old subjects. The analysis of persistence with therapy revealed that 3176 individuals (78.5%) were occasional antipsychotic drug users, and that occasional use was more frequent among individuals receiving conventional antipsychotic drugs than among individuals receiving novel antipsychotic drugs. This difference was not explained by differences in the occurrence of neurologic adverse reactions, as shown by the concurrent prescribing of anticholinergic drugs, which was fairly similar between the two groups of new drug users. Additionally, we found that conventioal antipsychotic drugs were more often used in older individuals, where occasional use is very frequent, while novel antipsychotic drugs were more often prescribed in young and adult individuals, where regular use is more frequent. Conclusions An epidemiologically relevant proportion of everyday individuals is annually exposed to antipsychotic drugs. The distribution of prevalence and incidence rates by age highlighted an emerging public health issue related to the adverse and beneficial consequences of antipsychotic drug exposure in the elderly. The finding that persistence with therapy was longer in new users of novel antipsychotic drugs compared with new users of conventional agents might be explained by the different demographic and clinical characteristics of individuals receiving these two drug classes and not by the different tolerability profile of these two drug classes. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Constitutional Jurisdiction and the Consolidation of Democracy

POLITICS & POLICY, Issue 1 2009
DIETER NOHLEN
This lecture elaborates on the kind of relationship that exists between constitutional jurisdiction and democratic consolidation by applying the comparative method to cover Latin American political,and especially judicial,systems. The argument is that constitutional jurisdiction is influenced by the very same factors that either favor or constrain democratic consolidation and that it exerts no negative influence over democratic consolidation. However, Nohlen identifies patterns of behavior that both judges and politicians are encouraged to adopt that strengthen the judiciary, and with it democratic stability, by fostering among the citizenry a culture of constitutionality. Nohlen also hopes to show that departures from those patterns of behavior even while conditions for democratic consolidation have not been terribly adverse, can be identified in the behavior of key actors in the period preceding and throughout, the populist turn that is now affecting Ecuadorean, Venezuelan, and Bolivian politics. [source]

Is Pregnancy After Breast Cancer Safe?

THE BREAST JOURNAL, Issue 4 2010
Julie A. Kranick MA
Abstract:, The impact of treatment on subsequent fertility and the safety of childbearing are major complicating factors for young women diagnosed with breast cancer. As national data indicate women are postponing first pregnancy to older ages; therefore, many young patients are seeking clinical guidance regarding the safety of conception and treatment options that may not prevent subsequent pregnancy. Newly developed chemotherapy protocols of brief duration have improved life expectancy enabling some women to consider childbearing. This study was conducted to compare prognosis among breast cancer patients with and without a subsequent pregnancy. Medical record review of female members of a Northern California prepaid health care plan enabled the identification of 107 women with one or more subsequent pregnancies and 344 cases without a pregnancy, who were diagnosed between 1968 and 1995. Sets were matched on age, year and stage at diagnosis, months of survival and recurrence status at conception. Among the matched sets, neither risk of recurrence nor death differed significantly by subsequent pregnancy history during an average 12 years of follow-up (adjusted hazard ratio [HR] recurrence: 1.2 [0.8, 2.0]; adjusted HR death: 1.0 [0.6, 1.9]). Women interested in preserving their fertility and considering pregnancy are a self-selected population; therefore, to reduce potential bias, cases were matched on recurrence status at time of conception. Although the number of cases was limited, subgroup analyzes indicated a small, nonsignificant adverse effect among women who conceived within 12 months of diagnosis. This analysis of carefully matched cases provides reassurance that long-term prognosis was not adversely affected by subsequent pregnancy. [source]

ORIGINAL ARTICLE: Thrombin Activatable Fibrinolysis Inhibitor and Clot Lysis Time in Pregnant Patients with Antiphospholipid Syndrome: Relationship with Pregnancy Outcome and Thrombosis

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2009
Maria Angeles Martinez-Zamora
Problem, Antiphospholipid syndrome (APS) pregnancies are associated with thrombotic obstetric complications, despite treatment. This study evaluated Thrombin Activatable Fibrinolysis Inhibitor (TAFI) levels, TAFI gene polymorphisms and Clot Lysis Time (CLT) in pregnant patients with APS in relation to pregnancy outcome and thrombosis. Method of study, Group 1 consisted of 67 pregnant patients with APS. Group 2 included 66 pregnant patients with uneventful term pregnancies and delivery. Patients were sampled during each trimester and at baseline. TAFI antigen and CLT and two polymorphisms of the TAFI gene, Ala147Thr and +1542C/G, were determined. Results, Significantly prolonged CLT was found at baseline in Group 1. Allele distribution of the TAFI gene polymorphisms was similar in both groups. Basal TAFI and CLT in patients with APS having an adverse or a good obstetrical outcome were similar. Comparison of TAFI and CLT baseline levels in patients with APS with or without previous thrombosis showed no statistical differences. Conclusion, Patients with APS have impairment in fibrinolysis evidenced by prolonged CLT at baseline. TAFI and CLT do not seem to be useful as markers of obstetric outcome or risk of thrombosis in patients with APS. [source]