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Sample records for adverse treatment effects

  1. Adverse effects of orthodontic treatment: A clinical perspective

    PubMed Central

    Talic, Nabeel F.

    2011-01-01

    Orthodontic treatment is associated with a number of adverse effects, such as root resorption, pain, pulpal changes, periodontal disease, and temporomandibular dysfunction (TMD). Orthodontists should be aware of these effects and associated risk factors. Risk factors linked to root resorption include the duration of treatment, length, and shape of the root, trauma history, habits, and genetic predisposition. PMID:24151415

  2. Stimulant Treatment over Five Years: Adherence, Effectiveness, and Adverse Effects.

    ERIC Educational Resources Information Center

    Charach, Alice; Ickowicz, Abel; Schachar, Russell

    2004-01-01

    Objective: To evaluate the impact of adherence and medication status on effectiveness and adverse effects of stimulant use in children with attention-deficit/hyperactivity disorder (ADHD) over 5 years. Method: Seventy-nine of 91 participants in a 12-month randomized controlled trial of methylphenidate and parent groups enrolled in a follow-up…

  3. Ecchymoses as an adverse effect of fluoxetine treatment.

    PubMed

    Fountoulakis, Konstantinos N; Samolis, Stavros; Iacovides, Apostolos; St Kaprinis, George

    2007-07-30

    We report a case of a 28-year-old major depressive female patient who manifested ecchymoses following fluoxetine use. After substitution of sertraline, her depression resolved after 4 weeks and ecchymoses 1.5 months latter. This is an unexplored side-effect with unknown long-term consequences that warrants further study.

  4. The Adverse Effect of Hypertension in the Treatment of Thyroid Cancer with Multi-Kinase Inhibitors

    PubMed Central

    Ancker, Ole Vincent; Wehland, Markus; Bauer, Johann; Infanger, Manfred; Grimm, Daniela

    2017-01-01

    The treatment of thyroid cancer has promising prospects, mostly through the use of surgical or radioactive iodine therapy. However, some thyroid cancers, such as progressive radioactive iodine-refractory differentiated thyroid carcinoma, are not remediable with conventional types of treatment. In these cases, a treatment regimen with multi-kinase inhibitors is advisable. Unfortunately, clinical trials have shown a large number of patients, treated with multi-kinase inhibitors, being adversely affected by hypertension. This means that treatment of thyroid cancer with multi-kinase inhibitors prolongs progression-free and overall survival of patients, but a large number of patients experience hypertension as an adverse effect of the treatment. Whether the prolonged lifetime is sufficient to develop sequelae from hypertension is unclear, but late-stage cancer patients often have additional diseases, which can be complicated by the presence of hypertension. Since the exact mechanisms of the rise of hypertension in these patients are still unknown, the only available strategy is treating the symptoms. More studies determining the pathogenesis of hypertension as a side effect to cancer treatment as well as outcomes of dose management of cancer drugs are necessary to improve future therapy options for hypertension as an adverse effect to cancer therapy with multi-kinase inhibitors. PMID:28335429

  5. Potential adverse effects of amphetamine treatment on brain and behavior: a review.

    PubMed

    Berman, S M; Kuczenski, R; McCracken, J T; London, E D

    2009-02-01

    Amphetamine stimulants have been used medically since early in the twentieth century, but they have a high abuse potential and can be neurotoxic. Although they have long been used effectively to treat attention deficit hyperactivity disorder (ADHD) in children and adolescents, amphetamines are now being prescribed increasingly as maintenance therapy for ADHD and narcolepsy in adults, considerably extending the period of potential exposure. Effects of prolonged stimulant treatment have not been fully explored, and understanding such effects is a research priority. Because the pharmacokinetics of amphetamines differ between children and adults, reevaluation of the potential for adverse effects of chronic treatment of adults is essential. Despite information on the effects of stimulants in laboratory animals, profound species differences in susceptibility to stimulant-induced neurotoxicity underscore the need for systematic studies of prolonged human exposure. Early amphetamine treatment has been linked to slowing in height and weight growth in some children. Because the number of prescriptions for amphetamines has increased several fold over the past decade, an amphetamine-containing formulation is the most commonly prescribed stimulant in North America, and it is noteworthy that amphetamines are also the most abused prescription medications. Although early treatment does not increase risk for substance abuse, few studies have tracked the compliance and usage profiles of individuals who began amphetamine treatment as adults. Overall, there is concern about risk for slowed growth in young patients who are dosed continuously, and for substance abuse in patients first medicated in late adolescence or adulthood. Although most adult patients also use amphetamines effectively and safely, occasional case reports indicate that prescription use can produce marked psychological adverse events, including stimulant-induced psychosis. Assessments of central toxicity and adverse

  6. Telithromycin: review of adverse effects.

    PubMed

    2014-11-01

    Telithromycin is a macrolide antibiotic that has been marketed since the early 2000s. It has not been shown to be more effective against any bacteria than other macrolide antibiotics. Its antibacterial activity is in no way remarkable. In early 2014, we reviewed its adverse effect profile using data from periodic safety update reports, drug regulatory agencies, and detailed published case reports. In addition to the adverse effect profile telithromycin shares with the other macrolides, it provokes several specific adverse effects: visual disturbances due to impaired accommodation; taste and smell disorders; severe liver damage; worsening of myasthenia gravis; rhabdomyolysis; and loss of consciousness. Prolongation of the QT interval with standard oral doses is a worrisome adverse effect. In practice, it is better not to use telithromycin as it exposes patients to disproportionate, serious adverse effects. When treatment with a macrolide antibiotic appears necessary, it is prudent to choose a different macrolide, such as spiramycin or azithromycin, which have fewer adverse effects.

  7. Adverse effects of shock waves and strategies for improved treatment in shock wave lithotripsy

    NASA Astrophysics Data System (ADS)

    McAteer, James A.; Evan, Andrew P.; Connors, Bret A.; Williams, James C.; Willis, Lynn R.

    2005-04-01

    Lithotripter SWs rupture blood vessels in the kidney. This acute trauma, accompanied by a fall in renal function, can lead to significant long-term effects such as profound scarring of the kidney cortex and renal papillaea permanent loss of functional renal mass. SWL has been linked to new-onset hypertension in some patients, and recent studies suggest that multiple lithotripsies can actually alter a patient's stone disease leading to formation of stones (brushite) that are harder to break. Cavitation and shear appear to play a role in stone breakage and tissue damage. Progress in understanding these mechanisms, and the renal response to SWs, has led to practical strategies to improve treatment. Slowing the SW-rate, or initiating treatment at low kV/power both improve stone breakage and reduce the number of potentially tissue-damaging SWs needed to achieve comminution. The observation that SWs cause transient vasoconstriction in the kidney has led to studies in pigs showing that a pre-conditioning dose of low-energy SWs significantly reduces trauma from subsequent high-energy SWs. Thus, SWs can induce adverse effects in the kidney, but what we have learned about the mechanisms of SW action suggests strategies that could make lithotripsy safer and more effective. [Work supported by NIH-DK43881, DK55674.

  8. [Changes of menstruation patterns and adverse effects during the treatment of LNG-IUS for symptomatic adenomyosis].

    PubMed

    Li, L; Leng, J H; Zhang, J J; Jia, S Z; Li, X Y; Shi, J H; Dai, Y; Zhang, J R; Li, T; Xu, X X; Liu, Z Z; You, S S; Chang, X Y; Lang, J H

    2016-09-25

    Objective: To investigate the changes of mestruation patterns and adverse effects during the treatment of levonorgestrel-releasing intrauterine system(LNG-IUS)for symptomatic adenomyosis in a prospective cohort study. Methods: From December, 2006 to December, 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in Peking Union Medical College Hospital were given LNG-IUS. Before and after placement of IUS, all patients' parameters were recorded, including carrying status of IUS, symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, menstruation patterns and adverse effects. Risk factors for changes of menstruation patterns and adverse effects, and their impact on treatment effects were analyzed. Results: Totally 1 100 cases met inclusion criteria, with median age 36 years(range 20-44 years), median follow-up 35 months(range 1 -108 months). During follow-up changes of menstruation patterns increased significantly with amenorrhea and shortened-menstruation being the most common manifestations. On 3, 6, 12, 24, 36, 48 and 60 months after the placement of LNG-IUS, 0, 5.8%(43/744), 6.9%(47/682), 10.1%(60/595), 17.3%(87/502), 27.2%(104/383)and 29.6%(82/277)patients achieved amenorrhea respectively(P<0.01). Total and subclassification of adverse effects decreased significantly(P<0.01). Within 12 months and >12 months after placement, abdominal pain and body weight increasing ≥5 kg/year were the most common adverse effects. Changes of menstruation patterns, total and subclassifications of adverse effects were neither dependent on patient parameters, treatment modes and treatment effects, nor could predict future LNG-IUS carrying status(all P> 0.05). After taking out of LNG-IUS, most changes of menstruation and adverse effects disappeared. Conclusions: During the treatment of LNG-IUS for symptomatic adenomyosis, changes of menstruation patterns increase gradually with amenorrhea and shortened

  9. Bullous pemphigoid: corticosteroid treatment and adverse effects in long-term care patients.

    PubMed

    Spivey, Justin; Nye, Ann Marie

    2013-07-01

    Bullous pemphigoid (BP) is the most common autoimmune bullous disease. It primarily presents in elderly patients older than 70 years of age. The presentation can vary with localized or generalized disease that variably affects mucosal tissue. Therapy primarily consists of administration of topical and systemic corticosteroids. Topical corticosteroids are effective with less adverse effects compared with systemic steroids. Other therapies, such as steroid-sparing agents and plasma exchanges, have been recommended and studied to some degree, but these require more evidence before they can be routinely recommended. A 68-year-old African-American female resident of a nursing facility develops a rash and is evaluated at a dermatology clinic. Since the resident has many medications and concomitant diseases, the physician at first suspected a drug rash. On subsequent visits, the resident undergoes multiple punch biopsies and is diagnosed with BP. Treatment is initiated with topical steroids, systemic steroids, and oral minocycline. On a follow-up visit, the resident is showing improvement of her BP. However, the resident's hypertension and hyperglycemia are now uncontrolled as a result of the discontinuation of hydrochlorothiazide and the initiation of steroid therapy. This case highlights the dangers of corticosteroids in patients, especially the elderly, who have multiple comorbidities.

  10. Adverse Late and Long-Term Treatment Effects in Adult Allogeneic Hematopoietic Stem Cell Transplant Survivors.

    PubMed

    Mosesso, Kara

    2015-11-01

    Hematopoietic stem cell transplantation (HSCT) has become the standard of care for many malignant and nonmalignant hematologic diseases that don't respond to traditional therapy. There are two types: autologous transplantation (auto-HSCT), in which an individual's stem cells are collected, stored, and infused back into that person; and allogeneic transplantation (allo-HSCT), in which healthy donor stem cells are infused into a recipient whose bone marrow has been damaged or destroyed. There have been numerous advancements in this field, leading to marked increases in the number of transplants performed annually. This article--the first of several on cancer survivorship--focuses on the care of adult allo-HSCT survivors because of the greater complexity of their posttransplant course. The author summarizes potential adverse late and long-term treatment-related effects, with special focus on the evaluation and management of several cardiovascular disease risk factors that can occur either independently or concurrently as part of the metabolic syndrome. These risk factors are potentially modifiable with appropriate nursing interventions and lifestyle modifications.

  11. Late-onset Tay-Sachs disease: adverse effects of medications and implications for treatment.

    PubMed

    Shapiro, B E; Hatters-Friedman, S; Fernandes-Filho, J A; Anthony, K; Natowicz, M R

    2006-09-12

    The authors conducted a retrospective and brief prospective study of adverse effects of approximately 350 medications in 44 adults with late-onset Tay-Sachs disease (LOTS). Some medications were relatively safe, whereas others, particularly haloperidol, risperidone, and chlorpromazine, were associated with neurologic worsening.

  12. Adverse Effect of Child Abuse Victimization among Substance-Using Women in Treatment.

    ERIC Educational Resources Information Center

    Kang, Sung-Yeon; Magura, Stephen; Laudet, Alexandre; Whitney, Shirley

    1999-01-01

    Study examined adverse effects of childhood sexual/physical abuse among substance-abusing women with children. Several significant differences between abused and nonabused women were found in service outcomes. Abused women had more problems relating to drug use and psychiatric/psychological adjustment at follow-up. Findings support a need for…

  13. Preferences for Analgesic Treatments Are Influenced by Probability of the Occurrence of Adverse Effects and the Time to Reach Maximal Therapeutic Effects

    PubMed Central

    Lin, Chia-Shu; Wu, Shih-Yun; Wu, Long-Ting

    2015-01-01

    Research on shared medical decision-making suggested that both the potency of a treatment and the probability of it being successful influence individual treatment preferences. Patients also need to consider the negative attributes of treatments, such as the occurrence of adverse effects or a slow start to the therapeutic effects. It remains unclear how these attributes influence individual treatment preferences. We investigated how the analgesic effect, the adverse effect, and the time-course effect influenced the preference of analgesic treatments. Forty-five healthy volunteers participated in three hypothetical analgesic decision-making tasks. They were instructed to imagine that they were experiencing pain and choose between two hypothetical analgesic treatments: the more potent radical treatment and the less potent conservative treatment. The potency of a treatment was countered by the following attributes: the probability of working successfully, the probability of inducing an adverse effect, and the time required for the treatment to reach its maximal effect. We found that (a) when the overall probability that a treatment would induce an adverse effect decreased, the participants changed their preference from a conservative treatment to a radical treatment; (b) when the time-course for a treatment to reach its maximal effect was shortened, the participants changed their preference from a conservative treatment to a radical treatment, and (c) individual differences in prior clinical pain and the degree of imagined pain relief were associated with preferences. The findings showed that the adverse effects and the time course of treatments guide the analgesic treatment preferences, highlighting the importance of sharing information about negative attributes of treatments in pain management. The findings imply that patients may over-emphasize the occurrence of adverse effect or a slow time-course of treatment effect. In terms of shared medical decision

  14. Adverse effects of cannabis.

    PubMed

    2011-01-01

    Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to

  15. Long-term oral baclofen treatment in a child with cerebral palsy: electroencephalographic changes and clinical adverse effects.

    PubMed

    De Rinaldis, Marta; Losito, Luciana; Gennaro, Leonarda; Trabacca, Antonio

    2010-10-01

    Baclofen is widely used to control spasticity in children with cerebral palsy. Several publications described clinical adverse effects of baclofen oral treatment, but the effect of baclofen on seizure potentiation is still controversial. We describe a 10-year-old female patient with cerebral palsy, epilepsy, and mental retardation who developed clinical adverse effects (confusion, agitated state, insomnia, diffuse hypotonia, and hyporeflexia) and electroencephalographic (EEG) changes (quasiperiodic, generalized burst of sharp waves that take up >50% of standard EEG) during long-term oral baclofen treatment, after gradually increasing the dosage but still within the therapeutic dose. Our case showed clearly that the EEG changes in our patient, with a history of epilepsy in good control, have been induced by the baclofen increase, and we describe the possible mechanisms that could explain proconvulsive effect of baclofen.

  16. Dyskinesia as a new adverse effect of hormonal treatment in West syndrome.

    PubMed

    Sukhudyan, Biayna G; Dimova, Petia S; Capuano, Alessandro; Vigevano, Federico

    2014-03-01

    West syndrome is an age-dependent epileptic encephalopathy. Despite potential side effects, hormonal therapy remains the main treatment for West syndrome. Here, we report on 10 patients receiving steroid treatment who presented with unusual, mostly hyperkinetic, movements. Facial grimacing, repetitive mouth opening, adduction and abduction of upper and lower extremities, and periodical strabismus in different combinations were observed in all patients, independent of formulation, dose, duration, and efficacy of treatment. Symptoms disappeared in sleep and reappeared immediately on arousal. Dyskinesias stopped gradually after a month of discontinuation of treatment. Repeated EEGs did not show corresponding epileptiform activity. We conclude that these abnormal movements can be attributed to side effects of hormonal treatment.

  17. Stress Moderates the Effect of Childhood Trauma and Adversity on Recent Drinking in Treatment-seeking Alcohol-dependent Men

    PubMed Central

    Eames, Sarah F.; Businelle, Michael S.; Suris, Alina; Walker, Robrina; Rao, Uma; North, Carol S.; Xiao, Hong; Adinoff, Bryon

    2014-01-01

    Objective This study sought to clarify the relationship between childhood trauma and adversity with later alcohol consumption and the moderating effects of adult psychosocial stress. Method Seventy-seven recently abstinent alcohol-dependent men attending residential treatment programs were assessed. Childhood trauma/adversity was assessed with the Childhood Trauma Questionnaire (CTQ), drinks per drinking day (DDD) with the TimeLine Follow Back, and chronic psychosocial stress with the UCLA Stress Interview. Drinking and stress were retrospectively assessed for six months prior to the present treatment episode. Direct associations between childhood trauma/adversity and alcohol consumption and the moderating effects of recent psychosocial stress were assessed. All measures were considered as continuous variables. Results Pretreatment drinking severity (DDD) was associated with CTQ Total score (p = .009) and the Emotional Abuse (p < .001) and Physical Abuse (p < .01) subscales. UCLA Total Stress significantly moderated the effects of CTQ Total score on drinking severity (p = .04). Whereas higher CTQ scores were significantly associated with a greater amount of pretreatment drinking in participants with high UCLA stress scores (p = .01), CTQ scores were not associated with the amount of drinking in those with low UCLA stress scores (p = .63). Conclusions Childhood trauma predicts drinking severity in alcohol-dependent men and this effect is stronger in participants with ongoing stress in adult life. These findings suggest that early childhood trauma/adversity may sensitize stress-response systems. PMID:24635549

  18. Evolution of pharmacological obesity treatments: focus on adverse side-effect profiles.

    PubMed

    Krentz, A J; Fujioka, K; Hompesch, M

    2016-06-01

    Pharmacotherapy directed toward reducing body weight may provide benefits for both curbing obesity and lowering the risk of obesity-associated comorbidities; however, many weight loss medications have been withdrawn from the market because of serious adverse effects. Examples include pulmonary hypertension (aminorex), cardiovascular toxicity, e.g. flenfluramine-induced valvopathy, stroke [phenylpropanolamine (PPA)], excess non-fatal cardiovascular events (sibutramine), and neuro-psychiatric issues (rimonabant; approved in Europe, but not in the USA). This negative experience has helped mould the current drug development and approval process for new anti-obesity drugs. Differences between the US Food and Drug Administration (FDA) and the European Medicines Agency, however, in perceptions of risk-benefit considerations for individual drugs have resulted in discrepancies in approval and/or withdrawal of weight-reducing medications. Thus, two drugs recently approved by the FDA, i.e. lorcaserin and phentermine + topiramate extended release, are not available in Europe. In contrast, naltrexone sustained release (SR)/bupropion SR received FDA approval, and liraglutide 3.0 mg was recently approved in both the USA and Europe. Regulatory strategies adopted by the FDA to manage the potential for uncommon but potentially serious post-marketing toxicity include: (i) risk evaluation and mitigation strategy programmes; (ii) stipulating post-marketing safety trials; (iii) considering responder rates and limiting cumulative exposure by discontinuation if weight loss is not attained within a reasonable timeframe; and (iv) requiring large cardiovascular outcome trials before or after approval. We chronicle the adverse effects of anti-obesity pharmacotherapy and consider how the history of high-profile toxicity issues has shaped the current regulatory landscape for new and future weight-reducing drugs.

  19. Adverse effects reported in the use of gastroesophageal reflux disease treatments in children: a 10 years literature review.

    PubMed

    Cohen, Shlomi; Bueno de Mesquita, Mirjam; Mimouni, Francis B

    2015-08-01

    Gastroesophageal reflux (GER) is commonly observed in children, particularly during the first year of life. Pharmacological therapy is mostly reserved for symptomatic infants diagnosed with GER disease (GERD), usually as defined in a recent consensus statement. The purpose of the present article was to review the reported adverse effects of pharmacological agents used in the treatment of paediatric GERD. We conducted this review using the electronic journal database Pubmed and Cochrane database systematic reviews using the latest 10-year period (1 January 2003 to 31 December 2012). Our search strategy included the following keywords: omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole, rantidine, cimetidine, famotidine, nizatidine, domperidone, metoclopramide, betanechol, erythromycin, baclofen, alginate. We used Pubmed's own filter of: 'child: birth-18 years'. All full articles were reviewed and we only included randomized controlled trials retrieved from our search. We addressed a summary of our search on a drug-by-drug basis with regard to its mechanism of action and clinical applications, and reviewed all of the adverse effects reported and the safety profile of each drug. Adverse effects have been reported in at least 23% of patients treated with histamine H2 receptor antagonists (H2 RAs) and 34% of those treated with proton pump inhibitors (PPIs), and mostly include headaches, diarrhoea, nausea (H2 RAs and PPIs) and constipation (PPIs). Acid suppression may place immune-deficient infants and children, or those with indwelling catheters, at risk for the development of lower respiratory tract infections and nosocomial sepsis. Prokinetic agents have many adverse effects, without major benefits to support their routine use.

  20. Adverse effects reported in the use of gastroesophageal reflux disease treatments in children: a 10 years literature review

    PubMed Central

    Cohen, Shlomi; Bueno de Mesquita, Mirjam; Mimouni, Francis B

    2015-01-01

    Gastroesophageal reflux (GER) is commonly observed in children, particularly during the first year of life. Pharmacological therapy is mostly reserved for symptomatic infants diagnosed with GER disease (GERD), usually as defined in a recent consensus statement. The purpose of the present article was to review the reported adverse effects of pharmacological agents used in the treatment of paediatric GERD. We conducted this review using the electronic journal database Pubmed and Cochrane database systematic reviews using the latest 10-year period (1 January 2003 to 31 December 2012). Our search strategy included the following keywords: omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole, rantidine, cimetidine, famotidine, nizatidine, domperidone, metoclopramide, betanechol, erythromycin, baclofen, alginate. We used Pubmed’s own filter of: ’child: birth–18 years’. All full articles were reviewed and we only included randomized controlled trials retrieved from our search. We addressed a summary of our search on a drug-by-drug basis with regard to its mechanism of action and clinical applications, and reviewed all of the adverse effects reported and the safety profile of each drug. Adverse effects have been reported in at least 23% of patients treated with histamine H2 receptor antagonists (H2RAs) and 34% of those treated with proton pump inhibitors (PPIs), and mostly include headaches, diarrhoea, nausea (H2RAs and PPIs) and constipation (PPIs). Acid suppression may place immune-deficient infants and children, or those with indwelling catheters, at risk for the development of lower respiratory tract infections and nosocomial sepsis. Prokinetic agents have many adverse effects, without major benefits to support their routine use. PMID:25752807

  1. Simulation of effects of botulinum toxin on muscular mechanics in time course of treatment based on adverse extracellular matrix adaptations.

    PubMed

    Turkoglu, Ahu N; Yucesoy, Can A

    2016-05-03

    BTX effects on muscular mechanics are highly important, but their mechanism and variability in due treatment course is not well understood. Recent modeling shows that partial muscle paralysis per se causes restricted sarcomere shortening due to muscle fiber-extracellular matrix (ECM) mechanical interactions. This leads to two notable acute-BTX effects compared to pre-BTX treatment condition: (1) enhanced potential of active force production of the non-paralyzed muscle parts, and (2) decreased muscle length range of force exertion (ℓrange). Recent experiments also indicate increased ECM stiffness of BTX treated muscle. Hence, altered muscle fiber-ECM interactions and BTX effects are plausible in due treatment course. Using finite element modeling, the aim was to test the following hypotheses: acute-BTX treatment effects elevate with increased ECM stiffness in the long-term, and are also persistent post-BTX treatment. Model results confirm these hypotheses and show that restricted sarcomere shortening effect becomes more pronounced in the long-term and is persistent or reversed (for longer muscle lengths) post-BTX treatment. Consequently, force production capacity of activated sarcomeres gets further enhanced in the long-term. Remarkably, such enhanced capacity becomes permanent for the entire muscle post-treatment. Shift of muscle optimum length to a shorter length is more pronounced in the long-term, some of which remains permanent post-treatment. Compared to Pre-BTX treatment, a narrower ℓrange (20.3%, 27.1% and 3.4%, acute, long-term and post-BTX treatment, respectively) is a consistent finding. We conclude that ECM adaptations can affect muscular mechanics adversely both during spasticity management and post-BTX treatment. Therefore, this issue deserves major future attention.

  2. Fluidized bed ash and passive treatment reduce the adverse effects of acid mine drainage on aquatic organisms.

    PubMed

    Porter, Clint M; Nairn, Robert W

    2010-10-15

    Elevated concentrations of acidity and metals in acid mine drainage (AMD) may be effectively addressed by active and passive treatment technologies. However, typical evaluations consider only chemical water quality with little if any regard for biological metrics. Robust evaluations including both chemical and biological indicators of water quality improvement are needed. In this study, injection of alkaline fluidized bed ash (FBA) into a flooded underground coal mine was coupled with a five-cell passive treatment system to ameliorate an abandoned AMD discharge in eastern Oklahoma. The passive system included process units promoting both aerobic and anaerobic treatment mechanisms. Resulting water quality changes and biological responses were evaluated. Organisms of two distinct functional groups (the filter-feeding mollusk Corbicula fluminea and the wide-spectrum feeding fish Lepomis macrochirus) were exposed to mine waters in several treatment cells. The combination of treatment technologies was hypothesized to limit potential negative effects on these aquatic organisms. Tissues were harvested and analyzed for concentrations of several metals (Al, Fe, Mn, Mg, Ca, Ni, Cu and Zn) of interest. Organismal responses, such as hepatosomatic index, condition factor, and condition index, did not vary significantly among organisms exposed within different treatment cells when compared to non-AMD impaired waters. Metal tissue accumulation trends, compared to aqueous concentrations, were observed for Fe, Ni and Zn. Exposure experiments with these two organisms indicated that FBA introductions coupled with passive treatment decreased the potential adverse effects of AMD to biological systems.

  3. Adverse effects of antihypertensive drugs.

    PubMed

    Husserl, F E; Messerli, F H

    1981-09-01

    Early essential hypertension is asymptomatic and should remain so throughout treatment. In view of the increasing number of available antihypertensive agents, clinicians need to become familiar with the potential side effects of these drugs. By placing more emphasis on non-pharmacological treatment (sodium restriction, weight loss, exercise) and thoroughly evaluating each case in particular, the pharmacological regimen can be optimally tailored to the patient's needs. Potential side effects should be predicted and can often be avoided; if they become clinically significant they should be rapidly recognised and corrected. These side effects can be easily remembered in most instances, as they fall into 3 broad categories: (a) those caused by an exaggerated therapeutic effect; (b) those due to a non-therapeutic pharmacological effect; and (c) those caused by a non-therapeutic, non-pharmacological effect probably representing idiosyncratic reactions. This review focuses mainly on adverse effects of the second and third kind. Each group of drugs in general shares the common side effects of the first two categories, while each individual drug has its own idiosyncratic side effects.

  4. Adverse mandibular bone effects associated with kidney disease are only partially corrected with bisphosphonate and/or calcium treatment

    PubMed Central

    Allen, Matthew R.; Chen, Neal X.; Gattone, Vincent H.; Moe, Sharon M.

    2014-01-01

    Background/Aims Patients with chronic kidney disease (CKD) have high prevalence of periodontal disease that may predispose to tooth loss and inflammation. The goal of this study was to test the hypotheses that a genetic rat model of progressive CKD would exhibit altered oral bone properties and that treatment with either bisphosphonates or calcium could attenuate these adverse changes. Methods At 25 weeks of age, rats were treated with zoledronate, calcium gluconate, or their combination for 5 or 10 weeks. Mandible bone properties were assessed using micro-computed tomography to determine bone volume (BV/TV) and cement-enamel junction to alveolar crest distance (CEJ-AC). Results Untreated CKD animals had significantly lower BV/TV at both 30 (−5%) and 35 (−14%) weeks of age and higher CEJ-AC (+27 and 29%) compared to normal animals. CKD animals had significantly higher PTH compared to normal animals yet similar levels of C-reactive protein. Zoledronate-treatment normalized BV/TV over the first 5 weeks but this benefit was lost by 10 weeks. Calcium treatment, alone or in combination with zoledronate, was effective in normalizing BV/TV at both time points. Neither zoledronate nor calcium was able to correct the higher CEJ-AC caused by CKD. Calcium, but not zoledronate, significantly reduced serum parathyroid hormone (PTH) while neither treatment affected C-reactive protein. Conclusions 1) this progressive animal model of chronic kidney disease shows a clear mandibular skeletal phenotype consistent with periodontitis, 2) the periodontitis is not associated with systemic inflammation as measured by C-reactive protein, and 3) reducing PTH has positive effects on the mandible phenotype. PMID:24280830

  5. The neurobiological Correlates of Childhood Adversity and Implications for Treatment

    PubMed Central

    Tyrka, Audrey R.; Burgers, Darcy E.; Philip, Noah S.; Price, Lawrence H.; Carpenter, Linda L.

    2013-01-01

    Objective This paper provides an overview of research on the neurobiological correlates of childhood adversity and a selective review of treatment implications. Method Findings from a broad array of human and animal studies of early adversity were reviewed. Results Topics reviewed include neuroendocrine, neurotrophic, neuroimaging, and cognitive effects of adversity, as well as genetic and epigenetic influences. Effects of early life stress on treatment outcome are considered, and development of treatments designed to address the neurobiological abnormalities is discussed. Conclusion Early adversity is associated with abnormalities of several neurobiological systems that are implicated in the development of psychopathology and other medical conditions. Early life stress negatively impacts treatment outcome and individuals may require treatments that are specific to this condition. PMID:23662634

  6. Effect of Diabetes Mellitus on Tuberculosis Treatment Outcome and Adverse Reactions in Patients Receiving Directly Observed Treatment Strategy in India: A Prospective Study

    PubMed Central

    Siddiqui, Ali Nasir; Khayyam, Khalid Umer

    2016-01-01

    Despite successful implementation of directly observed treatment, short course (DOTS) in India, the growing number of diabetes mellitus (DM) patients appears to be a cause in the increasing tuberculosis (TB) incidence, affecting their management. In this regard, a prospective study was conducted on DOTS patients in three primary health care centers in urban slum region of South Delhi, India, to evaluate the effect of DM on sputum conversion, treatment outcome, and adverse drug reactions (ADR) due to anti-TB treatment. Eligible TB patients underwent blood glucose screening at treatment initiation. Disease presentation, clinical outcome, and ADRs were compared between patients of TB with and without DM. Out of 316 patients, the prevalence of DM was found to be 15.8%, in which 19.4% and 9.6% were PTB and EPTB patients, respectively. DM patients have observed higher sputum positivity (OR 1.247 95% CI; 0.539–2.886) at the end of 2-month treatment and poor outcome (OR 1.176 95% CI; 0.310–4.457) at the completion of treatment compared with non DM patients. Presence of DM was significantly associated (OR 3.578 95% CI; 1.114–11.494, p = 0.032) with the development of ADRs. DM influences the treatment outcome of PTB patients in our setting and also on the ADR incidence. PMID:27642601

  7. Thiocolchicoside: review of adverse effects.

    PubMed

    2016-02-01

    Thiocolchicoside has long been used as a muscle relaxant, despite a lack of proven efficacy beyond the placebo effect. Its chemical structure consists of colchicine, a sugar (ose) and a sulphur-containing radical (thio), and its adverse effects are therefore likely to be similar to those of colchicine. Using the standard Prescrire methodology, we reviewed the available data on the adverse effects of thiocolchicoside. Liver injury, pancreatitis, seizures, blood cell disorders, severe cutaneous disorders, rhabdomyolysis and reproductive disorders have all been recorded in the French and European pharmacovigilance databases and in the periodic updates that the companies concerned submit to regulatory agencies. These data do not specify the frequency of the disorders nor do they identify the most susceptible patient populations. Thiocolchicoside is teratogenic in experimental animals and also damages chromosomes. Human data are limited to a follow-up of about 30 pregnant women (no major malformations) and reports of altered spermatogenesis, including cases of azoospermia. In practice, there is no justification for exposing patients to the adverse effects of thiocolchicoside. It is better to use an effective, well-known analgesic for patients complaining of muscle pain, starting with paracetamol.

  8. Perioperative treatment with the new synthetic TLR-4 agonist GLA-SE reduces cancer metastasis without adverse effects.

    PubMed

    Matzner, Pini; Sorski, Liat; Shaashua, Lee; Elbaz, Ely; Lavon, Hagar; Melamed, Rivka; Rosenne, Ella; Gotlieb, Neta; Benbenishty, Amit; Reed, Steve G; Ben-Eliyahu, Shamgar

    2016-04-01

    The use of TLR agonists as an anti-cancer treatment is gaining momentum given their capacity to activate various host cellular responses through the secretion of inflammatory cytokines and type-I interferons. It is now also recognized that the perioperative period is a window of opportunity for various interventions aiming at reducing the risk of cancer metastases-the major cause of cancer related death. However, immune-stimulatory approach has not been used perioperatively given several contraindications to surgery. To overcome these obstacles, in this study, we used the newly introduced, fully synthetic TLR-4 agonist, Glucopyranosyl Lipid-A (GLA-SE), in various models of cancer metastases, and in the context of acute stress or surgery. Without exerting evident adverse effects, a single systemic administration of GLA-SE rapidly and dose dependently elevated both innate and adaptive immunity in the circulation, lungs and the lymphatic system. Importantly, GLA-SE treatment led to reduced metastatic development of a mammary adenocarcinoma and a colon carcinoma by approximately 40-75% in F344 rats and BALB/c mice, respectively, at least partly through elevating marginating-pulmonary NK cell cytotoxicity. GLA-SE is safe and well tolerated in humans, and currently is used as an adjuvant in phase-II clinical trials. Given that the TLR-4 receptor and its signaling cascade is highly conserved throughout evolution, our current results suggest that GLA-SE may be a promising immune stimulatory agent in the context of oncological surgeries, aiming to reduce long-term cancer recurrence.

  9. Adverse Effects of Psychotropic Medications: A Call to Action.

    PubMed

    Mago, Rajnish

    2016-09-01

    Adverse effects are common, bothersome, and a leading cause of discontinuation of treatment. The methodology for evaluating adverse effects of medications has been greatly neglected, however, especially in comparison to the methodology for assessment of efficacy of medications. Existing methods for assessment and reporting of adverse effects have important limitations leading to lack of much-needed data related to adverse effects. Lastly, there is little systematic research into management of most adverse effects. A series of recommendations are made in this article about how to improve identification, assessment, reporting, and management of adverse effects.

  10. [Finasteride adverse effects: An update].

    PubMed

    Carreño-Orellana, Néstor; Moll-Manzur, Catherina; Carrasco-Zuber, Juan Eduardo; Álvarez-Véliz, Sergio; Berroeta-Mauriziano, Daniela; Porras-Kusmanic, Ninoska

    2016-12-01

    Finasteride is a 5-α reductase inhibitor that is widely used in the management of benign prostate hyperplasia and male pattern hair loss. It is well known that these agents improve the quality of life in men suffering from these conditions. However, they are associated with some transient and even permanent adverse effects. The aim of this article is to clarify the controversies about the safety of finasteride by analyzing the evidence available in the literature.

  11. Alleviation of adverse effects of drought stress on growth and some potential physiological attributes in maize (Zea mays L.) by seed electromagnetic treatment.

    PubMed

    Javed, Namra; Ashraf, Muhammad; Akram, Nudrat Aisha; Al-Qurainy, Fahad

    2011-01-01

    Effects of varying preseed magnetic treatments on growth, chlorophyll pigments, photosynthesis, water relation attributes, fluorescence and levels of osmoprotectants in maize plants were tested under normal and drought stress conditions. Seeds of two maize cultivars were treated with different (T0 [0 mT], T1 [100 mT for 5 min], T2 [100 mT for 10 min], T3 [150 mT for 5 min] and T4 [150 mT for 10 min]) electromagnetic treatments. Drought stress considerably suppressed growth, chlorophyll a and b pigments, leaf water potential, photosynthetic rate (A), stomatal conductance (g(s)) and substomatal CO(2) concentration (C(i)), while it increased leaf glycinebetaine and proline accumulation in both maize cultivars. However, pretreated seeds with different magnetic treatments significantly alleviated the drought-induced adverse effects on growth by improving chlorophyll a, A, E, g(s), C(i) and photochemical quenching and nonphotochemical quenching, while it had no significant effect on other attributes. However, different magnetic treatments negatively affected the g(s) and C(i) particularly in cv. Agaiti-2002 under drought stress conditions. Of all magnetic treatments, 100 and 150 mT for 10 min were most effective in alleviating the drought-induced adverse effects. Overall, preseed electromagnetic treatments could be used to minimize the drought-induced adverse effects on different crop plants.

  12. Negative Effects of Psychological Treatments: An Exploratory Factor Analysis of the Negative Effects Questionnaire for Monitoring and Reporting Adverse and Unwanted Events

    PubMed Central

    Kottorp, Anders; Boettcher, Johanna; Andersson, Gerhard; Carlbring, Per

    2016-01-01

    Research conducted during the last decades has provided increasing evidence for the use of psychological treatments for a number of psychiatric disorders and somatic complaints. However, by focusing only on the positive outcomes, less attention has been given to the potential of negative effects. Despite indications of deterioration and other adverse and unwanted events during treatment, little is known about their occurrence and characteristics. Hence, in order to facilitate research of negative effects, a new instrument for monitoring and reporting their incidence and impact was developed using a consensus among researchers, self-reports by patients, and a literature review: the Negative Effects Questionnaire. Participants were recruited via a smartphone-delivered self-help treatment for social anxiety disorder and through the media (N = 653). An exploratory factor analysis was performed, resulting in a six-factor solution with 32 items, accounting for 57.64% of the variance. The derived factors were: symptoms, quality, dependency, stigma, hopelessness, and failure. Items related to unpleasant memories, stress, and anxiety were experienced by more than one-third of the participants. Further, increased or novel symptoms, as well as lack of quality in the treatment and therapeutic relationship rendered the highest self-reported negative impact. In addition, the findings were discussed in relation to prior research and other similar instruments of adverse and unwanted events, giving credence to the items that are included. The instrument is presently available in eleven different languages and can be freely downloaded and used from www.neqscale.com. PMID:27331907

  13. Negative Effects of Psychological Treatments: An Exploratory Factor Analysis of the Negative Effects Questionnaire for Monitoring and Reporting Adverse and Unwanted Events.

    PubMed

    Rozental, Alexander; Kottorp, Anders; Boettcher, Johanna; Andersson, Gerhard; Carlbring, Per

    2016-01-01

    Research conducted during the last decades has provided increasing evidence for the use of psychological treatments for a number of psychiatric disorders and somatic complaints. However, by focusing only on the positive outcomes, less attention has been given to the potential of negative effects. Despite indications of deterioration and other adverse and unwanted events during treatment, little is known about their occurrence and characteristics. Hence, in order to facilitate research of negative effects, a new instrument for monitoring and reporting their incidence and impact was developed using a consensus among researchers, self-reports by patients, and a literature review: the Negative Effects Questionnaire. Participants were recruited via a smartphone-delivered self-help treatment for social anxiety disorder and through the media (N = 653). An exploratory factor analysis was performed, resulting in a six-factor solution with 32 items, accounting for 57.64% of the variance. The derived factors were: symptoms, quality, dependency, stigma, hopelessness, and failure. Items related to unpleasant memories, stress, and anxiety were experienced by more than one-third of the participants. Further, increased or novel symptoms, as well as lack of quality in the treatment and therapeutic relationship rendered the highest self-reported negative impact. In addition, the findings were discussed in relation to prior research and other similar instruments of adverse and unwanted events, giving credence to the items that are included. The instrument is presently available in eleven different languages and can be freely downloaded and used from www.neqscale.com.

  14. Exercise can prevent and even reverse adverse effects of androgen suppression treatment in men with prostate cancer.

    PubMed

    Galvão, D A; Taaffe, D R; Spry, N; Newton, R U

    2007-01-01

    Side effects accompanying androgen deprivation therapy (ADT), including sarcopenia, loss of bone mass and reduction in muscle strength, can compromise physical function, particularly in older patients. Exercise, specifically resistance training, may be an effective and cost-efficient strategy to limit or even reverse some of these adverse effects during and following therapy. In this review, we discuss common morphological and physiological ADT-related side effects or 'Androgen Deprivation and Sarcopenia-Related Disorders' and the existing clinical trials incorporating physical exercise in prostate cancer patients receiving active therapy. Further, training concepts and guidelines are provided for prescribing resistance exercise programs for this population.

  15. Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effects.

    PubMed

    Sarris, J; Stough, C; Teschke, R; Wahid, Z T; Bousman, C A; Murray, G; Savage, K M; Mouatt, P; Ng, C; Schweitzer, I

    2013-11-01

    Presently, little is known about a number issues concerning kava (Piper methysticum), including (i) whether kava has any withdrawal or addictive effects; (ii) if genetic polymorphisms of the cytochrome (CYP) P450 2D6 liver enzyme moderates any potential adverse effects; and (iii) if medicinal application of kava has any negative or beneficial effect on sexual function and experience. The study design was a 6-week, double-blind, randomized controlled trial (n = 75) involving chronic administration of kava (one tablet of kava twice per day; 120 mg of kavalactones per day, titrated in non-response to two tablets of kava twice per day; 240 mg of kavalactones) or placebo for participants with generalized anxiety disorder. Results showed no significant differences across groups for liver function tests, nor were there any significant adverse reactions that could be attributed to kava. No differences in withdrawal or addiction were found between groups. Interesting, kava significantly increased female's sexual drive compared to placebo (p = 0.040) on a sub-domain of the Arizona Sexual Experience Scale (ASEX), with no negative effects seen in males. Further, it was found that there was a highly significant correlation between ASEX reduction (improved sexual function and performance) and anxiety reduction in the whole sample.

  16. Managing nonteratogenic adverse reactions to isotretinoin treatment for acne vulgaris.

    PubMed

    Reilly, Bridget K; Ritsema, Tamara S

    2015-07-01

    Isotretinoin is the strongest, most effective oral treatment for patients with severe acne vulgaris, with remission rates of 89% and higher. Because of its potency, isotretinoin causes many adverse reactions. This article reviews common and severe adverse reactions to isotretinoin and how providers can best manage these reactions. Because of inconclusive research on the correlation between isotretinoin and depression and irritable bowel syndrome, providers should ask patients about symptoms monthly. Prescribing micronized isotretinoin and starting at the lowest dose with gradual upward titration also can help reduce the incidence of adverse reactions.

  17. Current trends in the treatment of hepatitis C: interventions to avoid adverse effects and increase effectiveness of anti-HCV drugs

    PubMed Central

    Saleem, Ammara; Akhtar, Muhammad Furqan; Mushtaq, Muhammed Fahd; Saleem, Muhammad; Muhammad, Syed Taqi; Akhtar, Bushra; Sharif, Ali; Peerzada, Sohaib

    2016-01-01

    Viral hepatitis, an inflammatory liver disease, is caused by various genotypes of hepatitis C viruses (HCV). Hepatitis C slowly sprouts into fibrosis, which progresses to cirrhosis. Over a prolonged period of time compensated cirrhosis can advance to decompensated cirrhosis culminating in hepatic failure and death. Conventional treatment of HCV involves the administration of interferons. However, association of interferon with the adverse drug reactions led to the development of novel anti-HCV drugs given as monotherapy or in combination with the other drugs. Advances in drug delivery systems (DDS) improved the pharmacokinetic profile and stability of drugs, ameliorated tissue damages on extravasation and increased the targeting of affected sites. Liposomes and lipid based vehicles have been employed with polyethylene glycol (PEG) so as to stabilize the formulations as PEG drug complex. Sofosbuvir, a novel anti-HCV drug, is administered as monotherapy or in combination with daclatasvir, ledipasivir, protease inhibitors, ribavirin and interferon for the treatment of HCV genotypes 1, 2 and 3. These drug combinations are highly effective in eradicating the interferon resistance, recurrent HCV infection in liver transplant, concurrent HIV infection and preventing interferon related adverse effects. Further investigations to improve drug targeting and identification of new drug targets are highly warranted due to the rapid emergence of drug resistance in HCV. PMID:28096788

  18. Current trends in the treatment of hepatitis C: interventions to avoid adverse effects and increase effectiveness of anti-HCV drugs.

    PubMed

    Saleem, Ammara; Akhtar, Muhammad Furqan; Mushtaq, Muhammed Fahd; Saleem, Muhammad; Muhammad, Syed Taqi; Akhtar, Bushra; Sharif, Ali; Peerzada, Sohaib

    2016-01-01

    Viral hepatitis, an inflammatory liver disease, is caused by various genotypes of hepatitis C viruses (HCV). Hepatitis C slowly sprouts into fibrosis, which progresses to cirrhosis. Over a prolonged period of time compensated cirrhosis can advance to decompensated cirrhosis culminating in hepatic failure and death. Conventional treatment of HCV involves the administration of interferons. However, association of interferon with the adverse drug reactions led to the development of novel anti-HCV drugs given as monotherapy or in combination with the other drugs. Advances in drug delivery systems (DDS) improved the pharmacokinetic profile and stability of drugs, ameliorated tissue damages on extravasation and increased the targeting of affected sites. Liposomes and lipid based vehicles have been employed with polyethylene glycol (PEG) so as to stabilize the formulations as PEG drug complex. Sofosbuvir, a novel anti-HCV drug, is administered as monotherapy or in combination with daclatasvir, ledipasivir, protease inhibitors, ribavirin and interferon for the treatment of HCV genotypes 1, 2 and 3. These drug combinations are highly effective in eradicating the interferon resistance, recurrent HCV infection in liver transplant, concurrent HIV infection and preventing interferon related adverse effects. Further investigations to improve drug targeting and identification of new drug targets are highly warranted due to the rapid emergence of drug resistance in HCV.

  19. Treatment of adverse digitalis effects by hemoperfusion through columns with antidigoxin antibodies bound to agarose polyacrolein microsphere beads.

    PubMed

    Savin, H; Marcus, L; Margel, S; Ofarim, M; Ravid, M

    1987-05-01

    Ten patients with an array of moderate to severe adverse effects resulting from digitalis were effectively treated by hemoperfusion through small columns which contained antidigoxin antibodies bound to polyacrolein microspheres in agarose macrospheres (APAMB). The procedure was well tolerated. There was no detectable damage to formed blood elements and no changes in electrolytes, liver enzymes, or other related biochemical parameters. Despite some theoretic considerations to the contrary, the removal of a relatively small load of digoxin resulted in amelioration of the clinical symptoms and ECG abnormalities associated with digitalis. No rebound phenomena of intoxication or posthemoperfusion increase in digoxin serum levels were noted over the subsequent 5 to 6 days. A further increase in the capacity of the columns may render this method a safe and convenient emergency procedure for patients with digitalis toxicity.

  20. Clozapine Treatment of Childhood-Onset Schizophrenia: Evaluation of Effectiveness, Adverse Effects, and Long-Term Outcome

    ERIC Educational Resources Information Center

    Sporn, Alexandra L.; Vermani, Anoop; Greenstein, Deanna K.; Bobb, Aaron J.; Spencer, Edgar P.; Clasen, Liv S.; Tossell, Julia W.; Stayer, Catherine C.; Gochman, Peter A.; Lenane, Marge C.; Rapoport, Judith L.; Gogtay, Nitin

    2007-01-01

    Objective: Clozapine is a unique atypical antipsychotic with superior efficacy in treatment-resistant schizophrenia. Plasma concentration of clozapine and its major metabolite N-desmethylclozapine (NDMC) as well as the ratio of NDMC to clozapine have been reported to be predictors of clozapine response. Here we evaluate these as well as other…

  1. Adverse effects of new antiepileptic drugs.

    PubMed

    Onat, Filiz; Ozkara, Cigdem

    2004-04-01

    Starting with phenobarbital in the 1900s, it took almost 70-80 years to introduce old-generation agents for the treatment of epilepsy. Then, in eleven years, nine more new antiepileptic drugs were added to the armamentarium. These drugs produce a nearly 40-50% decrease in seizure incidence in refractory patients, but few patients have been able to achieve complete freedom from seizures. So the search for more effective drugs with minimal adverse effect profiles will continue. Although the new antiepileptic drugs do not demonstrate a superior efficacy compared to the older ones, they do offer some advantages in terms of tolerability, fewer drug interactions and simpler pharmacokinetics. However, our knowledge concerning their safety profiles can not yet be considered adequate due to the relatively short time these drugs have been on the market and to the limited number of patients exposed to them. The fact that the serious side effects of felbamate and vigabatrine appeared late after marketing should be taken as an important lesson because it implies the potential for unknown side effects at any time during treatment. Antiepileptic drug treatment should begin with diagnosis of the seizure and epileptic syndrome, followed by selection of the drug most appropriate for treatment of the individual patient, and continued with monitoring of not only the seizures but the adverse effect profile as well.

  2. [Gabapentin treatment in a female patient with panic disorder and adverse effects under carbamazepine during benzodiazepine withdrawal].

    PubMed

    Himmerich, Hubertus; Nickel, Thomas; Dalal, Mira A; Müller, Marianne B

    2007-03-01

    Despite their addictive potential, benzodiazepines belong to the most often prescribed drugs. We report on a patient with alprazolam dependence, who initially was treated with carbamazepine because of severe withdrawal symptoms. Due to liver enzyme elevation related to carbamazepine, we had to stop this treatment and instead of that started gabapentin treatment. Under this new therapy, the patient showed a dramatic relief of withdrawal symptoms and of the panic attacks recurring during withdrawal. Hence, due to their effectiveness and tolerability, newer anticonvulsants could be considered as medication for benzodiazepine withdrawal and as an alternative for benzodiazepine treatment in panic disorders.

  3. Computational identification of potential multitarget treatments for ameliorating the adverse effects of amyloid-β on synaptic plasticity

    PubMed Central

    Anastasio, Thomas J.

    2014-01-01

    The leading hypothesis on Alzheimer Disease (AD) is that it is caused by buildup of the peptide amyloid-β (Aβ), which initially causes dysregulation of synaptic plasticity and eventually causes destruction of synapses and neurons. Pharmacological efforts to limit Aβ buildup have proven ineffective, and this raises the twin challenges of understanding the adverse effects of Aβ on synapses and of suggesting pharmacological means to prevent them. The purpose of this paper is to initiate a computational approach to understanding the dysregulation by Aβ of synaptic plasticity and to offer suggestions whereby combinations of various chemical compounds could be arrayed against it. This data-driven approach confronts the complexity of synaptic plasticity by representing findings from the literature in a course-grained manner, and focuses on understanding the aggregate behavior of many molecular interactions. The same set of interactions is modeled by two different computer programs, each written using a different programming modality: one imperative, the other declarative. Both programs compute the same results over an extensive test battery, providing an essential crosscheck. Then the imperative program is used for the computationally intensive purpose of determining the effects on the model of every combination of ten different compounds, while the declarative program is used to analyze model behavior using temporal logic. Together these two model implementations offer new insights into the mechanisms by which Aβ dysregulates synaptic plasticity and suggest many drug combinations that potentially may reduce or prevent it. PMID:24847263

  4. Potential adverse effects of phytoestrogens.

    PubMed

    Whitten, P L; Lewis, C; Russell, E; Naftolin, F

    1995-03-01

    Evaluation of the potential benefits and risks offered by naturally occurring plant estrogens requires investigation of their potency and sites of action when consumed at natural dietary concentrations. Our investigations have examined the effects of a range of natural dietary concentrations of the most potent plant isoflavonoid, coumestrol, using a rat model and a variety of estrogen-dependent tissues and endpoints. Treatments of immature females demonstrated agonistic action in the reproductive tract, brain, and pituitary at natural dietary concentrations. Experiments designed to test for estrogen antagonism demonstrated that coumestrol did not conform to the picture of a classic antiestrogen. However, coumestrol did suppress estrous cycles in adult females. Developmental actions were examined by neonatal exposure of pups through milk of rat dams fed a coumestrol, control, or commercial soy-based diet during the critical period of the first 10 postnatal days or throughout the 21 days of lactation. The 10-day treatment did not significantly alter adult estrous cyclicity, but the 21-day treatment produced in a persistent estrus state in coumestrol-treated females by 132 days of age. In contrast, the 10-day coumestrol treatments produced significant deficits in the sexual behavior of male offspring. These findings illustrate the broad range of actions of these natural estrogens and the variability in potency across endpoints. This variability argues for the importance of fully characterizing each phytoestrogen in terms of its sites of action, balance of agonistic and antagonistic properties, natural potency, and short-term and long-term effects.

  5. Perspective on Lithotripsy Adverse Effects

    NASA Astrophysics Data System (ADS)

    Knoll, Thomas; Wendt-Nordahl, Gunnar

    2008-09-01

    Shock wave lithotripsy (SWL) is an effective and without any doubt the least invasive procedure to treat upper urinary tract calculi. Acute complications are rarely reported and do not require specific treatment in most cases. However, one should be aware that energy levels sufficient for stone breakage are capable of damaging tissue as well, and significant hematoma—not only in the kidney but as well in surrounding organs—has been observed. Furthermore, only little is known about the long-term effects of SWL. Some authors have reported an increased incidence of hypertension and possibly also diabetes mellitus. Such chronic diseases—if indeed related to prior SWL—may be a late result of acute SWL-related trauma but the discussion on the underlying pathogenesis is controversial. Many factors have to be considered, such as the natural history of recurrent stone formers, technical principles of SWL, and differences in treatment protocols. Promising studies are currently underway to optimize stone breakage while limiting potential collateral damage. With this progress, SWL remains a safe treatment option for most urinary calculi.

  6. Immunomodulatory drugs: Oral and systemic adverse effects

    PubMed Central

    Mattila, Riikka; Gomez-Font, Rafael; Meurman, Jukka H.

    2014-01-01

    Objectives: The main objectives are to present the different adverses effects of the immunomodulatory drugs that can impair the quality of life of the immunosupressed patients and study the impact of immunomodualtion on oral diseases. Immunomodulatory drugs have changed the treatment protocols of many diseases where immune functions play a central role, such as rheumatic diseases. Their effect on oral health has not been systematically investigated, however. Study Design: We review current data on the new immunomodulatory drugs from the oral health perspective based on open literature search of the topic. Results: These target specific drugs appear to have less drug interactions than earlier immunomodulating medicines but have nevertheless potential side effects such as activating latent infections. There are some data showing that the new immunomodulatory drugs may also have a role in the treatment of certain oral diseases such as lichen planus or ameliorating symptoms in Sjögren´s syndrome, but the results have not been overly promising. Conclusions: In general, data are sparse of the effect of these new drugs vs. oral diseases and there are no properly powered randomized controlled trials published on this topic. Key words:Immunomodulatory drugs, oral diseases, adverse effects, therapeutic action. PMID:23986016

  7. Clinicians' recognition of the metabolic adverse effects of antipsychotic medications.

    PubMed

    Buckley, Peter F; Miller, Del D; Singer, Beth; Arena, John; Stirewalt, Edna M

    2005-11-15

    There is a growing concern regarding the propensity of second generation antipsychotics (SGAs) to induce weight gain and metabolic adverse effects. Recent consensus guidelines have recommended assessment and monitoring procedures to appropriately detect and manage these adverse effects. This study addresses the appreciation and readiness of clinicians to implement management guidelines for these adverse effects. Respondents indicated awareness of the risks of treatment with SGAs. The extent of monitoring for metabolic adverse effects was low and inconsistent across measures and in frequency of evaluation. Ongoing efforts are needed to support and encourage change in clinician practice.

  8. Adverse effects of statins - myths and reality.

    PubMed

    Šimić, Iveta; Reiner, Željko

    2015-01-01

    Statins reduce cardiovascular mortality and morbidity as well as cardiovascular events in patients with a very high risk of cardiovascular disease (CVD) and also in subjects with high or moderate risk by reducing the levels of low-density lipoprotein cholesterol (LDL-C). Although they are considered to be drugs with a very good safety profile, because of their wide use there are many concerns that their adverse effects might compromise their proven beneficial effects. Therefore this article reviews all the data and provides an evidence- based insight what are the proven adverse effects of statins and what are the "myths" about them. The most important side effects include myopathy and rhabdomyolysis. Another side effect is increased activity of liver tests which occurs occasionally and is reversible. However, recent studies even suggest that statin therapy can improve hepatic steatosis. It is beyond any doubt that statins do slightly increase the incidence of type 2 diabetes mellitus in people with two or more components of metabolic syndrome but the cardiovascular benefits of such a treatment by far exceed this risk. Statin therapy has also been associated with some adverse renal effects, eg. acute renal failure, but recent data suggest even a possible protective effect of these drugs on renal dysfunction. Concerns that statins might increase cancer have not been proven. On the contrary, several studies have indicated a possible benefit of these drugs in patients with different types of cancer. Early concerns about cognitive dysfunction and memory loss associated with statins use could not be proven and most recent data even suggest a possible beneficial effect of statins in the prevention of dementia. Systematic reviews and clinical guidelines suggest that the cardiovascular benefits of statins by far out-weight non-cardiovascular harms in patients with cardiovascular risk.

  9. Differential behavioural and neurochemical outcomes from chronic paroxetine treatment in adolescent and adult rats: a model of adverse antidepressant effects in human adolescents?

    PubMed

    Karanges, Emily; Li, Kong M; Motbey, Craig; Callaghan, Paul D; Katsifis, Andrew; McGregor, Iain S

    2011-05-01

    Selective serotonin reuptake inhibitor use is associated with increased risk of suicidal ideation in adolescent humans, yet the neuropharmacological basis of this phenomenon is unknown. Consequently, we examined the behavioural and neurochemical effects of chronic paroxetine (PRX) treatment in adult and adolescent rats. Rats received PRX in their drinking water (target dose 10 mg/kg) for 22 d, during which time they were assessed for depression- and anxiety-like behaviours. Subsequent ex-vivo analyses examined serum PRX concentrations, striatal neurotransmitter content, and regional serotonin and dopamine transporter (SERT, DAT) binding density. After 11-12 d treatment, PRX-treated adolescent rats showed a significant inhibition of social interaction while adults were unaffected. After 19-20 d treatment, adolescents failed to show an antidepressant-like effect of PRX treatment on the forced swim test (FST), while PRX-treated adults showed a typical decrease in immobility and increase in swimming. Two PRX-treated adolescents died unexpectedly after the FST suggesting a compromised response to physical stress. Despite their greater apparent adverse reaction to the drug, adolescents had significantly lower plasma PRX than adults at day 22 of treatment. Chronic PRX treatment had similar effects in adults and adolescents on striatal 5-HT (unchanged relative to controls) and 5-HIAA levels (decreased), while markers of dopaminergic function (DOPAC, HVA, DA turnover) were increased in adults only. SERT density was up-regulated in the amygdala in PRX-treated adolescents only while DAT density in the nucleus accumbens was down-regulated only in PRX-treated adults. These data suggest that the immature rat brain responds differently to PRX and that this might be of use in modelling the atypical response of human adolescents to antidepressants. The age-specific PRX-induced changes in dopaminergic markers and SERT and DAT binding provide clues as to the neural mechanisms

  10. Adverse effects of mefloquine for the treatment of uncomplicated malaria in Thailand: A pooled analysis of 19, 850 individual patients

    PubMed Central

    Lee, Sue J.; ter Kuile, Feiko O.; Luxemburger, Christine

    2017-01-01

    Mefloquine (MQ) has been used for the treatment of malaria since the mid-1980s, first as monotherapy or as fixed combination with sulfadoxine-pyrimethamine (MSP) and since the mid-1990s in combination with artesunate. There is a renewed interested in MQ as part of a triple therapy for the treatment of multi-drug resistance P. falciparum malaria. The widespread use of MQ beyond south-East Asia has been constrained by reports of poor tolerability. Here we present the side effect profile of MQ for the treatment of uncomplicated malaria on the Thai-Myanmar/Cambodia borders. In total 19,850 patients received seven different regimens containing either 15 or 24–25 mg/kg of MQ, the latter given either as a single dose, or split over two or three days. The analysis focused on (predominantly) gastrointestinal and neuropsychiatric events as compared to the new fixed dose combination of MQ plus artesunate given as equal doses of 8 mg/kg MQ per day over three days. Gastrointestinal side effects were dose-dependent and associated with the severity of malaria symptoms. Serious neuropsychiatric side effects associated with MQ use were rare: for a single 25 mg/kg dose it was 11.9 per 10,000 treatments (95% confidence interval, CI, 4–285) vs. 7.8 (3–15) for the 15 mg/kg dose. The risk with 25 mg/kg was much higher when it was given as repeat dosing in patients who had failed treatment with 15 mg/kg MQ in the preceding month; (RR 6.57 (95% CI 1.33 to 32.4), p = 0.0077). MQ was best tolerated as 15 mg/kg or as 24 mg/kg when given over three days in combination with artesunate. We conclude that the tolerance of a single dose of MQ in the treatment of uncomplicated malaria is moderate, but can be improved by administering it as a split dose over three days. PMID:28192434

  11. Drug switch because of treatment-related adverse side effects in endocrine adjuvant breast cancer therapy: how often and how often does it work?

    PubMed

    Güth, Uwe; Myrick, Mary Elizabeth; Schötzau, Andreas; Kilic, Nerbil; Schmid, Seraina Margaretha

    2011-10-01

    Therapy-related adverse side effects are a main reason for non-persistence to adjuvant endocrine breast cancer therapy. This study reports frequency of drug-related adverse side effects that were so severe that a modification of the therapy was necessary. We evaluated how many patients discontinued adjuvant endocrine therapy because of these side effects (non-persistence). Last, we analyzed how often a drug switch was undertaken for this reason and how often this measure led to the patient successfully continuing their endocrine therapy. Data concerning all postmenopausal breast cancer patients (≤ 80 years), who initiated endocrine adjuvant therapy between 1998 and 2008 in a Swiss breast center (n = 400), were analyzed. Out of these 400 women, 37 (9.3%) were defined as being non-persistent to the therapy; out of these, 24 (64.9%) because of therapy-related side effects. About 78 patients (19.5%) suffered from severe therapy-related side effects that made a modification of therapy necessary. Out of these 78 cases, 14 patients (17.9%) stopped the therapy without attempting a drug switch (non-persistence). In 64 patients (82.1%; 16% of all women who started endocrine therapy), a drug switch was undertaken. Out of these 64 cases, in 52 cases (81.3%) endocrine therapy was completed after therapy modification. Patients who reported one major adverse effect were more likely to continue the endocrine therapy after a drug switch (P = 0.048) compared with those who suffered from at least two different side effects. In 10 of the 64 cases (15.6%), modification of the therapy was not successful and the patients stopped the treatment prematurely (non-persistence) because of ongoing side effects. In cases when therapy-related side effects occur, a drug switch is a promising step to further improve persistence and, by doing so, the outcome of breast cancer patients.

  12. Dapsone in the treatment of pemphigus vulgaris: adverse effects and its importance as a corticosteroid sparing agent*

    PubMed Central

    Quaresma, Maria Victória; Bernardes Filho, Fred; Hezel, Janaína; Peretti, Murilo Calvo; Kac, Bernard Kawa; Azulay-Abulafia, Luna

    2015-01-01

    Pemphigus vulgaris is an autoimmune disease characterized by suprabasal blisters with acantholysis, which has a fatal course in a large number of untreated patients. Systemic corticosteroid therapy is considered first-line therapy. Adjuvant treatment with the goal of sparing corticosteroids include, among others, dapsone. This drug is not without side effects and its use requires clinical and laboratory control. We present a patient with PV initially managed with suboptimal dose of prednisone, evolving into drug-induced hepatitis after introduction of dapsone. PMID:26312673

  13. [Cardiovascular pharmacotherapy. Risks and adverse effects].

    PubMed

    Voigt, N; Heijman, J; Dobrev, D

    2014-03-01

    Adverse side effects of drugs are a significantly underestimated problem in modern medicine. In this review article, we summarize common adverse side effects of cardiovascular drugs. In particular, we highlight the factors promoting these adverse side effects in patients, including reduced hepatic or renal clearance in elderly patients that often requires dosage adjustment. Pharmacodynamic and pharmacokinetic interactions between drugs (e.g. through the cytochrome P450 system or P-glycoproteins) can modify the plasma concentration of many compounds, thereby also increasing the likelihood of unwanted side effects. The most prominent cardiac side effects include arrhythmias, e.g. atrioventricular (AV) block, drug-induced long-QT syndrome and torsade de pointes and altered inotropy. Non-cardiac side effects are subsequently discussed grouped by drug class. A better understanding of the risks and side effects of cardiovascular drugs is expected to reduce the mortality and morbidity associated with adverse side effects.

  14. Regular treatment with formoterol for chronic asthma: serious adverse events

    PubMed Central

    Cates, Christopher J; Cates, Matthew J

    2014-01-01

    Background Epidemiological evidence has suggested a link between beta2-agonists and increases in asthma mortality. There has been much debate about possible causal links for this association, and whether regular (daily) long-acting beta2-agonists are safe. Objectives The aim of this review is to assess the risk of fatal and non-fatal serious adverse events in trials that randomised patients with chronic asthma to regular formoterol versus placebo or regular short-acting beta2-agonists. Search methods We identified trials using the Cochrane Airways Group Specialised Register of trials. We checked websites of clinical trial registers for unpublished trial data and Food and Drug Administration (FDA) submissions in relation to formoterol. The date of the most recent search was January 2012. Selection criteria We included controlled, parallel design clinical trials on patients of any age and severity of asthma if they randomised patients to treatment with regular formoterol and were of at least 12 weeks’ duration. Concomitant use of inhaled corticosteroids was allowed, as long as this was not part of the randomised treatment regimen. Data collection and analysis Two authors independently selected trials for inclusion in the review. One author extracted outcome data and the second author checked them. We sought unpublished data on mortality and serious adverse events. Main results The review includes 22 studies (8032 participants) comparing regular formoterol to placebo and salbutamol. Non-fatal serious adverse event data could be obtained for all participants from published studies comparing formoterol and placebo but only 80% of those comparing formoterol with salbutamol or terbutaline. Three deaths occurred on regular formoterol and none on placebo; this difference was not statistically significant. It was not possible to assess disease-specific mortality in view of the small number of deaths. Non-fatal serious adverse events were significantly increased when

  15. Oral Palmitoylethanolamide Treatment Is Associated with Reduced Cutaneous Adverse Effects of Interferon-β1a and Circulating Proinflammatory Cytokines in Relapsing-Remitting Multiple Sclerosis.

    PubMed

    Orefice, Nicola S; Alhouayek, Mireille; Carotenuto, Antonio; Montella, Silvana; Barbato, Franscesco; Comelli, Albert; Calignano, Antonio; Muccioli, Giulio G; Orefice, Giuseppe

    2016-04-01

    Palmitoylethanolamide (PEA) is an endogenous lipid mediator known to reduce pain and inflammation. However, only limited clinical studies have evaluated the effects of PEA in neuroinflammatory and neurodegenerative diseases. Multiple sclerosis (MS) is a chronic autoimmune and inflammatory disease of the central nervous system. Although subcutaneous administration of interferon (IFN)-β1a is approved as first-line therapy for the treatment of relapsing-remitting MS (RR-MS), its commonly reported adverse events (AEs) such as pain, myalgia, and erythema at the injection site, deeply affect the quality of life (QoL) of patients with MS. In this randomized, double-blind, placebo-controlled study, we tested the effect of ultramicronized PEA (um-PEA) added to IFN-β1a in the treatment of clinically defined RR-MS. The primary objectives were to estimate whether, with um-PEA treatment, patients with MS perceived an improvement in pain and a decrease of the erythema width at the IFN-β1a injection site in addition to an improvement in their QoL. The secondary objectives were to evaluate the effects of um-PEA on circulating interferon-γ, tumor necrosis factor-α, and interleukin-17 serum levels, N-acylethanolamine plasma levels, Expanded Disability Status Scale (EDSS) progression, and safety and tolerability after 1 year of treatment. Patients with MS receiving um-PEA perceived an improvement in pain sensation without a reduction of the erythema at the injection site. A significant improvement in QoL was observed. No significant difference was reported in EDSS score, and um-PEA was well tolerated. We found a significant increase of palmitoylethanolamide, anandamide and oleoylethanolamide plasma levels, and a significant reduction of interferon-γ, tumor necrosis factor-α, and interleukin-17 serum profile compared with the placebo group. Our results suggest that um-PEA may be considered as an appropriate add-on therapy for the treatment of IFN-β1a-related adverse effects in

  16. Systematic Review and Meta-Analysis of the Clinical Efficacy and Adverse Effects of Chinese Herbal Decoction for the Treatment of Gout

    PubMed Central

    Liu, Xiaoyu; Chen, Pinyi; Liu, Ling; Zhang, Yanqi; Wu, Yazhou; Pettigrew, Julia Christine; Cheng, Dixiang; Yi, Dong

    2014-01-01

    Background In East Asia, numerous reports describe the utilization of traditional Chinese herbal decoctions to treat gout. However, the reported clinical effects vary. Objectives In this study, we reviewed and analyzed a large number of randomized controlled clinical trials to systematically assess the clinical efficacy and adverse reactions of Chinese herbal decoctions for treating gout. Methods We performed a comprehensive search of databases, such as PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese biomedical literature database, et al. In addition, we manually searched the relevant meeting information in the library of the Third Military Medical University. Results Finally, 17 randomized controlled trials with a sample size of 1,402 cases met the criteria and were included in the study. The results of the meta-analysis showed that when gout had progressed to the stage of acute arthritis, there was no significant difference in clinical efficacy between Chinese herbal decoctions and traditional Western medicine, as indicated based on the following parameters: serum uric acid (standardized mean difference (SMD):0.35, 95% confidence interval (CI): 0.03 to 0.67), C reactive protein (SMD: 0.25, 95% CI: −0.18 to 0.69), erythrocyte sedimentation rate (SMD: 0.21, 95% CI: −0.02 to 0.45) and overall clinical response (relative risk (RR): 1.05, 95% CI: 1.01 to 1.10). However, the Chinese herbal decoction was significantly better than traditional Western medicine in controlling adverse drug reactions (RR: 0.06, 95% CI: 0.03 to 0.13). Conclusions Through a systematic review of the clinical efficacy and safety of Chinese herbal decoctions and traditional Western medicine for the treatment of gout, we found that Chinese herbal decoction and traditional Western medicine led to similar clinical efficacy, but the Chinese herbal decoctions were superior to Western medicine in terms of controlling adverse drug reactions. PMID:24465466

  17. The adverse effects of kava.

    PubMed

    Kava, R

    2001-03-01

    In Fiji, kava is also known as yaqona or grog. A convenient sample of 300 kava drinkers in Nadi, Lautoka, Ba and Sigatoka were studied to see whether local people in Fiji experienced side effects of kava use. Because males usually consume kava in Fiji, we approached specific groups of people and asked them to participate in the survey. To evaluate the side effects of kava consumption, we interviewed housewives of male kava drinkers regarding specific effects of kava. We interviewed these housewives during kava drinking sessions since they were usually not taking part in the kava drinking. We also interviewed employers of these kava drinkers and the market vendors in Nadi Town since they were closely involved with kava drinkers. Wives of kava users felt deprived of basic family needs due to the amount of money spent on kava. In Urban schools, 64% males and 46.2% had tried kava. The present study aims to assess the prevalence of side effects of kava usage among a community sample of kava drinkers in Fiji and to compare the result with some of the side effects provided by other studies. The questionnaire also asked how much kava was consumed and the reasons. Since kava use is very much part of our everyday culture and existence, convincing people to change their behavior and kava consumption is a major tasks. I hope that this study would emphasize the need at a national level to educate people on the harmful effects of kava and the need for the health ministry to view very heavy kava intake as contributing to morbidity in Fiji.

  18. Adverse effects of marijuana use.

    PubMed

    Feeney, Kathleen E; Kampman, Kyle M

    2016-05-01

    Marijuana has consistently been reported as the most commonly used illicit substance in the United States each year. Currently, the legalization of marijuana is up for debate across the nation. While marijuana use is prevalent among the adolescent population, research has shown that there can be devastating effects on health and well-being. A review of the literature shows that marijuana use can have a negative impact on physical health, psychological well-being, and multiple psychosocial outcomes. Adolescents who used marijuana more frequently and began using marijuana at an earlier age experienced worse outcomes and long-lasting effects.

  19. Rare and very rare adverse effects of clozapine

    PubMed Central

    De Fazio, Pasquale; Gaetano, Raffaele; Caroleo, Mariarita; Cerminara, Gregorio; Maida, Francesca; Bruno, Antonio; Muscatello, Maria Rosaria; Moreno, Maria Jose Jaén; Russo, Emilio; Segura-García, Cristina

    2015-01-01

    Clozapine (CLZ) is the drug of choice for the treatment of resistant schizophrenia; however, its suitable use is limited by the complex adverse effects’ profile. The best-described adverse effects in the literature are represented by agranulocytosis, myocarditis, sedation, weight gain, hypotension, and drooling; nevertheless, there are other known adverse effects that psychiatrists should readily recognize and manage. This review covers the “rare” and “very rare” known adverse effects of CLZ, which have been accurately described in literature. An extensive search on the basis of predefined criteria was made using CLZ and its combination with adverse effects as keywords in electronic databases. Data show the association between the use of CLZ and uncommon adverse effects, including ischemic colitis, paralytic ileus, hematemesis, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudo-pheochromocytoma, periorbital edema, and parotitis, which are influenced by other variables including age, early diagnosis, and previous/current pharmacological therapies. Some of these adverse effects, although unpredictable, are often manageable if promptly recognized and treated. Others are serious and potentially life-threatening. However, an adequate knowledge of the drug, clinical vigilance, and rapid intervention can drastically reduce the morbidity and mortality related to CLZ treatment. PMID:26273202

  20. Combining antiangiogenic therapy with neoadjuvant chemotherapy increases treatment efficacy in stage IIIA (N2) non-small cell lung cancer without increasing adverse effects

    PubMed Central

    Zhao, Xiaoliang; Su, Yanjun; You, Jian; Gong, Liqun; Zhang, Zhenfa; Wang, Meng; Zhao, Zhenqing; Zhang, Zhen; Li, Xiaolin; Wang, Changli

    2016-01-01

    To evaluate the safety and efficacy of combining Endostar antiangiogenic therapy with neoadjuvant chemotherapy for the treatment of stage IIIA (N2) NSCLC, we conducted a randomized, controlled, open-label clinical study of 30 NSCLC patients. Patients were randomly assigned to the test or control groups, which received either two cycles of an NP neoadjuvant chemotherapy regimen combined with Endostar or the NP regimen alone, respectively, at a 2:1 ratio. Efficacy was assessed after 3 weeks, and surgical resection occurred within 4 weeks, in the 26 patients who successfully completed treatment. While total response rates (RR) and clinical benefit rates (CBR) did not differ between the experimental groups, total tumor regression rates (TRR) were higher in the test group than in the control group. Median DFS and OS also did not differ between the test and control groups. Clinical perioperative indicators, including intraoperative blood loss, number of dissected lymph node groups, duration of postoperative indwelling catheter use, and time to postoperative discharge, were comparable in the test and control groups. Finally, hematological and non-hematological toxicities and postoperative pathological indicators, including down-staging ratio, complete resection ratio, and metastatic lymph node ratio, also did not differ between the groups. Overall, combining Endostar with NP neoadjuvant chemotherapy increased therapeutic efficacy without increasing adverse effects in stage IIIA-N2 NSCLC patients. This study is registered with ClinicalTrials.gov (number NCT02497118). PMID:27566586

  1. Regular treatment with salmeterol for chronic asthma: serious adverse events

    PubMed Central

    Cates, Christopher J; Cates, Matthew J

    2014-01-01

    Background Epidemiological evidence has suggested a link between beta2-agonists and increases in asthma mortality. There has been much debate about possible causal links for this association, and whether regular (daily) long-acting beta2-agonists are safe. Objectives The aim of this review is to assess the risk of fatal and non-fatal serious adverse events in trials that randomised patients with chronic asthma to regular salmeterol versus placebo or regular short-acting beta2-agonists. Search methods We identified trials using the Cochrane Airways Group Specialised Register of trials. We checked websites of clinical trial registers for unpublished trial data and FDA submissions in relation to salmeterol. The date of the most recent search was August 2011. Selection criteria We included controlled parallel design clinical trials on patients of any age and severity of asthma if they randomised patients to treatment with regular salmeterol and were of at least 12 weeks’ duration. Concomitant use of inhaled corticosteroids was allowed, as long as this was not part of the randomised treatment regimen. Data collection and analysis Two authors independently selected trials for inclusion in the review. One author extracted outcome data and the second checked them. We sought unpublished data on mortality and serious adverse events. Main results The review includes 26 trials comparing salmeterol to placebo and eight trials comparing with salbutamol. These included 62,815 participants with asthma (including 2,599 children). In six trials (2,766 patients), no serious adverse event data could be obtained. All-cause mortality was higher with regular salmeterol than placebo but the increase was not significant (Peto odds ratio (OR) 1.33 (95% CI 0.85 to 2.08)). Non-fatal serious adverse events were significantly increased when regular salmeterol was compared with placebo (OR 1.15 95% CI 1.02 to 1.29). One extra serious adverse event occurred over 28 weeks for every 188 people

  2. Adverse effects of falciparum and vivax malaria and the safety of antimalarial treatment in early pregnancy: a population-based study

    PubMed Central

    McGready, R; Lee, SJ; Wiladphaingern, J; Ashley, EA; Rijken, MJ; Boel, M; Simpson, JA; Paw, MK; Pimanpanarak, M; Mu, Oh; Singhasivanon, P; White, NJ; Nosten, FH

    2012-01-01

    Summary Background The effects of malaria and its treatment in the first trimester of pregnancy remain an area of concern. We aimed to assess the outcome of malaria-exposed and malaria-unexposed first-trimester pregnancies of women from the Thai–Burmese border and compare outcomes after chloroquine-based, quinine-based, or artemisinin-based treatments. Methods We analysed all antenatal records of women in the first trimester of pregnancy attending Shoklo Malaria Research Unit antenatal clinics from May 12, 1986, to Oct 31, 2010. Women without malaria in pregnancy were compared with those who had a single episode of malaria in the first trimester. The association between malaria and miscarriage was estimated using multivariable logistic regression. Findings Of 48 426 pregnant women, 17 613 (36%) met the inclusion criteria: 16 668 (95%) had no malaria during the pregnancy and 945 (5%) had a single episode in the first trimester. The odds of miscarriage increased in women with asymptomatic malaria (adjusted odds ratio 2·70, 95% CI 2·04–3·59) and symptomatic malaria (3·99, 3·10–5·13), and were similar for Plasmodium falciparum and Plasmodium vivax. Other risk factors for miscarriage included smoking, maternal age, previous miscarriage, and non-malaria febrile illness. In women with malaria, additional risk factors for miscarriage included severe or hyperparasitaemic malaria (adjusted odds ratio 3·63, 95% CI 1·15–11·46) and parasitaemia (1·49, 1·25–1·78 for each ten-fold increase in parasitaemia). Higher gestational age at the time of infection was protective (adjusted odds ratio 0·86, 95% CI 0·81–0·91). The risk of miscarriage was similar for women treated with chloroquine (92 [26%] of 354), quinine (95 [27%) of 355), or artesunate (20 [31%] of 64; p=0·71). Adverse effects related to antimalarial treatment were not observed. Interpretation A single episode of falciparum or vivax malaria in the first trimester of pregnancy can cause

  3. Adverse immunologic effects of antithyroid drugs.

    PubMed Central

    Wing, S S; Fantus, I G

    1987-01-01

    Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described. A review of the literature revealed 53 similar cases over a 35-year period. Rash, fever, arthralgias and granulocytopenia were the most common manifestations. Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal. The clinical evidence suggests that an immunologic mechanism is involved. A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus. Thus, the reactions do not represent a true drug-induced lupus syndrome. Current hypotheses and experimental data regarding the cause of the reactions are reviewed. No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy. Cross-reactivity between the two antithyroid drugs can be expected. Except for minor symptoms (e.g., mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism. In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful. PMID:3539299

  4. [Laser trabeculoplasty: therapeutic options and adverse effects].

    PubMed

    Wacker, T; Eckert, S

    2010-01-01

    Laser trabeculoplasty is a simple method for treating glaucoma and ocular hypertension and has few adverse effects. There are different laser systems for reducing the intraocular pressure of patients with glaucoma and ocular hypertension. Complications include transient intraocular pressure elevation, iritis, and anterior synechiae.

  5. [Management of adverse effects with antituberculosis chemotherapy].

    PubMed

    Tsuyuguchi, Kazunari; Wada, Masako

    2011-02-01

    discontinuation and true worsening of pulmonary tuberculosis due to drug resistance requiring change in therapy. Dr. Masanori Akira reported that presence of ground-glass attenuation and/or consolidation by HRCT suggests transient worsening or drug-induced pneumonia, whereas presence of centrilobular nodules and/or tree-in bud suggests true worsening. We believe that these findings from the symposium will add useful information for management of adverse effects and be helpful for implementation of antituberculosis chemotherapy. (1) Hepatotoxicity of antituberculosis drugs: Shinsho YOSHIBA (Sempo Tokyo Takanawa Hospital) Antituberculosis drugs are sometimes hepatotoxic. Doctors who are responsible for the treatment of patients with tuberculosis should always be aware of their hepatotoxicity, because it seldom leads to fulminant hepatic failure. The Japanese Society for Tuberculosis proposed criteria based on the levels of AST, ALT and bilirubin for the prevention of such grave hepatic injury in 2006. In recent years attempts have been made to predict fulminant hepatic failure (FHF) before patients develop coma. Yoshiba's formula using prothrombin time, etiology, cholinesterase and bilirubin is widely accepted as useful to predict FHF. Introduction of the formula to this area is recommended. (2) Desensitization therapy for allergic reactions of antituberculous drugs: Yoshihiro KOBASHI, Mikio OKA (Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School) We evaluated the usefulness of desensitization therapy for patients showing allergic reactions of INH and RFP according to the guideline proposed by the Japanese Society for Tuberculosis. Adverse reactions were 22 patients with drug eruption, 22 with drug fever and 6 with drug fever plus eruption. The clinical effect of desensitization therapy was good in 27 out of 36 patients for RFP (75%), and in 19 out of 24 patients for INH (79%). The comparative study between patient group with success desensitization

  6. Enduring psychobiological effects of childhood adversity.

    PubMed

    Ehlert, Ulrike

    2013-09-01

    This mini-review refers to recent findings on psychobiological long-term consequences of childhood trauma and adverse living conditions. The continuum of trauma-provoked aftermath reaches from healthy adaptation with high resilience, to severe maladjustment with co-occurring psychiatric and physical pathologies in children, adolescents and adults. There is increasing evidence of a strong interconnectivity between genetic dispositions, epigenetic processes, stress-related hormonal systems and immune parameters in all forms of (mal)-adjustment to adverse living conditions. Unfavorable constellations of these dispositions and systems, such as low cortisol levels and elevated markers of inflammation in maltreated children, seem to promote the (co)-occurrence of psychiatric and physical pathologies such as posttraumatic stress disorder, obesity, or diabetes. Although findings from prospective study designs support a deepened understanding of causal relations between adverse living conditions, including traumatic experiences, during childhood and its psychobiological effects, so far, little is known about the temporal coincidence of stress-sensitive developmental stages during childhood and adolescence and trauma consequences. Taken together, childhood adversity is a severe risk factor for the onset of psychobiological (mal)-adjustment, which has to be explained under consideration of diverse physiological systems and developmental stages of childhood and adolescence.

  7. Metabolic and adverse effects of diuretics.

    PubMed

    Wilcox, C S

    1999-11-01

    Diuretics are among the most frequently prescribed drugs. They enjoy a very high clinical reputation for safety and efficacy. However, more than 3 decades of clinical investigation have disclosed a number of abnormalities in fluid electrolyte handling, metabolism, and other adverse effects that can complicate therapy with diuretic drugs. Some of these complications are a direct extension of the wanted action of the drug. These include extracellular fluid volume depletion, associated orthostatic hypotension, and prerenal azotemia. Others are not a direct action of the diuretic, but can be explained as an intranephronal compensation to the diuretic action. These include hypokalemia, in part to increased potassium secretion secondary to the enhanced tubular fluid flow and aldosterone secretion induced by diuretic administration. Metabolic abnormalities are usually mild. Hyperglycemia and carbohydrate intolerance have been related to diuretic-induced hypokalemia, which inhibits insulin secretion by the beta cells, and reductions in extracellular fluid volume and cardiac output. This is compounded by increases in catecholamines from sympathetic nerve activity which decrease peripheral glucose utilization. A mild increase in serum cholesterol concentration is seen frequently during initiation of diuretic therapy, but during steady state therapy after 6 to 12 months, values usually return to baseline. Knowledge of the more common adverse effects induced by diuretics helps the physician in predicting patients at risk and taking effective steps to anticipate or treat adverse responses.

  8. Neuropsychiatric Adverse Effects of Amphetamine and Methamphetamine.

    PubMed

    Harro, Jaanus

    2015-01-01

    Administration of amphetamine and methamphetamine can elicit psychiatric adverse effects at acute administration, binge use, withdrawal, and chronic use. Most troublesome of these are psychotic states and aggressive behavior, but a large variety of undesirable changes in cognition and affect can be induced. Adverse effects occur more frequently with higher dosages and long-term use. They can subside over time but some persist long-term. Multiple alterations in the gray and white matter of the brain assessed as changes in tissue volume or metabolism, or at molecular level, have been associated with amphetamine and methamphetamine use and the psychiatric adverse effects, but further studies are required to clarify their causal role, specificity, and relationship with preceding states and traits and comorbidities. The latter include other substance use disorders, mood and anxiety disorders, attention deficit hyperactivity disorder, and antisocial personality disorder. Amphetamine- and methamphetamine-related psychosis is similar to schizophrenia in terms of symptomatology and pathogenesis, and these two disorders share predisposing genetic factors.

  9. Model assessment of individual tumor control rate and adverse effects in comparing locally advanced cervical cancer treatment using intracavitary with and without interstitial brachytherapy

    PubMed Central

    Mehta, Keyur J; Yaparpalvi, Ravindra; Shankar, Viswanathan; Bodner, William; Garg, Madhur; Rivera, Amanda; Tomé, Wolfgang A.; Kalnicki, Shalom

    2016-01-01

    Purpose This study assessed the modeled probability of tumor control and organ at risk toxicities in locally advanced cervical cancer in patients treated by external beam radiation plus brachytherapy using intracavitary combined with interstitial brachytherapy (IC/IS) vs. intracavitary brachytherapy (IC) alone. Material and methods Twenty cervical cancer patients with a mean HR-CTV volume of 47.4 cm3 and a mean width of 54 mm were planned with both IC/IS and IC brachytherapy alone. A probit model was utilized to model 3-year (3-yr) local control rate (LC), 3-yr cancer specific survival rate (CSS), and the adverse effect (AE) of the organ at risk by using a modeled data set from multiple institutions. Modeling results were used to estimate the LC, CSS, and AE of the treatments in this study. Results Using the IC/IS technique, an EQD2 increase of 12.3 Gy to D90 (from 76.1 Gy to 88.3 Gy) of HR-CTV is expected to increase 3-yr LC and 3-yr CSS by 12.5%, and 11.0%, respectively. Comparing IC/IS to IC alone, the expected G2+ AE were 7.7% vs. 7.9% for the bladder, and 5.9% vs. 6.8% for the rectum. Conclusions The IC/IS technique improved dose coverage to the HR-CTV without significantly increasing dose to 2 cm3 of the organ at risk (OAR) surrounding it. With different regimens of EBRT combined with BT, IC/IS can be used to increase the probability of LC and CSS, or decrease the risk of AE. PMID:28115959

  10. Adverse effect of mild temperature hyperthermia combined with hexamethylenetetramine compared to its effect combined with tirapazamine in the treatment of solid tumors.

    PubMed

    Masunaga, Shin-Ichiro; Tano, Keizo; Nakamura, Jun; Watanabe, Masami; Kashino, Genro; Suzuki, Minoru; Kinashi, Yuko; Ono, Koji

    2010-01-01

    This study aimed to assess the effect on solid tumors of mild temperature hyperthermia (MTH) combined with hexamethylenetetramine (HMTA) or tirapazamine (TPZ). Squamous cell carcinoma (SCC VII) tumor-bearing mice were continuously administered 5-bromo-2'-deoxyuridine (BrdU) to label intratumor proliferating (P) cells. Mice received HMTA or TPZ through intraperitoneal single or subcutaneous continuous administration, with or without MTH (40°C, 60 min), followed or not by γ-ray irradiation or cisplatin treatment. After HMTA or TPZ administration without γ-ray irradiation or cisplatin treatment, immediately after γ-ray irradiation, or 1 h after cisplatin treatment, the response of quiescent (Q) cells was assessed in terms of micronucleus frequency using immunofluorescence staining for BrdU. The response of the total (P + Q) tumor cells was determined based on a comparison with non-BrdU-treated tumors. Without MTH, HMTA and TPZ had a nearly equal radiosensitizing and cisplatin sensitivity-enhancing effect on both total and Q cells. With MTH, radio- and cisplatin-sensitizing effects by HMTA were reduced, particularly in the Q cells. In contrast, the enhancing effects of TPZ were increased, particularly in the Q cells. Continuous administration of HMTA and TPZ resulted in higher radio- and cisplatin-sensitizing effects than intraperitoneal single administration. In terms of tumor cytotoxicity as a whole, including Q cells, the administration of γ-ray irradiation or cisplatin treatment combined with continuous HMTA administration is promising, taking into account the clinical use of HMTA. However, MTH should not be combined with HMTA administration.

  11. Environmental Perchlorate Exposure: Potential Adverse Thyroid Effects

    PubMed Central

    Leung, Angela M.; Pearce, Elizabeth N.; Braverman, Lewis E.

    2014-01-01

    Purpose of review This review will present a general overview of the sources, human studies, and proposed regulatory action regarding environmental perchlorate exposure. Recent findings Some recent studies have reported significant associations between urinary perchlorate concentrations, thyroid dysfunction, and decreased infant IQ in groups who would be particularly susceptible to perchlorate effects. An update regarding the recent proposed regulatory actions and potential costs surrounding amelioration of perchlorate contamination is provided. Summary The potential adverse thyroidal effects of environmental perchlorate exposure remain controversial, and further research is needed to further define its relationship to human health among pregnant and lactating women and their infants. PMID:25106002

  12. Adverse effects of oral antiviral therapy in chronic hepatitis B

    PubMed Central

    Kayaaslan, Bircan; Guner, Rahmet

    2017-01-01

    Oral nucleoside/nucleotide analogues (NAs) are currently the backbone of chronic hepatitis B (CHB) infection treatment. They are generally well-tolerated by patients and safe to use. To date, a significant number of patients have been treated with NAs. Safety data has accumulated over the years. The aim of this article is to review and update the adverse effects of oral NAs. NAs can cause class adverse effects (i.e., myopathy, neuropathy, lactic acidosis) and dissimilar adverse effects. All NAs carry a “Black Box” warning because of the potential risk for mitochondrial dysfunction. However, these adverse effects are rarely reported. The majority of cases are associated with lamivudine and telbivudine. Adefovir can lead to dose- and time-dependent nephrotoxicity, even at low doses. Tenofovir has significant renal and bone toxicity in patients with human immunodeficiency virus (HIV) infection. However, bone and renal toxicity in patients with CHB are not as prominent as in HIV infection. Entecavir and lamivudine are not generally associated with renal adverse events. Entecavir has been claimed to increase the risk of lactic acidosis in decompensated liver disease and high Model for End-Stage Liver Disease scores. However, current studies reported that entecavir could be safely used in decompensated cirrhosis. An increase in fetal adverse events has not been reported with lamivudine, telbivudine and tenofovir use in pregnant women, while there is no adequate data regarding entecavir and adefovir. Further long-term experience is required to highlight the adverse effects of NAs, especially in special patient populations, including pregnant women, elderly and patients with renal impairment. PMID:28261380

  13. SMARTS (Systematic Monitoring of Adverse events Related to TreatmentS): The development of a pragmatic patient-completed checklist to assess antipsychotic drug side effects

    PubMed Central

    Fleischhacker, W Wolfgang; Peuskens, Joseph; Cavallaro, Roberto; Lean, Michael EJ; Morozova, Margarita; Reynolds, Gavin; Azorin, Jean-Michel; Thomas, Pierre; Möller, Hans-Jürgen

    2014-01-01

    Objectives: Antipsychotic drug side effects are common and can cause stigmatisation, decreased quality of life, poor adherence, and secondary morbidity and mortality. Systematic assessment of anticipated side effects is recommended as part of good clinical care, but is uncommon in practice and patients may not spontaneously report side effects. We aimed to develop a simple patient-completed checklist to screen systematically for potential antipsychotic side effects. Methods: The SMARTS checklist was developed over a series of group meetings by an international faculty of 12 experts (including psychiatrists, a general physician and a psychopharmacologist) based on their clinical experience and knowledge of the literature. The emphasis is on tolerability (i.e. assessment of side effects that ‘trouble’ the patient) as subjective impact of side effects is most relevant to medication adherence. The development took account of feedback from practising psychiatrists in Europe, the Middle East and Africa, a process that contributed to face validity. Results: The SMARTS checklist assesses whether patients are currently ‘troubled’ by 11 well-established potential antipsychotic side effects. Patients provide their responses to these questions by circling relevant side effects. An additional open question enquires about any other possible side effects. The checklist has been translated into Italian and Turkish. Conclusions: The SMARTS checklist aims to strike a balance between brevity and capturing the most common and important antipsychotic side effects. It is appropriate for completion by patients prior to a clinical consultation, for example, in the waiting room. It can then form the focus for a more detailed clinical discussion about side effects. It can be used alone or form part of a more comprehensive assessment of antipsychotic side effects including blood tests and a physical examination when appropriate. The checklist assesses current problems and can be used

  14. Agomelatine: a review of adverse effects.

    PubMed

    2013-03-01

    More pharmacovigilance data on agomelatine became available in 2012. The main sources of information were surveillance data from the French national monitoring system, EU periodic safety update reports (PSURs), and the European pharmacovigilance database. The principal adverse effects of agomelatine consist of hepatic, pancreatic, neuropsychiatric, muscular and cutaneous disorders. The harms associated with agomelatine, which has no proven efficacy in depression, clearly outweigh the benefits. Until regulatory agencies decide to withdraw agomelatine from the market, it is up to healthcare professionals to protect patients from this unnecessarily dangerous drug.

  15. [Adverse drug effects in the community pharmacy].

    PubMed

    Arnet, Isabelle; Seidling, Hanna M; Hersberger, Kurt E

    2015-12-01

    Community pharmacists represent an important pillar for the identification and the reporting of adverse drug effects (ADE}. Thanks to their broad view on the pharmacotherapy, over-the-counter medication included, they contribute greatly to the improvement of drug safety. In principle, the community pharmacy will face three groups of ADE which require specific attention. This article deals with these specific ADE groups and presents some illustrative examples from daily practice. Furthermore, we suggest some solutions to identify potential relevant interactions - including herbal-drug interactions - and give tips for daily practice, along with some often overseen cutaneous ADE.

  16. Association of a probiotic to a Helicobacter pylori eradication regimen does not increase efficacy or decreases the adverse effects of the treatment: a prospective, randomized, double-blind, placebo-controlled study

    PubMed Central

    2013-01-01

    Background The treatment for the eradication of Helicobacter pylori (H. pylori) is complex; full effectiveness is rarely achieved and it has many adverse effects. In developing countries, increased resistance to antibiotics and its cost make eradication more difficult. Probiotics can reduce adverse effects and improve the infection treatment efficacy. If the first-line therapy fails a second-line treatment using tetracycline, furazolidone and proton-pump inhibitors has been effective and low cost in Brazil; however it implies in a lot of adverse effects. The aim of this study was to minimize the adverse effects and increase the eradication rate applying the association of a probiotic compound to second-line therapy regimen. Methods Patients with peptic ulcer or functional dyspepsia infected by H. pylori were randomized to treatment with the furazolidone, tetracycline and lansoprazole regimen, twice a day for 7 days. In a double-blind study, patients received placebo or a probiotic compound (Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum and Streptococcus faecium) in capsules, twice a day for 30 days. A symptom questionnaire was administered in day zero, after completion of antibiotic therapy, after the probiotic use and eight weeks after the end of the treatment. Upper digestive endoscopy, histological assessment, rapid urease test and breath test were performed before and eight weeks after eradication treatment. Results One hundred and seven patients were enrolled: 21 men with active probiotic and 19 with placebo plus 34 women with active probiotic and 33 with placebo comprising a total of 55 patients with active probiotic and 52 with placebo. Fifty-one patients had peptic ulcer and 56 were diagnosed as functional dyspepsia. The per-protocol eradication rate with active probiotic was 89.8% and with placebo, 85.1% (p = 0.49); per intention to treat, 81.8% and 79.6%, respectively (p = 0.53). The rate of adverse effects at 7 days with the

  17. Adverse effects of differential parental attention1

    PubMed Central

    Sajwaj, Thomas E.; Pinkston, Susan; Cordua, Glenn; Jackson, Carolyn; Herbert, Emily W.; Pinkston, Elsie M.; Hayden, M. Loeman

    1973-01-01

    In two independent parent training projects (Kansas and Mississippi), mothers of deviant young children were observed to follow almost all child behaviors with attention. The mothers were then trained to use differential attention procedures to increase their child's appropriate behaviors and to decrease deviant behaviors. Contrary to expectations, the differential attention procedure produced substantial increases in deviant behavior for four of the children. This adverse effect was maintained over many sessions and was replicated in single organism, reversal designs. A fifth child showed no change. A sixth child showed some improvement. However, this effect was not recovered in a second application of differential attention, and the child became worse. The results underline the importance of subject generality in applied behavior analysis and strongly suggest that service programs using operant techniques must carefully evaluate their effects on behavior. PMID:16795386

  18. Hypogonadism secondary to hyperprolactinaemia: successful treatment but adverse consequences.

    PubMed

    Narayanan, R P; Bujawansa, S; Qureshi, Z; Rimmer, M; Heald, A

    2012-05-01

    It is accepted that care must be taken in initiating testosterone replacement in hypogonadal individuals with historically low androgen levels. However less is reported about the influence of restoration of normal endogenous testosterone production on behaviour.Here we report how the adverse sequelae of successful treatment of hypogonadism secondary to hyperprolactinaemia, manifesting as irritability and low threshold to aggression, were managed through a joint approach between psychiatrist and physician.

  19. The NAS Perchlorate Review: Adverse Effects?

    SciTech Connect

    Johnston, Richard B.; Corley, Richard; Cowan, Linda; Utiger, Robert D.

    2005-11-01

    To the editor: Drs. Ginsberg and Rice argue that the reference dose for perchlorate of 0.0007 mg/kg per day recommended by the National Academies’ Committee to Assess the Health Implications of Perchlorate Ingestion is not adequately protective. As members of the committee, we disagree. Ginsberg and Rice base their conclusion on three points. The first involves the designation of the point of departure as a NOEL (no-observed-effect level) versus a LOAEL (lowest-observed-adverse- effect level). The committee chose as its point of departure a dose of perchlorate (0.007 mg/kg per day) that when given for 14 days to 7 normal subjects did not cause a significant decrease in the group mean thyroid iodide uptake (Greer et al. 2002). Accordingly, the committee considered it a NOEL. Ginsberg and Rice focus on the fact that only 7 subjects were given that dose, and they 1seem to say that attention should be paid only to the results in those subjects in whom there was a 1fall in thyroid iodide uptake, and that the results in those in whom there was no fall or an increase should be ignored. They consider the dose to be a LOAEL because of the fall in uptake in those few subjects. It is important to note that a statistically significant decrease of, for example, 5% or even 10%, would not be biologically important and, more important, would not be sustained. For example, in another study (Braverman et al. 2004), administration of 0.04 mg/kg per day to normal subjects for 6 months had no effect on thyroid iodide uptake when measured at 3 and 6 months, and no effect on serum thyroid hormone or thyrotropin concentrations measured monthly (inspection of Figure 5A in the paper by Greer et al. suggests that this dose would inhibit thyroid iodide uptake by about 25% if measured at 2 weeks). The second issue involves database uncertainty. In clinical studies, perchlorate has been administered prospectively to 68 normal subjects for 2 weeks to 6 months. In one study (Brabant et al. 1992

  20. 36 CFR 800.5 - Assessment of adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Assessment of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.5 Assessment of adverse effects. (a) Apply criteria of adverse effect. In consultation with the SHPO/THPO and any Indian tribe or Native...

  1. 36 CFR 800.6 - Resolution of adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Resolution of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.6 Resolution of adverse effects. (a) Continue... the undertaking that could avoid, minimize, or mitigate adverse effects on historic properties....

  2. Minimizing AED adverse effects: improving quality of life in the interictal state in epilepsy care.

    PubMed

    St Louis, Erik K; Louis, Erik K

    2009-06-01

    The goals of epilepsy therapy are to achieve seizure freedom while minimizing adverse effects of treatment. However, producing seizure-freedom is often overemphasized, at the expense of inducing adverse effects of treatment. All antiepileptic drugs (AEDs) have the potential to cause dose-related, "neurotoxic" adverse effects (i.e., drowsiness, fatigue, dizziness, blurry vision, and incoordination). Such adverse effects are common, especially when initiating AED therapy and with polytherapy. Dose-related adverse effects may be obviated in most patients by dose reduction of monotherapy, reduction or elimination of polytherapy, or substituting for a better tolerated AED. Additionally, all older and several newer AEDs have idiosyncratic adverse effects which usually require withdrawal in an affected patient, including serious rash (i.e., Stevens-Johnson Syndrome, toxic epidermal necrolysis), hematologic dyscrasias, hepatotoxicity, teratogenesis in women of child bearing potential, bone density loss, neuropathy, and severe gingival hyperplasia. Unfortunately, occurrence of idiosyncratic AED adverse effects cannot be predicted or, in most cases, prevented in susceptible patients. This article reviews a practical approach for the definition and identification of adverse effects of epilepsy therapies, and reviews the literature demonstrating that adverse effects result in detrimental quality of life in epilepsy patients. Strategies for minimizing AED adverse effects by reduction or elimination of AED polytherapy, appropriately employing drug-sparing therapies, and optimally administering AEDs are outlined, including tenets of AED selection, titration, therapeutic AED laboratory monitoring, and avoidance of chronic idiosyncratic adverse effects.

  3. Adverse effects of common medications on male fertility.

    PubMed

    Samplaski, Mary K; Nangia, Ajay K

    2015-07-01

    An increasing number of patients require long-term medication regimens at a young age, but the adverse effects of medications on male reproduction are often inadequately considered, recognized and investigated. Medications can affect male reproduction through central hormonal effects, direct gonadotoxic effects, effects on sperm function or on sexual function. For example, exogenous testosterone inhibits spermatogenesis through central suppression of the hypothalamic-pituitary-gonadal hormonal axis. 5α-reductase inhibitors can impair sexual function, decrease semen volume and negatively affect sperm parameters, depending on dose and treatment duration. α-Blockers might decrease seminal emission and cause retrograde ejaculation, depending on the receptor specificity and dose of the agent. Phosphodiesterase inhibitors seem to have variable effects based on the isoform inhibited and evidence is conflicting. Antihypertensive and psychotropic agents can affect sperm, sexual function and hormonal parameters. For antibiotics, the literature on effects on sperm and sperm function is limited and dated. Many chemotherapeutic agents have a direct gonadotoxic effect, depending on agents used, dosing and number of treatment cycles. Overall, many medications commonly used in urology can have effects on male fertility (mostly reversible) but conclusive evidence in humans is often limited. Men should be counselled appropriately about potential drug-related adverse effects on their fertility.

  4. Combined treatment with acupuncture reduces effective dose and alleviates adverse effect of L-dopa by normalizing Parkinson's disease-induced neurochemical imbalance.

    PubMed

    Kim, Seung-Nam; Doo, Ah-Reum; Park, Ji-Yeun; Choo, Hyunwoo J; Shim, Insop; Park, Jongbae J; Chae, Younbyoung; Lee, Bena; Lee, Hyejung; Park, Hi-Joon

    2014-01-28

    This study first showed the behavioural benefits of novel combination therapy of L-dopa with acupuncture on Parkinson's disease, and its underlying mechanisms within basal ganglia. The previous study reported that acupuncture may improve the motor function of a Parkinson's disease (PD) mouse model by increasing the dopamine efflux and turnover ratio of dopamine. Hence, we hypothesised that combining L-dopa with acupuncture would have a behavioural benefit for those with PD. We performed unilateral injections of 6-OHDA into the striatum of C57Bl/6 mice to model hemi-Parkinsonian attributes. To test motor function and dyskinetic anomalies, we examined cylinder behaviour and abnormal involuntary movement (AIM), respectively. We found that (1) a 50% reduced dose of L-dopa (7.5 mg/kg) combined with acupuncture showed an improvement in motor function that was comparable to mice given the standard dose of L-dopa treatment (15 mg/kg) only, and that (2) the combination treatment (L-dopa +acupuncture) was significantly superior in reducing AIM scores when equivalent doses of L-dopa were used. The combination treatment also significantly reduces the abnormal increase of GABA contents in the substantia nigra compared to the standard L-dopa treatment. Furthermore, abnormal expression of FosB, the immediate early gene of L-dopa induced dyskinesia (LID), was mitigated in the striatum by the combination treatment. All of these results indicate that acupuncture enhances the benefits of L-dopa on motor function with reduced dose of L-dopa and alleviating LID by normalising neurochemical imbalance within the basal ganglia.

  5. Combined treatment with acupuncture reduces effective dose and alleviates adverse effect of l-dopa by normalizing Parkinson’s disease-induced neurochemical imbalance

    PubMed Central

    Kim, Seung-Nam; Doo, Ah-Reum; Park, Ji-Yeun; Choo, Hyunwoo J.; Shim, Insop; Park, Jongbae J.; Chae, Younbyoung; Lee, Bena; Lee, Hyejung; Park, Hi-Joon

    2014-01-01

    This study first showed the behavioural benefits of novel combination therapy of l-dopa with acupuncture on Parkinson’s disease, and its underlying mechanisms within basal ganglia. The previous study reported that acupuncture may improve the motor function of a Parkinson’s disease (PD) mouse model by increasing the dopamine efflux and turnover ratio of dopamine. Hence, we hypothesised that combining l-dopa with acupuncture would have a behavioural benefit for those with PD. We performed unilateral injections of 6-OHDA into the striatum of C57Bl/6 mice to model hemi-Parkinsonian attributes. To test motor function and dyskinetic anomalies, we examined cylinder behaviour and abnormal involuntary movement (AIM), respectively. We found that (1) a 50% reduced dose of l-dopa (7.5 mg/kg) combined with acupuncture showed an improvement in motor function that was comparable to mice given the standard dose of l-dopa treatment (15 mg/kg) only, and that (2) the combination treatment (l-dopa +acupuncture) was significantly superior in reducing AIM scores when equivalent doses of l-dopa were used. The combination treatment also significantly reduces the abnormal increase of GABA contents in the substantia nigra compared to the standard l-dopa treatment. Furthermore, abnormal expression of FosB, the immediate early gene of l-dopa induced dyskinesia (LID), was mitigated in the striatum by the combination treatment. All of these results indicate that acupuncture enhances the benefits of l-dopa on motor function with reduced dose of l-dopa and alleviating LID by normalising neurochemical imbalance within the basal ganglia. PMID:24321617

  6. Adverse effects of cow's milk in infants.

    PubMed

    Ziegler, Ekhard E

    2007-01-01

    The feeding of cow's milk has adverse effects on iron nutrition in infants and young children. Several different mechanisms have been identified that may act synergistically. Probably most important is the low iron content of cow's milk. It makes it difficult for the infant to obtain the amounts of iron needed for growth. A second mechanism is the occult intestinal blood loss, which occurs in about 40% of normal infants during feeding of cow's milk. Loss of iron in the form of blood diminishes with age and ceases after 1 year of age. A third factor is calcium and casein provided by cow's milk in high amounts. Calcium and casein both inhibit the absorption of dietary nonheme iron. Infants fed cow's milk receive much more protein and minerals than they need. The excess has to be excreted in the urine. The high renal solute load leads to higher urine concentration during the feeding of cow's milk than during the feeding of breast milk or formula. When fluid intakes are low and/or when extrarenal water losses are high, the renal concentrating ability of infants may be insufficient for maintaining water balance in the face of high water use for excretion of the high renal solute. The resulting negative water balance, if prolonged, can lead to serious dehydration. There is strong epidemiological evidence that the feeding of cow's milk or formulas with similarly high potential renal solute load places infants at an increased risk of serious dehydration. The feeding of cow's milk to infants is undesirable because of cow's milk's propensity to lead to iron deficiency and because it unduly increases the risk of severe dehydration.

  7. Pharmacogenomics of statins: understanding susceptibility to adverse effects

    PubMed Central

    Kitzmiller, Joseph P; Mikulik, Eduard B; Dauki, Anees M; Murkherjee, Chandrama; Luzum, Jasmine A

    2016-01-01

    Statins are a cornerstone of the pharmacologic treatment and prevention of atherosclerotic cardiovascular disease. Atherosclerotic disease is a predominant cause of mortality and morbidity worldwide. Statins are among the most commonly prescribed classes of medications, and their prescribing indications and target patient populations have been significantly expanded in the official guidelines recently published by the American and European expert panels. Adverse effects of statin pharmacotherapy, however, result in significant cost and morbidity and can lead to nonadherence and discontinuation of therapy. Statin-associated muscle symptoms occur in ~10% of patients on statins and constitute the most commonly reported adverse effect associated with statin pharmacotherapy. Substantial clinical and nonclinical research effort has been dedicated to determining whether genetics can provide meaningful insight regarding an individual patient’s risk of statin adverse effects. This contemporary review of the relevant clinical research on polymorphisms in several key genes that affect statin pharmacokinetics (eg, transporters and metabolizing enzymes), statin efficacy (eg, drug targets and pathways), and end-organ toxicity (eg, myopathy pathways) highlights several promising pharmacogenomic candidates. However, SLCO1B1 521C is currently the only clinically relevant pharmacogenetic test regarding statin toxicity, and its relevance is limited to simvastatin myopathy. PMID:27757045

  8. Evidence for Adverse Phonatory Change Following an Inhaled Combination Treatment

    ERIC Educational Resources Information Center

    Erickson, Elizabeth; Sivasankar, Mahalakshmi

    2010-01-01

    Purpose: Voice problems are reported as a frequent side effect of inhaled combination (IC) treatments. The purpose of this experimental study was to investigate whether IC treatments are detrimental to phonation. We hypothesized that IC treatment would significantly increase phonation threshold pressure (PTP) and perceived phonatory effort (PPE),…

  9. The adverse health effects of chronic cannabis use.

    PubMed

    Hall, Wayne; Degenhardt, Louisa

    2014-01-01

    This paper summarizes the most probable of the adverse health effects of regular cannabis use sustained over years, as indicated by epidemiological studies that have established an association between cannabis use and adverse outcomes; ruled out reverse causation; and controlled for plausible alternative explanations. We have also focused on adverse outcomes for which there is good evidence of biological plausibility. The focus is on those adverse health effects of greatest potential public health significance--those that are most likely to occur and to affect a substantial proportion of regular cannabis users. These most probable adverse effects of regular use include a dependence syndrome, impaired respiratory function, cardiovascular disease, adverse effects on adolescent psychosocial development and mental health, and residual cognitive impairment.

  10. 36 CFR 800.7 - Failure to resolve adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... effects. 800.7 Section 800.7 Parks, Forests, and Public Property ADVISORY COUNCIL ON HISTORIC PRESERVATION PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.7 Failure to resolve adverse effects. (a) Termination of consultation. After consulting to resolve adverse effects pursuant to § 800.6(b)(2), the...

  11. [Pharmacology of misoprostol (pharmacokinetic data, adverse effects and teratogenic effects)].

    PubMed

    Aubert, J; Bejan-Angoulvant, T; Jonville-Bera, A-P

    2014-02-01

    Misoprostol is a synthetic analogue of prostaglandin E1. It is used in gynaecology because of its properties of myometrium smooth muscle cells contraction and its effects on the cervix. Misoprostol oral bioavailability is low and several authors have assessed whether the administration by other routes increased its pharmacodynamic effects. This paper summarizes the pharmacokinetic studies after other routes of administration: vaginal, sublingual, buccal or rectal. It also provides an update on its adverse effects and teratogenic effects.

  12. Adverse reactions to snake antivenom, and their prevention and treatment.

    PubMed

    de Silva, H Asita; Ryan, Nicole M; de Silva, H Janaka

    2016-03-01

    Antivenom is the mainstay of treatment of snakebite envenoming. However, adverse reactions to snake antivenom that is available are common in many parts of the world where snakebite is prevalent. Both acute (anaphylactic or pyrogenic) and delayed (serum sickness type) reactions occur. Acute reactions are usually mild but severe systemic anaphylaxis may develop, often within an hour or so of exposure to antivenom. Serum sickness after antivenom has a delayed onset between 5 and 14 days after its administration. Ultimately, the prevention reactions will depend mainly on improving the quality of antivenom. Until these overdue improvements take place, doctors will have to depend on pharmacological prophylaxis, where the search for the best prophylactic agent is still on-going, as well as careful observation of patients receiving antivenom in preparation for prompt management of acute as well as delayed reactions when they occur.

  13. Statins as Targeted "Magical Pills" for the Conservative Treatment of Endometriosis: May Potential Adverse Effects on Female Fertility Represent the "Dark Side of the Same Coin"? A Systematic Review of Literature.

    PubMed

    Vitagliano, Amerigo; Noventa, Marco; Quaranta, Michela; Gizzo, Salvatore

    2016-04-01

    The aim of the study was to analyze all the available evidence from both in vitro and in vivo studies regarding the efficacy of statin therapy in the treatment of endometriosis, evaluating the potential efficacy, side effects, and contraindications of their administration in humans. We focused on defining the potential benefits that the administration of statins may have on patients affected by endometriosis and the possible adverse effects of such a therapy on ovarian function and fertility profile. According to our article selection criteria, we included in the review in vitro and in vivo studies performed on human or animal models. The systematic review of literature identified 24 eligible articles, 12 of which reported evidence regarding the effects of statins on endometrial/endometriotic cells and 12 regarding their effects on ovarian function and fertility. All articles seem to emphasize the utility of statin administration in the treatment of endometriosis due to their anti-proliferative/proapoptotic effects, their ability to reduce cell viability and migration, and the inhibition of angiogenesis and anti-inflammatory activities. Regarding the potential adverse effects on gonadal activities, steroidogenesis and fertility function, no conclusive data were collected in human models (excluding women affected by polycystic ovary syndrome in which significant decline of androgen levels was reported after statin treatment), while contrasting results were reported by studies conducted in in vitro and in vivo in animal models. Despite evidence supporting statins as the potential therapeutic agent for a targeted conservative treatment of endometriosis, the uncertainties regarding their impact on gonadal function may not define them as an appropriate therapy for all young fertile women.

  14. Using Literature-Based Discovery to Explain Adverse Drug Effects.

    PubMed

    Hristovski, Dimitar; Kastrin, Andrej; Dinevski, Dejan; Burgun, Anita; Žiberna, Lovro; Rindflesch, Thomas C

    2016-08-01

    We report on our research in using literature-based discovery (LBD) to provide pharmacological and/or pharmacogenomic explanations for reported adverse drug effects. The goal of LBD is to generate novel and potentially useful hypotheses by analyzing the scientific literature and optionally some additional resources. Our assumption is that drugs have effects on some genes or proteins and that these genes or proteins are associated with the observed adverse effects. Therefore, by using LBD we try to find genes or proteins that link the drugs with the reported adverse effects. These genes or proteins can be used to provide insight into the processes causing the adverse effects. Initial results show that our method has the potential to assist in explaining reported adverse drug effects.

  15. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 29 2013-07-01 2013-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  16. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 28 2011-07-01 2011-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  17. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 29 2012-07-01 2012-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  18. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 28 2014-07-01 2014-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  19. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  20. Nonhemostatic adverse effects of anticoagulants and antiplatelet agents.

    PubMed

    Walenga, Jeanine M; Thethi, Indermohan; Lewis, Bruce E

    2012-11-01

    The topic of adverse effects of drugs is now receiving due attention in both the lay and medical communities. For drugs of the coagulation disorder class, such as anticoagulants and antiplatelet agents, the obvious adverse effects are bleeding from a dose too high and thrombosis from a dose too low. However, these drugs have other potential adverse effects that are not directly related to blood coagulation, yet cannot be dismissed due to their medical importance. There has been a recent advancement of several new drugs in this category and this number will soon grow as more drugs are reaching the end of their clinical trials. This article will discuss the nonhemostatic adverse effects of anticoagulants and antiplatelet drugs. As the adverse effects of bleeding and thrombosis will be excluded, this article will be in contrast to the typical discussions on the anticoagulant and antiplatelet drug classes.

  1. Effect of Two Different Methods of Initiating Atomoxetine on the Adverse Event Profile of Atomoxetine

    ERIC Educational Resources Information Center

    Greenhill, Laurence L.; Newcorn, Jeffrey H.; Gao, Haitao; Feldman, Peter D.

    2007-01-01

    Objective: To compare the effects of two different methods for initiating atomoxetine in terms of the incidence of early adverse events. Method: Data on atomoxetine treatment-emergent adverse events in youths, ages 6 to 18 years, were analyzed from five randomized, double-blind, placebo-controlled, acute-phase studies. Two studies involve…

  2. Periodontal treatment during pregnancy decreases the rate of adverse pregnancy outcome: a controlled clinical trial

    PubMed Central

    SANT’ANA, Adriana Campos Passanezi; de CAMPOS, Marinele R.; PASSANEZI, Selma Campos; de REZENDE, Maria Lúcia Rubo; GREGHI, Sebastião Luiz Aguiar; PASSANEZI, Euloir

    2011-01-01

    Objectives The aim of this study was to evaluate the effects of non-surgical treatment of periodontal disease during the second trimester of gestation on adverse pregnancy outcomes. Material and Methods Pregnant patients during the 1st and 2nd trimesters at antenatal care in a Public Health Center were divided into 2 groups: NIG – "no intervention" (n=17) or IG- "intervention" (n=16). IG patients were submitted to a non-surgical periodontal treatment performed by a single periodontist consisting of scaling and root planning (SRP), professional prophylaxis (PROPH) and oral hygiene instruction (OHI). NIG received PROPH and OHI during pregnancy and were referred for treatment after delivery. Periodontal evaluation was performed by a single trained examiner, blinded to periodontal treatment, according to probing depth (PD), clinical attachment level (CAL), plaque index (PI) and sulcular bleeding index (SBI) at baseline and 35 gestational weeks-28 days post-partum. Primary adverse pregnancy outcomes were preterm birth (<37 weeks), low birth weight (<2.5 kg), late abortion (14-24 weeks) or abortion (<14 weeks). The results obtained were statistically evaluated according to OR, unpaired t test and paired t test at 5% significance level. Results No significant differences were observed between groups at baseline examination. Periodontal treatment resulted in stabilization of CAL and PI (p>0.05) at IG and worsening of all periodontal parameters at NIG (p<0.0001), except for PI. Significant differences in periodontal conditions of IG and NIG were observed at 2nd examination (p<0.001). The rate of adverse pregnancy outcomes was 47.05% in NIG and 6.25% in IG. Periodontal treatment during pregnancy was associated to a decreased risk of developing adverse pregnancy outcomes [OR=13.50; CI: 1.47-123.45; p=0.02]. Conclusions Periodontal treatment during the second trimester of gestation contributes to decrease adverse pregnancy outcomes. PMID:21552714

  3. Adverse health effects of non-medical cannabis use.

    PubMed

    Hall, Wayne; Degenhardt, Louisa

    2009-10-17

    For over two decades, cannabis, commonly known as marijuana, has been the most widely used illicit drug by young people in high-income countries, and has recently become popular on a global scale. Epidemiological research during the past 10 years suggests that regular use of cannabis during adolescence and into adulthood can have adverse effects. Epidemiological, clinical, and laboratory studies have established an association between cannabis use and adverse outcomes. We focus on adverse health effects of greatest potential public health interest-that is, those that are most likely to occur and to affect a large number of cannabis users. The most probable adverse effects include a dependence syndrome, increased risk of motor vehicle crashes, impaired respiratory function, cardiovascular disease, and adverse effects of regular use on adolescent psychosocial development and mental health.

  4. Managing patients with side effects and adverse events to immunoglobulin therapy.

    PubMed

    Azizi, Gholamreza; Abolhassani, Hassan; Asgardoon, Mohammad Hossein; Shaghaghi, Shiva; Negahdari, Babak; Mohammadi, Javad; Rezaei, Nima; Aghamohammadi, Asghar

    2016-01-01

    Immunoglobulin therapy has not only served as a lifesaving approach for the prevention and treatment of infections in primary and secondary immunodeficiency diseases, but has also been used as an immunomodulatory agent for autoimmune and inflammatory disorders and to provide passive immunity for some infectious diseases. Most of the adverse effects associated with immunoglobulin therapy are mild, transient and self-limiting. However, serious side effects also occur. Therefore, to minimize the adverse events of immunoglobulin therapy, specialist review of patient clinical status and immunoglobulin products, in addition to selection of appropriate treatment strategy for the management of patients with associated side effects and adverse events, are crucial.

  5. Adverse effects of antiretroviral therapy for HIV infection.

    PubMed

    Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S G

    2004-01-20

    Long-term remission of HIV-1 disease can be readily achieved by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients.

  6. Transient Adverse Side Effects During Neurofeedback Training: A Randomized, Sham-Controlled, Double Blind Study.

    PubMed

    Rogel, Ainat; Guez, Jonathan; Getter, Nir; Keha, Eldad; Cohen, Tzlil; Amor, Tali; Todder, Doron

    2015-09-01

    The benefits of clinical neurofeedback training are well known, however, its adverse side-effects are less studied. This research focuses on the transient adverse side effects of neurofeedback training via a double-blind, sham/controlled methodology. Thirty healthy undergraduate students volunteers were randomly divided into three treatment groups: increasing a modified Sensory Motor Rhythm, increasing Upper Alpha, and Sham/control group who receive a random reward. The training sessions were administered for a total of ten sessions. Questionnaires of transient adverse side effects were completed by all volunteers before each session. The results suggest that similar to most medical treatments, neurofeedback can cause transient adverse side effects. Moreover, most participants reported experiencing some side effects. The side effects can be divided into non-specific side effect, associated with the neurofeedback training in general and specific ones associated with the particular protocol. Sensory Motor Rhythm protocol seems to be the most sensitive to side effects.

  7. Adverse effects of gentamicin in scarlet macaws and galahs.

    PubMed

    Flammer, K; Clark, C H; Drewes, L A; Wilson, R C; Fiorello-Barrett, J

    1990-03-01

    The adverse effects of administration of gentamicin (5 mg/kg of body weight, IM, q 12 h) for 7 days were studied in healthy scarlet macaws (Ara macao) and galahs (Eolophus roseicapillus; cockatoos). Polydipsia and polyuria developed in each species, but were greater and persisted longer in the cockatoos. Peak water intake in the cockatoos more than quadrupled, and remained increased for 23 days after cessation of gentamicin administration. Plasma aspartate transaminase activity increased significantly (P less than 0.05) after treatment in the macaws, and plasma aspartate transaminase and lactate dehydrogenase activities increased in the cockatoos. Single IM administration of gentamicin (5 mg/kg) resulted in mean (+/- SEM) plasma concentration of 20.6 (+/- 1.85) micrograms/ml at 0.5 hour for either species of birds. There were no significant differences between mean plasma gentamicin concentrations for cockatoos and macaws at any time after drug administration, except at 12 hours, when values for cockatoos were significantly (P less than 0.05) greater than those for macaws. The elimination half-life for gentamicin after IM administration of 5 and 10 mg/kg was 1.17 and 1.07 hours, respectively, for macaws and 1.23 and 1.44 hours, respectively, for cockatoos. Correlation between drug disposition and adverse side effects could not be detected.

  8. Pharmacovigilance, risks and adverse effects of self-medication.

    PubMed

    Montastruc, Jean-Louis; Bondon-Guitton, Emmanuelle; Abadie, Delphine; Lacroix, Isabelle; Berreni, Aurélia; Pugnet, Grégory; Durrieu, Geneviève; Sailler, Laurent; Giroud, Jean-Paul; Damase-Michel, Christine; Montastruc, François

    2016-04-01

    Self-medication means resorting to one or more drugs in order to treat oneself without the help of a doctor. This phenomenon is developing fast. In this review, we will discuss the main definitions of self-medication; we will then present a few important characteristics of this therapeutic practice: prevalence, reasons, populations involved and drugs used. Whilst the theoretical risks of self-medication have been abundantly discussed in the literature (adverse effects, interactions, product, dosage or treatment duration errors, difficulty in self-diagnosis, risk of addiction or abuse…), there is in fact very little detailed pharmacovigilance data concerning the characteristics and the consequences of this usage in real life. This study therefore describes the all too rare data that is available: patients, clinical characteristics, "seriousness" and drugs involved in the adverse effects of self-medication. It also discusses leads to be followed in order to minimize medication risks, which are obviously not well known and clearly not sufficiently notified.

  9. Adverse effects of public health interventions: a conceptual framework.

    PubMed

    Lorenc, Theo; Oliver, Kathryn

    2014-03-01

    Public health interventions may have a range of adverse effects. However, there is limited guidance as to how evaluations should address the possibility of adverse effects. This discussion paper briefly presents a framework for thinking about the potential harms of public health interventions, focusing on the following categories: direct harms; psychological harms; equity harms; group and social harms; and opportunity harms. We conclude that the possibility of adverse effects needs to be taken into account by those implementing and evaluating interventions, and requires a broad perspective on the potential impacts of public health strategies.

  10. Diversity and intensity of adverse events in the treatment of hypertension with barnidipine.

    PubMed

    van der Velden, J W; Beudeker, H J; Nishi, M

    1998-01-01

    Calcium antagonists (CaAs) are divided into three structural classes, typically represented by verapamil, diltiazem and nifedipine. As a group, the principal (type I) adverse effects of these drugs relate to the pharmacological action of calcium channel blockade, namely vasodilation, and include dizziness, flushing, palpitations and peripheral oedema. The clinical safety of the new dihydropyridine CaA, barnidipine, has been assessed in more than 12 clinical trials, including 2041 patients who have been treated with one or more doses of barnidipine (dose of up to 50 mg). Adverse events with barnidipine are of mild to moderate intensity, most commonly of type I, occurring in the early phase of treatment. The incidence of serious adverse events and the rate of withdrawals are low. Hence, barnidipine is likely to be well tolerated in general clinical use.

  11. Effect of thyroid hormone status and concomitant medication on statin induced adverse effects in hyperlipidemic patients.

    PubMed

    Berta, E; Harangi, M; Zsíros, N; Nagy, E V; Paragh, G; Bodor, M

    2014-06-01

    Statins are effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, adverse effects induced by statins are the major barrier of maximalizing cardiovascular risk reduction. Hypothyroidism and administration of drugs metabolized on the same cytochrome P450 (CYPP450) pathways where statin biotransformation occurs represent a significant risk factor for statin induced adverse effects including myopathy. Simvastatin, atorvastatin and lovastatin are metabolized by CYP3A4, fluvastatin by CYP2C9, while rosuvastatin by CYP2C9 and 2C19. We investigated the levels of the free thyroid hormones and CYP metabolism of concomitant medication in 101 hyperlipidemic patients (age 61.3 +/- 9.9 ys) with statin induced adverse effects including myopathy (56 cases; 55.4%), hepatopathy (39 cases; 38.6%) and gastrointestinal adverse effects (24 cases; 23.8%). Abnormal thyroid hormone levels were found in 5 patients (4.95%); clinical hypothyroidism in 2 and hyperthyroidism in 3 cases. 11 patients had a positive history for hypothyroidism (10.9%). Myopathy occured in one patient with hypothyroidism and two patients with hyperthyroidism. There were no significant differences in the TSH, fT4 and fT3 levels between patients with statin induced myopathy and patients with other types of adverse effects. 78 patients (77.2%) were administered drugs metabolized by CYP isoforms also used by statins (3A4: 66 cases (65.3%); 2C9: 67 cases (66.3%); 2C19: 54 cases (53.5%)). Patients with myopathy took significantly more drugs metabolized by CYP3A4 compared to patients with other types of adverse effects (p < 0.05). More myopathy cases were found in patients on simvastatin treatment (52% vs. 38%, ns.), while significantly less patients with myopathy were on fluvastatin treatment (13% vs. 33%, p < 0.05) compared to patients with other types of statin induced adverse effects. Both abnormal thyroid hormone status and administration of drugs metabolized by CYP

  12. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate for... sheepherding) in the following States, and for Florida sugarcane work, shall be computed by adjusting the...

  13. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate for... sheepherding) in the following States, and for Florida sugarcane work, shall be computed by adjusting the...

  14. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate for... sheepherding) in the following States, and for Florida sugarcane work, shall be computed by adjusting the...

  15. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate for... sheepherding) in the following States, and for Florida sugarcane work, shall be computed by adjusting the...

  16. Adverse Effects of Psychotropic Medications in Children: Predictive Factors

    PubMed Central

    Ninan, Ajit; Stewart, Shannon L.; Theall, Laura A.; Katuwapitiya, Shehan; Kam, Chester

    2014-01-01

    Objective: Despite limited information related to efficacy in children, psychotropic medications are commonly prescribed as a first-line treatment for a range of psychiatric diagnoses in children in a variety of clinical settings. Usage has increased over the past three decades. Although psychotropic medications are often effective at treating psychiatric symptoms, the risk of adverse effects (AE) in children is unclear. The current research seeks to identify the mental health characteristics of those children at highest risk of experiencing potential AE from psychotropic medications. Methods: Psychotropic medication monitoring checklists were used to record possible AE for 99 pediatric clients in a tertiary mental health residential treatment centre for the duration of one to eight weeks. Client characteristics, including the number of diagnoses and behavioural variables, were explored for predictive value of potential AE observed. Results: Results showed that the total number of potential AE was positively predicted by the number of DSM-IV categories diagnosed, as well as behavioural symptoms of impulsiveness and uncooperativeness. Conclusions: The findings of this study indicate that the number of potential AE from psychotropic medications may be predictable based on client characteristics. Predicting this likelihood during initial assessment can be useful in directing and monitoring treatment, as well as preventing serious events related to medication use. PMID:25320615

  17. Adverse effects of herbal medicines: an overview of systematic reviews.

    PubMed

    Posadzki, Paul; Watson, Leala K; Ernst, Edzard

    2013-02-01

    This overview of systematic reviews (SRs) aims to evaluate critically the evidence regarding the adverse effects of herbal medicines (HMs). Five electronic databases were searched to identify all relevant SRs, with 50 SRs of 50 different HMs meeting our inclusion criteria. Most had only minor weaknesses in methods. Serious adverse effects were noted only for four HMs: Herbae pulvis standardisatus, Larrea tridentate, Piper methysticum and Cassia senna. The most severe adverse effects were liver or kidney damage, colon perforation, carcinoma, coma and death. Moderately severe adverse effects were noted for 15 HMs: Pelargonium sidoides, Perna canaliculus, Aloe vera, Mentha piperita, Medicago sativa, Cimicifuga racemosa, Caulophyllum thalictroides, Serenoa repens, Taraxacum officinale, Camellia sinensis, Commifora mukul, Hoodia gordonii, Viscum album, Trifolium pratense and Stevia rebaudiana. Minor adverse effects were noted for 31 HMs: Thymus vulgaris, Lavandula angustifolia Miller, Boswellia serrata, Calendula officinalis, Harpagophytum procumbens, Panax ginseng, Vitex agnus-castus, Crataegus spp., Cinnamomum spp., Petasites hybridus, Agave americana, Hypericum perforatum, Echinacea spp., Silybum marianum, Capsicum spp., Genus phyllanthus, Ginkgo biloba, Valeriana officinalis, Hippocastanaceae, Melissa officinalis, Trigonella foenum-graecum, Lagerstroemia speciosa, Cnicus benedictus, Salvia hispanica, Vaccinium myrtillus, Mentha spicata, Rosmarinus officinalis, Crocus sativus, Gymnema sylvestre, Morinda citrifolia and Curcuma longa. Most of the HMs evaluated in SRs were associated with only moderately severe or minor adverse effects.

  18. Adverse Health Effects of Nighttime Lighting

    NASA Astrophysics Data System (ADS)

    Motta, M.

    2012-06-01

    The effects of poor lighting and glare on public safety are well-known, as are the harmful environmental effects on various species and the environment in general. What is less well-known is the potential harmful medical effects of excessive poor nighttime lighting. A significant body of research has been developed over the last few years regarding this problem. One of the most significant effects is the startling increased risk for breast cancer by excessive exposure to nighttime lighting. The mechanism is felt to be by disruption of the circadian rhythm and suppression of melatonin production from the pineal gland. Melatonin has an anticancer effect that is lost when its production is disrupted. I am in the process of developing a monograph that will summarize this important body of research, to be presented and endorsed by the American Medical Association, and its Council of Science and Public health. This paper is a brief overall summary of this little known potential harmful effect of poor and excessive nighttime lighting.

  19. Multidisciplinary approach to identification and remedial intervention for adverse late effects of cancer therapy

    SciTech Connect

    McCalla, J.L.

    1985-03-01

    Because of advances in surgical technique, radiation therapy, and combined chemotherapy regimens, there has been a dramatic improvement in the survival of children with pediatric malignancies. All treatment modalities are associated with adverse effects that may be manifested months to years after therapy. This article has provided an overview of the physiologic and psychologic adverse effects of antineoplastic therapy and described the multidisciplinary approach used by one institution to identify and initiate appropriate remedial intervention. Nurses can learn to assist in the identification of adverse late effects, provide support to the family, and facilitate appropriate intervention.

  20. Adverse effects of stress on microbiota

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The complex communities of microorganisms that colonize the gastrointestinal tract impact the health status of an animal. The health of an animal as well as production traits are also affected by exposure to stress. The aim of present study was to evaluate the effects of dehorning stress on the gut ...

  1. Potential adverse health effects of wood smoke

    SciTech Connect

    Pierson, W.E.; Koenig, J.Q.; Bardana, E.J. Jr.

    1989-09-01

    The use of wood stoves has increased greatly in the past decade, causing concern in many communities about the health effects of wood smoke. Wood smoke is known to contain such compounds as carbon monoxide, nitrogen oxides, sulfur oxides, aldehydes, polycyclic aromatic hydrocarbons, and fine respirable particulate matter. All of these have been shown to cause deleterious physiologic responses in laboratory studies in humans. Some compounds found in wood smoke--benzo(a)pyrene and formaldehyde--are possible human carcinogens. Fine particulate matter has been associated with decreased pulmonary function in children and with increased chronic lung disease in Nepal, where exposure to very high amounts of wood smoke occurs in residences. Wood smoke fumes, taken from both outdoor and indoor samples, have shown mutagenic activity in short-term bioassay tests. Because of the potential health effects of wood smoke, exposure to this source of air pollution should be minimal.29 references.

  2. [Statin-induced adverse effects -- facts and genes].

    PubMed

    Harangi, Mariann; Zsíros, Noémi; Juhász, Lilla; Paragh, György

    2013-01-20

    Statin therapy is considered to be safe and rarely associated with serious adverse events. However, a significant proportion of patients on statin therapy show some degree of intolerance which can lead to decreased adherence to statin therapy. The authors summarize the symptoms, signs and frequencies of the most common statin-induced adverse effects and their most important risk factors including some single nucleotide polymorphisms and gene mutations. Also, they review the available approaches to detect and manage the statin-intolerant patients.

  3. Treatment with Tacrolimus and Sirolimus Reveals No Additional Adverse Effects on Human Islets In Vitro Compared to Each Drug Alone but They Are Reduced by Adding Glucocorticoids

    PubMed Central

    Kloster-Jensen, Kristine; Sahraoui, Afaf; Vethe, Nils Tore; Korsgren, Olle; Bergan, Stein; Foss, Aksel; Scholz, Hanne

    2016-01-01

    Tacrolimus and sirolimus are important immunosuppressive drugs used in human islet transplantation; however, they are linked to detrimental effects on islets and reduction of long-term graft function. Few studies investigate the direct effects of these drugs combined in parallel with single drug exposure. Human islets were treated with or without tacrolimus (30 μg/L), sirolimus (30 μg/L), or a combination thereof for 24 hrs. Islet function as well as apoptosis was assessed by glucose-stimulated insulin secretion (GSIS) and Cell Death ELISA. Proinflammatory cytokines were analysed by qRT-PCR and Bio-Plex. Islets exposed to the combination of sirolimus and tacrolimus were treated with or without methylprednisolone (1000 μg/L) and the expression of the proinflammatory cytokines was investigated. We found the following: (i) No additive reduction in function and viability in islets existed when tacrolimus and sirolimus were combined compared to the single drug. (ii) Increased expression of proinflammatory cytokines mRNA and protein levels in islets took place. (iii) Methylprednisolone significantly decreased the proinflammatory response in islets induced by the drug combination. Although human islets are prone to direct toxic effect of tacrolimus and sirolimus, we found no additive effects of the drug combination. Short-term exposure of glucocorticoids could effectively reduce the proinflammatory response in human islets induced by the combination of tacrolimus and sirolimus. PMID:26885529

  4. Adverse effects of isolation in hospitalised patients: a systematic review.

    PubMed

    Abad, C; Fearday, A; Safdar, N

    2010-10-01

    The use of transmission precautions such as contact isolation in patients known to be colonised or infected with multidrug-resistant organisms is recommended in healthcare institutions. Although essential for infection control, contact isolation has recently been associated with adverse effects in patients. We undertook a systematic review to determine whether contact isolation leads to psychological or physical problems for patients. Studies were included if (1) hospitalised patients were placed under isolation precautions for an underlying medical indication, and (2) any adverse events related to the isolation were evaluated. We found 16 studies that reported data regarding the impact of isolation on patient mental well-being, patient satisfaction, patient safety or time spent by healthcare workers in direct patient care. The majority showed a negative impact on patient mental well-being and behaviour, including higher scores for depression, anxiety and anger among isolated patients. A few studies also found that healthcare workers spent less time with patients in isolation. Patient satisfaction was adversely affected by isolation if patients were kept uninformed of their healthcare. Patient safety was also negatively affected, leading to an eight-fold increase in adverse events related to supportive care failures. We found that contact isolation may negatively impact several dimensions of patient care. Well-validated tools are necessary to investigate these results further. Large studies examining a number of safety indicators to assess the adverse effects of isolation are needed. Patient education may be an important step to mitigate the adverse psychological effects of isolation and is recommended.

  5. Adverse effects of the radioprotector WR2721

    SciTech Connect

    Cairnie, A.B.

    1983-04-01

    S-2-(3-Aminopropylamino)ethylphosphorothioic acid (WR2721) has radioprotective properties, but it is also toxic - in man it causes nausea and vomiting. Since radiation also causes nausea and vomiting it is important to know whether WR2721 would increase or decrease the likelihood of nausea and vomiting after radiation. This question was investigated in rats using the phenomenon of aversion to the taste of saccharin, which is readily inducible and is understood to be controlled in rats by the same pathways that control nausea and vomiting in man. The taste aversion was induced by giving 0.2 Gy /sup 60/Co ..gamma.. radiation 30 min after drinking 0.1% saccharin, or WR2721 immediately after the saccharin, or giving both radiation and WR2721. There were appropriate controls. In sham-irradiated rats, WR2721 (40 or 200 mg/kg, but not 8 mg/kg) produced a significant taste aversion. When WR2721 (40 or 200 mg/kg) was given immediately after the saccharin to irradiated rats it increased the taste aversion significantly, but it did not have any effect at 8 mg/kg. It was concluded that at doses which were optimal for radioprotection (approx.200 mg/kg) or lower, WR2721 increased in rats the taste aversion induced by radiation. By inference if conditioned taste aversion is an appropriate paradigm, WR2721 would increase nausea and vomiting in man induced by radiation.

  6. Adverse effects of thyroid hormone preparations and antithyroid drugs.

    PubMed

    Bartalena, L; Bogazzi, F; Martino, E

    1996-07-01

    Thyroid hormone preparations, especially thyroxine, are widely used either at replacement doses to correct hypothyroidism or at suppressive doses to abolish thyrotropin (thyroid-stimulating hormone) secretion in patients with differentiated thyroid carcinoma after total thyroidectomy or with diffuse/ nodular nontoxic goitre. In order to suppress thyrotropin secretion, it is necessary to administer slightly supraphysiological doses of thyroxine. Possible adverse effects of this therapy include cardiovascular changes (shortening of systolic time intervals, increased frequency of atrial premature beats and, possibly, left ventricular hypertrophy) and bone changes (reduced bone density and bone mass), but the risk of these adverse effects can be minimised by carefully monitoring serum free thyroxine and free liothyronine (triiodothyronine) measurements and adjusting the dosage accordingly. Thionamides [thiamazole (methimazole), carbimazole, propylthiouracil] are the most widely used antithyroid drugs. They are given for long periods of time and cause adverse effects in 3 to 5% of patients. In most cases, adverse effects are minor and transient (e.g. skin rash, itching, mild leucopenia). The most dangerous effect is agranulocytosis, which occurs in 0.1 to 0.5% of patients. This life-threatening condition can now be effectively treated by granulocyte colony-stimulating factor administration. Other major adverse effects (aplastic anaemia, thrombocytopenia, lupus erythematosus-like syndrome, vasculitis) are exceedingly rare.

  7. [Desired effects and adverse effects of cannabis use].

    PubMed

    Drewe, J

    2003-06-01

    Although the use of cannabis shows no pronounced acute toxicity, acute psychological and psychomotor disturbances are observed occasionally after intake of single doses. Cannabis use can result in relevant impairment of driving ability. The risk is enhanced by concomitant use of alcohol. This augments the effect of cannabis significantly. After chronic use, significantly more psychotic symptoms become manifest, and there is a risk for developing psychological and physical dependence. Young age and pre-existing psychological disturbances increase the risk of these adverse effects. Chronic marijuana smoking is associated with increased toxicity and the risk of cancer of the respiratory tract. There is evidence of disturbance of the immune system and teratogenic effects of chronic cannabis use.

  8. Early Adverse Events and Attrition in SSRI Treatment: A Suicide Assessment Methodology Study (SAMS) Report

    PubMed Central

    Warden, Diane; Trivedi, Madhukar H.; Wisniewski, Stephen R.; Kurian, Benji; Zisook, Sidney; Kornstein, Susan G.; Friedman, Edward S.; Miyahara, Sachiko; Leuchter, Andrew F.; Fava, Maurizio; Rush, John

    2011-01-01

    Adverse events during selective serotonin reuptake inhibitor (SSRI) treatment are frequent and may lead to premature treatment discontinuation. If attrition is associated with early worsening of side effects or the frequency, intensity, or burden of side effects, interventions to maximize retention could be focused on patients with these events. Outpatient participants (n=265) with nonpsychotic major depressive disorder entered an 8-week trial with an SSRI. At baseline and week 2, specific side effects were evaluated with the Systematic Assessment for Treatment Emergent Events – Systematic Inquiry, and at week 2 the Frequency, Intensity, and Burden of Side Effects Rating globally assessed side effects. Attrition was defined by those participants who left treatment after week 2 but before week 8. No specific week 2 side effect, either treatment emergent or with worsening intensity, was independently associated with attrition. Global ratings of side effect frequency, intensity, or burden at week 2 were also not associated with subsequent attrition. Neither global ratings nor specific side effects at week 2 were related to patient attrition during SSRI treatment. Other factors appear to contribute to patient decisions about continuing with treatment. PMID:20473060

  9. Probable Nootropicinduced Psychiatric Adverse Effects: A Series of Four Cases

    PubMed Central

    Ajaltouni, Jean

    2015-01-01

    The misuse of nootropics—any substance that may alter, improve, or augment cognitive performance, mainly through the stimulation or inhibition of certain neurotransmitters—may potentially be dangerous and deleterious to the human brain, and certain individuals with a history of mental or substance use disorders might be particularly vulnerable to their adverse effects. We describe four cases of probable nootropic-induced psychiatric adverse effects to illustrate this theory. To the best of our knowledge this has not been previously reported in the formal medical literature. We briefly describe the most common classes of nootropics, including their postulated or proven methods of actions, their desired effects, and their adverse side effects, and provide a brief discussion of the cases. Our objective is to raise awareness among physicians in general and psychiatrists and addiction specialists in particular of the potentially dangerous phenomenon of unsupervised nootropic use among young adults who may be especially vulnerable to nootropics’ negative effects. PMID:27222762

  10. Misuse of topical corticosteroids: A clinical study of adverse effects

    PubMed Central

    Dey, Vivek Kumar

    2014-01-01

    Background: Misuse of topical corticosteroids is a widespread phenomenon among young people in India, especially women. The practice is associated with significant adverse effects and poor awareness of these effects among the general public. Aim: This study was conducted to examine the misuse and adverse effects of topical corticosteroids among the people in Bastar region in Chhattisgarh state of India. Materials and Methods: Data collected from patients presenting with at least one of the adverse effects of topical corticosteroids as the chief complaint, from November 2010 to October 2011. Results: Out of the 6723 new patients, 379 (5.63%) had presented with misuse and adverse effects of topical corticosteroids, of whom 78.89% were females. More than 65% of the patients were in the age group 10-29 years. The main reason for using the topical corticosteroids was to lighten skin colour and treat melasma and suntan. Acne (37.99%) and telangiectasia (18.99%) were the most common adverse effects noted. Conclusions: Misuse of topical corticosteroids has a huge impact on dermatological practice, leading to a significant proportion of visits to the dermatologist. This hydra-headed problem needs multi-dimensional interventions, involving educational, legal and managerial approaches with cooperation from different sectors of society. PMID:25396124

  11. Ropinirole: new indication. Restless legs: disproportionate adverse effects.

    PubMed

    2006-10-01

    (1) The restless legs syndrome consists of unpleasant sensory and motor symptoms of varying intensity in the lower limbs. Symptoms occur at rest, seated or lying down, are more intense in the evening and at night, and are relieved by moving the limb. This syndrome does not cause serious physical complications. When sleep disturbances occur, non drug methods should be tried first. (2) Ropinirole is a dopaminergic agonist initially marketed for the treatment of Parkinson's disease. It is the first drug to be approved for restless legs syndrome in France. (3) Three double-blind randomised placebo-controlled trials with similar designs showed minimal differences on a composite rating scale. After 12 weeks of treatment, ropinirole led to an improvement of about 3 points on a 40-point scale compared with placebo. (4) A 12-week double-blind randomised controlled trial and including patients who had "responded" to ropinirole showed a lower relapse rate in the group that continued to use ropinirole (32.6%) instead of switching to placebo (57.8%). However, we do not know if this was because of continued drug efficacy or a rebound effect in the placebo group. (5) The adverse effects of ropinirole in patients with restless legs syndrome had already been observed in the treatment of Parkinson's disease, and included nausea, vomiting, drowsiness, a sudden urge to sleep, syncope, hypotension, and hallucinations. (6) An increase in the severity of restless legs symptoms, typically seen with levodopa, was not evaluated in clinical trials of ropinirole. Some cases have nevertheless been reported. They describe the appearance of symptoms increasingly early in the evening, then in the afternoon, or as a rebound effect in the morning or the latter part of the night. Their intensity increases and can affect other parts of the body. (7) In practice, ropinirole has a negative risk-benefit balance in restless legs syndrome, which is a minor health disorder.

  12. Long-term antidepressant use: patient perspectives of benefits and adverse effects

    PubMed Central

    Cartwright, Claire; Gibson, Kerry; Read, John; Cowan, Ondria; Dehar, Tamsin

    2016-01-01

    Long-term antidepressant treatment has increased and there is evidence of adverse effects; however, little is known about patients’ experiences and views of this form of treatment. This study used mixed methods to examine patients’ views and experiences of long-term antidepressant treatment, including benefits and concerns. Data from 180 patients, who were long-term users of antidepressants (3–15 years), were extracted from an anonymous online survey of patients’ experiences of antidepressants in New Zealand. Participants had completed rating scales about the effectiveness of antidepressants, levels of depression before and during antidepressant use, quality of life, and perceived adverse effects. Two open-ended questions allowed participants to comment on personal experiences. The majority (89.4%) reported that antidepressants had improved their depression although 30% reported moderate-to-severe depression on antidepressants. Common adverse effects included withdrawal effects (73.5%), sexual problems (71.8%), and weight gain (65.3%). Adverse emotional effects, such as feeling emotionally numb (64.5%) and addicted (43%), were also common. While the majority of patients were pleased with the benefits of antidepressant treatment, many were concerned about these adverse effects. Some expressed a need for more information about long-term risks and increased information and support to discontinue. PMID:27528803

  13. Adverse effects of anabolic steroids in athletes. A constant threat.

    PubMed

    Maravelias, C; Dona, A; Stefanidou, M; Spiliopoulou, C

    2005-09-15

    Anabolic-androgenic steroids (AAS) are used as ergogenic aids by athletes and non-athletes to enhance performance by augmenting muscular development and strength. AAS administration is often associated with various adverse effects that are generally dose related. High and multi-doses of AAS used for athletic enhancement can lead to serious and irreversible organ damage. Among the most common adverse effects of AAS are some degree of reduced fertility and gynecomastia in males and masculinization in women and children. Other adverse effects include hypertension and atherosclerosis, blood clotting, jaundice, hepatic neoplasms and carcinoma, tendon damage, psychiatric and behavioral disorders. More specifically, this article reviews the reproductive, hepatic, cardiovascular, hematological, cerebrovascular, musculoskeletal, endocrine, renal, immunologic and psychologic effects. Drug-prevention counseling to athletes is highlighted and the use of anabolic steroids is must be avoided, emphasizing that sports goals may be met within the framework of honest competition, free of doping substances.

  14. Osteoblasts mediate the adverse effects of glucocorticoids on fuel metabolism

    PubMed Central

    Brennan-Speranza, Tara C.; Henneicke, Holger; Gasparini, Sylvia J.; Blankenstein, Katharina I.; Heinevetter, Uta; Cogger, Victoria C.; Svistounov, Dmitri; Zhang, Yaqing; Cooney, Gregory J.; Buttgereit, Frank; Dunstan, Colin R.; Gundberg, Caren; Zhou, Hong; Seibel, Markus J.

    2012-01-01

    Long-term glucocorticoid treatment is associated with numerous adverse outcomes, including weight gain, insulin resistance, and diabetes; however, the pathogenesis of these side effects remains obscure. Glucocorticoids also suppress osteoblast function, including osteocalcin synthesis. Osteocalcin is an osteoblast-specific peptide that is reported to be involved in normal murine fuel metabolism. We now demonstrate that osteoblasts play a pivotal role in the pathogenesis of glucocorticoid-induced dysmetabolism. Osteoblast-targeted disruption of glucocorticoid signaling significantly attenuated the suppression of osteocalcin synthesis and prevented the development of insulin resistance, glucose intolerance, and abnormal weight gain in corticosterone-treated mice. Nearly identical effects were observed in glucocorticoid-treated animals following heterotopic (hepatic) expression of both carboxylated and uncarboxylated osteocalcin through gene therapy, which additionally led to a reduction in hepatic lipid deposition and improved phosphorylation of the insulin receptor. These data suggest that the effects of exogenous high-dose glucocorticoids on insulin target tissues and systemic energy metabolism are mediated, at least in part, through the skeleton. PMID:23093779

  15. Neurological adverse effects of methylphenidate may be misdiagnosed as meningoencephalitis.

    PubMed

    Snell, Luke Blagdon; Bakshi, Dinkar

    2015-06-16

    We present a case of adverse neurological effects of methylphenidate therapy for attention deficit and hyperactivity disorder (ADHD). A 7-year-old boy presented to the emergency department (ED) having developed ataxic gait, orofacial dyskinesias and choreoathetosis of the limbs. The results of all blood investigations, EEG and CT scan of the head were unremarkable. Subsequently, a detailed history revealed he was being treated for ADHD, being started on methylphenidate in the past 3 months. Discontinuation of methylphenidate led to significant and rapid amelioration of neurological adverse effects.

  16. The Useage of Opioids and their Adverse Effects in Gastrointestinal Practice: A Review

    PubMed Central

    Khansari, MahmoudReza; Sohrabi, MasourReza; Zamani, Farhad

    2013-01-01

    Opium is one of the oldest herbal medicines currently used as an analgesic, sedative and antidiarrheal treatment. The effects of opium are principally mediated by the μ-, κ- and δ-opioid receptors. Opioid substances consist of all natural and synthetic alkaloids that are derived from opium. Most of their effects on gastrointestinal motility and secretion result from suppression of neural activity. Inhibition of gastric emptying, increase in sphincter tone, changes in motor patterns, and blockage of peristalsis result from opioid use. Common adverse effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, dependency and tolerance, and respiratory depression. The most common adverse effect of opioid use is constipation. Although stool softeners are frequently used to decrease opioid-induced bowel dysfunction, however they are not efficacious. Possibly, the use of specific opioid receptor antagonists is a more suitable approach. Opioid antagonists, both central and peripheral, could affect gastrointestinal function and visceromotor sensitivity, which suggests an important role for endogenous opioid peptides in the control of gastrointestinal physiology. Underlying diseases or medications known to influence the central nervous system (CNS) often accelerate the opioid’s adverse effects. However, changing the opioid and/or route of administration could also decrease their adverse effects. Appropriate patient selection, patient education and discussion regarding potential adverse effects may assist physicians in maximizing the effectiveness of opioids, while reducing the number and severity of adverse effects. PMID:24829664

  17. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental...

  18. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental...

  19. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental...

  20. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental...

  1. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) IDENTIFICATION AND PROTECTION OF UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION Initially Determining What Information Is Unclassified Controlled Nuclear Information §...

  2. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) IDENTIFICATION AND PROTECTION OF UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION Initially Determining What Information Is Unclassified Controlled Nuclear Information §...

  3. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) IDENTIFICATION AND PROTECTION OF UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION Initially Determining What Information Is Unclassified Controlled Nuclear Information §...

  4. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) IDENTIFICATION AND PROTECTION OF UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION Initially Determining What Information Is Unclassified Controlled Nuclear Information §...

  5. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) IDENTIFICATION AND PROTECTION OF UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION Initially Determining What Information Is Unclassified Controlled Nuclear Information §...

  6. Skin-lightening cosmetics: frequent, potentially severe adverse effects.

    PubMed

    2011-09-01

    Skin-lightening cosmetics are used by many women and men around the world. The products contain a variety of substances, which are often unknown to the users. Most of these products include topical corticosteroids, hydroquinone and mercury salts. Many other substances may be added. Several surveys and cohort studies, including several thousand individuals, have shown that regular application of skin-lightening cosmetics to large surface areas can have irreversible cutaneous adverse effects, such as patchy hyper- or hypopigmentation, skin atrophy, stretch marks and delayed wound healing, and can also mask or, on the contrary, promote or reactivate skin infections. Cases of skin cancer have been attributed to skin-lightening cosmetics. A Senegalese cohort study of 147 women showed a statistically significant increase in the risk of hypertension and diabetes linked to the use of skin-lightening agents. Other systemic adverse effects attributed to skin-lightening cosmetics include Cushing's syndrome, adrenal insufficiency, nephrotic syndrome, neurological disorders, and ocular disorders. Hypersensitivity reactions, including anaphylaxis, have also been attributed to these products. Many skin-lightening cosmetics contain substances that can harm the unborn child. For example, tretinoin is teratogenic while salicylic acid is feto-toxic. In practice, users are often unaware of the risk of severe adverse effects associated with skin-lightening cosmetics. Users should be informed of these adverse effects and encouraged to stop using these products, especially when skin disorders appear.

  7. 36 CFR 800.5 - Assessment of adverse effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.5 Assessment of adverse effects. (a) Apply... have been identified subsequent to the original evaluation of the property's eligibility for the... qualities of a property of religious and cultural significance to an Indian tribe or Native...

  8. Ziconotide: new drug. Limited analgesic efficacy, too many adverse effects.

    PubMed

    2008-10-01

    (1) When oral morphine does not relieve severe pain and when there is no specific treatment for the underlying cause, the first option is to try subcutaneous or intravenous administration. If this standard treatment fails or is poorly tolerated, intrathecal injection is usually preferred as the direct route to the central nervous system. However, one-quarter to one-half of patients still do not achieve adequate pain relief, and adverse effects are relatively frequent; (2) Ziconotide is not an opiate and is not related to the usual classes of drugs that interfere with nervous transmission in the posterior horn of the spinal cord. Marketing authorization has been granted for "severe, chronic pain in patients who require intrathecal analgesia". The Summary of Product Characteristics (SPC) recommends continuous infusion via an intrathecal catheter connected to a pump; (3) Clinical evaluation of ziconotide does not include any trials versus morphine in patients with nociceptive pain, or any trials versus tricyclic or antiepileptic drugs in patients with neurogenic pain; (4) In a trial in 220 patients in whom systemic morphine had failed, the mean pain score on a 100-mm visual analogue scale was 69.8 mm after three weeks on ziconotide, compared to 75.8 mm with placebo. This difference, although statistically significant, is clinically irrelevant. The proportion of "responders" (reduction of at least 30% in the initial pain score) was respectively 16.1% and 12.0% (no statistically significant difference); (5) The two other placebo-controlled trials included 112 patients with pain linked to cancer or HIV infection, and 257 patients with non-cancer pain. After a titration phase lasting 5 to 6 days, a combined analysis of the two trials showed that the mean pain score was 48.8 mm with ziconotide and 68.4 mm with placebo (statistically significant difference). However, many patients did not complete the titration phase. Efficacy also appeared to differ according to the type

  9. Mixed-effects Poisson regression analysis of adverse event reports

    PubMed Central

    Gibbons, Robert D.; Segawa, Eisuke; Karabatsos, George; Amatya, Anup K.; Bhaumik, Dulal K.; Brown, C. Hendricks; Kapur, Kush; Marcus, Sue M.; Hur, Kwan; Mann, J. John

    2008-01-01

    SUMMARY A new statistical methodology is developed for the analysis of spontaneous adverse event (AE) reports from post-marketing drug surveillance data. The method involves both empirical Bayes (EB) and fully Bayes estimation of rate multipliers for each drug within a class of drugs, for a particular AE, based on a mixed-effects Poisson regression model. Both parametric and semiparametric models for the random-effect distribution are examined. The method is applied to data from Food and Drug Administration (FDA)’s Adverse Event Reporting System (AERS) on the relationship between antidepressants and suicide. We obtain point estimates and 95 per cent confidence (posterior) intervals for the rate multiplier for each drug (e.g. antidepressants), which can be used to determine whether a particular drug has an increased risk of association with a particular AE (e.g. suicide). Confidence (posterior) intervals that do not include 1.0 provide evidence for either significant protective or harmful associations of the drug and the adverse effect. We also examine EB, parametric Bayes, and semiparametric Bayes estimators of the rate multipliers and associated confidence (posterior) intervals. Results of our analysis of the FDA AERS data revealed that newer antidepressants are associated with lower rates of suicide adverse event reports compared with older antidepressants. We recommend improvements to the existing AERS system, which are likely to improve its public health value as an early warning system. PMID:18404622

  10. Indoor air pollution: Acute adverse health effects and host susceptibility

    SciTech Connect

    Zummo, S.M.; Karol, M.H.

    1996-01-01

    Increased awareness of the poor quality of indoor air compared with outdoor air has resulted in a significant amount of research on the adverse health effects and mechanisms of action of indoor air pollutants. Common indoor air agents are identified, along with resultant adverse health effects, mechanisms of action, and likely susceptible populations. Indoor air pollutants range from biological agents (such as dust mites) to chemical irritants (such as nitrogen dioxide, carbon monoxide, sulfur dioxide, formaldehyde, and isocyanates). These agents may exert their effects through allergic as well as nonallergic mechanisms. While the public does not generally perceive poor indoor air quality as a significant health risk, increasing reports of illness related to indoor air and an expanding base of knowledge on the health effects of indoor air pollution are likely to continue pushing the issue to the forefront.

  11. Effect of wettability on adverse mobility immiscible floods

    SciTech Connect

    Vives, M.T.; Chang, Y.C.; Mohanty, K.K.

    1995-12-31

    Many immiscible displacements in reservoirs occur at adverse mobility. Effect of wettability on these displacements is not well understood and often ignored in reservoir simulation. Recent macroscopic theories of viscous fingering treat adverse immiscible flows similar to miscible flows, the mixing in the fingered region being controlled by a Todd-Longstaff-type functional form. The wettability of the medium is taken into account only through the use of appropriate relative permeabilities. The goal of this paper is to understand the macroscopic bypassing in adverse mobility immiscible floods. Immiscible displacements are conducted in a quarter 5-spot model in both drainage and imbibition modes at similar effective mobility ratios and viscous-to-gravity numbers. The level of bypassing and gravity override is visualized and measured. Tertiary water-alternating-gas (WAG) displacements are also conducted at various WAG ratios and viscosity ratios. Fractional flow analysis and numerical simulation are used to understand these displacements. Experiments show that macroscopic viscous fingering is present in adverse viscosity immiscible displacements where no saturation shock is expected from 1-D fractional flow theory. Bypassing due to both fingering and gravity override is higher in the drainage mode than in the imbibition mode, with other key parameters being the same. Optimum WAG ratio in water-wet rock is a function of oil/solvent viscosity ratio. The macroscopic flow theory needs to include capillarity and viscous fingering to match these experimental findings.

  12. Energy Drink Consumption: Beneficial and Adverse Health Effects

    PubMed Central

    Alsunni, Ahmed Abdulrahman

    2015-01-01

    Consumption of energy drinks has been increasing dramatically in the last two decades, particularly amongst adolescents and young adults. Energy drinks are aggressively marketed with the claim that these products give an energy boost to improve physical and cognitive performance. However, studies supporting these claims are limited. In fact, several adverse health effects have been related to energy drink; this has raised the question of whether these beverages are safe. This review was carried out to identify and discuss the published articles that examined the beneficial and adverse health effects related to energy drink. It is concluded that although energy drink may have beneficial effects on physical performance, these products also have possible detrimental health consequences. Marketing of energy drinks should be limited or forbidden until independent research confirms their safety, particularly among adolescents. PMID:26715927

  13. Adverse Effects of Bisphosphonates: Implications for Osteoporosis Management

    PubMed Central

    Kennel, Kurt A.; Drake, Matthew T.

    2009-01-01

    Bisphosphonates are widely prescribed and highly effective at limiting the bone loss that occurs in many disorders characterized by increased osteoclast-mediated bone resorption, including senile osteoporosis in both men and women, glucocorticoid-associated osteoporosis, and malignancies metastatic to bone. Although they are generally well tolerated, potential adverse effects may limit bisphosphonate use in some patients. Optimal use of bisphosphonates for osteoporosis requires adequate calcium and vitamin D intake before and during therapy. The World Health Organization fracture risk assessment algorithm is currently available to determine absolute fracture risk in patients with low bone mass and is a useful tool for clinicians in identifying patients most likely to benefit from pharmacological intervention to limit fracture risk. This fracture risk estimate may facilitate shared decision making, especially when patients are wary of the rare but serious adverse effects that have recently been described for this class of drugs. PMID:19567717

  14. Energy Drink Consumption: Beneficial and Adverse Health Effects.

    PubMed

    Alsunni, Ahmed Abdulrahman

    2015-10-01

    Consumption of energy drinks has been increasing dramatically in the last two decades, particularly amongst adolescents and young adults. Energy drinks are aggressively marketed with the claim that these products give an energy boost to improve physical and cognitive performance. However, studies supporting these claims are limited. In fact, several adverse health effects have been related to energy drink; this has raised the question of whether these beverages are safe. This review was carried out to identify and discuss the published articles that examined the beneficial and adverse health effects related to energy drink. It is concluded that although energy drink may have beneficial effects on physical performance, these products also have possible detrimental health consequences. Marketing of energy drinks should be limited or forbidden until independent research confirms their safety, particularly among adolescents.

  15. Caregiver Acceptance of Adverse Effects and Use of Cholinesterase Inhibitors in Alzheimer's Disease

    ERIC Educational Resources Information Center

    Oremus, Mark; Wolfson, Christina; Vandal, Alain C.; Bergman, Howard; Xie, Qihao

    2007-01-01

    Caregivers play a determining role in choosing treatments for persons with Alzheimer's disease. The objective of this study was to examine caregivers' willingness to have persons with Alzheimer's disease continue taking cholinesterase inhibitors in the event that any 1 of 11 adverse effects was to occur. Data were gathered via postal questionnaire…

  16. Mechanisms and assessment of statin-related muscular adverse effects.

    PubMed

    Moßhammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mörike, Klaus

    2014-09-01

    Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers.

  17. A replication of the study ‘Adverse effects of spinal manipulation: a systematic review’

    PubMed Central

    2012-01-01

    Objective To assess the significance of adverse events after spinal manipulation therapy (SMT) by replicating and critically reviewing a paper commonly cited when reviewing adverse events of SMT as reported by Ernst (J Roy Soc Med 100:330–338, 2007). Method Replication of a 2007 Ernst paper to compare the details recorded in this paper to the original source material. Specific items that were assessed included the time lapse between treatment and the adverse event, and the recording of other significant risk factors such as diabetes, hyperhomocysteinemia, use of oral contraceptive pill, any history of hypertension, atherosclerosis and migraine. Results The review of the 32 papers discussed by Ernst found numerous errors or inconsistencies from the original case reports and case series. These errors included alteration of the age or sex of the patient, and omission or misrepresentation of the long term response of the patient to the adverse event. Other errors included incorrectly assigning spinal manipulation therapy (SMT) as chiropractic treatment when it had been reported in the original paper as delivered by a non-chiropractic provider (e.g. Physician). The original case reports often omitted to record the time lapse between treatment and the adverse event, and other significant clinical or risk factors. The country of origin of the original paper was also overlooked, which is significant as chiropractic is not legislated in many countries. In 21 of the cases reported by Ernst to be chiropractic treatment, 11 were from countries where chiropractic is not legislated. Conclusion The number of errors or omissions in the 2007 Ernst paper, reduce the validity of the study and the reported conclusions. The omissions of potential risk factors and the timeline between the adverse event and SMT could be significant confounding factors. Greater care is also needed to distinguish between chiropractors and other health practitioners when reviewing the application of SMT

  18. Genetic Predictors of Adverse Radiotherapy Effects: The Gene-PARE project

    SciTech Connect

    Ho, Alice Y.; Atencio, David P.; Peters, Sheila; Stock, Richard G.; Cesaretti, Jamie A.; Green, Sheryl; Formenti, Silvia C.; Haffty, Bruce; Drumea, Karen; Leitzin, Larisa M.D.; Kuten, Abraham; Azria, David; Ozsahin, Mahmut; Overgaard, Jens; Andreassen, Christian N.; Trop, Cynthia S.; Park, Janelle; Rosenstein, Barry S. |||. E-mail: barry.rosenstein@mssm.edu

    2006-07-01

    Purpose: The development of adverse effects resulting from the radiotherapy of cancer limits the use of this treatment modality. The validation of a test capable of predicting which patients would be most likely to develop adverse responses to radiation treatment, based on the possession of specific genetic variants, would therefore be of value. The purpose of the Genetic Predictors of Adverse Radiotherapy Effects (Gene-PARE) project is to help achieve this goal. Methods and Materials: A continuously expanding biorepository has been created consisting of frozen lymphocytes and DNA isolated from patients treated with radiotherapy. In conjunction with this biorepository, a database is maintained with detailed clinical information pertaining to diagnosis, treatment, and outcome. The DNA samples are screened using denaturing high performance liquid chromatography (DHPLC) and the Surveyor nuclease assay for variants in ATM, TGFB1, XRCC1, XRCC3, SOD2, and hHR21. It is anticipated that additional genes that control the biologic response to radiation will be screened in future work. Results: Evidence has been obtained that possession of variants in genes, the products of which play a role in radiation response, is predictive for the development of adverse effects after radiotherapy. Conclusions: It is anticipated that the Gene-PARE project will yield information that will allow radiation oncologists to use genetic data to optimize treatment on an individual basis.

  19. Multidisciplinary Treatments, Patient Characteristics, Context of Care, and Adverse Incidents in Older, Hospitalized Adults

    PubMed Central

    Shever, Leah L.; Titler, Marita G.

    2012-01-01

    The purpose of this study was to examine factors that contribute to adverse incidents by creating a model that included patient characteristics, clinical conditions, nursing unit context of care variables, medical treatments, pharmaceutical treatments, and nursing treatments. Data were abstracted from electronic, administrative, and clinical data repositories. The sample included older adults hospitalized during a four-year period at one, academic medical facility in the Midwestern United States who were at risk for falling. Relational databases were built and a multistep, statistical model building analytic process was used. Total registered nurse (RN) hours per patient day (HPPD) and HPPDs dropping below the nursing unit average were significant explanatory variables for experiencing an adverse incident. The number of medical and pharmaceutical treatments that a patient received during hospitalization as well as many specific nursing treatments (e.g., restraint use, neurological monitoring) were also contributors to experiencing an adverse incident. PMID:22530112

  20. Energy drink use and adverse effects among emergency department patients.

    PubMed

    Nordt, Sean Patrick; Vilke, Gary M; Clark, Richard F; Lee Cantrell, F; Chan, Theodore C; Galinato, Melissa; Nguyen, Vincent; Castillo, Edward M

    2012-10-01

    Energy drink usage is common and contains caffeine or other stimulants. We evaluated demographics, prevalence, reasons and adverse effects with consuming energy beverages. Cross-sectional study of a convenience sample of patients recruited from two San Diego Emergency Departments from January to December 2009. One-thousand-two-hundred-ninety-eight subjects participated of which 52.6% were male. Ethnicity: Caucasian 48.3%, African American 17%, Hispanic 18%, Other 16.7%. Age ranges: 18-29 years (38.4%), 30-54 years (49.6%) and greater than 55 years (12%). Reasons for use: 57% to "increase energy", 9.5% for studying/work projects, 2.4% while prolonged driving, improve sports performance 2%, with ethanol 6.3%, "other" reasons 22.1%. Adverse reactions reported by 33.5% (429) patients. Two-hundred-eighty report feeling "shaky/jittery", insomnia 136, palpitations 150, gastrointestinal upset 82, headache 68, chest pain 39, and seizures in 6. Eighty-five patients reported co-ingestion with illicit "stimulants" including cocaine and methamphetamine. We identified one-third of patients reported at least one adverse effect. Whilst most were not severe, a small number were serious e.g., seizures. In addition, some report purposely ingesting with illicit drugs.

  1. Cutaneous adverse reaction to furosemide treatment: New clinical findings

    PubMed Central

    Arribas, María Teresa Verde; Mena, Javier Miana; Pérez, Manuel Gascón

    2006-01-01

    Abstract A poodle was admitted for investigation of pruritus and a lesional pattern of erythema and alopecia located in the dorsolumbar area. After differential diagnosis ruling out several processes a rare side effect to furosemide, not yet described in canine medicine was confirmed as the possible causative agent. PMID:16808231

  2. Predictors of Spontaneous and Systematically Assessed Suicidal Adverse Events in the Treatment of SSRI Resistant Depression in Adolescents (TORDIA) Study

    PubMed Central

    Brent, David; Emslie, Graham; Clarke, Greg; Asarnow, Joan Rosenbaum; Spirito, Anthony; Ritz, Louise; Vitiello, Benedetto; Iyengar, Satish; Birmaher, Boris; Ryan, Neal; Zelazny, Jamie; Onorato, Matthew; Kennard, Betsy; Mayes, Taryn; DeBar, Lynn; McCracken, James; Strober, Michael; Suddath, Robert; Leonard, Henrietta; Porta, Giovanna; Keller, Marty

    2013-01-01

    Objective The authors sought to identify predictors of self-harm adverse events in treatment-resistant, depressed adolescents during the first 12 weeks of treatment. Method Depressed adolescents (N=334) who had not responded to a previous trial with an SSRI antidepressant were randomized to a switch to either another SSRI or venlafaxine, with or without cognitive behavior therapy. Self-harm events, i.e., suicidal and non-suicidal self-injury adverse events were assessed by spontaneous report for the first 181 participants, and by systematic weekly assessment for the last 153 participants. Results Higher rates of suicidal (20.8% vs. 8.8%) and nonsuicidal self-injury (17.6% vs. 2.2%), but not serious adverse events (8.4% vs. 7.3%) were detected with systematic monitoring. Median time to a suicidal event was 3 weeks, predicted by high baseline suicidal ideation, family conflict, and drug and alcohol use. Median time to nonsuicidal self-injury was 2 weeks, predicted by previous history of nonsuicidal self-injury. While there were no main effects of treatment, venlafaxine treatment was associated with a higher rate of self-harm adverse events in those with higher suicidal ideation. Adjunctive use of benzodiazepines, while in a small number of participants (N=10) was associated with higher rate of both suicidal and nonsuicidal self-injury adverse events. Conclusions Since predictors of suicidal adverse events also predict poor response to treatment, and many of these events occurred early in treatment, improving the speed of response to depression, by targeting of family conflict, suicidal ideation, and drug use may help to reduce their incidence. The relationship of venlafaxine and of benzodiazepines to selfharm events requires further study and clinical caution. PMID:19223438

  3. Prevalence of Adverse Effects Post-Brachytherapy on Women with Uterine Cervix Cancer in Durango, Mexico

    SciTech Connect

    Herrera, Higmar; Yanez, Elvia

    2010-12-07

    This work aimed at determining the local prevalence of adverse effects on women with CaCu that recieved LDR brachytherapy treatment at CECAN. The data was extracted from the patient's and medical physics' departement records. Non Gaussian statistics was used due to dose distribution characteristics. A total of 103 patients were studied with average age of 55{+-}13 years and Ia-IV FIGO clinical clasification. The observed prevalence is higher than that reported by other studies. It was observed that patients with proctitis were prescribed a slightly higher dose than those without adverse effects (90% confidence). Patients with proctitis also presented higher age (95% confidence) when compared with the mean of the studied population. The inverse applies to the group with other adverse effects, its average age is lower than the mean (90% confidence).

  4. Distinguishing hazards and harms, adverse drug effects and adverse drug reactions : implications for drug development, clinical trials, pharmacovigilance, biomarkers, and monitoring.

    PubMed

    Aronson, Jeffrey K

    2013-03-01

    The terms 'adverse drug effects' and 'adverse drug reactions' are commonly used interchangeably, but they have different implications. Adverse drug reactions arise when a compound (e.g. a drug or metabolite, a contaminant or adulterant) is distributed in the same place as a body tissue (e.g. a receptor, enzyme, or ion channel), and the encounter results in an adverse effect (a physiological or pathological change), which results in a clinically appreciable adverse reaction. Both the adverse effect and the adverse reaction have manifestations by which they can be recognized: adverse effects are usually detected by laboratory tests (e.g. biochemical, haematological, immunological, radiological, pathological) or by clinical investigations (e.g. endoscopy, cardiac catheterization), and adverse reactions by their clinical manifestations (symptoms and/or signs). This distinction suggests five scenarios: (i) adverse reactions can result directly from adverse effects; (ii) adverse effects may not lead to appreciable adverse reactions; (iii) adverse reactions can occur without preceding adverse effects; (iv) adverse effects and reactions may be dissociated; and (v) adverse effects and reactions can together constitute syndromes. Defining an adverse drug reaction as "an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product" suggests a definition of an adverse drug effect: "a potentially harmful effect resulting from an intervention related to the use of a medicinal product, which constitutes a hazard and may or may not be associated with a clinically appreciable adverse reaction and/or an abnormal laboratory test or clinical investigation, as a marker of an adverse reaction."

  5. Risk of adverse pregnancy and perinatal outcomes after high technology infertility treatment: a comprehensive systematic review.

    PubMed

    Palomba, Stefano; Homburg, Roy; Santagni, Susanna; La Sala, Giovanni Battista; Orvieto, Raoul

    2016-11-04

    In the literature, there is growing evidence that subfertile patients who conceived after infertility treatments have an increased risk of pregnancy and perinatal complications and this is particularly true for patients who conceived through use of high technology infertility treatments. Moreover, high technology infertility treatments include many concomitant clinical and biological risk factors. This review aims to summarize in a systematic fashion the current evidence regarding the relative effect of the different procedures for high technology infertility treatments on the risk of adverse pregnancy and perinatal outcome. A literature search up to August 2016 was performed in IBSS, SocINDEX, Institute for Scientific Information, PubMed, Web of Science and Google Scholar and an evidence-based hierarchy was used to determine which articles to include and analyze. Data on prepregnancy maternal factors, low technology interventions, specific procedures for male factor, ovarian tissue/ovary and uterus transplantation, and chromosomal abnormalities and malformations of the offspring were excluded. The available evidences were analyzed assessing the level and the quality of evidence according to the Oxford Centre for Evidence-Based Medicine guidelines and the Grading of Recommendations Assessment, Development, and Evaluation system, respectively. Current review highlights that every single procedure of high technology infertility treatments can play a crucial role in increasing the risk of pregnancy and perinatal complications. Due to the suboptimal level and quality of the current evidence, further well-designed studies are needed.

  6. Maternal adverse effects of different antenatal magnesium sulphate regimens for improving maternal and infant outcomes: a systematic review

    PubMed Central

    2013-01-01

    Background Antenatal magnesium sulphate, widely used in obstetrics to improve maternal and infant outcomes, may be associated with adverse effects for the mother sufficient for treatment cessation. This systematic review aimed to quantify maternal adverse effects attributed to treatment, assess how adverse effects vary according to different regimens, and explore women’s experiences with this treatment. Methods Bibliographic databases were searched from their inceptions to July 2012 for studies of any design that reported on maternal adverse effects associated with antenatal magnesium sulphate given to improve maternal or infant outcomes. Primary outcomes were life-threatening adverse effects of treatment (death, cardiac arrest, respiratory arrest). For randomised controlled trials, data were meta-analysed, and risk ratios (RR) pooled using fixed-effects or random-effects models. For non-randomised studies, data were tabulated by design, and presented as RR, odds ratios or percentages, and summarised narratively. Results A total of 143 publications were included (21 randomised trials, 15 non-randomised comparative studies, 32 case series and 75 reports of individual cases), of mixed methodological quality. Compared with placebo or no treatment, magnesium sulphate was not associated with an increased risk of maternal death, cardiac arrest or respiratory arrest. Magnesium sulphate significantly increased the risk of 'any adverse effects’ overall (RR 4.62, 95% CI 2.42-8.83; 4 trials, 13,322 women), and treatment cessation due to adverse effects (RR 2.77; 95% CI 2.32-3.30; 5 trials, 13,666 women). Few subgroup differences were observed (between indications for use and treatment regimens). In one trial, a lower dose regimen (2 g/3 hours) compared with a higher dose regimen (5 g/4 hours) significantly reduced treatment cessation (RR 0.05; 95% CI 0.01-0.39, 126 women). Adverse effect estimates from studies of other designs largely supported data from randomised

  7. Lycopersicon esculentum (Tomato) Prevents Adverse Effects of Lead on Blood Constituents

    PubMed Central

    SALAWU, Emmanuel O

    2010-01-01

    Background: Lead is known for its adverse effects on various organs and systems. In this study, the ability of lead to adversely affect blood parameters was investigated, and Lycopersicon esculentum, or commonly known as tomato (a source of antioxidants), was administered orally in the form of tomato paste (TP) to reduce the adverse effects of lead. Methods: The study involved 56 Wistar rats divided equally into 4 groups of 14 rats each: Control, LAG, TPG, and LA+TPG. Control and TPG rats were given distilled water ad libitum, while LAG and LA+TPG rats were given 1% lead (II) acetate (LA) per day. TPG and LA+TPG rats were additionally treated with 1.5 ml of TP per day. All treatments lasted for 10 weeks, after which the rats were weighed and sacrificed, and haematological and biochemical parameters were measured. The independent samples t test was used to analyse the results. Results: Lead caused significant reductions in the following parameters: weight; packed cell volume; red blood cell and white blood cell counts; the percentages of lymphocytes and monocytes; total serum protein, albumin, and globulin levels; and plasma superoxide dismutase and catalase activities. In contrast, lead caused a significant increase in the percentage of neutrophils and the plasma malondialdehyde concentration. TP, however, significantly prevented the adverse effects of LA. Conclusion: The oral administration of TP prevents the adverse effects of lead on blood constituents. PMID:22135544

  8. Adverse health effects of anabolic-androgenic steroids.

    PubMed

    van Amsterdam, Jan; Opperhuizen, Antoon; Hartgens, Fred

    2010-06-01

    Anabolic-androgenic steroids (AAS) are synthetic drugs derived from testosterone. Illegally, these drugs are regularly self-administered by body builders and power lifters to enhance their sportive performance. Adverse side effects of AAS include sexual dysfunction, alterations of the cardiovascular system, psyche and behavior, and liver toxicity. However, severe side effects appear only following prolonged use of AAS at high dose and their occurrence is limited. Occasionally, AAS abuse may be linked to certain social and psychological traits of the user, like low self-esteem, low self-confidence, suffered hostility, childhood conduct disorder, and tendency to high-risk behavior. The overwhelming stereotype about AAS is that these compounds cause aggressive behavior in males. However, the underlying personality traits of a specific subgroup of the AAS abusers, who show aggression and hostility, may be relevant, as well. Use of AAS in combination with alcohol largely increases the risk of violence and aggression. The dependence liability of AAS is very low, and withdrawal effects are relatively mild. Based on the scores for acute and chronic adverse health effects, the prevalence of use, social harm and criminality, AAS were ranked among 19 illicit drugs as a group of drugs with a relatively low harm.

  9. Macrophages are involved in hexachlorobenzene-induced adverse immune effects

    SciTech Connect

    Ezendam, Janine . E-mail: Janine.Ezendam@rivm.nl; Kosterman, Kevin; Spijkerboer, Henneke; Bleumink, Rob; Hassing, Ine; Rooijen, Nico van; Vos, Joseph G.; Pieters, Raymond

    2005-11-15

    Hexachlorobenzene (HCB) is a persistent environmental pollutant that causes adverse immune effects in man and rat. The Brown Norway (BN) rat is very susceptible to HCB-induced immunopathology and oral exposure causes inflammatory skin and lung lesions, splenomegaly, lymph node (LN) enlargement, and increased serum levels of IgE and anti-ssDNA IgM. T cells play an important role but do not account for all adverse effects induced by HCB. Macrophages are probably also important and the relationship between macrophages and T cells was further investigated. To eliminate macrophages clodronate-liposomes were used. Furthermore, a kinetic study was performed to obtain insight in the early phase of the HCB-induced immune response. Also, experiments were performed to detect specific memory T cells. Therefore, an adoptive transfer study was performed. Our results indicate that macrophages are indeed involved in HCB-induced skin lesions, lung eosinophilia, and elevation of IgM against ssDNA. Kinetics showed that both skin and lung lesions appeared early after exposure. Moreover, immune effects could not be adaptively transferred. Thus, both macrophages and T cells are involved in HCB-induced immune effects but HCB exposure does not lead to specific T cell sensitization. Presumably, HCB exposure induces macrophage activation, thereby generating adjuvant signals that polyclonally stimulate T cells. Together, these events may lead to the observed immunopathology in BN rats.

  10. Adverse Psychiatric Effects Associated with Herbal Weight-Loss Products

    PubMed Central

    Bersani, F. Saverio; Coviello, Marialuce; Imperatori, Claudio; Francesconi, Marta; Hough, Christina M.; Valeriani, Giuseppe; De Stefano, Gianfranco; Bolzan Mariotti Posocco, Flaminia; Santacroce, Rita; Minichino, Amedeo; Corazza, Ornella

    2015-01-01

    Obesity and overeating are among the most prevalent health concerns worldwide and individuals are increasingly using performance and image-enhancing drugs (PIEDs) as an easy and fast way to control their weight. Among these, herbal weight-loss products (HWLPs) often attract users due to their health claims, assumed safety, easy availability, affordable price, extensive marketing, and the perceived lack of need for professional oversight. Reports suggest that certain HWLPs may lead to onset or exacerbation of psychiatric disturbances. Here we review the available evidence on psychiatric adverse effects of HWLPs due to their intrinsic toxicity and potential for interaction with psychiatric medications. PMID:26457296

  11. [Progresses on adverse health effects of automobile exhaust].

    PubMed

    Cheng, Yibin; Jin, Yinlong; Liu, Yingchun

    2003-09-01

    The progresses on the latest studies at home and abroad on adverse health effects of automobile exhaust were reviewed in this paper. Particulates and poisonous gases from automobile exhaust were considered to be harmful to respiratory system, immune system and reproductive system. It showed that increased prevalence of respiratory disease (e.g. chronic bronchitis and asthma), and decreased lung function, immunity were associated with automobile exhaust. The carcinogenic potential from the exposure to automobile exhausts needs to be further explored because the carcinogenesis is multifactorial.

  12. Diagnosis and Treatment of Adverse Local Tissue Reactions at the Head-Neck Junction.

    PubMed

    Cooper, Herbert J

    2016-07-01

    Modular junctions in total hip arthroplasty are susceptible to mechanically assisted crevice corrosion, leading to the release of metal wear debris. Adverse local tissue reactions result from an immune-mediated biological reaction to this debris and can have a profound effect on the surrounding periarticular soft tissue envelope. Patients often present with pain or muscle weakness and demonstrate elevated serum cobalt and chromium levels. Serum inflammatory markers and synovial fluid tests help distinguish these reactions from deep infection in the majority of cases; however, the presence of amorphous material or fragmented cells can lead to difficulty in some cases. Advanced cross-sectional imaging is essential in establishing the diagnosis. Early revision surgery is generally the treatment of choice for symptomatic adverse local tissue reaction from corrosion at the modular head-neck junction. The existing stem is retained, and a new ceramic head is placed on the existing trunnion whenever possible. This strategy generally leads to short-term improvement of symptoms with reliable clinical outcomes; however, longer term results are presently lacking.

  13. Adverse effects of bisphenol A on male reproductive function.

    PubMed

    Manfo, Faustin Pascal Tsagué; Jubendradass, Rajamanickam; Nantia, Edouard Akono; Moundipa, Paul Fewou; Mathur, Premendu Prakash

    2014-01-01

    BPA is a ubiquitous environmental contaminant, resulting mainly from manufacturing,use or disposal of plastics of which it is a component, and the degradation of industrial plastic-related wastes. Growing evidence from research on laboratory animals, wildlife, and humans supports the view that BPA produces an endocrine disrupting effect and adversely affects male reproductive function. To better understand the adverse effects caused by exposure to BPA, we performed an up-to-date literature review on the topic, with particular emphasis on in utero exposure, and associated effects on spermatogenesis, steroidogenesis, and accessory organs.BPA studies on experimental animals show that effects are generally more detrimental during in utero exposure, a critical developmental stage for the embryo. BPA has been found to produce several defects in the embryo, such as feminization of male fetuses, atrophy of the testes and epididymides, increased prostate size, shortening of AGD, disruption of BTB, and alteration of adult sperm parameters (e.g.,sperm count, motility, and density). BPA also affects embryo thyroid development.During the postnatal and pubertal periods and adulthood, BPA affects the hypothalamic-pituitary-testicular axis by modulating hormone (e.g., LH and FSH,androgen and estrogen) synthesis, expression and function of respective receptors(ER, AR). These effects alter sperm parameters. BPA also induces oxidative stress in the testis and epididymis, by inhibiting antioxidant enzymes and stimulating lipid peroxidation. This suggests that employing antioxidants may be a promising strategy to relieve BPA-induced disturbances.Epidemiological studies have also provided data indicating that BPA alters male reproductive function in humans. These investigations revealed that men occupationally exposed to BPA had high blood/urinary BPA levels, and abnormal semen parameters. BPA-exposed men also showed reduced libido and erectile ejaculatory difficulties; moreover, the

  14. Adverse effects of outdoor pollution in the elderly.

    PubMed

    Simoni, Marzia; Baldacci, Sandra; Maio, Sara; Cerrai, Sonia; Sarno, Giuseppe; Viegi, Giovanni

    2015-01-01

    With fewer newborns and people living longer, older people are making up an increasing fraction of the total population. Epidemiological evidence shows that older-age-related health problems affect a wide and expanding proportion of the world population. One of the major epidemiological trends of this century is the rise of chronic diseases that affect more elderly than younger people. A total of 3.7 million premature deaths worldwide in 2012 are attributable to outdoor air pollution; the susceptibility to adverse effects of air pollution is expected to differ widely between people and within the same person, and also over time. Frailty history, a measure of multi-system decline, modifies cumulative associations between air pollution and lung function. Moreover, pre-existing diseases may determine susceptibility. In the elderly, due to comorbidity, exposure to air pollutants may even be fatal. Rapid and not-well-planned urbanization is associated with high level of ambient air pollution, mainly caused by vehicular exhausts. In general, there is sufficient evidence of the adverse effects related to short-term exposure, while fewer studies have addressed the longer-term health effects. Increased pollution exposures have been associated with increased mortality, hospital admissions/emergency-room visits, mainly due to exacerbations of chronic diseases or to respiratory tract infections (e.g., pneumonia). These effects may also be modulated by ambient temperature and many studies show that the elderly are mostly vulnerable to heat waves. The association between heat and mortality in the elderly is well-documented, while less is known regarding the associations with hospital admissions. Chronic exposure to elevated levels of air pollution has been related to the incidence of chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), asthma, and emphysema. There is also growing evidence suggesting adverse effects on lung function related to long-term exposure

  15. Adverse effects of outdoor pollution in the elderly

    PubMed Central

    Baldacci, Sandra; Maio, Sara; Cerrai, Sonia; Sarno, Giuseppe; Viegi, Giovanni

    2015-01-01

    With fewer newborns and people living longer, older people are making up an increasing fraction of the total population. Epidemiological evidence shows that older-age-related health problems affect a wide and expanding proportion of the world population. One of the major epidemiological trends of this century is the rise of chronic diseases that affect more elderly than younger people. A total of 3.7 million premature deaths worldwide in 2012 are attributable to outdoor air pollution; the susceptibility to adverse effects of air pollution is expected to differ widely between people and within the same person, and also over time. Frailty history, a measure of multi-system decline, modifies cumulative associations between air pollution and lung function. Moreover, pre-existing diseases may determine susceptibility. In the elderly, due to comorbidity, exposure to air pollutants may even be fatal. Rapid and not-well-planned urbanization is associated with high level of ambient air pollution, mainly caused by vehicular exhausts. In general, there is sufficient evidence of the adverse effects related to short-term exposure, while fewer studies have addressed the longer-term health effects. Increased pollution exposures have been associated with increased mortality, hospital admissions/emergency-room visits, mainly due to exacerbations of chronic diseases or to respiratory tract infections (e.g., pneumonia). These effects may also be modulated by ambient temperature and many studies show that the elderly are mostly vulnerable to heat waves. The association between heat and mortality in the elderly is well-documented, while less is known regarding the associations with hospital admissions. Chronic exposure to elevated levels of air pollution has been related to the incidence of chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), asthma, and emphysema. There is also growing evidence suggesting adverse effects on lung function related to long-term exposure

  16. Adverse health effects of high-effort/low-reward conditions.

    PubMed

    Siegrist, J

    1996-01-01

    In addition to the person-environment fit model (J. R. French, R. D. Caplan, & R. V. Harrison, 1982) and the demand-control model (R. A. Karasek & T. Theorell, 1990), a third theoretical concept is proposed to assess adverse health effects of stressful experience at work: the effort-reward imbalance model. The focus of this model is on reciprocity of exchange in occupational life where high-cost/low-gain conditions are considered particularly stressful. Variables measuring low reward in terms of low status control (e.g., lack of promotion prospects, job insecurity) in association with high extrinsic (e.g., work pressure) or intrinsic (personal coping pattern, e.g., high need for control) effort independently predict new cardiovascular events in a prospective study on blue-collar men. Furthermore, these variables partly explain prevalence of cardiovascular risk factors (hypertension, atherogenic lipids) in 2 independent studies. Studying adverse health effects of high-effort/low-reward conditions seems well justified, especially in view of recent developments of the labor market.

  17. Symptomatic sinus bradycardia: A rare adverse effect of intravenous ondansetron

    PubMed Central

    Moazzam, Md Shahnawaz; Nasreen, Farah; Bano, Shahjahan; Amir, Syed Hussain

    2011-01-01

    Ondansetron is a serotonin receptor antagonist which has been used frequently to reduce the incidence of post-operative nausea and vomiting in laparoscopic surgery. It has become very popular drug for the prevention of post-operative nausea and vomiting due to its superiority in-terms of efficacy as well as lack of side effects and drug interactions. Although cardiovascular adverse effects of this drug are rare, we found a case of symptomatic sinus bradycardia in a 43-year-old female patient, going for laparoscopic cholecystectomy, who developed the same after she was given intravenous ondansetron in operation theater during premedication. Hence, we report this case, as the rare possibility of encountering bradycardia effect after intravenous administration of ondansetron should be born in mind. PMID:21655029

  18. Possible adverse effects of frying with vegetable oils.

    PubMed

    Dobarganes, Carmen; Márquez-Ruiz, Gloria

    2015-04-01

    The question of whether heated fats in the diet may be detrimental to health is nowadays of the upmost concern, but finding an answer is not easy and requires careful consideration of different aspects of lipid oxidation. This review is divided into two sections. The first part deals with the nature of the new compounds formed at high temperature in the frying process as well as their occurrence in the diet while the second part focuses on their possible nutritional and physiological effects. Oxidation products present in abused frying fats and oils are the compounds most suspected of impairing the nutritional properties of the oils or involving adverse physiological effects. The recent studies on their health implications include those related to their fate and those focused on their effects in metabolic pathways and the most prevalent diseases.

  19. Cutaneous Adverse Events Associated with Interferon-β Treatment of Multiple Sclerosis.

    PubMed

    Kolb-Mäurer, Annette; Goebeler, Matthias; Mäurer, Mathias

    2015-07-02

    Interferons are widely used platform therapies as disease-modifying treatment of patients with multiple sclerosis. Although interferons are usually safe and well tolerated, they frequently cause dermatological side effects. Here, we present a multiple sclerosis (MS) patient treated with interferon-β who developed new-onset psoriasis. Both her MS as well as her psoriasis finally responded to treatment with fumarates. This case illustrates that interferons not only cause local but also systemic adverse events of the skin. These systemic side effects might indicate that the Th17/IL-17 axis plays a prominent role in the immunopathogenesis of this individual case and that the autoimmune process might be deteriorated by further administration of interferons. In conclusion, we think that neurologists should be aware of systemic cutaneous side effects and have a closer look on interferon-associated skin lesions. Detection of psoriasiform lesions might indicate that interferons are probably not beneficial in the individual situation. We suggest that skin lesions may serve as biomarkers to allocate MS patients to adequate disease-modifying drugs.

  20. Adverse testicular effects of Botox® in mature rats

    SciTech Connect

    Breikaa, Randa M.; Mosli, Hisham A.; Nagy, Ayman A.; Abdel-Naim, Ashraf B.

    2014-03-01

    Botox® injections are taking a consistently increasing place in urology. Intracremasteric injections, particularly, have been applied for cryptorchidism and painful testicular spasms. Studies outlining their safety for this use are, however, scanty. Thus, the present study aimed at evaluating possible testicular toxicity of Botox® injections and their effect on male fertility. Mature rats were given intracremasteric Botox® injections (10, 20 and 40 U/kg) three times in a two-week interval. Changes in body and testes weights were examined and gonadosomatic index compared to control group. Semen quality, sperm parameters, fructose, protein, cholesterol and triglycerides contents were assessed. Effects on normal testicular function were investigated by measuring testosterone levels and changes in enzyme activities (lactate dehydrogenase-X and acid phosphatase). To draw a complete picture, changes in oxidative and inflammatory states were examined, in addition to the extent of connective tissue deposition between seminiferous tubules. In an attempt to have more accurate information about possible spermatotoxic effects of Botox®, flowcytometric analysis and histopathological examination were carried out. Botox®-injected rats showed altered testicular physiology and function. Seminiferous tubules were separated by dense fibers, especially with the highest dose. Flowcytometric analysis showed a decrease in mature sperms and histopathology confirmed the findings. The oxidative state was, however, comparable to control group. This study is the first to show that intracremasteric injections of Botox® induce adverse testicular effects evidenced by inhibited spermatogenesis and initiation of histopathological changes. In conclusion, decreased fertility may be a serious problem Botox® injections could cause. - Highlights: • Botox® injections are the trend nowadays, for both medical and non-medical uses. • They were recently suggested for cryptorchidism and

  1. Managing treatment-related adverse events associated with egfr tyrosine kinase inhibitors in advanced non-small-cell lung cancer

    PubMed Central

    Hirsh, V.

    2011-01-01

    Non-small-cell lung cancer (nsclc) has the highest prevalence of all types of lung cancer, which is the second most common cancer and the leading cause of cancer-related mortality in Canada. The need for more effective and less toxic treatment options for nsclc has led to the development of agents targeting the epidermal growth factor receptor (egfr)–mediated signalling pathway, such as egfr tyrosine kinase inhibitors (egfr-tkis). Although egfr-tkis are less toxic than traditional anti-neoplastic agents, they are commonly associated with acneiform-like rash and diarrhea. This review summarizes the clinical presentation and causes of egfr-tki–induced rash and diarrhea, and presents strategies for effective assessment, monitoring, and treatment of these adverse effects. Strategies to improve the management of egfr-tki–related adverse events should improve clinical outcomes, compliance, and quality of life in patients with advanced nsclc. PMID:21655159

  2. Post-Finasteride Adverse Effects in Male Androgenic Alopecia: A Case Report of Vitiligo.

    PubMed

    Motofei, Ion G; Rowland, David L; Georgescu, Simona R; Tampa, Mircea; Paunica, Stana; Constantin, Vlad D; Balalau, Cristian; Manea, Mirela; Baleanu, Bogdan C; Sinescu, Ioanel

    2017-01-01

    Finasteride has proved to be relatively safe and effective in the therapeutic management of male androgenic alopecia. However, literature data report several endocrine imbalances inducing various adverse effects, which often persist after treatment cessation in the form of post-finasteride syndrome. Here we present the case of a 52-year-old man receiving finasteride (1 mg/day) who developed an uncommon adverse effect represented by generalized vitiligo 2 months after finasteride discontinuation. Associated adverse effects encountered were represented by mild sexual dysfunction (as determined by the International Index of Erectile Function, IIEF) and moderate depressive symptoms (according to DSM-V criteria), all of these manifestations aggregating within/as a possible post-finasteride syndrome. Further studies should develop and compare several therapeutic approaches, taking into account not only compounds that decrease the circulating dihydrotestosterone level but also those that could block the dihydrotestosterone receptors (if possible, compounds with selective tropism towards the skin). In addition, the possibility of predicting adverse effects of finasteride (according to hand preference and sexual orientation) should be taken into account.

  3. Denosumab. Limited efficacy in fracture prevention, too many adverse effects.

    PubMed

    2011-06-01

    The standard drug for postmenopausal osteoporotic women with a high risk of fracture is alendronic acid, used in conjunction with non-drug measures. There are no drugs with demonstrated efficacy on the risk of fracture in castrated men with prostate cancer. Denosumab, a monoclonal antibody that inhibits a cytokine acting mainly on bone cells and lymphocytes, has been authorised in the European Union for use in both these settings. There are no trials comparing denosumab versus alendronic acid for symptomatic fracture prevention. In two trials involving 1189 and 504 women, the incidence of clinical fractures, recorded as simple adverse effects, did not differ significantly between the groups. In a placebo-controlled trial in about 7900 elderly osteoporotic women, denosumab significantly reduced the incidence of symptomatic vertebral fractures (0.8% versus 2.6% after 3 years) and hip fractures (0.7% versus 1.2%). An indirect comparison, providing weak evidence, suggests that denosumab is less effective than alendronic acid. In a placebo-controlled trial in 1468 castrated men with prostate cancer, denosumab did not reduce the incidence of symptomatic fractures after 3 years. Only the incidence of vertebral fractures, detected on routine radiographs, showed a statistically significant decline (1.5% versus 3.5%). Denosumab has numerous adverse effects. In placebo-controlled trials, this monoclonal antibody was associated with a higher incidence of deep-seated infections such as endocarditis, cancer, and skin rash. More data are needed on the risk of pancreatitis, long-term bone disorders (atypical fractures, delayed fracture healing, osteonecrosis of the jaw), hypocalcaemia and cataracts, all of which were reported in clinical trials. In practice, denosumab is not sufficiently effective to outweigh its established and potential risks in postmenopausal osteoporotic women or in castrated men with prostate cancer.

  4. Potential adverse effects of oseltamivir in rats: males are more vulnerable than females.

    PubMed

    El-Sayed, Wael M; Al-Kahtani, Mohamed Ali

    2011-09-01

    Oseltamivir is the most widely used antiviral drug for the treatment and prophylaxis of influenza. However, not much is known about its adverse effects. The potential side effects were investigated in male and female rats (140-170 g). Oseltamivir was administered at 2.2 mg·kg(-1)·day(-1) for 5 days. For both genders, treatment with oseltamivir resulted in significant reductions in the hepatic activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase. Also for both genders, oseltamivir produced modest reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic glutathione content. For both genders, neither the kidney functions nor protein profile was affected by oseltamivir. Oseltamivir also caused significant elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the activity of γ-glutamyl transpeptidase, in both genders. For male animals only, oseltamivir treatment elevated the serum level of total cholesterol as well as the activity of serum alanine aminotransferase, and reduced the hepatic activities of superoxide dismutase and catalase. Oseltamivir caused oxidative stress and acute toxicity in the liver, and disrupted the cholesterol and lipid metabolism but was less likely to cause serious drug interactions. There was a sexual differentiation in these adverse effects, with adverse effects being more evident in male rats.

  5. Penicillamine revisited: historic overview and review of the clinical uses and cutaneous adverse effects.

    PubMed

    Ishak, Rim; Abbas, Ossama

    2013-06-01

    Penicillamine is a well-known heavy metal chelator, classically used in the treatment of Wilson disease, rheumatoid arthritis, and cystinuria. From a dermatologic standpoint, penicillamine was found to be useful in the treatment of systemic sclerosis. The successful therapeutic uses of penicillamine have been hindered by its numerous adverse effects, both cutaneous and extra-cutaneous. It is a unique drug since it provokes a diversity of dermatologic manifestations that include (1) acute hypersensitivity reactions, (2) dermopathies characterized by elastic fiber abnormalities including elastosis perforans serpiginosa and pseudo-pseudoxanthoma elasticum, (3) autoimmune disorders such as pemphigus and penicillamine-induced lupus erythematosus-like syndrome, and (4) miscellaneous dermatoses that result from undefined mechanisms. These cutaneous adverse effects may correlate with the dosage and duration of penicillamine therapy as well as the disease being treated.

  6. [Asthma and polyposis. Efficacy and adverse effect of endonasal ethmoidectomy. Results apropos of 70 patients].

    PubMed

    Korchia, D; Thomassin, J M; Doris, J M; Badier, M

    1992-01-01

    The authors report the efficacy and adverse effects of intranasal ethmoidectomy in 70 patients with asthma and persistent severe symptoms from nasosinal polyposis despite repeated prior treatment. The efficacy was defined according to the evolution of symptoms and endoscopic findings. Adverse effects were evaluated according to subjective clinical and therapeutic data in all 70 patients. In addition, 25 patients had complete pre and post-operative pulmonary function tests. The results confirm that intranasal micro-surgery does not increase the severity of asthma. On the other hand, no significant improvement in bronchial function was noted after ethmoidectomy. Finally, the authors emphasize the poorer results obtained in Widal's disease and the importance, after the failure of medical treatment, of using of sufficiently extensive surgical procedure in order to decrease the incidence of recurrences.

  7. Predicting Nonauditory Adverse Radiation Effects Following Radiosurgery for Vestibular Schwannoma: A Volume and Dosimetric Analysis

    SciTech Connect

    Hayhurst, Caroline; Monsalves, Eric; Bernstein, Mark; Gentili, Fred; Heydarian, Mostafa; Tsao, May; Schwartz, Michael; Prooijen, Monique van; Millar, Barbara-Ann; Menard, Cynthia; Kulkarni, Abhaya V.; Laperriere, Norm; Zadeh, Gelareh

    2012-04-01

    Purpose: To define clinical and dosimetric predictors of nonauditory adverse radiation effects after radiosurgery for vestibular schwannoma treated with a 12 Gy prescription dose. Methods: We retrospectively reviewed our experience of vestibular schwannoma patients treated between September 2005 and December 2009. Two hundred patients were treated at a 12 Gy prescription dose; 80 had complete clinical and radiological follow-up for at least 24 months (median, 28.5 months). All treatment plans were reviewed for target volume and dosimetry characteristics; gradient index; homogeneity index, defined as the maximum dose in the treatment volume divided by the prescription dose; conformity index; brainstem; and trigeminal nerve dose. All adverse radiation effects (ARE) were recorded. Because the intent of our study was to focus on the nonauditory adverse effects, hearing outcome was not evaluated in this study. Results: Twenty-seven (33.8%) patients developed ARE, 5 (6%) developed hydrocephalus, 10 (12.5%) reported new ataxia, 17 (21%) developed trigeminal dysfunction, 3 (3.75%) had facial weakness, and 1 patient developed hemifacial spasm. The development of edema within the pons was significantly associated with ARE (p = 0.001). On multivariate analysis, only target volume is a significant predictor of ARE (p = 0.001). There is a target volume threshold of 5 cm3, above which ARE are more likely. The treatment plan dosimetric characteristics are not associated with ARE, although the maximum dose to the 5th nerve is a significant predictor of trigeminal dysfunction, with a threshold of 9 Gy. The overall 2-year tumor control rate was 96%. Conclusions: Target volume is the most important predictor of adverse radiation effects, and we identified the significant treatment volume threshold to be 5 cm3. We also established through our series that the maximum tolerable dose to the 5th nerve is 9 Gy.

  8. ADVERSE PRE- AND POSTNATAL EVENTS REPORTED TO FDA IN ASSOCIATION WITH MATERNAL ATENOLOL TREATMENT IN PREGNANCY

    EPA Science Inventory

    Atenolol is a beta-adrenoreceptor blocker used for treatment of hypertension in pregnancy. This study evaluates the reporting frequency of adverse pre- and postnatal outcomes in a series of 70 cases of maternal exposure during gestation, derived from 140 reports to FDA with Ateno...

  9. Does Cannabidiol Protect Against Adverse Psychological Effects of THC?

    PubMed

    Niesink, Raymond J M; van Laar, Margriet W

    2013-10-16

    The recreational use of cannabis can have persistent adverse effects on mental health. Delta-9-tetrahydrocannabinol (THC) is the main psychoactive constituent of cannabis, and most, if not all, of the effects associated with the use of cannabis are caused by THC. Recent studies have suggested a possible protective effect of another cannabinoid, cannabidiol (CBD). A literature search was performed in the bibliographic databases PubMed, PsycINFO, and Web of Science using the keyword "cannabidiol." After removing duplicate entries, 1295 unique titles remained. Based on the titles and abstracts, an initial selection was made. The reference lists of the publications identified in this manner were examined for additional references. Cannabis is not a safe drug. Depending on how often someone uses, the age of onset, the potency of the cannabis that is used and someone's individual sensitivity, the recreational use of cannabis may cause permanent psychological disorders. Most recreational users will never be faced with such persistent mental illness, but in some individuals cannabis use leads to undesirable effects: cognitive impairment, anxiety, paranoia, and increased risks of developing chronic psychosis or drug addiction. Studies examining the protective effects of CBD have shown that CBD can counteract the negative effects of THC. However, the question remains of how the laboratory results translate to the types of cannabis that are encountered by real-world recreational users.

  10. Adverse reactions after community treatment of onchocerciasis with ivermectin in Guatemala.

    PubMed

    Zea-Flores, R; Richards, F O; González-Peralta, C; Castro Ramirez, J; Zea-Flores, G; Collins, R C; Cupp, E

    1992-01-01

    Male and female residents on a Guatemalan coffee plantation where Onchocerca volvulus infections were hyperendemic were offered oral ivermectin (100-200 micrograms/kg) as part of a community-wide treatment programme for onchocerciasis. Forty-five persons were treated and then questioned daily for 28 d about changes in their health. Those with complaints were monitored until all signs and symptoms had resolved. Sixty-seven percent complained of some adverse event after treatment; 60% developed observable adverse reactions attributed clinically to ivermectin. No reaction was life-threatening; the most common were oedema (53%) and fever (47%). Expulsion of intestinal helminths was reported by 38%. Almost all reactions began 24-48 h after treatment; their mean duration was 5 d, despite treatment with acetaminophen and antihistamines. Three patients had oedematous changes lasting over 2 weeks. Incidence, but not severity, of reactions was related to the pretreatment density of microfilariae in skin.

  11. Redox nanoparticle therapeutics to cancer--increase in therapeutic effect of doxorubicin, suppressing its adverse effect.

    PubMed

    Yoshitomi, Toru; Ozaki, Yuki; Thangavel, Sindhu; Nagasaki, Yukio

    2013-11-28

    The ultimate goal of cancer chemotherapy is to achieve a cure without causing any adverse effects. We have developed a pH-sensitive redox nanoparticle (RNP(N)), which disintegrates under acidic conditions and exposes nitroxide radicals, leading to strongly scavenging reactive oxygen species (ROS). After intravenous administration of RNP(N) to tumor bearing mice, it effectively accumulated in tumors due to the leaky neovascular and immature lymphatic system and scavenged ROS, resulting in suppression of inflammation and activation of NF-кB, after disintegration of RNP(N) in the tumors. Pre-administration of RNP(N) prior to treatments with anticancer agents, doxorubicin, to tumor-bearing mice significantly suppressed the progression of tumor size, compared to low-molecular weight 4-hydroxy-TEMPO. Interestingly, the administration of RNP(N) suppressed adverse effects of doxorubicin to normal organs due to the scavenging ROS and suppression of inflammation, which was confirmed by reduction in lactate dehydrogenase and creatine phosphokinase activities in plasma. RNP(N) is thus anticipated as a novel and ideal adjuvant for cancer chemotherapy.

  12. Safety Profile of Finasteride: Distribution of Adverse Effects According to Structural and Informational Dichotomies of the Mind/Brain.

    PubMed

    Motofei, Ion G; Rowland, David L; Manea, Mirela; Georgescu, Simona R; Păunică, Ioana; Sinescu, Ioanel

    2017-02-04

    Finasteride is currently used extensively for male androgenic alopecia and benign prostatic hyperplasia; however, some adverse effects are severe and even persistent after treatment cessation, the so-called 'post-finasteride syndrome'. The following most severe adverse effects-sexual dysfunction and depression-often occur together and may potentiate one other, a fact that could explain (at least in part) the magnitude and persistence of finasteride adverse effects. This paper presents the pharmacological action of finasteride and the corresponding adverse effects, the biological base explaining the occurrence, persistence and distribution of these adverse effects, and a possible therapeutic solution for post-finasteride syndrome. The distribution of finasteride adverse effects is presented within a comprehensive and modern neuro-endocrine perspective related to structural and informational dichotomies of the brain. Understanding the variation of finasteride side effects among different populations would be necessary not only to delineate the safety profile of finasteride for different subgroups of men (a subject may or may not be affected by a certain anti-hormonal compound dependent on the individual neuro-endocrine profile), but also as a possible premise for a therapeutic approach of finasteride adverse effects. Such therapeutic approach should include administration of exogenous hormones, which are deficient in men with post-finasteride syndrome, namely dihydrotestosterone (in right-handed men) or progesterone/dihydroprogesterone (in left-handed subjects).

  13. The Adverse Effects of Air Pollution on the Nervous System

    PubMed Central

    Genc, Sermin; Zadeoglulari, Zeynep; Fuss, Stefan H.; Genc, Kursad

    2012-01-01

    Exposure to ambient air pollution is a serious and common public health concern associated with growing morbidity and mortality worldwide. In the last decades, the adverse effects of air pollution on the pulmonary and cardiovascular systems have been well established in a series of major epidemiological and observational studies. In the recent past, air pollution has also been associated with diseases of the central nervous system (CNS), including stroke, Alzheimer's disease, Parkinson's disease, and neurodevelopmental disorders. It has been demonstrated that various components of air pollution, such as nanosized particles, can easily translocate to the CNS where they can activate innate immune responses. Furthermore, systemic inflammation arising from the pulmonary or cardiovascular system can affect CNS health. Despite intense studies on the health effects of ambient air pollution, the underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests that air pollution-induced neuroinflammation, oxidative stress, microglial activation, cerebrovascular dysfunction, and alterations in the blood-brain barrier contribute to CNS pathology. A better understanding of the mediators and mechanisms will enable the development of new strategies to protect individuals at risk and to reduce detrimental effects of air pollution on the nervous system and mental health. PMID:22523490

  14. Parenteral Lipid Tolerance and Adverse Effects: Fat Chance for Trouble?

    PubMed

    Wanten, Geert J A

    2015-09-01

    Lipid emulsions (LEs) are indispensable sources of fuel calories and (essential) fatty acids (FAs) in modern parenteral nutrition formulations. The use of LE, however, also remains associated with the development of adverse effects. Intolerance for LE mostly becomes apparent upon the development of patient complaints or disturbed blood function tests, mainly of the liver. These issues may be associated with the composition, stability, or the infusion rate of the emulsion. Also, altered balances of (anti)oxidants or the presence or absence of protective or toxic bioactive agents such as phytosterols and tocopherol in LE may lead to complications, especially in already vulnerable patients with an inflammatory condition. While the oldest available LEs are based on pure soybean oil (SO-LE), rich in the proinflammatory ω-6 polyunsaturated fatty acid linoleic acid, more recent next-generation LEs where alternative FA sources such as olive and fish oil (partially) replace soybean oil to lower the content of linoleic acid seem safe and effective. Especially LEs containing fish oil (FO-LE) have less proinflammatory characteristics that promise to convey beneficial effects on immune system and organ functions, although much of the available evidence awaits more robust clinical validation.

  15. Persistent constipation and abdominal adverse events with newer treatments for constipation

    PubMed Central

    Sonu, Irene; Triadafilopoulos, George; Gardner, Jerry D

    2016-01-01

    Background Clinical trials of several new treatments for opioid-induced constipation (OIC), chronic idiopathic constipation (CIC) and constipation-predominant irritable bowel syndrome (IBS-C) have focused on differences between subjects relieved of constipation with placebo and active treatment. Patients and clinicians however, are more interested in the probability these treatments provide actual relief of constipation and its associated symptoms. Methods We searched the medical literature using MEDLINE and Cochrane central register of controlled trials. Randomised, placebo-controlled trials that examined the use of methylnaltrexone, naloxegol, lubiprostone, prucalopride or linaclotide in adults with OIC, CIC and IBS-C were eligible for inclusion. The primary efficacy measure was relief of constipation. Adverse event data for abdominal symptoms were also analysed. Key results and findings 25 publications were included in our analyses. The proportion of constipated individuals with active treatment was significantly lower than the proportion with placebo; however, in 15 of these 20 trials analysed, a majority of patients remained constipated with active treatment. Analyses of adverse event data revealed that the percentage of participants who experienced abdominal pain, diarrhoea and flatulence with active treatment was higher than that with placebo in the majority of trials analysed. Conclusions Newer pharmacological treatments for constipation are superior to placebo in relieving constipation, but many patients receiving active treatment may remain constipated. In addition, all 5 of the treatments studied are accompanied by no change or a possible increase in the prevalence of abdominal symptoms, such as abdominal pain, diarrhoea and flatulence. PMID:27486521

  16. Identification and Characterization of Adverse Effects in 21st Century Toxicology

    EPA Science Inventory

    The ILSI Health and Environmental Sciences Institute Project Committee on Distinguishing Adverse from Non-Adverse / Adaptive Effects held a workshop in May 2011 to discuss approaches to identifying adverse effects in the context of the 2007 NRC committee report titled “Toxicity T...

  17. Quality of life and adverse effects of olanzapine versus risperidone therapy in patients with schizophrenia.

    PubMed

    Chaves, Katarina Melo; Serrano-Blanco, Antoni; Ribeiro, Susana Barbosa; Soares, Luiz Alberto Lira; Guerra, Gerlane Coelho Bernardo; do Socorro Costa Feitosa Alves, Maria; de Araújo Júnior, Raimundo Fernandes; de Paula Soares Rachetti, Vanessa; Filgueira Júnior, Antônio; de Araújo, Aurigena Antunes

    2013-03-01

    This cross-sectional study aimed to compare the effects of treatment with an atypical antipsychotic drug (olanzapine or risperidone) on quality of life (QoL) and to document adverse effects in 115 patients diagnosed with schizophrenia who attended the ambulatory service of Hospital Dr. João Machado, Natal, Rio Grande do Norte, Brazil. Socioeconomic, sociodemographic, and clinical variables were compared. The QoL Scale validated for Brazil (QLS-BR) was used to evaluate QoL, and adverse effects were assessed using the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. Data were analyzed using the χ(2) test and Student's t test, with a significance level of 5 %. Patients in both drug groups showed severe impairment in the occupational domain of the QLS-BR. Global QLS-BR scores indicated impairment among risperidone users and severe impairment among olanzapine users. The most significant side effects were associated with risperidone, including asthenia/lassitude/fatigue, somnolence/sedation, paresthesia, change in visual accommodation, increased salivation, diarrhea, orthostatic posture, palpitations/tachycardia, erythema, photosensitivity, weight loss, galactorrhea, decreased sexual desire, erectile/orgasmic dysfunction, vaginal dryness, headache, and physical dependence. QoL was impaired in patients using olanzapine and in those using risperidone. Risperidone use was associated with psychic, neurological, and autonomous adverse effects and other side effects.

  18. Systematic Review of Adverse Effects: A Further Step towards Modernization of Acupuncture in China

    PubMed Central

    Wu, Junyi; Hu, Yanmei; Zhu, Yin; Yin, Ping; Litscher, Gerhard; Xu, Shifen

    2015-01-01

    As a further step towards the modernization of acupuncture, the objective of this review was to figure out the frequency and severity of adverse complications and events in acupuncture treatment reported from 1980 to 2013 in China. All first-hand case reports of acupuncture-related complications and adverse events that could be identified in the scientific literature were reviewed and classified according to the type of complication and adverse event, circumstance of the event, and long-term patient outcome. The selected case reports were published between 1980 and 2013 in 3 databases. Relevant papers were collected and analyzed by 2 reviewers. Over the 33 years, 182 incidents were identified in 133 relevant papers. Internal organ, tissue, or nerve injury is the main complications of acupuncture especially for pneumothorax and central nervous system injury. Adverse effects also included syncope, infections, hemorrhage, allergy, burn, aphonia, hysteria, cough, thirst, fever, somnolence, and broken needles. Qualifying training of acupuncturists should be systemized and the clinical acupuncture operations should be standardized in order to effectively prevent the occurrence of acupuncture accidents, enhance the influence of acupuncture, and further popularize acupuncture to the rest of the world. PMID:26339265

  19. Adverse reactions of Achilles tendon xanthomas in three hypercholesterolemic patients after treatment intensification with niacin and bile acid sequestrants.

    PubMed

    Lakey, Wanda C; Greyshock, Nicole; Guyton, John R

    2013-01-01

    Multiple cholesterol-reducing therapies have been shown to induce the regression of tendon xanthoma in patients with familial hypercholesterolemia. We present 3 cases of adverse reactions in Achilles tendon xanthomas after the addition of niacin and bile acid sequestrants to ongoing statin therapy. Reduction in tendon dimensions and marked softening of xanthomas were interpreted as cholesterol removal from heavily infiltrated tissue sites. In 2 cases, changes in the xanthomas occurred despite only minor lipoprotein improvements, raising the possibility of direct drug effects in cholesterol-infiltrated tissue. Intriguingly, recent studies have described niacin receptor-mediated effects in macrophages. In summary, although adverse reactions in Achilles tendon xanthomas appear to be infrequent, clinicians should be aware of this phenomenon in their patients after intensifying lipid treatments, especially with the use of niacin in patients with familial hypercholesterolemia. Xanthoma responses may provide clues to new pharmacologic effects in cholesterol-infiltrated tissues.

  20. CORAL: model for no observed adverse effect level (NOAEL).

    PubMed

    Toropov, Andrey A; Toropova, Alla P; Pizzo, Fabiola; Lombardo, Anna; Gadaleta, Domenico; Benfenati, Emilio

    2015-08-01

    The in vivo repeated dose toxicity (RDT) test is intended to provide information on the possible risk caused by repeated exposure to a substance over a limited period of time. The measure of the RDT is the no observed adverse effect level (NOAEL) that is the dose at which no effects are observed, i.e., this endpoint indicates the safety level for a substance. The need to replace in vivo tests, as required by some European Regulations (registration, evaluation authorization and restriction of chemicals) is leading to the searching for reliable alternative methods such as quantitative structure-activity relationships (QSAR). Considering the complexity of the RDT endpoint, for which data quality is limited and depends anyway on the study design, the development of QSAR for this endpoint is an attractive task. Starting from a dataset of 140 organic compounds with NOAEL values related to oral short term toxicity in rats, we developed a QSAR model based on optimal descriptors calculated with simplified molecular input-line entry systems and the graph of atomic orbitals by the Monte Carlo method, using CORAL software. Three different splits into the training, calibration, and validation sets are studied. The mechanistic interpretation of these models in terms of molecular fragment with positive or negative contributions to the endpoint is discussed. The probabilistic definition for the domain of applicability is suggested.

  1. Shocking Results on the Adverse Effects of CO2 Exposures

    NASA Technical Reports Server (NTRS)

    James, John T.

    2012-01-01

    Carbon dioxide (CO2) is released in large quantities from humans while they live and work in spacecraft or work outside the spacecraft during extravehicular activity (EVA). Removal of this anthropogenic pollutant requires major resources, and these resources increase dramatically as the levels of CO2 set to protect human health and performance are reduced. The current Spacecraft Maximum Allowable Concentration of CO2 aboard the ISS is 0.7% or 5.3 mmHg; however, according to Chits (mission action requests), NASA and its international partners have agreed to control CO2 levels to less than 4 mmHg. In the meantime, retrospective investigations attempting to associate crew symptoms with elevated CO2 levels over the life if the International Space Station (ISS) are underway to determine if this level is sufficient to protect against health and performance decrements. Anecdotal reports suggest that crewmembers are not able to perform complex tasks as readily in spaceflight as they were able during ground-based training. While physiological effects of CO2 have been studied for many decades, it is only recently that the effects of CO2 on higher reasoning capabilities have been studied. The initial results are shocking. For example, one study published in the respected journal Environmental Health Perspectives showed obvious adverse effects of CO2 exposures on higher reasoning at 1.9 mmHg. The implications and limitations of this study are paramount in determining future CO2 SMACs for human spaceflight, both aboard the ISS and in exploration-class missions. Key Words: carbon dioxide, spacecraft, air quality, toxic effects

  2. Adverse testicular effects of Botox® in mature rats.

    PubMed

    Breikaa, Randa M; Mosli, Hisham A; Nagy, Ayman A; Abdel-Naim, Ashraf B

    2014-03-01

    Botox® injections are taking a consistently increasing place in urology. Intracremasteric injections, particularly, have been applied for cryptorchidism and painful testicular spasms. Studies outlining their safety for this use are, however, scanty. Thus, the present study aimed at evaluating possible testicular toxicity of Botox® injections and their effect on male fertility. Mature rats were given intracremasteric Botox® injections (10, 20 and 40 U/kg) three times in a two-week interval. Changes in body and testes weights were examined and gonadosomatic index compared to control group. Semen quality, sperm parameters, fructose, protein, cholesterol and triglycerides contents were assessed. Effects on normal testicular function were investigated by measuring testosterone levels and changes in enzyme activities (lactate dehydrogenase-X and acid phosphatase). To draw a complete picture, changes in oxidative and inflammatory states were examined, in addition to the extent of connective tissue deposition between seminiferous tubules. In an attempt to have more accurate information about possible spermatotoxic effects of Botox®, flowcytometric analysis and histopathological examination were carried out. Botox®-injected rats showed altered testicular physiology and function. Seminiferous tubules were separated by dense fibers, especially with the highest dose. Flowcytometric analysis showed a decrease in mature sperms and histopathology confirmed the findings. The oxidative state was, however, comparable to control group. This study is the first to show that intracremasteric injections of Botox® induce adverse testicular effects evidenced by inhibited spermatogenesis and initiation of histopathological changes. In conclusion, decreased fertility may be a serious problem Botox® injections could cause.

  3. [Adverse effects of selective serotonin reuptake inhibitors use during the third trimester of pregnancy and prevention guidelines].

    PubMed

    Mejías, Consuelo; Rodríguez-Pinilla, Elvira; Fernández Martín, Paloma; Martínez-Frías, María Luisa

    2007-04-21

    Selective Serotonin Reuptake Inhibitors (SSRIs) have become the drug of choice for the treatment of depression and have shown to be effective in the treatment for other mental disorders. Recently, several articles have reported about the adverse effects observed in newborns after maternal exposure to these drugs during the last trimester of pregnancy. In this work, a review of literature is presented, regarding the above mentioned adverse effects. Moreover, some guidelines for the rational use of these drugs during the last trimester of pregnancy and for the management of prenatally exposed newborns are provided.

  4. Immune-mediated Adverse Effects of Anti-CTLA-4 Antibody Therapy in Metastatic Melanoma

    PubMed Central

    Quirk, Shannon K.; Shure, Anna K.; Agrawal, Devendra K.

    2015-01-01

    Ipilimumab, an antibody that blocks cytotoxic T lymphocyte-associated antigen-4 (CTLA-4; CD152), was approved by the Food and Drug Administration (FDA) in 2011 for the treatment of unresectable stage III or IV malignant melanoma. Although the addition of this particular immunotherapy has broadened treatment options, immune-related adverse events (irAEs) are associated with ipilimumab therapy, including dermatologic effects, colitis and diarrhea, endocrine effects, hepatotoxicity, ocular effects, renal effects, neurologic effects, and others. In this article, a critical evaluation of the underlying mechanisms of irAEs associated with anti-CTLA-4 therapy is presented. Additionally, potentially beneficial effects of combinational therapies to alleviate ipilimumab-induced irAEs in malignant melanoma are discussed. Future research is warranted to elucidate the efficacy of such combination therapies as well as specific biomarkers that would help to predict a clinical response to ipilimumab in patients with malignant melanoma. PMID:26118951

  5. Periodontal Treatment Reduces Risk of Adverse Respiratory Events in Patients With Chronic Obstructive Pulmonary Disease

    PubMed Central

    Shen, Te-Chun; Chang, Pei-Ying; Lin, Cheng-Li; Chen, Chia-Hung; Tu, Chih-Yen; Hsia, Te-Chun; Shih, Chuen-Ming; Hsu, Wu-Huei; Sung, Fung-Chang; Kao, Chia-Hung

    2016-01-01

    Abstract Treatment of periodontal diseases has been associated with benefit outcomes for patients with chronic obstructive pulmonary disease (COPD). However, no population-based cohort study has been conducted. We evaluated this relationship by retrospective cohort study using a large population data. Using the National Health Insurance claims data of Taiwan, we identified 5562 COPD patients with periodontal diseases who had received periodontal treatment as the treatment group. The comparison group was selected at a 1:1 ratio matched by the propensity score estimated with age, sex, date of COPD diagnosis and periodontal treatment, and comorbidities. Both groups were followed up for 5 years to compare risks of acute exacerbation, pneumonia, and acute respiratory failure. The incidence rates of adverse respiratory events were significantly lower in the treatment group than in the comparison group: 3.79 versus 4.21 per 100 person-years for emergency room visits, 2.75 versus 3.65 per 100 person-years for hospitalizations, and 0.66 versus 0.75 per 100 person-years for intensive care unit admissions. The treatment group also had a 37% reduced risk of deaths (1.81 vs 2.87 per 100 person-years), with an adjusted hazard ratio of 0.57 (95% confidence interval 0.52–0.62). Periodontal treatment for COPD patients could reduce the risk of adverse respiratory events and mortality. The adequate periodontal health care is important for COPD patients with periodontal diseases. PMID:27196497

  6. Managing adverse events associated with vismodegib in the treatment of basal cell carcinoma.

    PubMed

    Fife, Kate; Herd, Robert; Lalondrelle, Susan; Plummer, Ruth; Strong, Amy; Jones, Sarah; Lear, John T

    2017-01-01

    Basal cell carcinomas are the most common form of skin cancer. Some develop into advanced cases not suitable for standard therapy. Vismodegib is the first-in-class oral hedgehog pathway inhibitor (which is dysregulated in 90% of basal cell carcinomas), and has demonstrated efficacy for advanced disease in clinical trials. An UK expert panel met to discuss management strategies for adverse events associated with vismodegib (most commonly taste disturbances, muscle cramps and alopecia). Managing patient expectations and implementing treatment breaks were considered important strategies. Quinine was useful to alleviate muscle cramps. For taste disturbances, food swaps alongside dietician referral were suggested. The experts concluded that these common adverse events can be successfully managed to allow optimum treatment duration of vismodegib.

  7. Enzymes approved for human therapy: indications, mechanisms and adverse effects.

    PubMed

    Baldo, Brian A

    2015-02-01

    Research and drug developments fostered under orphan drug product development programs have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of rare disorders. The introduction and regulatory approval of 20 different recombinant enzymes has enabled, often for the first time, effective enzyme-replacement therapy for some lysosomal storage disorders, including Gaucher (imiglucerase, taliglucerase, and velaglucerase), Fabry (agalsidase alfa and beta), and Pompe (alglucosidase alfa) diseases and mucopolysaccharidoses I (laronidase), II (idursulfase), IVA (elosulfase), and VI (galsulfase). Approved recombinant enzymes are also now used as therapy for myocardial infarction (alteplase, reteplase, and tenecteplase), cystic fibrosis (dornase alfa), chronic gout (pegloticase), tumor lysis syndrome (rasburicase), leukemia (L-asparaginase), some collagen-based disorders such as Dupuytren's contracture (collagenase), severe combined immunodeficiency disease (pegademase bovine), detoxification of methotrexate (glucarpidase), and vitreomacular adhesion (ocriplasmin). The development of these efficacious and safe enzyme-based therapies has occurred hand in hand with some remarkable advances in the preparation of the often specifically designed recombinant enzymes; the manufacturing expertise necessary for commercial production; our understanding of underlying mechanisms operative in the different diseases; and the mechanisms of action of the relevant recombinant enzymes. Together with information on these mechanisms, safety findings recorded so far on the various adverse events and problems of immunogenicity of the recombinant enzymes used for therapy are presented.

  8. Adverse effects of lactational exposure to chlorpyrifos in suckling rats.

    PubMed

    Mansour, S A; Mossa, A H

    2010-02-01

    The present study was undertaken to evaluate the oxidative damage, biochemical and histopathological alterations in sucking rats whose mothers were exposed to the insecticide chlorpyrifos (CPF). Dams were administered CPF, via oral route. Doses equalled 0.01 mg kg(-1) body weight (b.wt.; acceptable daily intake, ADI), 1.00 mg kg(-1) b.wt. (no observed adverse effects level, NOAEL) and 1.35 mg kg(-1) b.wt. (1/100 lethal dose [LD(50)]) from postnatal day 1 until day 20 after delivery. At two high doses of CPF, the body weight gain and relative liver and kidney weight of suckling pups were significantly decreased. Exposure of the mothers to CPF caused increase in lipid peroxidation (LPO) and decrease in superoxide dismutase (SOD) and glutathione-s-transferase (GST) in lactating pups. CPF altered the level of the marker parameters related to the liver and kidneys. Consistent histological changes were found in the liver and kidneys of the subjected pups, especially at the higher doses. The results suggested that the transfer of CPF intoxication through the mother's milk has resulted in oxidative stress and biochemical and histopathological alterations in the suckling pups. The data of this study may be considered as a contribution to the problem of lactational transfer of the relatively less persistent OP pesticides, such as CPF.

  9. Second-Generation Antipsychotics and Extrapyramidal Adverse Effects

    PubMed Central

    Jakovcevski, Igor

    2014-01-01

    Antipsychotic-induced extrapyramidal adverse effects are well recognized in the context of first-generation antipsychotic drugs. However, the introduction of second-generation antipsychotics, with atypical mechanism of action, especially lower dopamine receptors affinity, was met with great expectations among clinicians regarding their potentially lower propensity to cause extrapyramidal syndrome. This review gives a brief summary of the recent literature relevant to second-generation antipsychotics and extrapyramidal syndrome. Numerous studies have examined the incidence and severity of extrapyramidal syndrome with first- and second-generation antipsychotics. The majority of these studies clearly indicate that extrapyramidal syndrome does occur with second-generation agents, though in lower rates in comparison with first generation. Risk factors are the choice of a particular second-generation agent (with clozapine carrying the lowest risk and risperidone the highest), high doses, history of previous extrapyramidal symptoms, and comorbidity. Also, in comparative studies, the choice of a first-generation comparator significantly influences the results. Extrapyramidal syndrome remains clinically important even in the era of second-generation antipsychotics. The incidence and severity of extrapyramidal syndrome differ amongst these antipsychotics, but the fact is that these drugs have not lived up to the expectation regarding their tolerability. PMID:24995318

  10. Adverse cognitive effects of antiepileptic pharmacotherapy: Each additional drug matters.

    PubMed

    Witt, Juri-Alexander; Elger, Christian E; Helmstaedter, Christoph

    2015-11-01

    The study was set up to evaluate the impact of the total drug load of antiepileptic pharmacotherapy on cognition. Retrospective analyses were based on 834 patients with epilepsy who underwent a brief routine assessment of executive function and verbal memory (EpiTrack Plus) at our department. The total drug load was quantified in two ways: (1) number of concurrent antiepileptic drugs (AEDs) and (2) total drug load according to the defined daily dose (DDD) provided by the World Health Organization. The cognitive measures showed higher inverse correlations with the number of AEDs (executive function: r=-0.35, p<0.001; memory: r=-0.22, p<0.001) than with the total DDD (executive function: r=-0.27, p<0.001; memory: r=-0.17, p<0.001). Reanalysis with statistical control for disease severity hardly changed the aforementioned results. With each additional drug in polytherapy, we observed a significantly lower performance in executive function. In this regard an additional explorative approach revealed that regimens combining AEDs with favorable cognitive profiles were associated with higher cognitive performance. Correlations between indicators of disease severity and drug load indices were low: altogether explaining only up to 9% of the observed variance in drug load. The findings demonstrate a considerable adverse effect of a higher drug load on cognition, especially on executive functions. Simply counting the number of drugs may be sufficient as a rough estimate of the risk of side effects. However, the combination of AEDs with favorable cognitive profiles may attenuate the negative effect of the total drug load.

  11. Vitamin D mitigates the adverse effects of obesity on breast cancer in mice.

    PubMed

    Swami, Srilatha; Krishnan, Aruna V; Williams, Jasmaine; Aggarwal, Abhishek; Albertelli, Megan A; Horst, Ronald L; Feldman, Brian J; Feldman, David

    2016-04-01

    Obesity is an established risk factor for postmenopausal breast cancer (BCa), insulin resistance, and vitamin D deficiency, and all contribute to increased synthesis of mammary estrogens, the drivers of estrogen receptor-positive (ER+) BCa growth. As both dietary vitamin D and calcitriol treatments inhibit breast estrogen synthesis and signaling, we hypothesized that vitamin D would be especially beneficial in mitigating the adverse effects of obesity on ER+BCa. To assess whether obesity exerted adverse effects on BCa growth and whether vitamin D compounds could reduce these unfavorable effects, we employed a diet-induced obesity (DIO) model in ovariectomized C57BL/6 mice. Breast tumor cells originally from syngeneic Mmtv-Wnt1 transgenic mice were then implanted into the mammary fat pads of lean and obese mice. DIO accelerated the initiation and progression of the mammary tumors. Treatments with either calcitriol or dietary vitamin D reduced the adverse effects of obesity causing a delay in tumor appearance and inhibiting continued tumor growth. Beneficial actions of treatments with vitamin D or calcitriol on BCa and surrounding adipose tissue included repressed Esr1, aromatase, and Cox2 expression; decreased tumor-derived estrogen and PGE2; reduced expression of leptin receptors; and increased adiponectin receptors. We demonstrate that vitamin D treatments decreased insulin resistance, reduced leptin, and increased adiponectin signaling and also regulated the LKB1/AMPK pathway contributing to an overall decrease in local estrogen synthesis in the obese mice. We conclude that calcitriol and dietary vitamin D, acting by multiple interrelated pathways, mitigate obesity-enhanced BCa growth in a postmenopausal setting.

  12. Apoptosis May Explain the Pharmacological Mode of Action and Adverse Effects of Isotretinoin, Including Teratogenicity.

    PubMed

    Melnik, Bodo C

    2017-02-08

    Isotretinoin (13-cis retinoic acid) is the most effective sebum-suppressive drug for the treatment of severe acne. Its effect depends on sebocyte apoptosis, which results from isotretinoin-induced expression of the apoptotic protein tumour necrosis factor-related apoptosis-inducing ligand, insulin-like growth factor-binding protein-3 and neutrophil gelatinase-associated lipocalin. This review proposes that the pharmacological mode of action of isotretinoin in the treatment of severe acne, acute promyelocytic leukaemia, and neuroblastoma results from apoptosis. Furthermore, apoptosis may be the underlying and unifying mechanism of the adverse effects of isotretinoin on neural crest cells (teratogenicity), hippocampal neurones (depression), epidermal keratinocytes and mucosa cells (mucocutaneous side-effects), hair follicle cells (telogen effluvium), intestinal epithelial cells (inflammatory bowel disease), skeletal muscle cells (myalgia and release of creatine kinase), and hepatocytes (release of transaminases and very low-density lipoproteins). Genetic variants of components of the apoptotic signalling cascade, such as RARA polymorphisms, might explain variations in the magnitude of isotretinoin-induced apoptotic signalling and apparently identify subgroups of patients who experience either stronger adverse effects with isotretinoin therapy or resistance to treatment.

  13. Undesirable and adverse effects of tooth-whitening products: a review.

    PubMed

    Goldberg, Michel; Grootveld, Martin; Lynch, Edward

    2010-02-01

    Hydrogen peroxide (H(2)O(2)) is a powerful oxidising agent. It gives rise to agents known to be effective bleaching agents. The mechanisms of bleaching involve the degradation of the extracellular matrix and oxidation of chromophores located within enamel and dentin. However, H(2)O(2) produces also local undesirable effects on tooth structures and oral mucosa. In clinical conditions, the daily low-level doses used to produce tooth whitening never generate general acute and sub-acute toxic effects. Genotoxicity and carcinogenicity only occur at concentrations that are never reached during dental treatments. Some transient adverse effects have been reported on the oral mucosa and the digestive tract if the product is swallowed. Local effects may occur on the oral mucosa and dental tissues during whitening, namely, pulp sensitivity, cervical resorption, release of selected components of dental restorative materials, and alteration of the enamel surface. Most of the local effects are dependent of the technique and concentration of the product so far used, but as the results of bleaching obtained are not stable, repeated treatments add to the adverse effects. The informed decision to administer or not and the control of bleaching effects should stand in the hand of dental surgeons and certainly not as it appears at present, as cosmetics sold without any restriction despite the potential health hazards of peroxides.

  14. Evidence for adverse effect of perinatal glucocorticoid use on the developing brain

    PubMed Central

    2014-01-01

    The use of glucocorticoids (GCs) in the perinatal period is suspected of being associated with adverse effects on long-term neurodevelopmental outcomes for preterm infants. Repeated administration of antenatal GCs to mothers at risk of preterm birth may adversely affect fetal growth and head circumference. Fetal exposure to excess GCs during critical periods of brain development may profoundly modify the limbic system (primarily the hippocampus), resulting in long-term effects on cognition, behavior, memory, co-ordination of the autonomic nervous system, and regulation of the endocrine system later in adult life. Postnatal GC treatment for chronic lung disease in premature infants, particularly involving the use of dexamethasone, has been shown to induce neurodevelopmental impairment and increases the risk of cerebral palsy. In contrast to studies involving postnatal dexamethasone, long-term follow-up studies for hydrocortisone therapy have not revealed adverse effects on neurodevelopmental outcomes. In experimental studies on animals, GCs has been shown to impair neurogenesis, and induce neuronal apoptosis in the immature brains of newborn animals. A recent study has demonstrated that dexamethasone-induced hypomyelination may result from the apoptotic degeneration of oligodendrocyte progenitors in the immature brain. Thus, based on clinical and experimental studies, there is enough evidence to advice caution regarding the use of GCs in the perinatal period; and moreover, the potential long-term effects of GCs on brain development need to be determined. PMID:24778691

  15. [Usefulness and adverse effects of intrathecal metrizamide instillation (author's transl)].

    PubMed

    Masuzawa, H; Shimizu, H; Sano, K

    1979-08-01

    Radiographic quality as well as adverse effects of intrathecal metrizamide instillation was prospectively investigated in thirty-three clinical cases admitted to the department of neurosurgery, University of Tokyo Hospital, and Kantoh Teishin Hospital. Metrizamide CT cisternography was performed in fifteen cases using in most cases 10 ml of 170 mg I/ml solution through lumbar route. Eleven cases exhibited "normal" pattern CSF circulation and the remaining four, "delayed" pattern. Eight cases (53%) experienced headache, nausea, and/or vomiting several hours after the instillation. All of these belong to the "normal" pattern group. Four cases of "normal" pattern received electroencephalographic examinations before and after metrizamide instillation. Three revealed appearance of negative spike and slow wave burst or sharp waves one to twenty-four hours after the instillation, along with penetration of metrizamide into brain parenchyma. Diagnostic quality was interpreted as "good" in eleven cases. Small acoustic neurinoma, pituitary adenoma, arachnoid cyst, and subdural hygroma were diagnosed among others. Metrizamide ventriculography was done in four cases. No untoward effect of significance was attributed to metrizamide per se. Cervical myelograpy and/or CT myelography was done in fourteen cases using, in most cases, 10 ml of metrizamide 170 mgI/ml. Polytome tomography with metrizamide instillation through lateral cervical puncture was highly diagnostic, whereas, ordinary X-ray with lumbar instillation yielded less satisfactory results. CT myelography in cases of subarachnoid block required good consideration on instillation site and positioning of the patient. Six cases (50%) among twelve cases where metrizamide had run into the cranial cavity experienced headache, nausea, and/or vomiting to a lesser degree than those of cisterno graphy. Metrizamide is the first contrast agent ever made which can be safely introduced into human subarachnoid space, if administered

  16. Phentermine/topiramate for weight reduction and treatment of adverse metabolic consequences in obesity.

    PubMed

    Bays, H E; Gadde, K M

    2011-12-01

    Phentermine hydrochloride is a noradrenergic sympathetic amine approved for decades by the U.S. Food and Drug Administration (FDA) at doses as high as 37.5 mg/day for the short-term treatment of obesity. Topiramate is a sulfamate-substituted monosaccharide marketed since 1996, and approved by the FDA for seizure disorders at doses up to 400 mg/day and for the prevention of migraine headaches at doses up to 100 mg/day. Clinical trial data suggest topiramate promotes weight loss. The prescribing information of neither agent describes adverse drug interactions with the other. The controlled-release formulation of phentermine and topiramate at low, medium and full doses (with full dose containing 15 mg of phentermine hydrochloride and 92 mg of topiramate) promotes weight reduction, with clinical trial data supporting improvement in adiposopathic consequences leading to metabolic diseases. Reported adverse events with this combination agent are as expected, based upon knowledge of the individual components.

  17. Efficacy of Rasayana Avaleha as adjuvant to radiotherapy and chemotherapy in reducing adverse effects

    PubMed Central

    Vyas, Purvi; Thakar, A. B.; Baghel, M. S.; Sisodia, Arvind; Deole, Yogesh

    2010-01-01

    Cancer is the most dreadful disease affecting mankind. The available treatments such as chemotherapy and radiotherapy have cytotoxic effects, which are hazardous to the normal cells of the patient, causing many unnecessary effects. This further leads to complications of the therapy, impaired health, and deterioration of quality of life, resulting in mandatory stoppage of the treatment. In the present study, the efficacy of an Ayurvedic formulation, Rasayana Avaleha, has been evaluated as an adjuvant medication to modern radiotherapy and chemotherapy. A total of 36 cancer patients were registered in this trial and were divided into two groups, group A and group B. In group A, the patients were treated with radiotherapy and chemotherapy along with adjuvant Rasayana Avaleha (RT + CT + RA), while in group B only radiotherapy and chemotherapy (RT + CT) were given, as the control group. After assessing the results, it was observed that Rasayana Avaleha gave better results in controlling the adverse effect of chemotherapy and radiotherapy in comparison with the control group. Therefore, Rasayana Avaleha has proved to be an effective adjuvant therapy in protecting patients from the adverse effects of chemotherapy and radiotherapy. PMID:22048532

  18. Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review

    PubMed Central

    Hirshburg, Jason M.; Kelsey, Petra A.; Therrien, Chelsea A.; Gavino, A. Carlo; Reichenberg, Jason S.

    2016-01-01

    Finasteride and dutasteride, both 5-alpha reductase inhibitors, are considered first-line treatment for androgenetic hair loss in men and used increasingly in women. In each case, patients are expected to take the medications indefinitely despite the lack of research regarding long-term adverse effects. Concerns regarding the adverse effects of these medications has led the United States National Institutes of Health to add a link for post-finasteride syndrome to its Genetic and Rare Disease Information Center. Herein, the authors report the results of a literature search reviewing adverse events of 5-alpha reductase inhibitors as they relate to prostate cancer, psychological effects, sexual health, and use in women. Several large studies found no increase in incidence of prostate cancer, a possible increase of high-grade cancer when detected, and no change in survival rate with 5-alpha reductase inhibitor use. Currently, there is no direct link between 5-alpha reductase inhibitor use and depression; however, several small studies have led to depression being listed as a side effect on the medication packaging. Sexual effects including erectile dysfunction and decreased libido and ejaculate were reported in as many as 3.4 to 15.8 percent of men. To date, there are very few studies evaluating 5-alpha reductase inhibitor use in women. Risks include birth defects in male fetuses if used in pregnancy, decreased libido, headache, gastrointestinal discomfort, and isolated reports of changes in menstruation, acne, and dizziness. Overall, 5-alpha reductase inhibitors were well-tolerated in both men and women, but not without risk, highlighting the importance of patient education prior to treatment. PMID:27672412

  19. A Fatal Adverse Effect of Barbiturate Coma Therapy: Dyskalemia

    PubMed Central

    Kwon, Hyun Mook; Baek, Jin Wook; Lee, Sang Pyung

    2016-01-01

    The management guideline for traumatic brain injury (TBI) recommends high-dose barbiturate therapy to control increased intracranial pressure refractory to other therapeutic options. High-dose barbiturate therapy, however, may cause many severe side effects; the commonly recognized ones include hypotension, immunosuppression, hepatic dysfunction, renal dysfunction, and prolonged decrease of cortical activity. Meanwhile, dyskalemia remains relatively uncommon. In this study, we report the case of a hypokalemic patient with severe rebound hyperkalemia, which occurred as a result of barbiturate coma therapy administered for TBI treatment. PMID:27857927

  20. Adverse effects in children after unintentional buprenorphine exposure.

    PubMed

    Geib, Ann-Jeannette; Babu, Kavita; Ewald, Michele Burns; Boyer, Edward W

    2006-10-01

    Buprenorphine in sublingual formulation was recently introduced to the American market for treatment of opioid dependence. We report a series of 5 toddlers with respiratory and mental-status depression after unintentional buprenorphine exposure. Despite buprenorphine's partial agonist activity and ceiling effect on respiratory depression, all children required hospital admission and either opioid-antagonist therapy or mechanical ventilation. Results of routine urine toxicology screening for opioids were negative in all cases. Confirmatory testing was sent for 1 child and returned with a positive result. The increasing use of buprenorphine as a home-based therapy for opioid addiction in the United States raises public health concerns for the pediatric population.

  1. Adverse effects of drugs used in the management of constipation and diarrhoea.

    PubMed

    Gattuso, J M; Kamm, M A

    1994-01-01

    Most laxatives, if used intermittently in the absence of contraindications, are relatively safe. Bulking agents may diminish absorption of some minerals and drugs, but this is not usually clinically significant. Ispaghula can cause serious allergic reactions. The chronic ingestion of stimulant laxatives has been blamed for the development of the 'cathartic colon', but there are no definitive studies which have demonstrated this. Dantron (danthron) preparations should only be used in older patients and the terminally ill because of the risk of hepatotoxicity with this drug. Oral oxyphenisatine should no longer be used. Senna would appear to be the stimulant laxative of choice during pregnancy and lactation. Bisacodyl is the polyphenolic derivative of choice. Lactulose, sorbitol and lactilol rarely cause significant adverse effects. Magnesium salt laxatives and phosphate enemas can cause serious metabolic disturbances in babies and young children. Liquid paraffin is contraindicated if there is any risk of aspiration. Interference with the absorption of fat soluble vitamins would not appear to be clinically significant. Docusate sodium may potentiate the hepatotoxicity of other drugs, but reports of this are rare. The role of cisapride in constipation has not been established. Antidiarrhoeal drugs are second line drugs whose use is aimed at minimising inconvenience and discomfort. No antidiarrhoeals can be recommended for children under 4 years of age. Loperamide is the drug of choice in older children and adults. The atropine component of diphenoxylate/atropine combinations can cause significant adverse effects. Bismuth salicylate is an inconvenient treatment for travellers' diarrhoea as large frequent doses of the liquid formulation are needed. Some bismuth can be absorbed and there is the potential to cause encephalopathy. Octreotide, methysergide and cholestyramine have a role for specific causes of diarrhoea only. Octreotide is effective in high output states

  2. Dermal fillers in aesthetics: an overview of adverse events and treatment approaches

    PubMed Central

    Funt, David; Pavicic, Tatjana

    2013-01-01

    Background The ever-expanding range of dermal filler products for aesthetic soft tissue augmentation is of benefit for patients and physicians, but as indications and the number of procedures performed increase, the number of complications will likely also increase. Objective To describe potential adverse events associated with dermal fillers and to provide structured and clear guidance on their treatment and avoidance. Methods Reports of dermal filler complications in the medical literature were reviewed and, based on the publications retrieved and the authors’ extensive experience, recommendations for avoiding and managing complications are provided. Results Different dermal fillers have widely varying properties, associated risks, and injection requirements. All dermal fillers have the potential to cause complications. Most are related to volume and technique, though some are associated with the material itself. The majority of adverse reactions are mild and transient, such as bruising and trauma-related edema. Serious adverse events are rare, and most are avoidable with proper planning and technique. Conclusion For optimum outcomes, aesthetic physicians should have a detailed understanding of facial anatomy; the individual characteristics of available fillers; their indications, contraindications, benefits, and drawbacks; and ways to prevent and avoid potential complications. PMID:24363560

  3. Endocrine and Metabolic Adverse Effects of Psychotropic Medications in Children and Adolescents

    ERIC Educational Resources Information Center

    Correll, Christoph U.; Carlson, Harold E.

    2006-01-01

    Objective: Despite increasing use of psychotropic medications in children and adolescents, data regarding their efficacy and safety are limited. Endocrine and metabolic adverse effects are among the most concerning adverse effects of commonly used psychotropic medications. Method: Selective review of endocrine and metabolic effects of psychotropic…

  4. Oral Bisphosphonate Related Osteonecrosis of the Jaw: A Challenging Adverse Effect

    PubMed Central

    2013-01-01

    Oral bisphosphonates are the most commonly prescribed antiresorptive drugs for the treatment of osteoporosis. However, there are several adverse effects associated with oral bisphosphonates including the bisphosphonate related osteonecrosis of the jaw (BRONJ). With a better understanding of this side effect, reported incidences for BRONJ in oral bisphosphonate users have increased in time. The pathogenesis of BRONJ has not been well determined. Several risk factors such as dentoalveolar surgery, therapy duration, and concomitant steroid usage have been linked to BRONJ. Conservative and surgical methods can be preferred in the treatment. Preventative measures are of great importance for the patients at high risk. In this paper, osteonecrosis of the jaw secondary to oral bisphosphonates was reviewed in order to increase awareness as well as to renew the current knowledge. PMID:23762600

  5. Long-term adverse effects after curative radiotherapy and radical prostatectomy: population-based nationwide register study

    PubMed Central

    Fridriksson, Jón Ö.; Folkvaljon, Yasin; Nilsson, Per; Robinson, David; Franck-Lissbrant, Ingela; Ehdaie, Behfar; Eastham, James A.; Widmark, Anders; Karlsson, Camilla T.; Stattin, Pär

    2016-01-01

    Abstract Objective: The aim of this study was to assess the risk of serious adverse effects after radiotherapy (RT) with curative intention and radical prostatectomy (RP). Materials and methods: Men who were diagnosed with prostate cancer between 1997 and 2012 and underwent curative treatment were selected from the Prostate Cancer data Base Sweden. For each included man, five prostate cancer-free controls, matched for birth year and county of residency, were randomly selected. In total, 12,534 men underwent RT, 24,886 underwent RP and 186,624 were controls. Adverse effects were defined according to surgical and diagnostic codes in the National Patient Registry. The relative risk (RR) of adverse effects up to 12 years after treatment was compared to controls and the risk was subsequently compared between RT and RP in multivariable analyses. Results: Men with intermediate- and localized high-risk cancer who underwent curative treatment had an increased risk of adverse effects during the full study period compared to controls: the RR of undergoing a procedures after RT was 2.64 [95% confidence interval (CI) 2.56–2.73] and after RP 2.05 (95% CI 2.00–2.10). The risk remained elevated 10–12 years after treatment. For all risk categories of prostate cancer, the risk of surgical procedures for urinary incontinence was higher after RP (RR 23.64, 95% CI 11.71–47.74), whereas risk of other procedures on the lower urinary tract and gastrointestinal tract or abdominal wall was higher after RT (RR 1.67, 95% CI 1.44–1.94, and RR 1.86, 95% CI 1.70–2.02, respectively). Conclusion: The risk of serious adverse effects after curative treatment for prostate cancer remained significantly elevated up to 12 years after treatment. PMID:27333148

  6. Effects of Extended-Release Guanfacine on ADHD Symptoms and Sedation-Related Adverse Events in Children with ADHD

    ERIC Educational Resources Information Center

    Faraone, Stephen V.; Glatt, Stephen J.

    2010-01-01

    Objective: Guanfacine extended release (GXR) is a selective alpha[subscript 2A]-adrenoceptor agonist that is shown to be an effective nonstimulant treatment for the symptoms of attention-deficit/hyperactivity disorder. This report documents the time course and predictors of symptom efficacy and sedation-related adverse events (AEs) that emerge…

  7. The lifelong effects of early childhood adversity and toxic stress.

    PubMed

    Boyce, W Thomas

    2014-01-01

    A rapidly expanding body of research indicates that early social environments characterized by adversity, subordination and stress, along with individual differences in susceptibility to such environments, create risks for lifelong chronic diseases, including declines in oral health. Emerging findings suggest that gene-environment interplay, resulting in epigenetically regulated differences in gene expression, underlie many such declines in health. The origins of these processes in early life reveal how many of the chronic morbidities of adulthood should be viewed as developmental disorders, with etiologic roots in childhood.

  8. Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian Working Group Consensus update.

    PubMed

    Mancini, G B John; Tashakkor, A Yashar; Baker, Steven; Bergeron, Jean; Fitchett, David; Frohlich, Jiri; Genest, Jacques; Gupta, Milan; Hegele, Robert A; Ng, Dominic S; Pearson, Glen J; Pope, Janet

    2013-12-01

    The Proceedings of a Canadian Working Group Consensus Conference, first published in 2011, provided a summary of statin-associated adverse effects and intolerance and management suggestions. In this update, new clinical studies identified since then that provide further insight into effects on muscle, cognition, cataracts, diabetes, kidney disease, and cancer are discussed. Of these, the arenas of greatest controversy pertain to purported effects on cognition and the emergence of diabetes during long-term therapy. Regarding cognition, the available evidence is not strongly supportive of a major adverse effect of statins. In contrast, the linkage between statin therapy and incident diabetes is more firm. However, this risk is more strongly associated with traditional risk factors for new-onset diabetes than with statin itself and any possible negative effect of new-onset diabetes during statin treatment is far outweighed by the cardiovascular risk reduction benefits. Additional studies are also discussed, which support the principle that systematic statin rechallenge, and lower or intermittent statin dosing strategies are the main methods for dealing with suspected statin intolerance at this time.

  9. Evidence behind FDA alerts for drugs with adverse cardiovascular effects: implications for clinical practice.

    PubMed

    Rackham, Daniel M; C Herink, Megan; Stevens, Ian G; Cardoza, Natalie M; Singh, Harleen

    2014-01-01

    The U.S. Food and Drug Administration (FDA) periodically publishes Drug Safety Communications and Drug Alerts notifying health care practitioners and the general public of important information regarding drug therapies following FDA approval. These alerts can result in both positive and negative effects on patient care. Most clinical trials are not designed to detect long-term safety end points, and postmarketing surveillance along with patient reported events are often instrumental in signaling the potential harmful effect of a drug. Recently, many cardiovascular (CV) safety announcements have been released for FDA-approved drugs. Because a premature warning could discourage a much needed treatment or prompt a sudden discontinuation, it is essential to evaluate the evidence supporting these FDA alerts to provide effective patient care and to avoid unwarranted changes in therapy. Conversely, paying attention to these warnings in cases involving high-risk patients can prevent adverse effects and litigation. This article reviews the evidence behind recent FDA alerts for drugs with adverse CV effects and discusses the clinical practice implications.

  10. How antibiotics can make us sick: the less obvious adverse effects of antimicrobial chemotherapy.

    PubMed

    Dancer, Stephanie J

    2004-10-01

    Antimicrobial agents are associated with side-effects, which are usually tolerated because the benefits of treatment outweigh the toxic effects. Clinicians know about these side-effects but are less likely to understand additional adverse events, such as the overgrowth of resistant microorganisms. Overgrowth can itself precipitate a secondary infection, which can be more difficult to treat. Resistant organisms then spread to other patients and the environment, and contribute to increasing antimicrobial resistance worldwide. Organisms exposed to antibiotics undergo molecular changes that might enhance virulence. Enhanced pathogenicity would affect patients, particularly if the organism is also multiply resistant. Clinicians have a responsibility to select the correct antibiotic as soon as they have diagnosed infection, but an absence of microbiological understanding and ignorance of the potential environmental effects have contributed to inappropriate prescribing. The less obvious results of antimicrobial consumption probably go unrecognised in routine clinical care.

  11. The effect of adverse information and positive promotion on women's preferences for prescribed contraceptive products.

    PubMed

    Knox, Stephanie A; Viney, Rosalie C; Gu, Yuanyuan; Hole, Arne R; Fiebig, Denzil G; Street, Deborah J; Haas, Marion R; Weisberg, Edith; Bateson, Deborah

    2013-04-01

    Recent rapid growth in the range of contraceptive products has given women more choice, but also adds complexity to the resultant decision of which product to choose. This paper uses a discrete choice experiment (DCE) to investigate the effect of adverse information and positive promotion on women's stated preferences for prescribed contraceptive products. In November 2007, 527 Australian women aged 18-49 years were recruited from an online panel. Each was randomly allocated to one of three information conditions. The control group only received basic information on contraceptive products. One treatment group also received adverse information on the risks of the combined oral pill. The other group received basic information and promotional material on the vaginal ring, newly introduced into Australia and on the transdermal patch, which is unavailable in Australia. Respondents completed 32 choice sets with 3 product options where each option was described by a product label: either combined pill, minipill, injection, implant, hormonal IUD, hormonal vaginal ring, hormonal transdermal patch or copper IUD; and by the attributes: effect on acne, effect on weight, frequency of administration, contraceptive effectiveness, doctor's recommendation, effect on periods and cost. Women's choices were analysed using a generalized multinomial logit model (G-MNL) and model estimates were used to predict product shares for each information condition. The predictions indicated that adverse information did not affect women's preferences for products relative to only receiving basic information. The promotional material increased women's preferences for the transdermal patch. Women in all groups had a low preference for the vaginal ring which was not improved by promotion. The findings highlight the need for researchers to pay attention to setting the context when conducting DCEs as this can significantly affect results.

  12. 40 CFR 172.57 - Submission of information regarding potential unreasonable adverse effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... adverse effects. Any person using a microbial pesticide in small-scale testing covered by this subpart who... potential unreasonable adverse effects. 172.57 Section 172.57 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS EXPERIMENTAL USE PERMITS Notification for...

  13. 40 CFR 152.125 - Submission of information pertaining to adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... to adverse effects. 152.125 Section 152.125 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Obligations and Rights of Registrants § 152.125 Submission of information pertaining to adverse effects. If at any time the...

  14. 40 CFR 152.125 - Submission of information pertaining to adverse effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... to adverse effects. 152.125 Section 152.125 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Obligations and Rights of Registrants § 152.125 Submission of information pertaining to adverse effects. If at any time the...

  15. 40 CFR 152.125 - Submission of information pertaining to adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... to adverse effects. 152.125 Section 152.125 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Obligations and Rights of Registrants § 152.125 Submission of information pertaining to adverse effects. If at any time the...

  16. 40 CFR 152.125 - Submission of information pertaining to adverse effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... to adverse effects. 152.125 Section 152.125 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Obligations and Rights of Registrants § 152.125 Submission of information pertaining to adverse effects. If at any time the...

  17. 40 CFR 172.57 - Submission of information regarding potential unreasonable adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... adverse effects. Any person using a microbial pesticide in small-scale testing covered by this subpart who... potential unreasonable adverse effects. 172.57 Section 172.57 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS EXPERIMENTAL USE PERMITS Notification for...

  18. 40 CFR 172.57 - Submission of information regarding potential unreasonable adverse effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... adverse effects. Any person using a microbial pesticide in small-scale testing covered by this subpart who... potential unreasonable adverse effects. 172.57 Section 172.57 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS EXPERIMENTAL USE PERMITS Notification for...

  19. 40 CFR 152.125 - Submission of information pertaining to adverse effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... to adverse effects. 152.125 Section 152.125 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Obligations and Rights of Registrants § 152.125 Submission of information pertaining to adverse effects. If at any time the...

  20. 40 CFR 172.57 - Submission of information regarding potential unreasonable adverse effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... adverse effects. Any person using a microbial pesticide in small-scale testing covered by this subpart who... potential unreasonable adverse effects. 172.57 Section 172.57 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS EXPERIMENTAL USE PERMITS Notification for...

  1. 40 CFR 172.57 - Submission of information regarding potential unreasonable adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... adverse effects. Any person using a microbial pesticide in small-scale testing covered by this subpart who... potential unreasonable adverse effects. 172.57 Section 172.57 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS EXPERIMENTAL USE PERMITS Notification for...

  2. 40 CFR 174.71 - Submission of information regarding adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... any information regarding adverse effects on human health or the environment alleged to have been... this part. This may include, for example, researchers performing field experiments, breeders making... information. (b) Adverse effects on human health or the environment for purposes of...

  3. 40 CFR 174.71 - Submission of information regarding adverse effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... any information regarding adverse effects on human health or the environment alleged to have been... this part. This may include, for example, researchers performing field experiments, breeders making... information. (b) Adverse effects on human health or the environment for purposes of...

  4. 40 CFR 174.71 - Submission of information regarding adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... any information regarding adverse effects on human health or the environment alleged to have been... this part. This may include, for example, researchers performing field experiments, breeders making... information. (b) Adverse effects on human health or the environment for purposes of...

  5. 40 CFR 174.71 - Submission of information regarding adverse effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... any information regarding adverse effects on human health or the environment alleged to have been... this part. This may include, for example, researchers performing field experiments, breeders making... information. (b) Adverse effects on human health or the environment for purposes of...

  6. 40 CFR 174.71 - Submission of information regarding adverse effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... any information regarding adverse effects on human health or the environment alleged to have been... this part. This may include, for example, researchers performing field experiments, breeders making... information. (b) Adverse effects on human health or the environment for purposes of...

  7. Adverse and beneficial effects of plant extracts on skin and skin disorders.

    PubMed

    Mantle, D; Gok, M A; Lennard, T W

    2001-06-01

    Plants are of relevance to dermatology for both their adverse and beneficial effects on skin and skin disorders respectively. Virtually all cultures worldwide have relied historically, or continue to rely on medicinal plants for primary health care. Approximately one-third of all traditional medicines are for treatment of wounds or skin disorders, compared to only 1-3% of modern drugs. The use of such medicinal plant extracts for the treatment of skin disorders arguably has been based largely on historical/anecdotal evidence, since there has been relatively little data available in the scientific literature, particularly with regard to the efficacy of plant extracts in controlled clinical trials. In this article therefore, adverse and beneficial aspects of medicinal plants relating to skin and skin disorders have been reviewed, based on recently available information from the peer-reviewed scientific literature. Beneficial aspects of medicinal plants on skin include: healing of wounds and burn injuries (especially Aloe vera); antifungal, antiviral, antibacterial and acaricidal activity against skin infections such as acne, herpes and scabies (especially tea tree (Melaleuca alternifolia) oil); activity against inflammatory/immune disorders affecting skin (e.g. psoriasis); and anti-tumour promoting activity against skin cancer (identified using chemically-induced two-stage carcinogenesis in mice). Adverse effects of plants on skin reviewed include: irritant contact dermatitis caused mechanically (spines, irritant hairs) or by irritant chemicals in plant sap (especially members of the Ranunculaceae, Euphorbiaceae and Compositae plant families); phytophotodermatitis resulting from skin contamination by plants containing furocoumarins, and subsequent exposure to UV light (notably members of the Umbelliferae and Rutaceae plant families); and immediate (type I) or delayed hypersensitivity contact reactions mediated by the immune system in individuals sensitized to plants

  8. A Traditional Chinese Medicine Xiao-Ai-Tong Suppresses Pain through Modulation of Cytokines and Prevents Adverse Reactions of Morphine Treatment in Bone Cancer Pain Patients.

    PubMed

    Cong, Yan; Sun, Kefu; He, Xueming; Li, Jinxuan; Dong, Yanbin; Zheng, Bin; Tan, Xiao; Song, Xue-Jun

    2015-01-01

    Treating cancer pain continues to possess a major challenge. Here, we report that a traditional Chinese medicine Xiao-Ai-Tong (XAT) can effectively suppress pain and adverse reactions following morphine treatment in patients with bone cancer pain. Visual Analogue Scale (VAS) and Quality of Life Questionnaire (EORTC QLQ-C30) were used for patient's self-evaluation of pain intensity and evaluating changes of adverse reactions including constipation, nausea, fatigue, and anorexia, respectively, before and after treatment prescriptions. The clinical trials showed that repetitive oral administration of XAT (200 mL, bid, for 7 consecutive days) alone greatly reduced cancer pain. Repetitive treatment with a combination of XAT and morphine (20 mg and 30 mg, resp.) produced significant synergistic analgesic effects. Meanwhile, XAT greatly reduced the adverse reactions associated with cancer and/or morphine treatment. In addition, XAT treatment significantly reduced the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α and increased the endogenous anti-inflammatory cytokine interleukin-10 in blood. These findings demonstrate that XAT can effectively reduce bone cancer pain probably mediated by the cytokine mechanisms, facilitate analgesic effect of morphine, and prevent or reduce the associated adverse reactions, supporting a use of XAT, alone or with morphine, in treating bone cancer pain in clinic.

  9. A Traditional Chinese Medicine Xiao-Ai-Tong Suppresses Pain through Modulation of Cytokines and Prevents Adverse Reactions of Morphine Treatment in Bone Cancer Pain Patients

    PubMed Central

    Cong, Yan; Sun, Kefu; He, Xueming; Li, Jinxuan; Dong, Yanbin; Zheng, Bin; Tan, Xiao; Song, Xue-Jun

    2015-01-01

    Treating cancer pain continues to possess a major challenge. Here, we report that a traditional Chinese medicine Xiao-Ai-Tong (XAT) can effectively suppress pain and adverse reactions following morphine treatment in patients with bone cancer pain. Visual Analogue Scale (VAS) and Quality of Life Questionnaire (EORTC QLQ-C30) were used for patient's self-evaluation of pain intensity and evaluating changes of adverse reactions including constipation, nausea, fatigue, and anorexia, respectively, before and after treatment prescriptions. The clinical trials showed that repetitive oral administration of XAT (200 mL, bid, for 7 consecutive days) alone greatly reduced cancer pain. Repetitive treatment with a combination of XAT and morphine (20 mg and 30 mg, resp.) produced significant synergistic analgesic effects. Meanwhile, XAT greatly reduced the adverse reactions associated with cancer and/or morphine treatment. In addition, XAT treatment significantly reduced the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α and increased the endogenous anti-inflammatory cytokine interleukin-10 in blood. These findings demonstrate that XAT can effectively reduce bone cancer pain probably mediated by the cytokine mechanisms, facilitate analgesic effect of morphine, and prevent or reduce the associated adverse reactions, supporting a use of XAT, alone or with morphine, in treating bone cancer pain in clinic. PMID:26617438

  10. Methemoglobinemia and adverse events in Plasmodium vivax malaria patients associated with high doses of primaquine treatment.

    PubMed

    Carmona-Fonseca, Jaime; Alvarez, Gonzalo; Maestre, Amanda

    2009-02-01

    Primaquine (PQ) is recommended to prevent relapses in patients with Plasmodium vivax malaria infection. However, treatment with PQ causes methemoglobinemia. In this study, we measured the methemoglobin (MetHB) levels in three groups of subjects who received PQ treatment at 0.58, 0.83, or 1.17 mg/kg/d. A total of 112 subjects were studied. MetHB levels were detected at > or = 4% in 46-50% 1 day after PQ treatment in all three groups and 4-9% of subjects had MetHB levels > or = 4% 15 days after treatment. Only subjects receiving the highest doses of PQ had mild and brief adverse events, and 17% of them were associated with treatment. We conclude that when PQ is administered under certain conditions (i.e., normal glucose-6-phosphate dehydrogenase activity, in non-pregnant subjects and with a light meal), daily doses as high as 1.17 mg/kg do not represent a serious risk of high MetHB levels to patients.

  11. Adverse Effects of Androgen Deprivation Therapy: Defining the Problem and Promoting Health Among Men with Prostate Cancer

    PubMed Central

    Saylor, Philip J.; Smith, Matthew R.

    2010-01-01

    Androgen deprivation therapy (ADT) plays a central role in the management of men with locally advanced, recurrent, and metastatic prostate cancer. Because most men diagnosed with prostate cancer will die of something other than their cancer, treatment-related adverse effects are highly relevant to their long-term health. Benefits of ADT in each clinical setting must be weighed against ADT-related adverse effects. ADT is detrimental to several metabolic end points and to bone health. ADT has been prospectively shown to cause decreased lean muscle mass, increased fat mass, weight gain, increased cholesterol and triglycerides, insulin resistance, and loss of bone mineral density. In population-based analyses it has been associated with an increased incidence of diabetes, clinical fractures, and cardiovascular disease. Data-driven recommendations for managing these adverse effects are needed. Currently the authors advocate the use of adapted practice guidelines developed to prevent diabetes, fractures, and coronary heart disease in the general population. PMID:20141678

  12. Effects of Timing of Adversity on Adolescent and Young Adult Adjustment.

    PubMed

    Kiff, Cara J; Cortes, Rebecca; Lengua, Lilana; Kosterman, Rick; Hawkins, J David; Mason, W Alex

    2012-06-01

    Effects of Timing of Adversity on Adolescent and Young Adult Adjustment Abstract Exposure to adversity during childhood and adolescence predicts adjustment across development. Further, adolescent adjustment problems persist into young adulthood. This study examined relations of contextual adversity with concurrent adolescent adjustment and prospective mental health and health outcomes in young adulthood. A longitudinal sample (N = 808) was followed from age 10 through 27. Perceptions of neighborhood in childhood predicted depression, alcohol use disorders, and HIV risk in young adulthood. Further, the timing of adversity was important in determining the type of problem experienced in adulthood. Youth adjustment predicted adult outcomes, and in some cases, mediated the relation between adversity and outcomes. These findings support the importance of adversity in predicting adjustment and elucidate factors that affect outcomes into young adulthood.

  13. Treatment Needs and Adverse Events Related to Dental Treatment under General Anesthesia for Individuals with Autism

    ERIC Educational Resources Information Center

    Rada, Robert E.

    2013-01-01

    Individuals with autism can be quite challenging to treat in a routine dental-office setting, especially when extensive dental treatment and disruptive behavioral issues exist. Individuals with autism may also be at higher risk for oral disease. Frequently, general anesthesia is the only method to facilitate completion of the needed dental…

  14. Cyproheptadine for prevention of neuropsychiatric adverse effects of efavirenz: a randomized clinical trial.

    PubMed

    Dabaghzadeh, Fatemeh; Ghaeli, Padideh; Khalili, Hossein; Alimadadi, Abbas; Jafari, Sirous; Akhondzadeh, Shahin; Khazaeipour, Zahra

    2013-03-01

    Cyproheptadine prevention of the neuropsychiatric adverse effects of an antiretroviral regimen including efavirenz has been evaluated in a randomized clinical trial. Twenty-five patients (16 males and 9 females with mean±SD ages of 36±9 years) in a cyproheptadine group, and 26 patients (17 males and 9 females with mean±SD ages of 34±7 years) in a control group completed the trial. Sexual contact and injection drug use were the main routs of HIV infection in both groups. The patients' neuropsychiatric adverse effects were evaluated based on the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Syndrome Scale, Beck Depression Scale, Pittsburgh Sleep Quality Inventory, Positive and Negative Suicide Ideation, and Somatization Subscale of Symptom Checklist 90 at baseline and 4 weeks after treatment. Cyproheptadine significantly decreased the scores of Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Syndrome Scale, Beck Depression Scale, Pittsburgh Sleep Quality Inventory, Positive and Negative Suicide Ideation of the patients after 4 weeks in comparison with control group. All of the scores increased in control group following antiretroviral therapy. Although short duration of the patients' follow-up was a major limitation of the study, the results of the study showed that cyprohepradine is effective in prevention of depression, anxiety, hallucination, aggressive behaviors, emotional withdrawal, poor rapport, poor impulse control, active social avoidance, suicidal ideation, and improved sleep quality of HIV-positive patients after initiation of antiretroviral therapy including efavirenz.

  15. Inhaled Diesel Emissions Generated with Cerium Oxide Nanoparticle Fuel Additive Induce Adverse Pulmonary and Systemic Effects

    EPA Science Inventory

    Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe res...

  16. Separate and Cumulative Effects of Adverse Childhood Experiences in Predicting Adult Health and Health Care Utilization

    ERIC Educational Resources Information Center

    Chartier, Mariette J.; Walker, John R.; Naimark, Barbara

    2010-01-01

    Objectives: Objectives of this population-based study were: (1) to examine the relative contribution of childhood abuse and other adverse childhood experiences to poor adult health and increased health care utilization and (2) to examine the cumulative effects of adverse childhood experiences on adult health and health care utilization. Methods:…

  17. PTH prevents the adverse effects of focal radiation on bone architecture in young rats

    PubMed Central

    Chandra, Abhishek; Lan, Shenghui; Zhu, Ji; Lin, Tiao; Zhang, Xianrong; Siclari, Valerie A.; Altman, Allison R.; Cengel, Keith A.; Liu, X. Sherry; Qin, Ling

    2013-01-01

    Radiation therapy is a common treatment regimen for cancer patients. However, its adverse effects on the neighboring bone could lead to fractures with a great impact on quality of life. The underlying mechanism is still elusive and there is no preventive or curative solution for this bone loss. Parathyroid hormone (PTH) is a current therapy for osteoporosis that has potent anabolic effects on bone. In this study, we found that focal radiation from frequent scans of the right tibiae in 1-month-old rats by micro-computed tomography severely decreased trabecular bone mass and deteriorated bone structure. Interestingly, PTH daily injections remarkably improved trabecular bone in the radiated tibiae with increases in trabecular number, thickness, connectivity, structure model index and stiffness, and a decrease in trabecular separation. Histomorphometric analysis revealed that radiation mainly decreased the number of osteoblasts and impaired their mineralization activity but had little effects on osteoclasts. PTH reversed these adverse effects and greatly increased bone formation to a similar level in both radiated and non-radiated bones. Furthermore, PTH protects bone marrow mesenchymal stem cells from radiation-induced damage, including a decrease in number and an increase in adipogenic differentiation. While radiation generated the same amount of free radicals in the bone marrow of vehicle-treated and PTH-treated animals, the percentage of apoptotic bone marrow cells was significantly attenuated in the PTH group. Taken together, our data demonstrate a radioprotective effect of PTH on bone structure and bone marrow and shed new light on a possible clinical application of anabolic treatment in radiotherapy. PMID:23466454

  18. European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia

    PubMed Central

    Steegmann, J L; Baccarani, M; Breccia, M; Casado, L F; García-Gutiérrez, V; Hochhaus, A; Kim, D-W; Kim, T D; Khoury, H J; Le Coutre, P; Mayer, J; Milojkovic, D; Porkka, K; Rea, D; Rosti, G; Saussele, S; Hehlmann, R; Clark, R E

    2016-01-01

    Most reports on chronic myeloid leukaemia (CML) treatment with tyrosine kinase inhibitors (TKIs) focus on efficacy, particularly on molecular response and outcome. In contrast, adverse events (AEs) are often reported as infrequent, minor, tolerable and manageable, but they are increasingly important as therapy is potentially lifelong and multiple TKIs are available. For this reason, the European LeukemiaNet panel for CML management recommendations presents an exhaustive and critical summary of AEs emerging during CML treatment, to assist their understanding, management and prevention. There are five major conclusions. First, the main purpose of CML treatment is the antileukemic effect. Suboptimal management of AEs must not compromise this first objective. Second, most patients will have AEs, usually early, mostly mild to moderate, and which will resolve spontaneously or are easily controlled by simple means. Third, reduction or interruption of treatment must only be done if optimal management of the AE cannot be accomplished in other ways, and frequent monitoring is needed to detect resolution of the AE as early as possible. Fourth, attention must be given to comorbidities and drug interactions, and to new events unrelated to TKIs that are inevitable during such a prolonged treatment. Fifth, some TKI-related AEs have emerged which were not predicted or detected in earlier studies, maybe because of suboptimal attention to or absence from the preclinical data. Overall, imatinib has demonstrated a good long-term safety profile, though recent findings suggest underestimation of symptom severity by physicians. Second and third generation TKIs have shown higher response rates, but have been associated with unexpected problems, some of which could be irreversible. We hope these recommendations will help to minimise adverse events, and we believe that an optimal management of them will be rewarded by better TKI compliance and thus better CML outcomes, together with better

  19. Activation of TREK-1 by morphine results in analgesia without adverse side effects.

    PubMed

    Devilliers, Maïly; Busserolles, Jérôme; Lolignier, Stéphane; Deval, Emmanuel; Pereira, Vanessa; Alloui, Abdelkrim; Christin, Marine; Mazet, Bruno; Delmas, Patrick; Noel, Jacques; Lazdunski, Michel; Eschalier, Alain

    2013-01-01

    Morphine is the gold-standard pain reliever for severe acute or chronic pain but it also produces adverse side effects that can alter the quality of life of patients and, in some rare cases, jeopardize the vital prognosis. Morphine elicits both therapeutic and adverse effects primarily through the same μ opioid receptor subtype, which makes it difficult to separate the two types of effects. Here we show that beneficial and deleterious effects of morphine are mediated through different signalling pathways downstream from μ opioid receptor. We demonstrate that the TREK-1 K(+) channel is a crucial contributor of morphine-induced analgesia in mice, while it is not involved in morphine-induced constipation, respiratory depression and dependence-three main adverse effects of opioid analgesic therapy. These observations suggest that direct activation of the TREK-1 K(+) channel, acting downstream from the μ opioid receptor, might have strong analgesic effects without opioid-like adverse effects.

  20. Adverse effects of drug therapies on male and female sexual function.

    PubMed

    Stadler, Th; Bader, M; Uckert, S; Staehler, M; Becker, A; Stief, C G

    2006-12-01

    Sexual dysfunctions (SD) are adverse effects of common drug therapies that have rarely been considered in investigations so far. Possibly it is barely known that many widespread and frequently prescribed medications and drug therapies can have significant impact on vascular and nerval processes as well as on endocrinologic and psychoneuroendocrinologic systems and therefore can influence sexual functions. Impotence and disorders of the erectile function can mainly be caused by antidopaminergic mechanisms, whereas ejaculatory disorders and anorgasmia often can be explained by antiserotoninergic effects. Anticholinergic and adrenoloytic agents can also cause a particular impairment of erectile functions. The following considerations will show that the detection and treatment of SD (also in women!) should be given much more attention since drug-induced SDs occur predominantly in indications where a SD itself can be a symptom of the disease.

  1. Multiple sclerosis disease-modifying therapies: adverse effect surveillance and management.

    PubMed

    Wingerchuk, Dean M

    2006-03-01

    There are five approved, partially effective, parenteral disease-modifying therapies for multiple sclerosis (MS), including three interferon-beta preparations, glatiramer acetate and the antineoplastic agent mitoxantrone. A sixth drug, natalizumab, was withdrawn from the market in 2005 but could return with increased safety measures. Careful surveillance for, and management of, the minor and serious adverse effects associated with these therapies in routine practice provides the best opportunity for maintaining compliance and achieving maximal therapeutic efficacy. This review outlines the strategies for the prevention, identification and management of the complications associated with administration and ongoing use of current MS therapies. These skills will become increasingly important to those caring for MS patients as contemporary treatment regimens become increasingly complex.

  2. Effectiveness of Micro-Blowing Technique in Adverse Pressure Gradients

    NASA Technical Reports Server (NTRS)

    Welch, Gerard E.; Larosiliere, Louis M.; Hwang, Danny P.; Wood, Jerry R.

    2001-01-01

    The impact of the micro-blowing technique (MBT) on the skin friction and total drag of a strut in a turbulent, strong adverse-pressure-gradient flow is assessed experimentally over a range of subsonic Mach numbers (0.3 less than M less than 0.7) and reduced blowing fractions (0 less than or equal to 2F/C (sub f,o) less than or equal to 1.75). The MBT-treated strut is situated along the centerline of a symmetric 2-D diffuser with a static pressure rise coefficient of 0.6. In agreement with presented theory and earlier experiments in zero-pressure-gradient flows, the effusion of blowing air reduces skin friction significantly (e.g., by 60% at reduced blowing fractions near 1.75). The total drag of the treated strut with blowing is significantly lower than that of the treated strut in the limit of zero-blowing; further, the total drag is reduced below that of the baseline (solid-plate) strut, provided that the reduced blowing fractions are sufficiently high. The micro-blowing air is, however, deficient in streamwise momentum and the blowing leads to increased boundary-layer and wake thicknesses and shape factors. Diffuser performance metrics and wake surveys are used to discuss the impact of various levels of micro-blowing on the aerodynamic blockage and loss.

  3. [Antibodies, human leukocyte antigens, and biomodulators in transfusion-related acute adverse effects].

    PubMed

    Martínez Álvarez, Julio César

    2013-01-01

    With the onset of the AIDS epidemic, major changes occurred in blood banking and transfusion medicine. These changes occurred mainly in donor selection and screening tests for infectious diseases, blood centers modified their organizational philosophy regarding quality. Transfusion of blood products are procedures that allow us to correct the haematology deficiencies for which was indicated. But today, despite the strict controls that precede transfusion,recipients may have undesirable effects, which are known as adverse effects or adverse reactions to transfusion. Antibodies and antigens of the HLA system plays a role in a series of events related to transfusion, such as immunological platelet refractoriness, febrile non-haemolytic transfusion reactions, transfusion related acute lung injury (TRALI) and transfusion-associated graft-versus-host disease. The determination of anti-HLA antibodies is evidence that in most developed countries is used on a daily basis in the regular assessment of patients multitransfused or waiting lists for organs from deceased donors. The biomodulators are able to modify biological responses which act in sequence to lead to the differentiation of T lymphocytes. These agents may subcategorizes those which facilitate a normal immune response, those stimulates the immune response, those are capable of inducing immunosuppression not cytotoxic, and those enhancing the ability of the host to tolerate damage by cytotoxic treatment (transfusion or transplant).

  4. Adverse effects of extra-articular corticosteroid injections: a systematic review

    PubMed Central

    2010-01-01

    Background To estimate the occurrence and type of adverse effects after application of an extra-articular (soft tissue) corticosteroid injection. Methods A systematic review of the literature was made based on a PubMed and Embase search covering the period 1956 to January 2010. Case reports were included, as were prospective and retrospective studies that reported adverse events of corticosteroid injection. All clinical trials which used extra-articular corticosteroid injections were examined. We divided the reported adverse events into major (defined as those needing intervention or not disappearing) and minor ones (transient, not requiring intervention). Results The search yielded 87 relevant studies:44 case reports, 37 prospective studies and 6 retrospective studies. The major adverse events included osteomyelitis and protothecosis; one fatal necrotizing fasciitis; cellulitis and ecchymosis; tendon ruptures; atrophy of the plantar fat was described after injecting a neuroma; and local skin effects appeared as atrophy, hypopigmentation or as skin defect. The minor adverse events effects ranged from skin rash to flushing and disturbed menstrual pattern. Increased pain or steroid flare after injection was reported in 19 studies. After extra-articular injection, the incidence of major adverse events ranged from 0-5.8% and that of minor adverse events from 0-81%. It was not feasible to pool the risk for adverse effects due to heterogeneity of study populations and difference in interventions and variance in reporting. Conclusion In this literature review it was difficult to accurately quantify the incidence of adverse effects after extra-articular corticosteroid injection. The reported adverse events were relatively mild, although one fatal reaction was reported. PMID:20836867

  5. Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis

    PubMed Central

    Trindade, E; Menon, D; Topfer, L A; Coloma, C

    1998-01-01

    BACKGROUND: The use of antidepressant medications and the resulting costs have increased dramatically in recent years, partly because of the introduction of selective serotonin reuptake inhibitors (SSRIs). An assessment of the clinical and economic aspects of SSRIs compared with the older tricyclic antidepressants (TCAs) was initiated to generate information for purchasers of these drugs as well as clinicians. One component of this study was an examination of the adverse effects associated with the use of these drugs. METHODS: Searches of bibliographic databases (for January 1980 through May 1996) and manual scanning of both peer-reviewed publications and other documents were used to identify double-blind, randomized controlled trials involving at least one SSRI and one TCA. For the study of adverse effects, only trials that had at least 20 patients in each trial arm and that reported rates of adverse effects in both arms were retained. In total 84 trials reporting on 18 adverse effects were available. Meta-analyses were undertaken to calculate pooled differences in rates of adverse effects. The question of whether the method of eliciting information from patients about adverse effects made a difference in the findings was also examined. Finally, differences in drop-out rates due to adverse effects were calculated. RESULTS: The crude rates of occurrence of adverse effects ranged from 4% (palpitations) to 26% (nausea) for SSRIs and from 4% (diarrhea) to 27% (dry mouth) for TCAs. The differences in the rates of adverse effects between the 2 types of drugs ranged from 14% more with SSRIs (for nausea) to 11% more with TCAs (for constipation). The results did not depend on the method of eliciting information from patients. There were no statistically significant differences between drug classes in terms of drop-outs due to adverse effects. INTERPRETATION: SSRIs and TCAs are both associated with adverse effects, although the key effects differ between the drug classes

  6. Diverse Effects on M1 Signaling and Adverse Effect Liability within a Series of M1 Ago-PAMs.

    PubMed

    Rook, Jerri M; Abe, Masahito; Cho, Hyekyung P; Nance, Kellie D; Luscombe, Vincent B; Adams, Jeffrey J; Dickerson, Jonathan W; Remke, Daniel H; Garcia-Barrantes, Pedro M; Engers, Darren W; Engers, Julie L; Chang, Sichen; Foster, Jarrett J; Blobaum, Anna L; Niswender, Colleen M; Jones, Carrie K; Conn, P Jeffrey; Lindsley, Craig W

    2017-01-10

    Both historical clinical and recent preclinical data suggest that the M1 muscarinic acetylcholine receptor is an exciting target for the treatment of Alzheimer's disease and the cognitive and negative symptom clusters in schizophrenia; however, early drug discovery efforts targeting the orthosteric binding site have failed to afford selective M1 activation. Efforts then shifted to focus on selective activation of M1 via either allosteric agonists or positive allosteric modulators (PAMs). While M1 PAMs have robust efficacy in rodent models, some chemotypes can induce cholinergic adverse effects (AEs) that could limit their clinical utility. Here, we report studies aimed at understanding the subtle structural and pharmacological nuances that differentiate efficacy from adverse effect liability within an indole-based series of M1 ago-PAMs. Our data demonstrate that closely related M1 PAMs can display striking differences in their in vivo activities, especially their propensities to induce adverse effects. We report the discovery of a novel PAM in this series that is devoid of observable adverse effect liability. Interestingly, the molecular pharmacology profile of this novel PAM is similar to that of a representative M1 PAM that induces severe AEs. For instance, both compounds are potent ago-PAMs that demonstrate significant interaction with the orthosteric site (either bitopic or negative cooperativity). However, there are subtle differences in efficacies of the compounds at potentiating M1 responses, agonist potencies, and abilities to induce receptor internalization. While these differences may contribute to the differential in vivo profiles of these compounds, the in vitro differences are relatively subtle and highlight the complexities of allosteric modulators and the need to focus on in vivo phenotypic screening to identify safe and effective M1 PAMs.

  7. The lifelong effects of early childhood adversity and toxic stress.

    PubMed

    Shonkoff, Jack P; Garner, Andrew S

    2012-01-01

    Advances in fields of inquiry as diverse as neuroscience, molecular biology, genomics, developmental psychology, epidemiology, sociology, and economics are catalyzing an important paradigm shift in our understanding of health and disease across the lifespan. This converging, multidisciplinary science of human development has profound implications for our ability to enhance the life prospects of children and to strengthen the social and economic fabric of society. Drawing on these multiple streams of investigation, this report presents an ecobiodevelopmental framework that illustrates how early experiences and environmental influences can leave a lasting signature on the genetic predispositions that affect emerging brain architecture and long-term health. The report also examines extensive evidence of the disruptive impacts of toxic stress, offering intriguing insights into causal mechanisms that link early adversity to later impairments in learning, behavior, and both physical and mental well-being. The implications of this framework for the practice of medicine, in general, and pediatrics, specifically, are potentially transformational. They suggest that many adult diseases should be viewed as developmental disorders that begin early in life and that persistent health disparities associated with poverty, discrimination, or maltreatment could be reduced by the alleviation of toxic stress in childhood. An ecobiodevelopmental framework also underscores the need for new thinking about the focus and boundaries of pediatric practice. It calls for pediatricians to serve as both front-line guardians of healthy child development and strategically positioned, community leaders to inform new science-based strategies that build strong foundations for educational achievement, economic productivity, responsible citizenship, and lifelong health.

  8. The Relationship Between Adverse Childhood Experiences and Recidivism in a Sample of Juvenile Offenders in Community-Based Treatment.

    PubMed

    Wolff, Kevin T; Baglivio, Michael T; Piquero, Alex R

    2015-11-12

    Adverse childhood experiences (ACEs) have been identified as a key risk factor for a range of negative life outcomes, including delinquency. Much less is known about how exposure to negative experiences relates to continued offending among juvenile offenders. In this study, we examine the effect of ACEs on recidivism in a large sample of previously referred youth from the State of Florida who were followed for 1 year after participation in community-based treatment. Results from a series of Cox hazard models suggest that ACEs increase the risk of subsequent arrest, with a higher prevalence of ACEs leading to a shorter time to recidivism. The relationship between ACEs and recidivism held quite well in demographic-specific analyses. Implications for empirical research on the long-term effects of traumatic childhood events and juvenile justice policy are discussed.

  9. [Hypertension and palmar plantar erythroderma. Management of adverse events of angiogenetic inhibitors in the treatment of renal cell carcinoma].

    PubMed

    Rolfes, N; Lümmen, G

    2011-11-01

    The introduction of angiogenesis inhibitors has altered the systemic therapy of metastatic renal cell carcinoma. Being a"permanent" medication, the management of side effects has special importance, for adverse events may limit therapy. Hypertension (up to 34% of cases) and palmar plantar erythroderma (6-30% of cases) are common side effects.Blood pressure should be monitored during therapy, and arterial hypertension should be treated with a standard medication. If a hypertensive emergency still occurs, a dose reduction or discontinuation of treatment might be indicated.Prophylaxis may prevent or extenuate palmar plantar erythroderma in many cases, enabling regular chemotherapy as planned. In cases with severe clinical symptoms a reduction or interruption of the dose will be necessary. In most cases local therapy is sufficient.

  10. Adverse Events in Healthy Individuals and MDR-TB Contacts Treated with Anti-Tuberculosis Drugs Potentially Effective for Preventing Development of MDR-TB: A Systematic Review

    PubMed Central

    Langendam, Miranda W.; Tiemersma, Edine W.; van der Werf, Marieke J.; Sandgren, Andreas

    2013-01-01

    A recent systematic review concluded that there is insufficient evidence on the effectiveness to support or reject preventive therapy for treatment of contacts of patients with multidrug resistant tuberculosis (MDR-TB). Whether preventive therapy is favorable depends both on the effectiveness and the adverse events of the drugs used. We performed a systematic review to assess adverse events in healthy individuals and MDR-TB contacts treated with anti-tuberculosis drugs potentially effective for preventing development of MDR-TB. We searched MEDLINE, EMBASE, and other databases (August 2011). Record selection, data extraction, and study quality assessment were done in duplicate. The quality of evidence was assessed using the GRADE approach. Of 6,901 identified references, 20 studies were eligible. Among the 16 studies in healthy volunteers (a total of 87 persons on either levofloxacin, moxifloxacin, ofloxacin, or rifabutin, mostly for 1 week), serious adverse events and treatment discontinuation due to adverse events were rare (<1 and <5%, respectively), but mild adverse events frequently occurred. Due to small sample sizes of the levofloxacin and ofloxacin studies an increased frequency of mild adverse events compared to placebo could not be demonstrated or excluded. For moxifloxacin the comparative results were inconsistent. In four studies describing preventive therapy of MDR-TB contacts, therapy was stopped for 58–100% of the included persons because of the occurrence of adverse events ranging from mild adverse events such as nausea and dizziness to serious events requiring treatment. The quality of the evidence was very low. Although the number of publications and quality of evidence are low, the available evidence suggests that shortly after starting treatment the occurrence of serious adverse events is rare. Mild adverse events occur more frequently and may be of importance because these may provoke treatment interruption. PMID:23326464

  11. Adverse events in healthy individuals and MDR-TB contacts treated with anti-tuberculosis drugs potentially effective for preventing development of MDR-TB: a systematic review.

    PubMed

    Langendam, Miranda W; Tiemersma, Edine W; van der Werf, Marieke J; Sandgren, Andreas

    2013-01-01

    A recent systematic review concluded that there is insufficient evidence on the effectiveness to support or reject preventive therapy for treatment of contacts of patients with multidrug resistant tuberculosis (MDR-TB). Whether preventive therapy is favorable depends both on the effectiveness and the adverse events of the drugs used. We performed a systematic review to assess adverse events in healthy individuals and MDR-TB contacts treated with anti-tuberculosis drugs potentially effective for preventing development of MDR-TB. We searched MEDLINE, EMBASE, and other databases (August 2011). Record selection, data extraction, and study quality assessment were done in duplicate. The quality of evidence was assessed using the GRADE approach. Of 6,901 identified references, 20 studies were eligible. Among the 16 studies in healthy volunteers (a total of 87 persons on either levofloxacin, moxifloxacin, ofloxacin, or rifabutin, mostly for 1 week), serious adverse events and treatment discontinuation due to adverse events were rare (<1 and <5%, respectively), but mild adverse events frequently occurred. Due to small sample sizes of the levofloxacin and ofloxacin studies an increased frequency of mild adverse events compared to placebo could not be demonstrated or excluded. For moxifloxacin the comparative results were inconsistent. In four studies describing preventive therapy of MDR-TB contacts, therapy was stopped for 58-100% of the included persons because of the occurrence of adverse events ranging from mild adverse events such as nausea and dizziness to serious events requiring treatment. The quality of the evidence was very low. Although the number of publications and quality of evidence are low, the available evidence suggests that shortly after starting treatment the occurrence of serious adverse events is rare. Mild adverse events occur more frequently and may be of importance because these may provoke treatment interruption.

  12. Long-term therapy in COPD: any evidence of adverse effect on bone?

    PubMed Central

    Langhammer, Arnulf; Forsmo, Siri; Syversen, Unni

    2009-01-01

    Patients with COPD have high risk for osteoporosis and fractures. Hip and vertebral fractures might impair mobility, and vertebral fractures further reduce lung function. This review discusses the evidence of bone loss due to medical treatment opposed to disease severity and risk factors for COPD, and therapeutic options for the prevention and treatment of osteoporosis in these patients. A review of the English-language literature was conducted using the MEDLINE database until June 2009. Currently used bronchodilators probably lack adverse effect on bone. Oral corticosteroids (OCS) increase bone resorption and decrease bone formation in a dose response relationship, but the fracture risk is increased more than reflected by bone densitometry. Inhaled corticosteroids (ICS) have been associated with both increased bone loss and fracture risk. This might be a result of confounding by disease severity, but high doses of ICS have similar effects as equipotent doses of OCS. The life-style factors should be modified, use of regular OCS avoided and use of ICS restricted to those with evidenced effect and probably kept at moderate doses. The health care should actively reveal risk factors, include bone densitometry in fracture risk evaluation, and give adequate prevention and treatment for osteoporosis. PMID:19888355

  13. Adverse effects of zilpaterol administration in horses: three cases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Three healthy horses were fed 0.17 mg/kg body weight of the beta-adrenergic agonist zilpaterol to determine zilpaterol elimination kinetics. Shortly after treatment, each horse developed skeletal muscle tremors, tachycardia, and serological abnormalities lasting several days. A 75% to 87.5% reduced ...

  14. Alcohol and cannabis: Comparing their adverse health effects and regulatory regimes.

    PubMed

    Hall, Wayne

    2016-11-28

    The claim that the adverse health effects of cannabis are much less serious than those of alcohol has been central to the case for cannabis legalisation. Regulators in US states that have legalised cannabis have adopted regulatory models based on alcohol. This paper critically examines the claim about adverse health effects and the wisdom of regulating cannabis like alcohol. First, it compares what we know about the adverse health effects of alcohol and cannabis. Second, it discusses the uncertainties about the long term health effects of sustained daily cannabis use. Third, it speculates about how the adverse health effects of cannabis may change after legalisation. Fourth, it questions the assumption that alcohol provides the best regulatory model for a legal cannabis market. Fifth, it outlines the major challenges in regulating cannabis under the liberal alcohol-like regulatory regimes now being introduced.

  15. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES... effects of deep seabed mining which cumulatively during commercial recovery have the potential for significant effect. These three effects also occur during mining system tests that may be conducted under...

  16. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES... effects of deep seabed mining which cumulatively during commercial recovery have the potential for significant effect. These three effects also occur during mining system tests that may be conducted under...

  17. Are hand preference and sexual orientation possible predicting factors for finasteride adverse effects in male androgenic alopecia?

    PubMed

    Motofei, Ion G; Rowland, David L; Georgescu, Simona R; Tampa, Mircea; Baleanu, Bogdan C; Paunica, Stana

    2016-07-01

    Sexual side effects of finasteride seem to be redoubtable, being encountered not only during therapy but also after treatment cessation. Consequently, any possible clinical/paraclinical elements that might predict these adverse effects would be useful in the selection of a therapeutic strategy for male androgenic alopecia. Previous published studies show that some compounds that interfere with sexual hormones can decrease sexual activation and response, according to hand preference (as reported for finasteride and tamoxifen) and according to sexual orientation (as noted for bicalutamide). Our preliminary published data and the arguments presented here suggest that these two individual parameters might be used by dermatologists in the therapeutic approach of male androgenic alopecia, so as to alert specific subsets of men, prior to treatment, of the potential increased risk for developing adverse effects to finasteride.

  18. Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal

    PubMed Central

    2016-01-01

    Although several chemical structural classes of synthetic cannabinoids (SCs) were recently classified as Schedule I substances, rates of use and cases of serious toxic effects remain high. While case reports and media bring attention to severe SC toxicity, daily SC use resulting in dependence and withdrawal is a significant concern that is often overlooked when discussing the risks of these drugs. There is a rich literature on evidence-based approaches to treating substance use disorders associated with most abused drugs, yet little has been published regarding how to best treat symptoms related to SC dependence given its recency as an emerging clinically significant issue. This review provides a background of the pharmacology of SCs, recent findings of adverse effects associated with both acute intoxication and withdrawal as a consequence of daily use, and treatment approaches that have been implemented to address these issues, with an emphasis on pharmacotherapies for managing detoxification. In order to determine prevalence of use in cannabis smokers, a population at high risk for SC use, we obtained data on demographics of SC users, frequency of use, and adverse effects over a 3.5-year period (2012–2015) in the New York City metropolitan area, a region with a recent history of high SC use. While controlled studies on the physiological and behavioral effects of SCs are lacking, it is clear that risks associated with using these drugs pertain not only to the unpredictable and severe nature of acute intoxication but also to the effects of long-term, chronic use. Recent reports in the literature parallel findings from our survey, indicating that there is a subset of people who use SCs daily. Although withdrawal has not been systematically characterized and effective treatments have yet to be elucidated, some symptom relief has been reported with benzodiazepines and the atypical antipsychotic, quetiapine. Given the continued use and abuse of SCs, empirical studies

  19. The adverse effects profile of levetiracetam in epilepsy: a more detailed look.

    PubMed

    Mbizvo, Gashirai K; Dixon, Pete; Hutton, Jane L; Marson, Anthony G

    2014-09-01

    The adverse effects profile of levetiracetam in epilepsy is still being fully described. We recently published a Cochrane Review evaluating the effectiveness of levetiracetam, added on to usual care, in treating drug-resistant focal epilepsy. The five most common adverse effects were reported and analysed with no scope for reporting any less common adverse effects than those. Here, we report and analyse the remaining adverse effects (including the five most common). These were (in decreasing order of frequency) somnolence; headache; asthenia; accidental injury; dizziness; infection; pharyngitis; pain; rhinitis; abdominal pain; flu syndrome; vomiting; diarrhoea; convulsion; nausea; increased cough; anorexia; upper respiratory tract infection; hostility; personality disorder; urinary tract infection; nervousness; depression; aggression; back pain; agitation; emotional liability; psychomotor hyperactivity; pyrexia; rash; ECG abnormalities; decreased appetite; nasal congestion; irritability; abnormal behaviour; epistaxis; insomnia; altered mood; anxiety; bloody urine; diplopia; dissociation; memory impairment; pruritis; increased appetite; acne; and stomach discomfort. Only somnolence and infection were significantly associated with levetiracetam. When adverse effects pertaining to infection were combined, these affected 19.7% and 15.1% of participants on levetiracetam and placebo (relative risk 1.16, CI 0.89-1.50, Chi(2) heterogeneity p = 0.13). Somnolence and infection further retained significance in adults while no single adverse effect was significant in children. This review updates the adverse effects profile data on levetiracetam use by empirically reporting its common and uncommon adverse effects and analysing their relative importance statistically using data from a group of trials that possess low Risk of Bias and high Quality of Evidence GRADE scores.

  20. Evaluation of Proper Usage of Glucocorticosteroid Inhalers and Their Adverse Effects in Asthmatic Patients

    PubMed Central

    Hejazi, Mohammad Esmayil; Shafiifar, Afsaneh; Mashayekhi, Siminozar

    2016-01-01

    Background: The frequent use of corticosteroid inhalers (CSIs), especially at higher doses, has been accompanied by concern about both systemic and local adverse reactions. The local adverse reactions of inhaled corticosteroids (ICSs) are considered to constitute infrequent and minor problems. However, while not usually serious, these local adverse reactions are of clinical importance. This study assessed the prevalence of local adverse reactions, their clinical features, role of inhaler devices and current measures that have been suggested to prevent the problem. Materials and Methods: This study was performed in YAS clinic in Tabriz on 500 asthmatic patients. A questionnaire about the patients’ demographic information, methods of using CSIs, local care after using CSIs, using spacer devices, doses of ICSs, and adverse reactions were filled then the patients were clinically examined for local adverse reactions. Results: Only 56% patients were using CSIs properly. In general, the incidence of complications was: oropharyngeal candidiasis 25.6%, laryngeal weakness 8.8%, choking 17.6%, tooth decay 15.2%, speechlessness 36.2%, taste decrease 20.8%, tongue burning 29.8% and tongue abrasion 27.8%. Conclusion: Persistent asthma can be effectively controlled with currently available CSIs. Although not life-threatening, local adverse reactions of ICSs are clinically significant and warrant attention. Use of spacer devices and changes in CSI usage, dosage amount and frequency and rinsing and gargling are the methods that have been used to reduce the incidence of local adverse reactions. PMID:27403173

  1. Does Regular Use of a Complementary Medicine of Olea Europe and Ficus carica Have Adverse Effects on Lipid Profile and Fasting Blood Glucose of Rheumatoid Arthritis (RA) Patients Under Treatment with DMARD Regimens Containing Methotrexate?

    PubMed Central

    Bahadori, Shahnaz; Ahmadzadeh, Arman; Shams Ardekani, Mohammad Reza; Kamalinejad, Mohammad; Keshavarz, Mansoor; Salamzadeh, Jamshid

    2016-01-01

    Rheumatoid arthritis (RA) patients are vulnerable to cardiovascular morbidity and mortality in which atherosclerosis plays a major role. In this study, the lipid profile and fasting blood sugar (FBS) of RA patients receiving a complementary medicine of olive and fig, as add-on therapy for routine disease-modifying antirheumatic drugs (DMARDs) regimen containing low dose methotrexate (MTX), were studied. A randomized controlled clinical trial was designed. Adult RA patients were randomly allocated in two groups receiving routine DMARDs regimen (control group) and routine DMARDs regimen plus the herbal supplementary formulation of olive oil, fig and olive fruits (intervention group). Patients were followed every 4 weeks for total study period of 16 weeks. In addition to demographic and medical history of the patients, the total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), the atherogenic index of plasma (AIP) defined as log(TG/HDL-C), and the fasting blood sugar (FBS) were determined and recorded. 56 patients (control = 27 and intervention = 29), with mean ± sd age of 50.9 ± 12.3 years completed the study. Average MTX dose received by intervention and control groups were 24.30 ± 18.39 and 17.61 ± 15.53 mg/week, respectively (p = 0.11). Repeated measures analysis of variance (ANOVA) revealed that differences between lipid profile indicators and FBS in the two study groups were not statistically significant (P>0.05). No additional substantial adverse reaction was seen in the study groups. Our findings are more reassuring for patients and their doctors to trust on the safety of the investigated complementary preparation to be used as add-on therapy to manage rheumatoid arthritis. PMID:28243292

  2. Metabolic and renal adverse effects of antiretroviral therapy in HIV-infected children and adolescents.

    PubMed

    Fortuny, Clàudia; Deyà-Martínez, Ángela; Chiappini, Elena; Galli, Luisa; de Martino, Maurizio; Noguera-Julian, Antoni

    2015-05-01

    Worldwide, the benefits of combined antiretroviral (ARV) therapy in morbidity and mortality due to perinatally acquired human immunodeficiency virus infection are beyond question and outweigh the toxicity these drugs have been associated with in HIV-infected children and adolescents to date. In puberty, abnormal body fat distribution is stigmatizating and leads to low adherence to ARV treatment. The other metabolic comorbidities (mitochondrial toxicity, dyslipidemias, insulin resistance and low bone mineral density) and renal toxicity, albeit nonsymptomatic in most children, are increasingly being reported and potentially put this population at risk for early cardiovascular or cerebrovascular atherosclerotic disease, diabetes, pathologic fractures or premature renal failure in the third and fourth decades of life. Evidence from available studies is limited because of methodological limitations and also because of several HIV-unrelated factors influencing, to some degree, the development of these conditions. Current recommendations for the prevention, diagnosis, monitoring and treatment of metabolic and renal adverse effects in HIV-children and adolescents are based on adult studies, observational pediatric studies and experts' consensus. Healthy lifestyle habits (regarding diet, exercise and refraining from toxic substances) and wise use of ARV options are the only preventive tools for the majority of patients. Should abnormal findings arise, switches in one or more ARV drugs have proved useful. Specific therapies are also available for some of these comorbidities, although the experience in the pediatric age is still very scarce. We aim to summarize the epidemiological, clinical and therapeutic aspects of metabolic and renal adverse effects in vertically HIV-infected children and adolescents.

  3. Assessment of wastewater treatment plant effluent on fish reproduction utilizing the adverse outcome pathway conceptual framework

    EPA Science Inventory

    Wastewater treatment plant (WWTP) effluents are a known contributor of chemical mixture inputs into the environment. Whole effluent testing guidelines were developed to screen these complex mixtures for acute toxicity. However, efficient and cost-effective approaches for screenin...

  4. Adverse effect of agroecosystem pond water on biological endpoints of common toad (Rhinella arenarum) tadpoles.

    PubMed

    Babini, María Selene; Bionda, Clarisa de Lourdes; Salas, Nancy Edith; Martino, Adolfo Ludovico

    2016-08-01

    Chemical prroducts used in farming and wastes from livestock can contaminate pond water in agroecosystems due to runoff. Amphibians using these ponds for breeding are probably exposed to pollutants, and serious consequences might be observed afterward at the population level. Assessment biological endpoints of anuran to water quality give a realistic estimate of the probability of occurrence of adverse effects and provide an early warning signal. In this study, the ecotoxicity of agroecosystem ponds from the south of Córdoba province, Argentina, was investigated. Ponds in four sites with different degrees of human disturbance were selected: three agroecosystems (A1, A2, A3) and a site without crops or livestock (SM). The effect of pond water quality on the biological endpoint of Rhinella arenarum tadpoles was examined using microcosms with pond water from sites. Biological endpoints assessed were as follows: mortality, growth, development, morphological abnormalities (in body shape, gut, and labial tooth row formula), behavior, and blood cell parameters (micronucleus and nuclear abnormalities). Results indicated that water from agroecosystems has adverse effect on early life stage of R. arenarum. High mortality and fewer metamorphs were recorded in the A1 and A3 treatments. Tadpoles and metamorphs from A1 and A2 treatments had lower body condition. Tadpoles from A1 and A3 showed the highest prevalence of morphological abnormalities. The lowest amount of tadpoles feeding and the highest percentage of tadpoles swimming on the surface were observed in treatments with agroecosystem pond water. The higher frequencies of micronuclei and nuclear abnormalities were recorded in tadpoles from A1, A2, and A3 treatments. We check the sensitivity of the biological endpoints of R. arenarum tadpoles like early warning indicators of water quality. We found that the poor water quality of agroecosystem ponds has impact on the health of the tadpoles, and this could affect the

  5. Adverse Effects of Osteocytic Constitutive Activation of ß-Catenin on Bone Strength and Bone Growth.

    PubMed

    Chen, Sixu; Feng, Jianquan; Bao, Quanwei; Li, Ang; Zhang, Bo; Shen, Yue; Zhao, Yufeng; Guo, Qingshan; Jing, Junjun; Lin, Shuxian; Zong, Zhaowen

    2015-07-01

    The activation of the canonical Wnt/β-catenin signaling pathway in both mesenchymal stem cells and osteoblasts has been demonstrated to increase bone mass, showing promise for the treatment of low bone volume conditions such as osteoporosis. However, the possible side effects of manipulating this pathway have not been fully addressed. Previously, we reported that the constitutive activation of ß-catenin in osteoblasts impaired vertebral linear growth. In the present study, β-catenin was constitutively activated in osteocytes by crossing Catnb+/lox(exon 3) mice with dentin matrix protein 1(DMP1)-Cre transgenic mice, and the effects of this activation on bone mass, bone growth and bone strength were then observed. DMP1-Cre was found to be predominantly expressed in osteocytes, with weak expression in a small portion of osteoblasts and growth plate chondrocytes. After the activation, the cancellous bone mass was dramatically increased, almost filling the entire bone marrow cavity in long bones. However, bone strength decreased significantly. Thinner and more porous cortical bone along with impaired mineralization were responsible for the decrease in bone strength. Furthermore, the mice showed shorter stature with impaired linear growth of the long bones. Moreover, the concentration of serum phosphate decreased significantly after the activation of ß-catenin, and a high inorganic phosphate (Pi) diet could partially rescue the phenotype of decreased mineralization level and impaired linear growth. Taken together, the constitutive activation of β-catenin in osteocytes may increase cancellous bone mass; however, the activation also had adverse effects on bone strength and bone growth. These adverse effects should be addressed before the adoption of any therapeutic clinical application involving adjustment of the Wnt/β-catenin signaling pathway.

  6. Adverse Events During Immunotherapy Against Grass Pollen-Induced Allergic Rhinitis - Differences Between Subcutaneous and Sublingual Treatment.

    PubMed

    Aasbjerg, Kristian; Dalhoff, Kim Peder; Backer, Vibeke

    2015-08-01

    Allergic rhinitis (AR) triggered by grass pollen is a common disease, affecting millions of people worldwide. Treatment consists of symptom-alleviating drugs, such as topical corticosteroids or antihistamines. Another option is potentially curative immunotherapy, currently available as sublingual and subcutaneous treatment. We investigated the potential differences in the prevalence and severity of adverse events related to subcutaneous and sublingual immunotherapy (SLIT) against grass pollen-induced AR. A thorough literature search was performed with PubMed and EMBASE. The findings were compared with the available summaries of product characteristics (SPC) and with commercial pharmacology databases (Micromedex). The majority of available safety data originate from registered products of standardized allergens. A surprisingly large percentage of drugs, especially those used in the United States, have no systematically collected safety data. No sufficiently powered randomized trials comparing sublingual and subcutaneous immunotherapy (SCIT) were available, but general safety assessments indicate that sublingual tablet treatment is safer than subcutaneous treatment. Not all commonly used immunotherapy drugs are officially registered, and not all have systematically collected safety data. This is especially true for older drugs used in the United States. In contrast, newer drugs that have undergone extensive clinical testing have better documentation, but unified collection of safety data is still lacking. Considering the evidence available, most drugs elicit similar side effects from the same organ systems, and symptoms from the sublingual drug classes are probably less severe. However, a head-to-head comparison of safety and efficacy is lacking.

  7. [Parkinson syndrome, a possible adverse effect of calcium inhibitors].

    PubMed

    Malaterre, H R; Lauribe, P; Paganelli, F; Ramond, B; Lévy, S

    1992-09-01

    The effects of calcium inhibitors are not limited to the muscles and may affect other systems and cause varied side effects. Two cases of Parkinsonian syndrome occurring after starting therapy with calcium inhibitors (verapamil in one case and diltiazem in the other) are reported. Complete regression of the symptoms after withdrawing the drugs was strongly in favour of a causal relationship. The condition could be due to inhibition of the calcium channels in the central nervous system disturbing neurotransmission. This seems to be a rare side effect as there have only been three other reported cases of secondary extrapyramidal syndromes in the literature. However, a Parkinsonian syndrome is very invalidating and clinicians using this family of drugs should be aware of this possible complication.

  8. Update on raloxifene: mechanism of action, clinical efficacy, adverse effects, and contraindications.

    PubMed

    Gizzo, Salvatore; Saccardi, Carlo; Patrelli, Tito Silvio; Berretta, Roberto; Capobianco, Giampiero; Di Gangi, Stefania; Vacilotto, Antonio; Bertocco, Anna; Noventa, Marco; Ancona, Emanuele; D'Antona, Donato; Nardelli, Giovanni Battista

    2013-06-01

    Raloxifene is the only selective estrogen receptor modulator approved for long-term treatment in the prevention of osteoporotic fractures and for the reduction of invasive breast cancer risk in post-menopausal women. The demonstrated beneficial effects on bone and mammalian tissue led clinical and molecular research to focus mainly on these organs, giving less attention to all other systemic effects. The aim of this review was to evaluate all described systemic effects of raloxifene, investigating its molecular and tissutal mechanism of action. A literature research was carried out in electronic databases MEDLINE, EMBASE, ScienceDirect, and the Cochrane Library in interval time between 2000 and 2012. Outcomes were considered in relation to positive/adverse effects concerning bone metabolism, lipid metabolism, coagulation pattern, menopausal symptoms, breast cancer onset, and endometrial cancer onset. Raloxifene acts as an estrogen agonist or antagonist depending on the tissue. This feature is related to specific actions on at least 2 distinct estrogen receptors, whose proportions vary according to tissue type. Raloxifene is a drug for the treatment of osteoporosis and for the prevention of estrogen receptor-positive breast cancer because it guarantees a safety profile on the endometrium. Raloxifene is furthermore an effective therapy in women with increased levels of plasma cholesterol. Raloxifene treatment shifts the coagulation pattern toward prothrombosis, and the patients should be exhaustively informed about the risks associated with therapy. Raloxifene does not show to affect memory and cognition. Finally, it is noteworthy that quality-of-life studies demonstrated some favorable effects of raloxifene.

  9. The (Adverse) Effects of Expanding Higher Education: Evidence from Italy

    ERIC Educational Resources Information Center

    Oppedisano, Veruska

    2011-01-01

    Over the period 1995-1998 Italy experienced an expansion of its higher education supply with the aim of reducing regional differences in educational attainment. This paper evaluates the effects of this policy on enrolment, drop out and academic performance. The paper combines differences across provinces in the number of campuses constructed with…

  10. Concrete blocks` adverse effects on indoor air and recommended solutions

    SciTech Connect

    Ruppersberger, J.S.

    1995-04-01

    Air infiltration through highly permeable concrete blocks can allow entry of various serious indoor air pollutants including radon. An easy approach to avoiding these pollutants is to select a less-air-permeable concrete block. Tests show that air permeability of concrete blocks can vary by a factor greater than 50 (0.63--35 standard L/min/m{sup 2} at 3 Pa). The surface texture of the blocks correlates well with air permeability; test results of smoother, closed-surface-texture blocks were usually less air-permeable. During construction, air infiltration can be minimized by capping walls and carefully sealing around openings for utilities or other penetrations. Structures with indoor air-quality problems due to soil-gas entry can be mitigated more effectively with less coating material if the blocks have a closed surface texture. All coatings evaluated--cementaceous block filler (which has the lowest applied cost and is more than 99.5% effective), surface bonding cement, water-based epoxy, polysulfide vinyl acrylic, and latex (three coats)--were highly effective (more than 98%) in reducing air permeability when adequately applied. Coating selection should be influenced by expected service life, considering surface condition and cost.

  11. Therapeutic and adverse effects of flunixin-meglumine in adult and young cats.

    PubMed

    Takata, Kenji; Hikasa, Yoshiaki; Satoh, Hiroshi

    2011-12-01

    In this study, we elucidated the difference in nonsteroidal anti-inflammatory drug sensitivities between young and adult cats on therapeutic and adverse effects. In the prevention of lipopolysaccharide (LPS)-induced hyperthermia using flunixin-meglumine, young (<3 months old) and adult (>12 months old) cats of both sexes were given LPS (0.3 µg/kg, i.v.), and body temperature was measured 24 hr later. Flunixin (1 mg/kg, s.c.) was administered 30 min before the LPS injection. LPS-induced hyperthermia was almost completely inhibited by pre-treatment with flunixin in both adult and young cats. In addition, flunixin showed almost the same antipyretic effects in both young and adult cats. The animals were administered flunixin (1 mg/kg, s.c.) once a day for 3 days, and sacrificed 24 hr later to examine the gastrointestinal mucosal lesions. In adult cats, flunixin caused many severe lesions in the small intestine. In contrast, very few gastrointestinal lesions were produced by flunixin in young cats. In the pharmacokinetics of flunixin, plasma concentrations of flunixin were analysed using a high performance liquid chromatography. There were no significant differences in plasma concentration of flunixin between young and adult cats from 0.5 to 4 hr after the injection. These results demonstrated that NSAIDs could be used more safely in young than in adult cats from the points of gastrointestinal adverse effects. Furthermore, this difference in gastrointestinal lesions between adult and young cats was not related with the plasma concentration of flunixin.

  12. PERTINENT DRY NEEDLING CONSIDERATIONS FOR MINIMIZING ADVERSE EFFECTS – PART ONE

    PubMed Central

    Halle, Rob J.

    2016-01-01

    ABSTRACT Background Dry needling is an evidence-based treatment technique that is accepted and used by physical therapists in the United States. This treatment approach focuses on releasing or inactivating muscular trigger points to decrease pain, reduce muscle tension, and assist patients with an accelerated return to active rehabilitation. Issue While commonly used, the technique has some patient risk and value of the treatment should be based on benefit compared to the potential risk. Adverse effects (AEs) with dry needling can be mild or severe, with overall incidence rates varying from zero to rates of approximately 10 percent. While mild AEs are the rule, any procedure that involves a needle insertion has the potential for an AE, with select regions and the underlying anatomy increasing the risk. Known significant AEs from small diameter needle insertion include pneumothorax, cardiac tamponade, hematoma, infection, central nervous system injury, and other complications. Purpose/Objective Underlying anatomy across individuals has variability, requiring an in-depth knowledge of anatomy prior to any needle placement. This commentary is an overview of pertinent anatomy in the region of the thorax, with a ‘part two’ that addresses the abdomen, pelvis, back, vasovagal response, informed consent and other pertinent issues. The purpose of the commentary is to minimize the risk of a dry needling AE. Conclusions/Implications Dry needling is an effective adjunct treatment procedure that is within the recognized scope of physical therapy practice. Physical therapy education and training provides practitioners with the anatomy, basic sciences, and clinical foundation to use this intervention safely and effectively. A safe and evidenced-based implementation of the procedure is based on a thorough understanding of the underlying anatomy and the potential risks, with risks coordinated with patients via informed consent. Levels of Evidence Level 5 PMID:27525188

  13. The uses and adverse effects of beryllium on health

    PubMed Central

    Cooper, Ross G.; Harrison, Adrian P.

    2009-01-01

    Context: This review describes the health effects of beryllium exposure in the workplace and the environment. Aim: To collate information on the consequences of occupational and environmental exposure to beryllium on physiological function and well being. Materials and Methods: The criteria used in the current review for selecting articles were adopted from proposed criteria in The International Classification of Functioning, Disability, and Health. Articles were classified based on acute and chronic exposure and toxicity of beryllium. Results: The proportions of utilized and nonutilized articles were tabulated. Years 2001–10 gave the greatest match (45.9%) for methodological parameters, followed by 27.71% for 1991–2000. Years 1971–80 and 1981–90 were not significantly different in the information published and available whereas years 1951–1960 showed a lack of suitable articles. Some articles were published in sources unobtainable through requests at the British Library, and some had no impact factor and were excluded. Conclusion: Beryllium has some useful but undoubtedly harmful effects on health and well-being. Measures need to be taken to prevent hazardous exposure to this element, making its biological monitoring in the workplace essential. PMID:20386622

  14. The Adverse Effects of Alcohol on Vitamin A Metabolism

    PubMed Central

    Clugston, Robin D.; Blaner, William S.

    2012-01-01

    The objective of this review is to explore the relationship between alcohol and the metabolism of the essential micronutrient, vitamin A; as well as the impact this interaction has on alcohol-induced disease in adults. Depleted hepatic vitamin A content has been reported in human alcoholics, an observation that has been confirmed in animal models of chronic alcohol consumption. Indeed, alcohol consumption has been associated with declines in hepatic levels of retinol (vitamin A), as well as retinyl ester and retinoic acid; collectively referred to as retinoids. Through the use of animal models, the complex interplay between alcohol metabolism and vitamin A homeostasis has been studied; the reviewed research supports the notion that chronic alcohol consumption precipitates a decline in hepatic retinoid levels through increased breakdown, as well as increased export to extra-hepatic tissues. While the precise biochemical mechanisms governing alcohol’s effect remain to be elucidated, its profound effect on hepatic retinoid status is irrefutable. In addition to a review of the literature related to studies on tissue retinoid levels and the metabolic interactions between alcohol and retinoids, the significance of altered hepatic retinoid metabolism in the context of alcoholic liver disease is also considered. PMID:22690322

  15. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  16. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  17. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  18. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  19. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  20. Adverse health effects of air pollutants in a nonsmoking population.

    PubMed

    Pope, C A

    1996-07-17

    Utah Valley has provided an interesting and unique opportunity to evaluate the health effects of respirable particulate air pollution (PM10). Residents of this valley are predominantly nonsmoking members of the Church of Jesus Christ of Latter-day Saints (Mormons). The area has moderately high average PM10 levels with periods of highly elevated PM10 concentrations due to local emissions being trapped in a stagnant air mass near the valley floor during low-level temperature inversion episodes. Due to a labor dispute, there was intermittent operation of the single largest pollution source, an old integrated steel mill. Levels of other common pollutants including sulfur dioxide, ozone, and acidic aerosol are relatively low. Studies specific to Utah Valley have observed that elevated PM10 concentrations are associated with: (1) decreased lung function; (2) increased incidence of respiratory symptoms; (3) increased school absenteeism; (4) increased respiratory hospital admissions; and (5) increased mortality, especially respiratory and cardiovascular mortality.

  1. Estradiol uptake, toxicity, metabolism, and adverse effects on cadmium-treated amphibian embryos.

    PubMed Central

    Fridman, Osvaldo; Corró, Lucrecia; Herkovits, Jorge

    2004-01-01

    The exposure of Bufo arenarum embryos to 25 micromol/L 17beta-estradiol (E2) resulted in 100% lethality within 48 hr, whereas 10 micromol//L E2 was the no observed effect concentration value for short-term chronic (7 days) exposure. The toxicity profile curves show that lethal effects were proportional to the E2 concentration and the time of exposure. The E2 uptake resulted in 20.1 ng E2/mg embryo at 8 hr posttreatment, but 67.3% of this value was achieved during the first 30 min of incubation with this estrogen. Regarding metabolism, the embryos synthesize estrone (E1) from E2 by means of 17beta-hydroxysteroid dehydrogenase. Simultaneous treatments of Bufo arenarum embryos with 1 mg/L Cd2+ and 0.1, 1, or 10 micromol/L E2 enhanced the lethality exerted by cadmium in 76.7, 80, and 83.3% of embryos, respectively. The results indicate that estrogenic endocrine disruptors could have an adverse effect on amphibian embryos and enhance the toxic effect of Cd on amphibian embryos. This study points to the possibility of using the AMPHITOX test as a screening method for potential endocrine disruption as well as the combined effects of chemical mixtures. PMID:15175173

  2. Risk factors for treatment-related adverse events in cancer-bearing dogs receiving piroxicam.

    PubMed

    Eichstadt, L R; Moore, G E; Childress, M O

    2016-10-06

    Piroxicam has antitumour effects in dogs with cancer, although side effects may limit its use. The purpose of this study was to retrospectively identify factors predisposing cancer-bearing dogs to adverse events (AEs) following piroxicam therapy. Medical records of dogs presented to the Purdue Veterinary Teaching Hospital between 2005 and 2015 were reviewed, and 137 dogs met the criteria for study inclusion. Toxic effects of piroxicam in these dogs were graded according to an established system. Multivariate logistic regression was used to estimate the extent to which certain factors affected the risk for AEs. Age [odds ratio (OR) 1.250, P = 0.009; 95% confidence interval (CI) 1.057-1.479] and concurrent use of gastroprotectant medications (OR 2.612, P = 0.025; 95% CI 1.127-6.056) significantly increased the risk for gastrointestinal AEs. The results of this study may help inform the risk versus benefit calculation for clinicians considering the use of piroxicam to treat dogs with cancer.

  3. Adverse Structural and Functional Effects of Marijuana on the Brain: Evidence Reviewed.

    PubMed

    Mandelbaum, David E; de la Monte, Suzanne M

    2017-01-01

    The growing use and legalization of cannabis are leading to increased exposures across all age groups, including in adolescence. The touting of its medicinal values stems from anecdotal reports related to treatment of a broad range of illnesses including epilepsy, multiple sclerosis, muscle spasms, arthritis, obesity, cancer, Alzheimer disease, Parkinson disease, post-traumatic stress, inflammatory bowel disease, and anxiety. However, anecdotal data and the high level of interest in this treatment must not obscure objective assessments of any potential and realized short- and long-term adverse effects of cannabis, particularly with respect to age of onset and chronicity of exposure. This critical review focuses on evidence-based research designed to assess both therapeutic benefits and harmful effects of cannabis exposure and is combined with an illustration of the neuropathologic findings in a fatal case of cannabis-induced psychosis. The literature and reported case provide strong evidence that chronic cannabis abuse causes cognitive impairment and damages the brain, particularly white matter, where cannabinoid 1 receptors abound. Contrary to popular perception, there are few objective data supporting preferential use of cannabis over conventional therapy for restoration of central nervous system structure and function in disease states such as multiple sclerosis, epilepsy, or schizophrenia. Additional research is needed to determine if subsets of individuals with various neurological and psychiatric diseases derive therapeutic benefits from cannabis.

  4. Adversity in Preschool-Aged Children: Effects on Salivary Interleukin-1β

    PubMed Central

    Tyrka, Audrey R.; Parade, Stephanie H.; Valentine, Thomas R.; Eslinger, Nicole M.; Seifer, Ronald

    2016-01-01

    Exposure to early life adversity is linked to impaired affective, cognitive, and behavioral functioning and increases risk for various psychiatric and medical conditions. Stress-induced increases in pro-inflammatory cytokines may be a biological mechanism of these effects. Few studies have examined cytokine levels in children experiencing early life adversity, and very little research has investigated cytokines or other markers of inflammation in saliva. In the present study, we examined salivary IL-1β and C-reactive protein (CRP) levels in relation to stress exposure in 40 children aged 3 to 5 years who were enrolled in a larger study of early life adversity. Childhood maltreatment status was assessed via review of child welfare records, and contextual stress exposure, traumatic life event history, and symptoms of psychopathology were assessed via caregiver interviews at a home visit. In a subsequent visit, salivary IL-1β and CRP were obtained before and after participation in four emotion-eliciting tasks. Number of past month contextual stressors, lifetime contextual stressors, and traumatic life events each demonstrated a significant main effect on IL-1β. Baseline IL-1β was positively associated with each of the significant main-effect adversities. Post-challenge IL-1β displayed positive associations with each adversity variable, but were not significant. CRP was not significantly associated with any of the adversity variables. Given evidence suggesting involvement of IL-1β in the neuropathology of psychiatric conditions, these results may have important implications for developmental outcomes. PMID:25997772

  5. Common Adverse Effects of Anti-TNF Agents on Gestation

    PubMed Central

    Antsaklis, Panagiotis; Galanopoulos, Nikolaos; Kontomanolis, Emmanuel

    2016-01-01

    Autoimmune disease has affected up to 50 million Americans, according to the American Autoimmune Related Diseases Association (AARDA) and 75 percent of those affected are women. These inflammatory diseases have variable activity and a lot of women will have to undergo major therapies during and after pregnancy. Many of the women suffering from these disease will improve during gestation. However a lot of women will require continuation of disease-modifying therapies (i.e., biological therapies) throughout pregnancy and post-partum involving many risks. In the past decade all gaze turned to biological therapies, as an attempt, to obtain even more effective medications in order to suppress the exacerbation of autoimmune disease, even at the most unfit circumstances such as pregnancy. The results are both satisfying and promising since increasingly proven thoughts prevail on making anti-TNF agents first-line medications, clearing up the limited knowledge over human influence. The purpose of this review is to summarize the results of the reports with the highest and representative range of patients of the last decade involving the use of anti-TNF agents during pregnancy. PMID:28044081

  6. Adverse effects of psychological therapy: An exploratory study of practitioners' experiences from child and adolescent psychiatry.

    PubMed

    Jonsson, Ulf; Johanson, Josefin; Nilsson, Elin; Lindblad, Frank

    2016-07-01

    The scientific knowledge about adverse effects of psychological therapies and how such effects should be detected is limited. It is possible that children and adolescents are particularly vulnerable and need specific support in order to express adverse effects. In this exploratory study, we used a qualitative approach to explore practitioners' experiences of this phenomenon. Fourteen practitioners providing psychological therapy within the Child and Adolescent Psychiatric Service were interviewed. Qualitative content analysis was applied to the data. Four overarching categories brought up by the practitioners were identified: vagueness of the concept (reflecting that the concept was novel and hard to define), psychotherapist-client interaction (encompassing aspects of the interaction possibly related to adverse effects), consequences for the young person (including a range of emotional, behavioural and social consequences) and family effects (e.g. professional complications and decreased autonomy for the parent). Professional discussions on these issues could improve psychological therapy for children and adolescents. Based on our findings and previous research, we propose three basic aspects to consider when adverse effects are detected and managed in this context: typology (form, severity and duration), aetiology (hypothesis about the causes) and perspective (adverse effects seen from the points of view of different interested parties).

  7. Response to treatment and adverse events associated with use of recombinant activated factor VII in children: a retrospective cohort study

    PubMed Central

    Cooper, James D.; Ritchey, Arthur K.

    2016-01-01

    Background: Recombinant activated factor VII (rFVIIa) is United States (US) Food and Drug Administration (FDA)-approved for patients with hemophilia with inhibitors or congenital factor VII deficiency. Initial reports of off-label use highlighted its efficacy, though newer reports have not repeated these findings. In both types of publication, though, secondary thromboses have been seen in adult patients. The data in children are less clear. Methods: This study analyzed all rFVIIa use at a large children’s hospital for characteristics and outcomes. Recipients of rFVIIa were identified retrospectively via the electronic medical record. Data on patient diagnosis, lab data, other treatments, adverse events, and outcomes were collected. Results: Over 33 months, 66 patient episodes were treated with a total of 606 doses (median = 2). The most common indication (36.4%) was gastrointestinal bleeding (24/66 patients). Only one patient received a dose for an approved labeled indication. For control of bleeding, 33.3% of courses were unsuccessful (19/57). Bleeding from multiple sites was associated with treatment failure. In 16.7% of patients (11/66), unexpected adverse thromboses developed within 1 week of completing a course of rFVIIa. Thromboses in both intra- and extra-corporeal sites were included if they compromised patient care. Conclusions: In the majority of cases reviewed, rFVIIa was successful in stopping or slowing serious bleeding episodes. It was least effective when a patient had diffuse bleeding at the time of administration. The thrombosis rate of 16.7% was higher than expected, though causality cannot be declared. Further investigation is needed to determine the risk–benefit ratio in children. PMID:28255432

  8. Assessment of Aerobic Exercise Adverse Effects during COPD Exacerbation Hospitalization

    PubMed Central

    Mesquita, Carolina Bonfanti; Caram, Laura M. O.; Dourado, Victor Zuniga; de Godoy, Irma; Tanni, Suzana Erico

    2017-01-01

    Introduction. Aerobic exercise performed after hospital discharge for exacerbated COPD patients is already recommended to improve respiratory and skeletal muscle strength, increase tolerance to activity, and reduce the sensation of dyspnea. Previous studies have shown that anaerobic activity can clinically benefit patients hospitalized with exacerbated COPD. However, there is little information on the feasibility and safety of aerobic physical activity performed by patients with exacerbated COPD during hospitalization. Objective. To evaluate the effects of aerobic exercise on vital signs in hospitalized patients with exacerbated COPD. Patients and Methods. Eleven COPD patients (63% female, FEV1: 34.2 ± 13.9% and age: 65 ± 11 years) agreed to participate. Aerobic exercise was initiated 72 hours after admission on a treadmill; speed was obtained from the distance covered in a 6-minute walk test (6MWT). Vital signs were assessed before and after exercise. Results. During the activity systolic blood pressure increased from 125.2 ± 13.6 to 135.8 ± 15.0 mmHg (p = 0.004) and respiratory rate from 20.9 ± 4.4 to 24.2 ± 4.5 rpm (p = 0.008) and pulse oximetry (SpO2) decreased from 93.8 ± 2.3 to 88.5 ± 5.7% (p < 0.001). Aerobic activity was considered intense, heart rate ranged from 99.2 ± 11.5 to 119.1 ± 11.1 bpm at the end of exercise (p = 0.092), and patients reached on average 76% of maximum heart rate. Conclusion. Aerobic exercise conducted after 72 hours of hospitalization in patients with exacerbated COPD appears to be safe. PMID:28265180

  9. Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery.

    PubMed

    Savulich, G; Riccelli, R; Passamonti, L; Correia, M; Deakin, J F W; Elliott, R; Flechais, R S A; Lingford-Hughes, A R; McGonigle, J; Murphy, A; Nutt, D J; Orban, C; Paterson, L M; Reed, L J; Smith, D G; Suckling, J; Tait, R; Taylor, E M; Sahakian, B J; Robbins, T W; Ersche, K D

    2017-03-07

    Naltrexone is an opioid receptor antagonist used in the management of alcohol dependence. Although the endogenous opioid system has been implicated in emotion regulation, the effects of mu-opioid receptor blockade on brain systems underlying negative emotional processing are not clear in addiction. Individuals meeting criteria for alcohol dependence alone (n=18, alcohol) and in combination with cocaine and/or opioid dependence (n=21, alcohol/drugs) and healthy individuals without a history of alcohol or drug dependence (n=21) were recruited. Participants were alcohol and drug abstinent before entered into this double-blind, placebo-controlled, randomized, crossover study. Functional magnetic resonance imaging was used to investigate brain response while viewing aversive and neutral images relative to baseline on 50 mg of naltrexone and placebo. We found that naltrexone modulated task-related activation in the medial prefrontal cortex and functional connectivity between the anterior cingulate cortex and the hippocampus as a function of childhood adversity (for aversive versus neutral images) in all groups. Furthermore, there was a group-by-treatment-by-condition interaction in the right amygdala, which was mainly driven by a normalization of response for aversive relative to neutral images under naltrexone in the alcohol/drugs group. We conclude that early childhood adversity is one environmental factor that influences pharmacological response to naltrexone. Pharmacotherapy with naltrexone may also have some ameliorative effects on negative emotional processing in combined alcohol and drug dependence, possibly due to alterations in endogenous opioid transmission or the kappa-opioid receptor antagonist actions of naltrexone.

  10. Interactive effects of social adversity and respiratory sinus arrhythmia activity on reactive and proactive aggression.

    PubMed

    Zhang, Wei; Gao, Yu

    2015-10-01

    Abnormal parasympathetic nervous system (PNS)-related cardiac activity has been linked to aggression. However, little is known about how it interacts with psychosocial adversity in predisposing to reactive-proactive aggression. In the current study, 84 male and female college students self-reported reactive and proactive aggression, and were assessed for respiratory sinus arrhythmia (RSA), a measure of PNS-related cardiac activity, during rest and when they contemplated an emotion-evoking decision-making task. Regression analyses showed that (a) resting RSA was positively linked to reactive aggression in conditions of high social adversity, and (b) RSA reactivity was positively associated with reactive but negatively associated with proactive aggression, in conditions of low social adversity. Main effects were not found for psychophysiological functioning or psychosocial adversity, suggesting the importance of their interaction. Findings support a biosocial basis for aggression and add additional support for the distinctions between reactive and proactive aggression.

  11. Local adverse effects associated with the use of inhaled corticosteroids in patients with moderate or severe asthma*

    PubMed Central

    Pinto, Charleston Ribeiro; Almeida, Natalie Rios; Marques, Thamy Santana; Yamamura, Laira Lorena Lima; Costa, Lindemberg Assunção; Souza-Machado, Adelmir

    2013-01-01

    OBJECTIVE: To describe and characterize local adverse effects (in the oral cavity, pharynx, and larynx) associated with the use of inhaled corticosteroids (ICSs) in patients with moderate or severe asthma. METHODS: This was a cross-sectional study involving a convenience sample of 200 asthma patients followed in the Department of Pharmaceutical Care of the Bahia State Asthma and Allergic Rhinitis Control Program Referral Center, located in the city of Salvador, Brazil. The patients were ≥ 18 years of age and had been using ICSs regularly for at least 6 months. Local adverse effects (irritation, pain, dry throat, throat clearing, hoarseness, reduced vocal intensity, loss of voice, sensation of thirst, cough during ICS use, altered sense of taste, and presence of oral candidiasis) were assessed using a 30-day recall questionnaire. RESULTS: Of the 200 patients studied, 159 (79.5%) were women. The mean age was 50.7 ± 14.4 years. In this sample, 55 patients (27.5%) were using high doses of ICS, with a median treatment duration of 38 months. Regarding the symptoms, 163 patients (81.5%) reported at least one adverse effect, and 131 (65.5%) had a daily perception of at least one symptom. Vocal and pharyngeal symptoms were identified in 57 (28.5%) and 154 (77.0%) of the patients, respectively. The most commonly reported adverse effects were dry throat, throat clearing, sensation of thirst, and hoarseness. CONCLUSIONS: Self-reported adverse effects related to ICS use were common among the asthma patients evaluated here. PMID:24068261

  12. Prospective Observational Study of Adverse Drug Reactions of Anticancer Drugs Used in Cancer Treatment in a Tertiary Care Hospital.

    PubMed

    Saini, V K; Sewal, R K; Ahmad, Yusra; Medhi, B

    2015-01-01

    Adverse drug reactions associated with the use of anticancer drugs are a worldwide problem and cannot be ignored. Adverse drug reactions can range from nausea, vomiting or any other mild reaction to severe myelosuppression. The study was planned to observe the suspected adverse drug reactions of cancer chemotherapy in patients aged >18 years having cancer attending Postgraduate Institute of Medical Education and Research, Chandigarh. During the study period, 101 patients of breast cancer and 73 patients of lung cancer were screened for occurrence of adverse drug reactions during their treatment with chemotherapy. About 87.36% patients experienced adverse drug reactions, 90.09% and 83.56% of breast and lung cancer patients experienced at least one adverse drug reaction respectively. In breast cancer patients, 41.58% patients were prescribed fluorouracil+doxorubicin+cyclophosphamide while paclitaxel was prescribed to 22.77% patients. Alopecia (54.94%), nail discolouration (43.96%), dysgeusia (38.46%), anorexia (30.77%), nausea (29.67%), and neuropathy (29.67%) were found to be very common in breast cancer patients treated with single/combined regimen. In lung cancer group of patients, cisplatin with docetaxel, cisplatin with pemetrexed and cisplatin with irinotecan were prescribed to 30.14, 24.65 and 17.81% patients, respectively. Dysgeusia (40.98%), diarrhoea (39.34%), anorexia (32.77%) and constipation (31.15%) and alopecia (31.15%) were commonly observed adverse drug reactions having lung cancer patients. Causality assessments using World Health Organization causality assessment scale showed that observed adverse drug reactions were of probable (64.67%) and possible (35.33%) categories. Alopecia, dysgeusia, anorexia, constipation diarrhoea, nausea, nail discoloration were more prevalent amongst the cancer patients undergoing chemotherapy.

  13. Pretreatment Predictors of Adverse Radiation Effects After Radiosurgery for Arteriovenous Malformation

    SciTech Connect

    Hayhurst, Caroline; Monsalves, Eric; Prooijen, Monique van; Cusimano, Michael; Tsao, May; Menard, Cynthia; Kulkarni, Abhaya V.; Schwartz, Michael; Zadeh, Gelareh

    2012-02-01

    Purpose: To identify vascular and dosimetric predictors of symptomatic T2 signal change and adverse radiation effects after radiosurgery for arteriovenous malformation, in order to define and validate preexisting risk models. Methods and Materials: A total of 125 patients with arteriovenous malformations (AVM) were treated at our institution between 2005 and 2009. Eighty-five patients have at least 12 months of clinical and radiological follow-up. Any new-onset headaches, new or worsening seizures, or neurological deficit were considered adverse events. Follow-up magnetic resonance images were assessed for new onset T2 signal change and the volume calculated. Pretreatment characteristics and dosimetric variables were analyzed to identify predictors of adverse radiation effects. Results: There were 19 children and 66 adults in the study cohort, with a mean age of 34 (range 6-74). Twenty-three (27%) patients suffered adverse radiation effects (ARE), 9 patients with permanent neurological deficit (10.6%). Of these, 5 developed fixed visual field deficits. Target volume and 12 Gy volume were the most significant predictors of adverse radiation effects on univariate analysis (p < 0.001). Location and cortical eloquence were not significantly associated with the development of adverse events (p = 0.12). No additional vascular parameters were identified as predictive of ARE. There was a significant target volume threshold of 4 cm{sup 3}, above which the rate of ARE increased dramatically. Multivariate analysis target volume and the absence of prior hemorrhage are the only significant predictors of ARE. The volume of T2 signal change correlates to ARE, but only target volume is predictive of a higher volume of T2 signal change. Conclusions: Target volume and the absence of prior hemorrhage is the most accurate predictor of adverse radiation effects and complications after radiosurgery for AVMs. A high percentage of permanent visual field defects in this series suggest the

  14. Dose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.

    PubMed

    Ojo, Olajumoke Omolara; Bhadauria, Smrati; Rath, Srikanta Kumar

    2013-01-01

    Salinomycin is used as an antibiotic in animal husbandry. Its implication in cancer therapy has recently been proposed. Present study evaluated the toxic effects of Salinomycin on male reproductive system of mice. Doses of 1, 3 or 5 mg/kg of Salinomycin were administered daily for 28 days. Half of the mice were sacrificed after 24 h of the last treatment and other half were sacrificed 28 days after withdrawal of treatment. Effects of SAL on body and reproductive organ weights were studied. Histoarchitecture of testis and epididymis was evaluated along with ultrastructural changes in Leydig cells. Serum and testicular testosterone and luteinizing hormones were estimated. Superoxide dismutase, reduced glutathione, lipid peroxidation, catalase and lactate dehydrogenase activities were measured. Spermatozoa count, morphology, motility and fertility were evaluated. Expression patterns of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage proteins (CYP11A1) were assessed by Western blotting. Salinomycin treatment was lethal to few mice and retarded body growth in others with decreased weight of testes and seminal vesicles in a dose dependent manner. Seminiferous tubules in testes were disrupted and the epithelium of epididymis showed frequent occurrence of vacuolization and necrosis. Leydig cells showed hypertrophied cytoplasm with shrunken nuclei, condensed mitochondria, proliferated endoplasmic reticulum and increased number of lipid droplets. Salinomycin decreased motility and spermatozoa count with increased number of abnormal spermatozoa leading to infertility. The testosterone and luteinizing hormone levels were decreased in testis but increased in serum at higher doses. Depletion of superoxide dismutase and reduced glutathione with increased lipid peroxidation in both testis and epididymis indicated generation of oxidative stress. Suppressed expression of StAR and CYP11A1 proteins indicates inhibition of steroidogenesis

  15. Dose-Dependent Adverse Effects of Salinomycin on Male Reproductive Organs and Fertility in Mice

    PubMed Central

    Ojo, Olajumoke Omolara; Bhadauria, Smrati; Rath, Srikanta Kumar

    2013-01-01

    Salinomycin is used as an antibiotic in animal husbandry. Its implication in cancer therapy has recently been proposed. Present study evaluated the toxic effects of Salinomycin on male reproductive system of mice. Doses of 1, 3 or 5 mg/kg of Salinomycin were administered daily for 28 days. Half of the mice were sacrificed after 24 h of the last treatment and other half were sacrificed 28 days after withdrawal of treatment. Effects of SAL on body and reproductive organ weights were studied. Histoarchitecture of testis and epididymis was evaluated along with ultrastructural changes in Leydig cells. Serum and testicular testosterone and luteinizing hormones were estimated. Superoxide dismutase, reduced glutathione, lipid peroxidation, catalase and lactate dehydrogenase activities were measured. Spermatozoa count, morphology, motility and fertility were evaluated. Expression patterns of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage proteins (CYP11A1) were assessed by Western blotting. Salinomycin treatment was lethal to few mice and retarded body growth in others with decreased weight of testes and seminal vesicles in a dose dependent manner. Seminiferous tubules in testes were disrupted and the epithelium of epididymis showed frequent occurrence of vacuolization and necrosis. Leydig cells showed hypertrophied cytoplasm with shrunken nuclei, condensed mitochondria, proliferated endoplasmic reticulum and increased number of lipid droplets. Salinomycin decreased motility and spermatozoa count with increased number of abnormal spermatozoa leading to infertility. The testosterone and luteinizing hormone levels were decreased in testis but increased in serum at higher doses. Depletion of superoxide dismutase and reduced glutathione with increased lipid peroxidation in both testis and epididymis indicated generation of oxidative stress. Suppressed expression of StAR and CYP11A1 proteins indicates inhibition of steroidogenesis

  16. Luteinizing hormone--releasing hormone agonists: a quick reference for prevalence rates of potential adverse effects.

    PubMed

    Walker, Lauren M; Tran, Susan; Robinson, John W

    2013-12-01

    Men with prostate cancer (PCa) frequently undergo androgen deprivation therapy (ADT), typically in the form of a depot injection of luteinizing hormone-releasing hormone agonists (LHRHa). LHRHa are associated with many adverse effects (eg, hot flashes, sexual dysfunction, loss of muscle mass, osteopenia, metabolic syndrome), which drastically impact patient quality of life. This literature review, which includes a comprehensive table documenting prevalence rates, provides a quick reference for health care professionals involved in the care of men undergoing ADT with LHRHa. Primary sources were acquired from PubMed using the search terms "androgen deprivation therapy" and each potentially adverse effect (eg, "androgen deprivation therapy and hot flashes"). Commonly cited review articles were also examined for citations of original studies containing prevalence rates. More than 270 articles were reviewed. In contrast to many existing reviews, rates are cited exclusively from original sources. The prevalence rates, obtained from original sources, suggest that more than half of documented adverse effects are experienced by as many as 40% or more of patients. A critique of the literature is also provided. Although there is a vast literature of both original and review articles on specific adverse effects of LHRHa, the quality of research on prevalence rates for some adverse effects is subpar. Many review articles contain inaccuracies and do not cite original sources. The table of prevalence rates will serve as a quick reference for health care providers when counseling patients and will aid in the development of evidence-based patient education materials.

  17. Ivermectin for the treatment of Wuchereria bancrofti filariasis. Efficacy and adverse reactions.

    PubMed

    Kumaraswami, V; Ottesen, E A; Vijayasekaran, V; Devi, U; Swaminathan, M; Aziz, M A; Sarma, G R; Prabhakar, R; Tripathy, S P

    1988-06-03

    Ivermectin treatment was evaluated for efficacy and side effects in 40 patients in South India who had microfilaremia and bancroftian filariasis. Ivermectin was administered once orally at four dose levels (range, 25 to 200 micrograms/kg), and at each it was found to be completely effective in clearing blood microfilariae within five to 12 days. In most patients, microfilariae reappeared by three months; by six months the levels averaged 14% to 32% of pretreatment values in the four study groups, and all groups showed equivalent efficacy. Detailed monitoring identified some side effects in almost all patients: usually fever, headache, light-headedness, myalgia, sore throat, or cough that occurred most prominently 18 to 36 hours after treatment. These were most frequent and severe in patients with the greatest microfilaremia, but only when treated with the two higher doses of ivermectin (100 and 200 micrograms/kg). The low-dose (25 micrograms/kg) ivermectin group, despite equivalent efficacy in parasite killing, had clinical reaction scores that were minimal and that were not correlated with parasitemia. Since efficacy and side effects of ivermectin therapy compare favorably with those reported for treatment with the standard antifilarial drug diethylcarbamazine citrate, the major advantage of single-oral-dose administration makes ivermectin the best candidate to replace diethylcarbamazine as the treatment of choice for bancroftian filariasis.

  18. Atenolol Exposure and Risk for Development of Adverse Metabolic Effects: A Pilot Study

    PubMed Central

    Navare, Hrishikesh A.; Frye, Reginald F.; Cooper-DeHoff, Rhonda M.; Shuster, Jonathan J.; Hall, Karen; Schmidt, Siegfried O. F.; Turner, Stephen T.; Johnson, Julie A.

    2010-01-01

    Study Objective To evaluate whether the level of systemic exposure to atenolol explains observed interindividual differences in adverse metabolic responses. Design Open-label, prospective, pharmacokinetic pilot substudy of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study. Setting General clinical research center. Patients Fifteen hypertensive adults (mean age 46 ± 8.9 yrs) who were enrolled in the PEAR study. Intervention Patients received atenolol therapy for at least 8 weeks, with 5 of those weeks at a dosage of 100 mg/day, and then underwent a 2-hour oral glucose tolerance test during a pharmacokinetic study visit. Measurements and Main Results Twenty-hour plasma atenolol concentrations were measured during the pharmacokinetic visit. Glucose and insulin levels were measured during the 2-hour oral glucose tolerance test, and fasting plasma lipid, glucose, and insulin levels were measured at baseline and after 8 weeks of atenolol treatment. A significant association was noted between atenolol area under the concentration-time curve (AUC) and change in fasting glucose level when adjusted for covariates (p=0.0025); the effect was strongest in women. No significant relationship was noted between plasma atenolol concentration and glucose AUC during oral glucose tolerance testing (r=0.08, p=0.78), nor between atenolol AUC and change in triglyceride levels (r=0.13, p=0.63). Conclusion Higher plasma atenolol exposure may be a risk factor for an increase in fasting plasma glucose level during atenolol treatment. These findings require confirmation in a larger sample. PMID:20795842

  19. Pharmacology, toxicology, clinical efficacy, and adverse effects of calcium polycarbophil, an enteral hydrosorptive agent.

    PubMed

    Danhof, I E

    1982-01-01

    Calcium polycarbophil is the calcium salt of polyacrylic acid crosslinked with divinyl glycol. It is chemically and physiologically inert. In dilute alkali it possesses marked hydrophilic capacity (60 to 100 times its weight), which is the basis for its therapeutic use. In daily dosages of 4 to 5 g in adults, it appears to be quite safe, is non-toxic, does not interfere with digestion or absorption, and does not cause gastrointestinal irritation. It appears to be effective in the treatment of both constipation and diarrhea due to functional or organic causes. Several days of continuous use are necessary before effectiveness becomes apparent. Clinical studies, of which there are relatively few, range from uncontrolled, unblinded evaluations of an almost anecdotal nature to well controlled, double-blind, crossover studies. Additional carefully controlled studies on dietary influences, exercise, and patient compliance would be helpful. Adverse effects, which are minimal, include epigastric fullness or heaviness, abdominal distention and bloating, and flatulence. As with all bulk-forming agents, calcium polycarbophil should not be used by persons who have stenotic lesions of the gastrointestinal tract.

  20. The adverse effect of phytoestrogens on the synthesis and secretion of ovarian oxytocin in cattle.

    PubMed

    Mlynarczuk, J; Wrobel, M H; Kotwica, J

    2011-02-01

    The current investigations were undertaken to study the mechanism of the adverse effect of phytoestrogens on the function of bovine granulosa (follicles >1< cm in diameter) and luteal cells from day 1-5, 6-10, 11-15, 16-19 of the oestrous cycle. The cells were incubated with genistein, daidzein or coumestrol (each at the dose of 1 × 10(-6) m). The viability and secretion of estradiol (E2), progesterone (P4) and oxytocin (OT) were measured after 72 h of incubation. Moreover, the expression of mRNA for neurophysin-I/OT (NP-I/OT; precursor of OT) and peptidyl-glycine-α-amidating monooxygenase (PGA, an enzyme responsible for post-translational OT synthesis) was determined after 8 h of treatment. None of the phytoestrogens used affected the viability of cells except for coumestrol. The increased secretion of E2 and P4 was only obtained by coumestrol (p<0.05) from granulosa cells from follicles <1cm in diameter and decreased from luteal cells on days 11-15 of the oestrous cycle, respectively. All three phytoestrogens stimulated (p<0.05) OT secretion from granulosa and luteal cells in all stages of the oestrous cycle and the expression of NP-I/OT mRNA in the both types of cells. The expression of mRNA for PGA was stimulated (p<0.05) by daidzein and coumestrol in granulosa cells, and by genistein and coumestrol in luteal cells. In conclusion, our results demonstrate that these phytoestrogens can impair the ovary function in cattle by adversely affecting the synthesis of OT in follicles and in corpus luteum. However, their influence on the ovarian steroids secretion was less evident.

  1. PERTINENT DRY NEEDLING CONSIDERATIONS FOR MINIMIZING ADVERSE EFFECTS – PART TWO

    PubMed Central

    Halle, Rob J.

    2016-01-01

    Background Dry needling (DN) is an evidence based treatment technique that is accepted and used by physical therapists in the United States. This clinical commentary is the second in a two-part series outlining some of the pertinent anatomy and other issues that are needed for optimal utilization of this treatment modality. Part one was an overview of the thorax with a summary of reported adverse effects (AEs) and the underlying anatomy that could be used to minimize patient risk. As is the case with any intervention, the technique of dry needling has some inherent patient risk. The incidence of AEs with this procedure is typically low, ranging from zero to approximately 10 percent. Knowledge of the underlying anatomy can be a key factor associated with decreasing the likelihood of an AE. Purpose/Objective The second part of this clinical commentary goes beyond the thorax, to explore the anatomy associated with dry needling the abdomen, pelvis, and back. In the abdomen, pelvis and back, dry needling can penetrate the peritoneal cavity or adjacent organs, resulting in AEs. A physiological reaction that is an AE secondary to a needle insertion, pain or fear, is an autonomic vasovagal response. Additionally, suggestions for dealing with the fearful patient, the obese patient, universal precautions, and other clinical considerations, are discussed. The purpose of parts one and part two of this clinical commentary is to minimize the risk of a dry needling AE. Conclusions/Implications Dry needling is an effective adjunctive treatment procedure that is within the recognized scope of practice of the physical therapist. An evidence-based implementation of the procedure must be based on a thorough understanding of the underlying anatomy and the potential risks, with risks communicated to patients via informed consent. Level of Evidence Level 5 PMID:27757293

  2. A review of the adverse effects and safety of noradrenergic antidepressants.

    PubMed

    Whiskey, Eromona; Taylor, David

    2013-08-01

    There are a variety of noradrenergic antidepressants available, most of which act by inhibiting neuronal noradrenaline re-uptake, although few drugs are specific for this action. Where drugs have numerous actions the adverse effects of noradrenaline reuptake may be difficult to isolate, although in this respect the adverse effects of reboxetine, a specific noradrenaline re-uptake inhibitor, are illuminating. Noradrenergic antidepressants typically cause minor changes in blood and heart rate, sweating and insomnia. Other pharmacological actions shown by non-specific antidepressants may act to worsen or mitigate these adverse effects. Noradrenergic drugs are less likely than selective serotonin reuptake inhibitors (SSRIs) to cause sexual dysfunction but more likely to cause urinary hesitancy. Doubts remain over the relative propensity for antidepressants with different modes of action to cause diabetes and hyponatraemia. Noradrenergic actions do not seem to confer a risk of death in overdose.

  3. Adverse Reactions Due to Directly Observed Treatment Strategy Therapy in Chinese Tuberculosis Patients: A Prospective Study

    PubMed Central

    Lv, Xiaozhen; Tang, Shaowen; Xia, Yinyin; Wang, Xiaomeng; Yuan, Yanli; Hu, Daiyu; Liu, Feiying; Wu, Shanshan; Zhang, Yuan; Yang, Zhirong; Tu, Dehua; Chen, Yixin; Deng, Peiyuan; Ma, Yu; Chen, Ru; Zhan, Siyan

    2013-01-01

    Background More than 1 million tuberculosis (TB) patients are receiving directly observed treatment strategy (DOTS) therapy in China every year. As to the profile of adverse drug reactions (ADRs) due to DOTS therapy, no consensus has been reached. There is no report regarding ADRs due to DOTS therapy with a large Chinese TB population. This study aimed to determine the incidence and prognosis of ADRs due to DOTS therapy, and to evaluate their impact on anti-TB treatment in China. Methods A prospective population-based cohort study was performed during 2007–2008. Sputum smear positive pulmonary TB patients who received DOTS therapy were included and followed up for six to nine months in 52 counties of four regions in China. The suspected ADRs were recorded and reviewed by Chinese State Food and Drug Administration. Results A total of 4304 TB patients were included in this study. 649 patients (15.08%) showed at least one ADR and 766 cases in total were detected. The incidence (count) of ADR based on affected organ was: liver dysfunction 6.34% (273), gastrointestinal disorders 3.74% (161), arthralgia 2.51% (108), allergic reactions 2.35% (101), neurological system disorders 2.04% (88), renal impairment 0.07% (3) and others 0.05% (2). Most cases of ADRs (95%) had a good clinical outcome, while two with hepatotoxicity and one with renal impairment died. Compared with patients without ADRs, patients with ADRs were more likely to have positive smear test results at the end of the intensive phase (adjusted OR, 2.00; 95%CI, 1.44–2.78) and unsuccessful anti-TB outcomes (adjusted OR, 2.58; 95%CI, 1.43–4.68). Conclusions The incidence of ADRs due to DOTS therapy was 15.08%. Those ADRs had a substantial impact on TB control in China. This highlighted the importance of developing strategies to ameliorate ADRs both to improve the quality of patient care and to control TB safely. PMID:23750225

  4. Migraine treatment and placebo effect.

    PubMed

    Speciali, José G; Peres, Mário; Bigal, Marcelo E

    2010-03-01

    Placebos are typically defined as physiologically inactive substances that elicit a therapeutic response. The antipode of the placebo effect is the nocebo effect, or the negative effects of placebo, where unpleasant symptoms (e.g., adverse events) emerge after the administration of placebo. Placebo analgesia is one of the most striking examples of the cognitive modulation of pain perception. Herein we focus on the importance of placebo in headache research. We first review the mechanisms of the placebo effect. We then focus on the importance of placebo in the acute treatment of migraine. We follow by discussing the importance of placebo on the preventive treatment of migraine and our perspectives for the 5 years to come regarding the study of the placebos.

  5. 40 CFR 159.184 - Toxic or adverse effect incident reports.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., respiratory, oral). (B) List signs/symptoms/adverse effects. (C) If laboratory tests were performed, list name... effect). (D) Route of exposure (e.g., skin, eye, respiratory, oral). (E) Time between exposure and onset... of systems supplied. (C) If finished water samples, water supply systems sampled. (D) If...

  6. On the Likelihood of Single-Walled Carbon Nanotubes Causing Adverse Marine Ecological Effects

    EPA Science Inventory

    This brief article discusses the ecological effects of single-walled carbon nanotubes (SWNTs)in the marine environment. Based on new research and a review of the scientific literature, the paper concludes that SWNTs are unlikely to cause adverse ecological effects in the marine ...

  7. The College Student and Marijuana: Research Findings Concerning Adverse Biological and Psychological Effects.

    ERIC Educational Resources Information Center

    Nicholi, Armand M., Jr.

    1983-01-01

    This paper focuses on current knowledge about adverse biological and psychological affects of marijuana use, with special reference to risks for college students. Short-term effects on intellectual functioning and perceptual-motor coordination and long-term effects on reproduction and motivation are highlighted. (PP)

  8. Adverse Effect of Prolonged Methylphenidate Treatment on Cardiac Functions

    ClinicalTrials.gov

    2012-09-19

    Attention Deficit Disorder With Hyperactivity; Attention Deficit Disorder; Attention Deficit Hyperactivity Disorder; Attention Deficit Disorders With Hyperactivity; Attention Deficit Hyperactivity Disorders

  9. Thiazolidinediones and their fluid-related adverse effects: facts, fiction and putative management strategies.

    PubMed

    Karalliedde, Janaka; Buckingham, Robin E

    2007-01-01

    Thiazolidinediones (TZDs) or glitazones are agents that are widely used for the treatment of type 2 diabetes mellitus. These drugs have a multitude of therapeutic effects including reduction in insulin resistance and hyperglycaemia, anti-inflammatory effects and amelioration of hypertension, microalbuminuria and hepatic steatosis. The TZD molecular target, peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear transcription factor, is expressed diffusely in humans, including many tissues comprising the cardiovascular and renal systems. This suggests a potential for TZDs to elicit perturbing effects on these systems, which are independent of their effects on glucose and lipid metabolism. One of the most common adverse effects of TZDs is fluid retention, which can result in, or exacerbate, oedema and congestive heart failure (CHF). The frequency of peripheral oedema is approximately 5% when TZDs are used in mono- or combination oral therapy, and about 15% when used with insulin. Patients with type 2 diabetes are at high risk of myriad morbid complications, including CHF. The development of CHF, particularly in the elderly, is a harbinger of premature mortality. TZD-induced oedema is largely peripheral, may have its origins in changes in haemodynamics, with some contribution from molecules, which regulate cell and tissue permeability (e.g. vascular endothelial growth factor and protein kinase Cbeta), and remains the preponderant manifestation of TZD-induced fluid retention even in those with existing heart failure. Preclinical and pilot clinical data attest to the fact that at least part of the fluid retention derives from a direct effect of TZDs on sodium reabsorption via the renal medullary collecting duct, a mechanism that is sensitive to diuretic agents that have this nephron segment as their site of action, in whole or in part (spironolactone, amiloride and hydrochlorothiazide). Our review suggests various potential clinical strategies by which

  10. Short-term medical benefits and adverse effects of weight loss.

    PubMed

    Pi-Sunyer, F X

    1993-10-01

    Weight loss reduces many of the health hazards associated with obesity including insulin resistance, diabetes mellitus, hypertension, dyslipidemia, sleep apnea, hypoxemia and hypercarbia, and osteoarthritis. Potential adverse effects of weight loss include a greater risk for gallstone formation and cholecystitis, excessive loss of lean body mass, water and electrolyte problems, mild liver dysfunction, and elevated uric acid levels. Less consequential problems such as diarrhea, constipation, hair loss, and cold intolerance may also occur. The short-term adverse effects are not severe enough to contraindicate weight loss, nor do they outweigh its short-term benefits.

  11. Trends in anti-D immune globulin for childhood immune thrombocytopenia: usage, response rates, and adverse effects.

    PubMed

    Long, Michelle; Kalish, Leslie A; Neufeld, Ellis J; Grace, Rachael F

    2012-03-01

    In 2010, the Food and Drug Administration (FDA) added a black box warning to anti-D immune globulin (Rho(D) immune globulin, anti-D) for immune thrombocytopenia (ITP) to warn of the complications related to severe hemolysis. The objective of this retrospective medical record review was to examine recent trends in anti-D use to treat ITP and rates of adverse events in a single large pediatric hematology program. Over a 7-year period, 176 (35%) of 502 ITP patients at our center received anti-D. Anti-D was the second most commonly prescribed drug for ITP from 2003 to 2010 overall and was given first most frequently (41%). Sixty-four percent of patients responded to anti-D, but 36% had adverse effects, including five patients requiring hospitalization. From 2003 to 2010, the use of anti-D as an initial therapy for ITP significantly decreased (P < 0.001). This trend preceded the 2010 FDA black box warning. In our experience, anti-D was associated with a significant number of adverse effects when used as a treatment for ITP, although none were life-threatening. Despite recent guidelines suggesting anti-D therapy for initial treatment for ITP, anti-D therapy for ITP has significantly decreased over the past 7 years.

  12. Trends in anti-D immune globulin for childhood immune thrombocytopenia: Usage, response rates, and adverse effects

    PubMed Central

    Long, Michelle; Kalish, Leslie A.; Neufeld, Ellis J.; Grace, Rachael F.

    2013-01-01

    In 2010, the Food and Drug Administration (FDA) added a black box warning to anti-D immune globulin (Rho(D) immune globulin, anti-D) for immune thrombocytopenia (ITP) to warn of the complications related to severe hemolysis. The objective of this retrospective medical record review was to examine recent trends in anti-D use to treat ITP and rates of adverse events in a single large pediatric hematology program. Over a 7-year period, 176 (35%) of 502 ITP patients at our center received anti-D. Anti-D was the second most commonly prescribed drug for ITP from 2003 to 2010 overall and was given first most frequently (41%). Sixty-four percent of patients responded to anti-D, but 36% had adverse effects, including five patients requiring hospitalization. From 2003 to 2010, the use of anti-D as an initial therapy for ITP significantly decreased (P < 0.001). This trend preceded the 2010 FDA black box warning. In our experience, anti-D was associated with a significant number of adverse effects when used as a treatment for ITP, although none were life-threatening. Despite recent guidelines suggesting anti-D therapy for initial treatment for ITP, anti-D therapy for ITP has significantly decreased over the past 7 years. PMID:22190130

  13. Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy?

    PubMed

    Reich, Martin M; Brumberg, Joachim; Pozzi, Nicolò G; Marotta, Giorgio; Roothans, Jonas; Åström, Mattias; Musacchio, Thomas; Lopiano, Leonardo; Lanotte, Michele; Lehrke, Ralph; Buck, Andreas K; Volkmann, Jens; Isaias, Ioannis U

    2016-09-21

    Thalamic deep brain stimulation is a mainstay treatment for severe and drug-refractory essential tremor, but postoperative management may be complicated in some patients by a progressive cerebellar syndrome including gait ataxia, dysmetria, worsening of intention tremor and dysarthria. Typically, this syndrome manifests several months after an initially effective therapy and necessitates frequent adjustments in stimulation parameters. There is an ongoing debate as to whether progressive ataxia reflects a delayed therapeutic failure due to disease progression or an adverse effect related to repeated increases of stimulation intensity. In this study we used a multimodal approach comparing clinical stimulation responses, modelling of volume of tissue activated and metabolic brain maps in essential tremor patients with and without progressive ataxia to disentangle a disease-related from a stimulation-induced aetiology. Ten subjects with stable and effective bilateral thalamic stimulation were stratified according to the presence (five subjects) of severe chronic-progressive gait ataxia. We quantified stimulated brain areas and identified the stimulation-induced brain metabolic changes by multiple (18)F-fluorodeoxyglucose positron emission tomography performed with and without active neurostimulation. Three days after deactivating thalamic stimulation and following an initial rebound of symptom severity, gait ataxia had dramatically improved in all affected patients, while tremor had worsened to the presurgical severity, thus indicating a stimulation rather than disease-related phenomenon. Models of the volume of tissue activated revealed a more ventrocaudal stimulation in the (sub)thalamic area of patients with progressive gait ataxia. Metabolic maps of both patient groups differed by an increased glucose uptake in the cerebellar nodule of patients with gait ataxia. Our data suggest that chronic progressive gait ataxia in essential tremor is a reversible cerebellar

  14. [Mental health of children, adolescents and young adults--part 1: prevalence, illness persistence, adversities, service use, treatment delay and consequences].

    PubMed

    Lambert, M; Bock, T; Naber, D; Löwe, B; Schulte-Markwort, M; Schäfer, I; Gumz, A; Degkwitz, P; Schulte, B; König, H H; Konnopka, A; Bauer, M; Bechdolf, A; Correll, C; Juckel, G; Klosterkötter, J; Leopold, K; Pfennig, A; Karow, A

    2013-11-01

    Numerous birth-control studies, epidemiological studies, and observational studies have investigated mental health and health care in childhood, adolescence and early adulthood, including prevalence, age at onset, adversities, illness persistence, service use, treatment delay and course of illness. Moreover, the impact of the burden of illness, of deficits of present health care systems, and the efficacy and effectiveness of early intervention services on mental health were evaluated. According to these data, most mental disorders start during childhood, adolescence and early adulthood. Many children, adolescents and young adults are exposed to single or multiple adversities, which increase the risk for (early) manifestations of mental diseases as well as for their chronicity. Early-onset mental disorders often persist into adulthood. Service use by children, adolescents and young adults is low, even lower than for adult patients. Moreover, there is often a long delay between onset of illness and first adequate treatment with a variety of linked consequences for a poorer psychosocial prognosis. This leads to a large burden of illness with respect to disability and costs. As a consequence several countries have implemented so-called "early intervention services" at the interface of child and adolescent and adult psychiatry. Emerging studies show that these health-care structures are effective and efficient. Part 1 of the present review summarises the current state of mental health in childhood, adolescence and early adulthood, including prevalence, age at onset, adversities, illness persistence, service use, and treatment delay with consequences.

  15. Adverse health effects due to arsenic exposure: Modification by dietary supplementation of jaggery in mice

    SciTech Connect

    Singh, Nrashant; Kumar, D.; Lal, Kewal; Raisuddin, S.; Sahu, Anand P.

    2010-02-01

    Populations of villages of eastern India and Bangladesh and many other parts of the world are exposed to arsenic mainly through drinking water. Due to non-availability of safe drinking water they are compelled to depend on arsenic-contaminated water. Generally, poverty level is high in those areas and situation is compounded by the lack of proper nutrition. The hypothesis that the deleterious health effects of arsenic can be prevented by modification of dietary factors with the availability of an affordable and indigenous functional food jaggery (sugarcane juice) has been tested in the present study. Jaggery contains polyphenols, vitamin C, carotene and other biologically active components. Arsenic as sodium-m-arsenite at low (0.05 ppm) and high (5 ppm) doses was orally administered to Swiss male albino mice, alone and in combination with jaggery feeding (250 mg/mice), consecutively for 180 days. The serum levels of total antioxidant, glutathione peroxidase and glutathione reductase were substantially reduced in arsenic-exposed groups, while supplementation of jaggery enhanced their levels in combined treatment groups. The serum levels of interleukin-1beta, interleukin-6 and TNF-alpha were significantly increased in arsenic-exposed groups, while in the arsenic-exposed and jaggery supplemented groups their levels were normal. The comet assay in bone marrow cells showed the genotoxic effects of arsenic, whereas combination with jaggery feeding lessened the DNA damage. Histopathologically, the lung of arsenic-exposed mice showed the necrosis and degenerative changes in bronchiolar epithelium with emphysema and thickening of alveolar septa which was effectively antagonized by jaggery feeding. These results demonstrate that jaggery, a natural functional food, effectively antagonizes many of the adverse effects of arsenic.

  16. Statin Adverse Effects: A Review of the Literature and Evidence for a Mitochondrial Mechanism

    PubMed Central

    Golomb, Beatrice A.; Evans, Marcella A.

    2009-01-01

    HMG-CoA reductase inhibitors (statins) are a widely used class of drug, and like all medications have potential for adverse effects (AEs). Here we review the statin AE literature, first focusing on muscle AEs as the most reported problem both in the literature and by patients. Evidence regarding the statin muscle AE mechanism, dose effect, drug interactions, and genetic predisposition is examined. We hypothesize, and provide evidence, that the demonstrated mitochondrial mechanisms for muscle AEs have implications to other nonmuscle AEs in patients treated with statins. In meta-analyses of randomized controlled trials (RCTs), muscle AEs are more frequent with statins than with placebo. A number of manifestations of muscle AEs have been reported, with rhabdomyolysis the most feared. AEs are dose dependent, and risk is amplified by drug interactions that functionally increase statin potency, often through inhibition of the cytochrome P450 (CYP)3A4 system. An array of additional risk factors for statin AEs are those that amplify (or reflect) mitochondrial or metabolic vulnerability, such as metabolic syndrome factors, thyroid disease, and genetic mutations linked to mitochondrial dysfunction. Converging evidence supports a mitochondrial foundation for muscle AEs associated with statins, and both theoretical and empirical considerations suggest that mitochondrial dysfunction may also underlie many non-muscle statin AEs. Evidence from RCTs and studies of other designs indicates existence of additional statin-associated AEs, such as cognitive loss, neuropathy, pancreatic and hepatic dysfunction, and sexual dysfunction. Physician awareness of statin AEs is reportedly low even for the AEs most widely reported by patients. Awareness and vigilance for AEs should be maintained to enable informed treatment decisions, treatment modification if appropriate, improved quality of patient care, and reduced patient morbidity. PMID:19159124

  17. Adverse endocrine and metabolic effects of psychotropic drugs: selective clinical review.

    PubMed

    Bhuvaneswar, Chaya G; Baldessarini, Ross J; Harsh, Veronica L; Alpert, Jonathan E

    2009-12-01

    The article critically reviews selected, clinically significant, adverse endocrine and metabolic effects associated with psychotropic drug treatments, including hyperprolactinaemia, hyponatraemia, diabetes insipidus, hypothyroidism, hyperparathyroidism, sexual dysfunction and virilization, weight loss, weight gain and metabolic syndrome (type 2 diabetes mellitus, dyslipidaemia and hypertension). Such effects are prevalent and complex, but can be managed clinically when recognized. They encourage continued critical assessment of benefits versus risks of psychotropic drugs and underscore the importance of close coordination of psychiatric and general medical care to improve long-term health of psychiatric patients. Options for management of hyperprolactinaemia include lowering doses, switching to agents such as aripiprazole, clozapine or quetiapine, managing associated osteoporosis, carefully considering the use of dopamine receptor agonists and ruling out stress, oral contraceptive use and hypothyroidism as contributing factors. Disorders of water homeostasis may include syndrome of inappropriate antidiuretic hormone (SIADH), managed by water restriction or slow replacement by hypertonic saline along with drug discontinuation. Safe management of diabetes insipidus, commonly associated with lithium, involves switching mood stabilizer and consideration of potassium-sparing diuretics. Clinical hypothyroidism may be a more useful marker than absolute cut-offs of hormone values, and may be associated with quetiapine, antidepressant and lithium use, and managed by thyroxine replacement. Hyper-parathyroidism requires comprehensive medical evaluation for occult tumours. Hypocalcaemia, along with multiple other psychiatric and medical causes, may result in decreased bone density and require evaluation and management. Strategies for reducing sexual dysfunction with psychotropics remain largely unsatisfactory. Finally, management strategies for obesity and metabolic syndrome

  18. Serious Adverse Events in Randomized Psychosocial Treatment Studies: Safety or Arbitrary Edicts?

    ERIC Educational Resources Information Center

    Petry, Nancy M.; Roll, John M.; Rounsaville, Bruce J.; Ball, Samuel A.; Stitzer, Maxine; Peirce, Jessica M.; Blaine, Jack; Kirby, Kimberly C.; McCarty, Dennis; Carroll, Kathleen M.

    2008-01-01

    Human subjects protection policies developed for pharmaceutical trials are now being widely applied to psychosocial intervention studies. This study examined occurrences of serious adverse events (SAEs) reported in multicenter psychosocial trials of the National Institute on Drug Abuse Clinical Trials Network. Substance-abusing participants (N =…

  19. Reporting and understanding the safety and adverse effect profile of mobile apps for psychosocial interventions: An update

    PubMed Central

    Naeem, Farooq; Gire, Nadeem; Xiang, Shuo; Yang, Megan; Syed, Yumeen; Shokraneh, Farhad; Adams, Clive; Farooq, Saeed

    2016-01-01

    Recent years have seen a rapidly increasing trend towards the delivery of health technology through mobile devices. Smartphones and tablet devices are thus becoming increasingly popular for accessing information and a wide range of services, including health care services. Modern mobile apps can be used for a variety of reasons, ranging from education for the patients and assistance to clinicians to delivery of interventions. Mobile phone apps have also been established to benefit patients in a scope of interventions across numerous medical specialties and treatment modalities. Medical apps have their advantages and disadvantages. It is important that clinicians have access to knowledge to make decisions regarding the use of medical apps on the basis of risk-benefit ratio. Mobile apps that deliver psycho social interventions offer unique challenges and opportunities. A number of reviews have highlighted the potential use of such apps. There is a need to describe, report and study their side effects too. The adverse effects associated with these apps can broadly be divided into: (1) those resulting from the security and safety concerns; (2) those arising from the use of a particular psycho social intervention; and (3) those due to the interaction with digital technology. There is a need to refine and reconsider the safety and adverse effects in this area. The safety profile of a mobile PSI app should describe its safety profile in: (1) privacy and security; (2) adverse effects of psychotherapy; and (3) adverse effects unique to the use of apps and the internet. This is, however, a very new area and further research and reporting is required to inform clinical decision making. PMID:27354959

  20. Reporting and understanding the safety and adverse effect profile of mobile apps for psychosocial interventions: An update.

    PubMed

    Naeem, Farooq; Gire, Nadeem; Xiang, Shuo; Yang, Megan; Syed, Yumeen; Shokraneh, Farhad; Adams, Clive; Farooq, Saeed

    2016-06-22

    Recent years have seen a rapidly increasing trend towards the delivery of health technology through mobile devices. Smartphones and tablet devices are thus becoming increasingly popular for accessing information and a wide range of services, including health care services. Modern mobile apps can be used for a variety of reasons, ranging from education for the patients and assistance to clinicians to delivery of interventions. Mobile phone apps have also been established to benefit patients in a scope of interventions across numerous medical specialties and treatment modalities. Medical apps have their advantages and disadvantages. It is important that clinicians have access to knowledge to make decisions regarding the use of medical apps on the basis of risk-benefit ratio. Mobile apps that deliver psycho social interventions offer unique challenges and opportunities. A number of reviews have highlighted the potential use of such apps. There is a need to describe, report and study their side effects too. The adverse effects associated with these apps can broadly be divided into: (1) those resulting from the security and safety concerns; (2) those arising from the use of a particular psycho social intervention; and (3) those due to the interaction with digital technology. There is a need to refine and reconsider the safety and adverse effects in this area. The safety profile of a mobile PSI app should describe its safety profile in: (1) privacy and security; (2) adverse effects of psychotherapy; and (3) adverse effects unique to the use of apps and the internet. This is, however, a very new area and further research and reporting is required to inform clinical decision making.

  1. The Role of Mindfulness in Reducing the Adverse Effects of Childhood Stress and Trauma

    PubMed Central

    Ortiz, Robin; Sibinga, Erica M.

    2017-01-01

    Research suggests that many children are exposed to adverse experiences in childhood. Such adverse childhood exposures may result in stress and trauma, which are associated with increased morbidity and mortality into adulthood. In general populations and trauma-exposed adults, mindfulness interventions have demonstrated reduced depression and anxiety, reduced trauma-related symptoms, enhanced coping and mood, and improved quality of life. Studies in children and youth also demonstrate that mindfulness interventions improve mental, behavioral, and physical outcomes. Taken together, this research suggests that high-quality, structured mindfulness instruction may mitigate the negative effects of stress and trauma related to adverse childhood exposures, improving short- and long-term outcomes, and potentially reducing poor health outcomes in adulthood. Future work is needed to optimize implementation of youth-based mindfulness programs and to study long-term outcomes into adulthood. PMID:28264496

  2. The Role of Mindfulness in Reducing the Adverse Effects of Childhood Stress and Trauma.

    PubMed

    Ortiz, Robin; Sibinga, Erica M

    2017-02-28

    Research suggests that many children are exposed to adverse experiences in childhood. Such adverse childhood exposures may result in stress and trauma, which are associated with increased morbidity and mortality into adulthood. In general populations and trauma-exposed adults, mindfulness interventions have demonstrated reduced depression and anxiety, reduced trauma-related symptoms, enhanced coping and mood, and improved quality of life. Studies in children and youth also demonstrate that mindfulness interventions improve mental, behavioral, and physical outcomes. Taken together, this research suggests that high-quality, structured mindfulness instruction may mitigate the negative effects of stress and trauma related to adverse childhood exposures, improving short- and long-term outcomes, and potentially reducing poor health outcomes in adulthood. Future work is needed to optimize implementation of youth-based mindfulness programs and to study long-term outcomes into adulthood.

  3. Potassium fertilization mitigates the adverse effects of drought on selected Zea mays cultivars

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the present study, the role of potassium (K) in mitigating the adverse effects of drought stress (DS) on 2 maize (Zea mays L.) cultivars, ‘Shaandan 9’ (S9; drought-tolerant) and ‘Shaandan 911’ (S911; drought-sensitive), was assessed. K application increased dry matter (DM) across all growth stage...

  4. ENVIRONMENTAL POLLUTANTS AND ADVERSE HUMAN HEALTH EFFECTS: HAZARD IDENTIFICATION USING INTERREGION COMPARISONS

    EPA Science Inventory

    Background: Associations between adverse health effects and environmental exposures are difficult to study, because exposures may be widespread, low-dose in nature, and common throughout the study population. Therefore, individual risk-factor epidemiology may not be the right to...

  5. ARE ENVIRONMENTAL EXPOSURES TO CHLOROPHENOXY HERBICIDES ASSOCIATED WITH AN INCREASE IN ADVERSE HUMAN HEALTH EFFECTS?

    EPA Science Inventory

    Background: Associations between adverse health effects and environmental exposures are difficult to study because exposures may be widespread, low-dose in nature, and common throughout the study population. Individual risk-factor epidemiology may not be able to initially ident...

  6. 40 CFR 161.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Flagging of studies for potential... Provisions § 161.34 Flagging of studies for potential adverse effects. (a) Any person who submits a study of... registration, or to satisfy a requirement imposed under FIFRA sec. 3(c)(2)(B), must submit with the study...

  7. 40 CFR 161.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Flagging of studies for potential... Provisions § 161.34 Flagging of studies for potential adverse effects. (a) Any person who submits a study of... registration, or to satisfy a requirement imposed under FIFRA sec. 3(c)(2)(B), must submit with the study...

  8. 40 CFR 161.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Flagging of studies for potential... Provisions § 161.34 Flagging of studies for potential adverse effects. (a) Any person who submits a study of... registration, or to satisfy a requirement imposed under FIFRA sec. 3(c)(2)(B), must submit with the study...

  9. The Risk of Adverse Impact in Selections Based on a Test with Known Effect Size

    ERIC Educational Resources Information Center

    De Corte, Wilfried; Lievens, Filip

    2005-01-01

    The authors derive the exact sampling distribution function of the adverse impact (AI) ratio for single-stage, top-down selections using tests with known effect sizes. Subsequently, it is shown how this distribution function can be used to determine the risk that a future selection decision on the basis of such tests will result in an outcome that…

  10. Cytidine 5'-diphosphocholine (CDP-choline) adversely effects on pilocarpine seizure-induced hippocampal neuronal death.

    PubMed

    Kim, Jin Hee; Lee, Dong Won; Choi, Bo Young; Sohn, Min; Lee, Song Hee; Choi, Hui Chul; Song, Hong Ki; Suh, Sang Won

    2015-01-21

    Citicoline (CDP-choline; cytidine 5'-diphosphocholine) is an important intermediate in the biosynthesis of cell membrane phospholipids. Citicoline serves as a choline donor in the biosynthetic pathways of acetylcholine and neuronal membrane phospholipids, mainly phosphatidylcholine. The ability of citicoline to reverse neuronal injury has been tested in animal models of cerebral ischemia and clinical trials have been performed in stroke patients. However, no studies have examined the effect of citicoline on seizure-induced neuronal death. To clarify the potential therapeutic effects of citicoline on seizure-induced neuronal death, we used an animal model of pilocarpine-induced epilepsy. Temporal lobe epilepsy (TLE) was induced by intraperitoneal injection of pilocarpine (25mg/kg) in adult male rats. Citicoline (100 or 300 mg/kg) was injected into the intraperitoneal space two hours after seizure onset and a second injection was performed 24h after the seizure. Citicoline was injected once per day for one week after pilocarpine- or kainate-induced seizure. Neuronal injury and microglial activation were evaluated at 1 week post-seizure. Surprisingly, rather than offering protection, citicoline treatment actually enhanced seizure-induced neuronal death and microglial activation in the hippocampus compared to vehicle treated controls. Citicoline administration after seizure-induction increased immunoglobulin leakage via BBB disruption in the hippocampus compared with the vehicle-only group. To clarify if this adverse effect of citicoline is generalizable across alternative seizure models, we induced seizure by kainate injection (10mg/kg, i.p.) and then injected citicoline as in pilocarpine-induced seizure. We found that citicoline did not modulate kainate seizure-induced neuronal death, BBB disruption or microglial activation. These results suggest that citicoline may not have neuroprotective effects after seizure and that clinical application of citicoline after

  11. Finasteride adverse effects in subjects with androgenic alopecia: A possible therapeutic approach according to the lateralization process of the brain.

    PubMed

    Motofei, Ion G; Rowland, David L; Georgescu, Simona R; Tampa, Mircea; Baconi, Daniela; Stefanescu, Emil; Baleanu, Bogdan C; Balalau, Cristian; Constantin, Vlad; Paunica, Stana

    2016-11-01

    Nowadays, finasteride is a relatively frequently prescribed drug in the therapeutic management of male androgenic alopecia. The reported adverse effects are notable in some patients, consisting in signs and symptoms that are encountered both during finasteride administration and after treatment cessation. Clinical and imagistic data show that cognition and sexuality are two distinct but interrelated environmental functions, most probable due to lateralization process of the brain. Specific for our topic, relatively recent published studies found that frequency and severity of finasteride adverse effects could be interrelated with hand preference and sexual orientation of the respective subjects. This paper tries to explain/support this interrelation through a psychophysiologic approach, to suggest how this premise could be further proved in dermatological practice, and to highlight its relevance in respect to therapeutic approach of male androgenic alopecia. As a possible therapeutic application, subjects having preference for a certain sexual orientation and/or predisposition for a given dominant hand could be advised before finasteride administration, that present an increased risk/sensitivity to develop adverse effects. Finally, even if finasteride and post-finasteride symptoms overlap to a large extent they should be, however, viewed as distinct physiopathologic entities, which could require perhaps different therapeutic approaches.

  12. Mixing and capping techniques for activated carbon based sediment remediation - Efficiency and adverse effects for Lumbriculus variegatus.

    PubMed

    Abel, Sebastian; Nybom, Inna; Mäenpää, Kimmo; Hale, Sarah E; Cornelissen, Gerard; Akkanen, Jarkko

    2017-05-01

    Activated carbon (AC) has been proven to be highly effective for the in-situ remediation of sediments contaminated with a wide range of hydrophobic organic contaminants (HOCs). However, adverse biological effects, especially to benthic organisms, can accompany this promising remediation potential. In this study, we compare both the remediation potential and the biological effects of several AC materials for two application methods: mixing with sediment (MIX) at doses of 0.1 and 1.0% based on sediment dw and thin layer capping (TLC) with 0.6 and 1.2 kg AC/m(2). Significant dose dependent reductions in PCB bioaccumulation in Lumbriculus variegatus of 35-93% in MIX treatments were observed. Contaminant uptake in TLC treatments was reduced by up to 78% and differences between the two applied doses were small. Correspondingly, significant adverse effects were observed for L. variegatus whenever AC was present in the sediment. The lowest application dose of 0.1% AC in the MIX system reduced L. variegatus growth, and 1.0% AC led to a net loss of organism biomass. All TLC treatments let to a loss of biomass in the test organism. Furthermore, mortality was observed with 1.2 kg AC/m(2) doses of pure AC for the TLC treatment. The addition of clay (Kaolinite) to the TLC treatments prevented mortality, but did not decrease the loss in biomass. While TLC treatments pose a less laborious alternative for AC amendments in the field, the results of this study show that it has lower remediation potential and could be more harmful to the benthic fauna.

  13. Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

    PubMed Central

    Croft, Ashley M; Herxheimer, Andrew

    2002-01-01

    Background Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. Presentation We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs) may be related to the development of severe or prolonged adverse reactions to mefloquine. Implications We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. Testing Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis. PMID:11914150

  14. Immune-Related Adverse Effects of Cancer Immunotherapy- Implications for Rheumatology.

    PubMed

    Cappelli, Laura C; Shah, Ami A; Bingham, Clifton O

    2017-02-01

    Immune checkpoint inhibitors (ICIs) are increasingly studied and used as therapy for a growing number of malignancies. ICIs work by blocking inhibitory pathways of T-cell activation, leading to an immune response directed against tumors. Such nonspecific immunologic activation can lead to immune-related adverse events (IRAEs). Some IRAEs, including inflammatory arthritis, sicca syndrome, myositis, and vasculitis, are of special interest to rheumatologists. As use of ICIs increases, recognition of these IRAEs and developing treatment strategies will become important. In this review, the current literature on rheumatic and musculoskeletal IRAEs is summarized. The incidence, clinical presentations, and treatment considerations are highlighted.

  15. From the exposome to mechanistic understanding of chemical-induced adverse effects.

    PubMed

    Escher, Beate I; Hackermüller, Jörg; Polte, Tobias; Scholz, Stefan; Aigner, Achim; Altenburger, Rolf; Böhme, Alexander; Bopp, Stephanie K; Brack, Werner; Busch, Wibke; Chadeau-Hyam, Marc; Covaci, Adrian; Eisenträger, Adolf; Galligan, James J; Garcia-Reyero, Natalia; Hartung, Thomas; Hein, Michaela; Herberth, Gunda; Jahnke, Annika; Kleinjans, Jos; Klüver, Nils; Krauss, Martin; Lamoree, Marja; Lehmann, Irina; Luckenbach, Till; Miller, Gary W; Müller, Andrea; Phillips, David H; Reemtsma, Thorsten; Rolle-Kampczyk, Ulrike; Schüürmann, Gerrit; Schwikowski, Benno; Tan, Yu-Mei; Trump, Saskia; Walter-Rohde, Susanne; Wambaugh, John F

    2017-02-01

    The exposome encompasses an individual's exposure to exogenous chemicals, as well as endogenous chemicals that are produced or altered in response to external stressors. While the exposome concept has been established for human health, its principles can be extended to include broader ecological issues. The assessment of exposure is tightly interlinked with hazard assessment. Here, we explore if mechanistic understanding of the causal links between exposure and adverse effects on human health and the environment can be improved by integrating the exposome approach with the adverse outcome pathway (AOP) concept that structures and organizes the sequence of biological events from an initial molecular interaction of a chemical with a biological target to an adverse outcome. Complementing exposome research with the AOP concept may facilitate a mechanistic understanding of stress-induced adverse effects, examine the relative contributions from various components of the exposome, determine the primary risk drivers in complex mixtures, and promote an integrative assessment of chemical risks for both human and environmental health.

  16. In Silico Elucidation of the Molecular Mechanism Defining the Adverse Effect of Selective Estrogen Receptor Modulators

    PubMed Central

    Xie, Lei; Wang, Jian; Bourne, Philip E

    2007-01-01

    Early identification of adverse effect of preclinical and commercial drugs is crucial in developing highly efficient therapeutics, since unexpected adverse drug effects account for one-third of all drug failures in drug development. To correlate protein–drug interactions at the molecule level with their clinical outcomes at the organism level, we have developed an integrated approach to studying protein–ligand interactions on a structural proteome-wide scale by combining protein functional site similarity search, small molecule screening, and protein–ligand binding affinity profile analysis. By applying this methodology, we have elucidated a possible molecular mechanism for the previously observed, but molecularly uncharacterized, side effect of selective estrogen receptor modulators (SERMs). The side effect involves the inhibition of the Sacroplasmic Reticulum Ca2+ ion channel ATPase protein (SERCA) transmembrane domain. The prediction provides molecular insight into reducing the adverse effect of SERMs and is supported by clinical and in vitro observations. The strategy used in this case study is being applied to discover off-targets for other commercially available pharmaceuticals. The process can be included in a drug discovery pipeline in an effort to optimize drug leads and reduce unwanted side effects. PMID:18052534

  17. CYP2D6 polymorphisms may predict occurrence of adverse effects to tamoxifen: a preliminary retrospective study

    PubMed Central

    Wickramage, Ishani; Tennekoon, Kamani Hemamala; Ariyaratne, Merenchi Arachchige Yasantha; Hewage, Asanka Sudeshini; Sundralingam, Tharmini

    2017-01-01

    association with SNPs tested. Conclusions CYP2D6 SNP combination 2988G>A, −1584C and 2850C>T, strongly suggestive of *41 reduced functional allele, is likely to be useful in predicting occurrence of adverse effect fatty liver in breast cancer patients on tamoxifen, thereby alternative treatment can be considered and lifestyle modifications implemented. Larger sample studies are recommended with the measurement of tamoxifen and metabolite levels. Alternative therapy should be considered for postmenopausal patients. PMID:28293118

  18. Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor

    PubMed Central

    Gibson, William S.; Jo, Hang Joon; Testini, Paola; Cho, Shinho; Felmlee, Joel P.; Welker, Kirk M.; Klassen, Bryan T.; Min, Hoon-Ki

    2016-01-01

    Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson’s disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal

  19. Rational therapy for diabetes: early recognition of adverse effects and avoidance of disruptive false alarms.

    PubMed

    Raz, Itamar; Eldor, Roy

    2012-05-01

    Corresponding to the uncontrolled diabetes pandemic, significant effort has been invested in developing new therapeutic options. Nevertheless, all medicines have possible adverse effects. Recently, a trend of 'scrutinizing' novel hypoglycaemic drug side effects based on scant scientific data has emerged. With recent publications highlighting possible dangers of rosiglitazone, insulin glargine, sitagliptin, exenatide and, most recently, pioglitazone, it seems that all means are valid and that every database is suitable, even if specifically defined as inadequate for the purpose of data analysis. The use of such data may lead authors to draw erroneous conclusions that may be granted unwarranted impact upon publication in leading scientific journals and eventually lead patients and misinformed physicians to wrongly change beneficial medication regimes. Adherence to strict scientific methodology, ongoing large clinical trials and creating adjudicated patient databases may facilitate early recognition of adverse effects while avoiding disruptive false alarms.

  20. General and specific effects of early-life psychosocial adversities on adolescent grey matter volume☆

    PubMed Central

    Walsh, Nicholas D.; Dalgleish, Tim; Lombardo, Michael V.; Dunn, Valerie J.; Van Harmelen, Anne-Laura; Ban, Maria; Goodyer, Ian M.

    2014-01-01

    Exposure to childhood adversities (CA) is associated with subsequent alterations in regional brain grey matter volume (GMV). Prior studies have focused mainly on severe neglect and maltreatment. The aim of this study was to determine in currently healthy adolescents if exposure to more common forms of CA results in reduced GMV. Effects on brain structure were investigated using voxel-based morphometry in a cross-sectional study of youth recruited from a population-based longitudinal cohort. 58 participants (mean age = 18.4) with (n = 27) or without (n = 31) CA exposure measured retrospectively from maternal interview were included in the study. Measures of recent negative life events (RNLE) recorded at 14 and 17 years, current depressive symptoms, gender, participant/parental psychiatric history, current family functioning perception and 5-HTTLPR genotype were covariates in analyses. A multivariate analysis of adversities demonstrated a general association with a widespread distributed neural network consisting of cortical midline, lateral frontal, temporal, limbic, and cerebellar regions. Univariate analyses showed more specific associations between adversity measures and regional GMV: CA specifically demonstrated reduced vermis GMV and past psychiatric history with reduced medial temporal lobe volume. In contrast RNLE aged 14 was associated with increased lateral cerebellar and anterior cingulate GMV. We conclude that exposure to moderate levels of childhood adversities occurring during childhood and early adolescence exerts effects on the developing adolescent brain. Reducing exposure to adverse social environments during early life may optimize typical brain development and reduce subsequent mental health risks in adult life. PMID:25061568

  1. Mining multi-item drug adverse effect associations in spontaneous reporting systems

    PubMed Central

    2010-01-01

    Background Multi-item adverse drug event (ADE) associations are associations relating multiple drugs to possibly multiple adverse events. The current standard in pharmacovigilance is bivariate association analysis, where each single drug-adverse effect combination is studied separately. The importance and difficulty in the detection of multi-item ADE associations was noted in several prominent pharmacovigilance studies. In this paper we examine the application of a well established data mining method known as association rule mining, which we tailored to the above problem, and demonstrate its value. The method was applied to the FDAs spontaneous adverse event reporting system (AERS) with minimal restrictions and expectations on its output, an experiment that has not been previously done on the scale and generality proposed in this work. Results Based on a set of 162,744 reports of suspected ADEs reported to AERS and published in the year 2008, our method identified 1167 multi-item ADE associations. A taxonomy that characterizes the associations was developed based on a representative sample. A significant number (67% of the total) of potential multi-item ADE associations identified were characterized and clinically validated by a domain expert as previously recognized ADE associations. Several potentially novel ADEs were also identified. A smaller proportion (4%) of associations were characterized and validated as known drug-drug interactions. Conclusions Our findings demonstrate that multi-item ADEs are present and can be extracted from the FDA’s adverse effect reporting system using our methodology, suggesting that our method is a valid approach for the initial identification of multi-item ADEs. The study also revealed several limitations and challenges that can be attributed to both the method and quality of data. PMID:21044365

  2. 75 FR 7293 - Temporary Agricultural Employment of H-2A Workers in the United States: 2010 Adverse Effect Wage...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-18

    ... collective bargaining rate, or the Federal or State minimum wage rate, in effect at the time work is...: 2010 Adverse Effect Wage Rates, Allowable Charges for Agricultural Workers' Meals, and Maximum Travel... Department of Labor (Department) is issuing this Notice to announce the new 2010 Adverse Effect Wage...

  3. Adverse effects of industrial multiwalled carbon nanotubes on human pulmonary cells

    PubMed Central

    Tabet, Lyes; Bussy, Cyrill; Amara, Nadia; Setyan, Ari; Grodet, Alain; Rossi, Michel J.; Pairon, Jean-Claude; Boczkowski, Jorge; Lanone, Sophie

    2009-01-01

    The aim of this study was to evaluate adverse effects of multi-walled carbon nanotubes (MWCNT) produced for industrial purposes, on the human epithelial cell line A549. MWCNT were dispersed in dipalmitoyl lecithin (DPL), a component of pulmonary surfactant, and the effects of dispersion in DPL were compared to those in 2 other media: ethanol (EtOH) and phosphate buffer saline (PBS). Effects of MWCNT were also compared to those of 2 asbestos fibers (chrysotile and crocidolite) and carbon black (CB) nanoparticles, not only in A549 cells, but also on mesothelial cells (MeT5A human cell line), used as an asbestos-sensitive cell type. MWCNT formed agglomerates on top of both cell lines (surface area 15–35 μm2), that were significantly larger and more numerous in PBS than in EtOH and DPL. Whatever the dispersion media, incubation with 100 μg/ml MWCNT induced a similar decrease in metabolic activity without changing cell membrane permeability or apoptosis. Neither MWCNT cellular internalization nor oxidative stress were observed. In contrast, asbestos fibers penetrated into the cells, decreased metabolic activity but not cell membrane permeability and increased apoptosis, without decreasing cell number. CB was internalized without any adverse effects. In conclusion, this study demonstrates that MWCNT produced for industrial purposes exert adverse effects without being internalized by human epithelial and mesothelial pulmonary cell lines. PMID:19034795

  4. Adverse effects of oral corticosteroids in relation to dose in patients with lung disease

    PubMed Central

    Walsh, L; Wong, C; Oborne, J; Cooper, S; Lewis, S; Pringle, M; Hubbard, R; Tattersfield, A

    2001-01-01

    BACKGROUND—The adverse effects of oral corticosteroids are widely recognised but there are few quantitative data on which to base advice to patients. In a two part cross sectional study we compared adverse effects in patients with lung disease taking oral corticosteroids and control subjects and related the adverse effects to corticosteroid dose in the patient group.
METHODS—Data on oral corticosteroid use, lifestyle, fractures, and other possible adverse effects were collected by questionnaire and compared between a community based cohort of patients taking continuous or frequent intermittent oral corticosteroids for asthma, chronic obstructive pulmonary disease, or alveolitis and age and sex matched control subjects. Dose related effects were explored in the corticosteroid group using cumulative dose quartiles and multiple logistic regression.
RESULTS—A total of 367 patients (⩾50 years, 48% female) and 734 control subjects completed the questionnaire. The cumulative incidence of fractures since the time of diagnosis was 23% for patients taking oral corticosteroids and 15% in the control group (odds ratio (OR) 1.8; 95% confidence interval (CI) 1.3 to 2.6). Patients were more likely to have had a fracture of the vertebrae (OR 10; 95% CI 2.9 to 34), hip (OR 6; 95% CI 1.2 to 30), and ribs or sternum (OR 3.2, 95% CI 1.6 to 6.6) than control subjects. They also reported a significant increase in cataracts, use of antacids, muscle weakness, back pain, bruising, oral candidiasis, and having fewer teeth. The effects of oral corticosteroids were dose related: the odds ratio for patients in the highest compared with the lowest cumulative dose quartile (median prednisolone dose 61 g versus 5 g) ranged from 2 for all fractures to 9 for vertebral fractures and bruising.
CONCLUSIONS—By quantifying the morbidity associated with the use of oral corticosteroids, this study should help to rationalise their long term use.

 PMID:11254818

  5. Adverse health effects and unhealthy behaviors among medical students using Facebook.

    PubMed

    Al-Dubai, Sami Abdo Radman; Ganasegeran, Kurubaran; Al-Shagga, Mustafa Ahmed Mahdi; Yadav, Hematram; Arokiasamy, John T

    2013-01-01

    Little is known about the relationships between adverse health effects and unhealthy behaviors among medical students using Facebook. The aim of this study was to determine the associations between adverse health effects and unhealthy behaviors with Facebook use. A cross-sectional study was conducted in a private university in Malaysia among 316 medical students. A self-administered questionnaire was used. It included questions on sociodemographics, pattern of Facebook use, social relationship, unhealthy behaviors, and health effects. Mean age was 20.5 (±2.7) years. All students had a Facebook account. The average daily Facebook surfing hours were 2.5 (±1.7). Significant associations were found between average hours of Facebook surfing and the following factors: isolation from family members and community, refusing to answer calls, musculoskeletal pain, headache, and eye irritation (P < 0.005). The average hours spent on Facebook were significantly associated with holding urination and defecation while online, surfing Facebook until midnight, and postponing, forgetting, or skipping meals (P < 0.005). The average hours spent on Facebook were associated with adverse health effects and unhealthy behaviors among medical students, as well as social isolation from the family and community.

  6. The adverse health effects of synthetic cannabinoids with emphasis on psychosis-like effects.

    PubMed

    van Amsterdam, Jan; Brunt, Tibor; van den Brink, Wim

    2015-03-01

    Cannabis use is associated with an increased risk of psychosis in vulnerable individuals. Cannabis containing high levels of the partial cannabinoid receptor subtype 1 (CB1) agonist tetrahydrocannabinol (THC) is associated with the induction of psychosis in susceptible subjects and with the development of schizophrenia, whereas the use of cannabis variants with relatively high levels of cannabidiol (CBD) is associated with fewer psychotic experiences. Synthetic cannabinoid receptor agonists (SCRAs) are full agonists and often more potent than THC. Moreover, in contrast to natural cannabis, SCRAs preparations contain no CBD so that these drugs may have a higher psychosis-inducing potential than cannabis. This paper reviews the general toxicity profile and the adverse effects of SCRAs with special emphasis on their psychosis-inducing risk. The review shows that, compared with the use of natural cannabis, the use of SCRAs may cause more frequent and more severe unwanted negative effects, especially in younger, inexperienced users. Psychosis and psychosis-like conditions seem to occur relatively often following the use of SCRAs, presumably due to their high potency and the absence of CBD in the preparations. Studies on the relative risk of SCRAs compared with natural cannabis to induce or evoke psychosis are urgently needed.

  7. Technical evaluation report, AGARD Fluid Dynamics Panel Symposium on Effects of Adverse Weather on Aerodynamics

    NASA Technical Reports Server (NTRS)

    Reinmann, J. J.

    1991-01-01

    The purpose of the meeting on Effects of Adverse Weather on Aerodynamics was to provide an update of the stae-of-the-art with respect to the prediction, simulation, and measurement of the effects of icing, anti-icing fluids, and various precipitation on the aerodynamic characteristics of flight vehicles. Sessions were devoted to introductory and survey papers and icing certification issues, to analytical and experimental simulation of ice frost contamination and its effects of aerodynamics, and to the effects of heavy rain and deicing/anti-icing fluids.

  8. Statistical Mining of Potential Drug Interaction Adverse Effects in FDA's Spontaneous Reporting System.

    PubMed

    Harpaz, Rave; Haerian, Krystl; Chase, Herbert S; Friedman, Carol

    2010-11-13

    Many adverse drug effects (ADEs) can be attributed to drug interactions. Spontaneous reporting systems (SRS) provide a rich opportunity to detect novel post-marketed drug interaction adverse effects (DIAEs), as they include populations not well represented in clinical trials. However, their identification in SRS is nontrivial. Most existing research have addressed the statistical issues used to test or verify DIAEs, but not their identification as part of a systematic large scale database-wide mining process as discussed in this work. This paper examines the application of a highly optimized and tailored implementation of the Apriori algorithm, as well as methods addressing data quality issues, to the identification of DIAEs in FDAs SRS.

  9. A Cohort Study on Long-Term Adverse Effects of Parental Drinking: Background and Study Design

    PubMed Central

    Lund, Ingunn Olea; Bukten, Anne; Storvoll, Elisabet E; Moan, Inger Synnøve; Skurtveit, Svetlana; Handal, Marte; Nordfjærn, Trond; Brunborg, Geir Scott; Rossow, Ingeborg

    2015-01-01

    Although many studies have addressed adverse outcomes in children of parents with alcohol abuse/dependence, less is known about the possible long-term effects of more normative patterns of parental alcohol consumption, including drinking at lower risk levels and heavy episodic or binge drinking. The extent of harm from parental drinking may therefore be underestimated. With this research proposal, we describe a project that aims to assess possible long-term adverse effects of parental drinking by combining survey and nationwide registry data. Advantages of a longitudinal general population cohort design include that it allows for detailed information on parental drinking through survey data and identification of possible negative long-term health and social outcomes from exposure to parental drinking 1–19 years after exposure through continuously updated nationwide registers. The rich information available from combining survey and registry data allows us to take into account important confounders, mediators, and moderators. PMID:26688663

  10. Assessing Granger Causality in Electrophysiological Data: Removing the Adverse Effects of Common Signals via Bipolar Derivations.

    PubMed

    Trongnetrpunya, Amy; Nandi, Bijurika; Kang, Daesung; Kocsis, Bernat; Schroeder, Charles E; Ding, Mingzhou

    2015-01-01

    Multielectrode voltage data are usually recorded against a common reference. Such data are frequently used without further treatment to assess patterns of functional connectivity between neuronal populations and between brain areas. It is important to note from the outset that such an approach is valid only when the reference electrode is nearly electrically silent. In practice, however, the reference electrode is generally not electrically silent, thereby adding a common signal to the recorded data. Volume conduction further complicates the problem. In this study we demonstrate the adverse effects of common signals on the estimation of Granger causality, which is a statistical measure used to infer synaptic transmission and information flow in neural circuits from multielectrode data. We further test the hypothesis that the problem can be overcome by utilizing bipolar derivations where the difference between two nearby electrodes is taken and treated as a representation of local neural activity. Simulated data generated by a neuronal network model where the connectivity pattern is known were considered first. This was followed by analyzing data from three experimental preparations where a priori predictions regarding the patterns of causal interactions can be made: (1) laminar recordings from the hippocampus of an anesthetized rat during theta rhythm, (2) laminar recordings from V4 of an awake-behaving macaque monkey during alpha rhythm, and (3) ECoG recordings from electrode arrays implanted in the middle temporal lobe and prefrontal cortex of an epilepsy patient during fixation. For both simulation and experimental analysis the results show that bipolar derivations yield the expected connectivity patterns whereas the untreated data (referred to as unipolar signals) do not. In addition, current source density signals, where applicable, yield results that are close to the expected connectivity patterns, whereas the commonly practiced average re-reference method

  11. Assessing Granger Causality in Electrophysiological Data: Removing the Adverse Effects of Common Signals via Bipolar Derivations

    PubMed Central

    Trongnetrpunya, Amy; Nandi, Bijurika; Kang, Daesung; Kocsis, Bernat; Schroeder, Charles E.; Ding, Mingzhou

    2016-01-01

    Multielectrode voltage data are usually recorded against a common reference. Such data are frequently used without further treatment to assess patterns of functional connectivity between neuronal populations and between brain areas. It is important to note from the outset that such an approach is valid only when the reference electrode is nearly electrically silent. In practice, however, the reference electrode is generally not electrically silent, thereby adding a common signal to the recorded data. Volume conduction further complicates the problem. In this study we demonstrate the adverse effects of common signals on the estimation of Granger causality, which is a statistical measure used to infer synaptic transmission and information flow in neural circuits from multielectrode data. We further test the hypothesis that the problem can be overcome by utilizing bipolar derivations where the difference between two nearby electrodes is taken and treated as a representation of local neural activity. Simulated data generated by a neuronal network model where the connectivity pattern is known were considered first. This was followed by analyzing data from three experimental preparations where a priori predictions regarding the patterns of causal interactions can be made: (1) laminar recordings from the hippocampus of an anesthetized rat during theta rhythm, (2) laminar recordings from V4 of an awake-behaving macaque monkey during alpha rhythm, and (3) ECoG recordings from electrode arrays implanted in the middle temporal lobe and prefrontal cortex of an epilepsy patient during fixation. For both simulation and experimental analysis the results show that bipolar derivations yield the expected connectivity patterns whereas the untreated data (referred to as unipolar signals) do not. In addition, current source density signals, where applicable, yield results that are close to the expected connectivity patterns, whereas the commonly practiced average re-reference method

  12. Magnesium Alleviates Adverse Effects of Lead on Growth, Photosynthesis, and Ultrastructural Alterations of Torreya grandis Seedlings

    PubMed Central

    Shen, Jie; Song, Lili; Müller, Karin; Hu, Yuanyuan; Song, Yang; Yu, Weiwu; Wang, Hailong; Wu, Jiasheng

    2016-01-01

    Magnesium (Mg2+) has been shown to reduce the physiological and biochemical stress in plants caused by heavy metals. To date our understanding of how Mg2+ ameliorates the adverse effects of heavy metals in plants is scarce. The potential effect of Mg2+ on lead (Pb2+) toxicity in plants has not yet been studied. This study was designed to clarify the mechanism of Mg2+-induced alleviation of lead (Pb2+) toxicity. Torreya grandis (T. grandis) seedlings were grown in substrate contaminated with 0, 700 and 1400 mg Pb2+ per kg-1 and with or without the addition of 1040 mg kg-1 Mg2+. Growth parameters, concentrations of Pb2+ and Mg2+ in the plants’ shoots and roots, photosynthetic pigment, gas exchange parameters, the maximum quantum efficiency (Fv/Fm), root oxidative activity, ultrastructure of chloroplasts and root growth were determined to analyze the effect of different Pb2+ concentrations on the seedlings as well as the potential ameliorating effect of Mg2+ on the Pb2+ induced toxicity. All measurements were tested by a one-way ANOVA for the effects of treatments. The growth of T. grandis seedlings cultivated in soils treated with 1400 mg kg-1 Pb2+ was significantly reduced compared with that of plants cultivated in soils treated with 0 or 700 mg kg-1 Pb2+. The addition of 1040 mg kg-1 Mg2+ improved the growth of the Pb2+-stressed seedlings, which was accompanied by increased chlorophyll content, the net photosynthetic rate and Fv/Fm, and enhanced chloroplasts development. In addition, the application of Mg2+ induced plants to accumulate five times higher concentrations of Pb2+ in the roots and to absorb and translocate four times higher concentrations of Mg2+ to the shoots than those without Mg2+ application. Furthermore, Mg2+ addition increased root growth and oxidative activity, and protected the root ultrastructure. To the best of our knowledge, our study is the first report on the mechanism of Mg2+-induced alleviation of Pb2+ toxicity. The generated results

  13. Neurodevelopment in children with intrauterine growth restriction: adverse effects and interventions.

    PubMed

    Wang, Yan; Fu, Wei; Liu, Jing

    2016-01-01

    Intrauterine growth restriction (IUGR) is associated with higher rates of fetal, perinatal, and neonatal morbidity and mortality. The consequences of IUGR include short-term metabolic, hematological and thermal disturbances that lead to metabolic syndrome in children and adults. Additionally, IUGR severely affects short- and long-term fetal brain development and brain function (including motor, cognitive and executive function) and neurobehavior, especially neuropsychology. This review details the adverse effects of IUGR on fetal brain development and discusses intervention strategies.

  14. Topiramate-induced somnambulism in a migraineur: a probable idiosyncratic adverse effect.

    PubMed

    Mathew, Thomas; Sarma, G R K; Nadig, Raghunandan; Varghese, Raji

    2012-04-15

    Somnambulism (sleepwalking) is a disorder of arousal that falls under "parasomnia" group and is more common in children. These phenomena occur as primary sleep events or secondary to systemic disease or can be drug induced. Medications that can cause sleepwalking include neuroleptics, hypnotics, lithium, amitriptyline, and β-blockers. This report presents an unusual adverse effect of topiramate on sleep in a patient with migraine.

  15. Tooth-Bleaching: A Review of the Efficacy and Adverse Effects of Various Tooth Whitening Products.

    PubMed

    Majeed, Abdul; Farooq, Imran; Grobler, Sias R; Rossouw, R J

    2015-12-01

    Tooth bleaching (whitening) is one of the most common and inexpensive method for treating discolouration of teeth. Dental aesthetics, especially tooth colour, is of great importance to majority of the people; and discolouration of even a single tooth can negatively influence the quality of life. Therefore, a review of the literature was carried out (limited to aesthetic tooth-bleaching) to provide a broad overview of the efficacy and adverse effects of various tooth whitening products on soft and hard oral tissues.

  16. Possible adverse effect of chromium in occupational exposure of tannery workers.

    PubMed

    Kornhauser, Carlos; Wróbel, Katarzyna; Wróbel, Kazimierz; Malacara, Juan Manuel; Nava, Laura Eugenia; Gómez, Leobardo; González, Rita

    2002-04-01

    Our aim was to investigate the adverse effects of occupational exposure to trivalent chromium. We measured chromium and iron levels in serum and urine and hemoglobin levels in tannery workers and unexposed persons. We studied three groups of subjects. Group 1 included 15 non-smoking male tannery workers highly exposed to chromium from tanning and retanning departments. Group 2 included 14 non-smoking male tannery workers with moderate chromium exposure from dying, drying and finishing departments. Group 3 included 11 healthy, non-smoking male subjects without direct chromium exposure. Higher serum chromium levels were observed in groups 1 and 2 with respect to group 3 (mean values respectively: 0.43; 0.25 and 0.13 microg x l(-1)). Urine chromium levels in group 1 were higher than those in controls (mean values: 1.78 and 1.35 microg x l(-1)). In group 1 an inverse association was found between serum chromium and urine iron (-0.524), urine chromium and hemoglobin (-0.594) and between the urine chromium to iron ratio and hemoglobin (-0.693, p<0.05). The results suggest a chromium adverse effect on iron metabolism, possibly associated with excessive body chromium accumulation. In conclusion, chromium urine test could be recommended for diagnosis of chromium adverse effect on iron metabolism. Further studies are needed to quantify the relationship between urine chromium and hemoglobin metabolism.

  17. A strategy for regulatory action when new adverse effects of a licensed product emerge.

    PubMed

    Aronson, Jeffrey K; Price, Deirdre; Ferner, Robin E

    2009-01-01

    Regulatory agencies grant product licences (marketing authorizations) for medicinal products in the light of evidence that the balance between benefit and harm in the population is favourable. Here we consider a framework for allowing regulatory agencies to make rational decisions when reviewing product licences in the light of new information about harms that change that balance. The regulator can revoke the product licence, restrict the product's availability or change the 'label' in different ways. We examine the features of the adverse effect that may be relevant in making the decision: namely, individual differences in susceptibility; the possibility of monitoring; and the availability of protective strategies. The balance of benefit and harm, and the time-course and dose relation of the adverse effect play important roles in the decision-making process. We set out how these factors can help determine the logical response to new information on the balance between benefit and harm, and provide a series of relevant examples. We believe that when regulatory agencies have to decide how to amend the product licence of a drug when new serious adverse effects cause concern, they would find it useful to adopt a framework of this kind, using different strategies for different cases. Our proposed framework could also be useful in risk management planning during drug development.

  18. Salicylic acid alleviates adverse effects of heat stress on photosynthesis through changes in proline production and ethylene formation.

    PubMed

    Khan, M Iqbal R; Iqbal, Noushina; Masood, Asim; Per, Tasir S; Khan, Nafees A

    2013-11-01

    We investigated the potential of salicylic acid (SA) in alleviating the adverse effects of heat stress on photosynthesis in wheat (Triticum aestivum L.) cv WH 711. Activity of ribulose 1,5-bisphosphate carboxylase (Rubisco), photosynthetic-nitrogen use efficiency (NUE), and net photosynthesis decreased in plants subjected to heat stress (40 °C for 6 h), but proline metabolism increased. SA treatment (0.5 mM) alleviated heat stress by increasing proline production through the increase in γ-glutamyl kinase (GK) and decrease in proline oxidase (PROX) activity, resulting in promotion of osmotic potential and water potential necessary for maintaining photosynthetic activity. Together with this, SA treatment restricted the ethylene formation in heat-stressed plants to optimal range by inhibiting activity of 1-aminocyclopropane carboxylic acid (ACC) synthase (ACS). This resulted in improved proline metabolism, N assimilation and photosynthesis. The results suggest that SA interacts with proline metabolism and ethylene formation to alleviate the adverse effects of heat stress on photosynthesis in wheat.

  19. Health-protective and Adverse Effects of the Apolipoprotein E ε2 Allele in Older Males

    PubMed Central

    Kulminski, Alexander M.; Ukraintseva, Svetlana V.; Arbeev, Konstantin G.; Manton, Kenneth G.; Oshima, Junko; Martin, George M.; Il'yasova, Dora; Yashin, Anatoli I.

    2009-01-01

    OBJECTIVES: To re-examine a health-protective role of the common Apolipoprotein E (APOE) polymorphism focusing on connections between the APOE ε2-containing genotypes and impairments in instrumental activities of daily living [IADL] in older (65+) males and females. To examine how these connections may be mediated by diagnosed coronary heart disease (CHD), Alzheimer's disease, colorectal cancer, macular degeneration (MD), and atherosclerosis. DESIGN: Retrospective cross-sectional study. SETTING: The unique disability-focused data from a genetic sub-sample of the 1999 National Long Term Care Survey linked with Medicare service use files. PARTICIPANTS: 1733 genotyped individuals interviewed on IADL disabilities. MEASUREMENTS: Indicators of IADL impairments, five geriatric disorders, and ε2-containing genotypes. RESULTS: The ε2/3 genotype is a major contributor to adverse associations between the ε2 allele and IADL disability in males [Odds Ratio (OR)=3.09, Confidence Interval (CI)=1.53-6.26)]. It shows, however, significant protective effects for CHD (OR=0.55, CI=0.33-0.92), while CHD is adversely associated with IADL disability (OR=2.18, CI=1.28-3.72). The presence of five diseases does not significantly alter the adverse association between ε2-containing genotypes and disability. Protective effects of the ε2/3 genotype for CHD (OR=0.52, CI=0.27-0.99) and deleterious effects for IADL (OR=3.50, CI=1.71-7.14) for males hold in multivariate models with both these factors included. No significant associations between the ε2-containing genotypes and IADL are found in females. CONCLUSIONS: The ε2 allele can play a dual role in males, protecting them against some health disorders, while promoting others. Strong adverse relationships with disability suggest that ε2-containing genotypes can be unfavorable factors for the health/well-being of aging males. PMID:18179501

  20. Second-generation antipsychotics: is there evidence for sex differences in pharmacokinetic and adverse effect profiles?

    PubMed

    Aichhorn, Wolfgang; Whitworth, Alexandra B; Weiss, Elisabeth M; Marksteiner, Josef

    2006-01-01

    Six second-generation antipsychotics (SGAs), aripiprazole, clozapine, olanzapine, quetiapine, risperidone and ziprasidone, are currently US FDA approved. The aim of this review is to investigate whether sex differences exist for efficacy and adverse effects of these drugs.Sex-related differences have been shown in the pharmacokinetics of cytochrome P450 (CYP), with a higher activity in females for CYP3A4 and CYP2D6. However, even if there are pharmacokinetic differences between females and males, significantly higher plasma concentrations in women have been demonstrated only for olanzapine and clozapine. To date, sex differences in adverse effects have not been well studied, but some adverse effects such as weight gain, hyperprolactinaemia and cardiac effects are reported to be particularly problematic for women. Most of the studies reviewed indicate that clozapine and olanzapine are associated with greater bodyweight gain than the other atypical antipsychotics, and that serious adverse effects such as metabolic syndrome, which includes increased visceral adiposity, hyperglycaemia, hypertension and dyslipidaemia induced by SGAs, are more frequent in females. According to most studies, the risk for cardiac adverse effects induced by SGAs is the same in male and female patients. Although women are at a lower risk of sudden cardiac death, they have a higher risk of induced long QT syndrome from antiarrhythmic and, probably, antipsychotic drugs. The propensity of sexual dysfunctions is higher with conventional antipsychotics than with SGAs. Additionally, there is some evidence that female sexual dysfunction is associated with high prolactin levels; however, whether the degree of prolactin level elevation is different between female and male patients remains controversial. There is no evidence for sex differences for any of the SGAs to cause a higher rate of extrapyramidal symptoms, acute dystonia or any other movement disturbance. Knowledge of the risks and benefits

  1. The effect of MMF dose and trough levels on adverse effects in pediatric heart transplant recipients.

    PubMed

    Siddiqi, Nida; Lamour, Jacqueline M; Hsu, Daphne T

    2015-09-01

    Limited pharmacokinetic and safety data exist for MMF in pediatric HTR. Previously targeted MPA-TL are 1.5-3.0 μg/mL. The objective of this study was to assess the outcomes targeting MPA-TL of 0.8-2.0 μg/mL in pediatric HTR. MPA-TL were retrospectively collected 2-12 months post-transplant. Acute rejection, infection, leukopenia, and GI complaints were then correlated with MPA-TL. A total of 355 MPA-TL from 22 HTR were included. Median age was 2.5 yr. Primary indication for transplant was dilated cardiomyopathy (64%). Mean MPA-TL was 1.7 ± 0.9 μg/mL. African American patients received significantly higher doses (702 ± 235 mg/m(2) ) compared with other races (p = 0.035). Leukopenia was less common in patients with SUB MPA vs. others (p = 0.01). MMF was discontinued for GI complaints in one patient and leukopenia in two patients. One SUB patient had acute rejection, and one SUP patient had infection. One-yr survival was 100%. Targeting a lower range for MPA-TL was not associated with significant rejection or infection. Despite lower MPA-TL, MMF was discontinued in 3/22 patients for adverse effects.

  2. Adverse Drug Effects and Preoperative Medication Factors Related to Perioperative Low-Dose Ketamine Infusions.

    PubMed

    Schwenk, Eric S; Goldberg, Stephen F; Patel, Ronak D; Zhou, Jon; Adams, Douglas R; Baratta, Jaime L; Viscusi, Eugene R; Epstein, Richard H

    2016-01-01

    High-dose opioid administration is associated with significant adverse events. Evidence suggests that low-dose ketamine infusions improve perioperative analgesia over conventional opioid management, but usage is highly variable. Ketamine's adverse drug effects (ADEs) are well known, but their prevalence during low-dose infusions in a clinical setting and how often they lead to infusion discontinuation are unknown. The purposes of this study were 3-fold: (1) to identify patient factors associated with initiation of ketamine infusions during spine surgery, (2) to identify specific spine procedures in which ketamine has been used most frequently, and (3) to identify ADEs associated with postoperative ketamine infusions and which ADEs most frequently led to discontinuation. Spine surgery was chosen because of its association with moderate to severe pain and a relatively high use of ketamine infusions in this population at our hospital.

  3. Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects.

    PubMed

    Streissguth, Ann P; Bookstein, Fred L; Barr, Helen M; Sampson, Paul D; O'Malley, Kieran; Young, Julia Kogan

    2004-08-01

    Clinical descriptions of patients with Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) suggest major problems with adaptive behavior. Five operationally defined adverse outcomes and 18 associated risk/protective factors were examined using a Life History Interview with knowledgeable informants of 415 patients with FAS or FAE (median age 14 years, range 6-51; median IQ 86, range 29-126). Eighty percent of these patients were not raised by their biological mothers. For adolescents and adults, the life span prevalence was 61% for Disrupted School Experiences, 60% for Trouble with the Law, 50% for Confinement (in detention, jail, prison, or a psychiatric or alcohol/drug inpatient setting), 49% for Inappropriate Sexual Behaviors on repeated occasions, and 35% for Alcohol/Drug Problems. The odds of escaping these adverse life outcomes are increased 2- to 4-fold by receiving the diagnosis of FAS or FAE at an earlier age and by being reared in good stable environments.

  4. Adverse events after endovascular treatment of chronic cerebro-spinal venous insufficiency (CCSVI) in patients with multiple sclerosis.

    PubMed

    Ghezzi, A; Annovazzi, P; Amato, M P; Capello, E; Cavalla, P; Cocco, E; Falcini, M; Gallo, A; Patti, F; Perini, P; Rodegher, M E; Rovaris, M; Rottoli, M R; Comi, G

    2013-06-01

    Although it is debated whether chronic cerebro-spinal venous insufficiency (CCSVI) plays a role in multiple sclerosis (MS) development, many patients undergo endovascular treatment (ET) of CCSVI. A study is ongoing in Italy to evaluate the clinical outcome of ET. Severe adverse events (AEs) occurred in 15/462 subjects at a variable interval after ET: jugular thrombosis in seven patients, tetraventricular hydrocephalus, stroke, paroxysmal atrial fibrillation, status epilepticus, aspiration pneumonia, hypertension with tachicardia, or bleeding of bedsore in the remaining seven cases. One patient died because of myocardial infarction 10 weeks after ET. The risk of severe AEs related to ET for CCSVI must be carefully considered.

  5. Sedimentary selenium as a causal factor for adverse biological effects: Toxicity thresholds and stream modeling

    SciTech Connect

    Va Derveer, W.; Canton, S.

    1995-12-31

    Selenium (Se) in the aquatic environment exhibits a strong association with particulate organic matter and as a result, measurements of waterborne concentration can be an unreliable predictor of bioaccumulation and adverse effects. Particulate-bound Se, typically measured as sedimentary Se, has been repeatedly implicated as a causal factor for Se bioaccumulation and subsequent potential for reproductive failures in fish and/or birds at sites receiving coal-fired power plant and refinery effluents as well as irrigation drainage. In fact, the premise that adverse biological effects are largely induced by sedimentary Se satisfies all of Hill`s criteria for a causal association. Despite these findings, most efforts to control Se continue to focus on waterborne concentrations because sedimentary toxicity thresholds are largely unknown. Sedimentary Se and associated biological effects data from studies of Se-bearing industrial effluent and irrigation drainage were compiled to initiate development of biological effects thresholds, The probability of adverse effects on fish or birds appears to be low up to a sedimentary Se concentration of about 2.8 {micro}g/g dry weight and high at 6.4 {micro}g/g dry weight (10th and 50th percentile of effects data, respectively). In addition, a preliminary regression model was derived for predicting dissolved to sedimentary Se transfer in streams as an interactive function of site-specific sedimentary organic carbon content (R{sup 2} = 0,870, p < 0.001) based on irrigation drainage studies in Colorado. This dissolved Se interaction with sedimentary organic carbon provides a possible explanation for the variable biological response to waterborne Se-organic-rich sites are predisposed to greater Se bioaccumulation and subsequent biological effects than organic-poor sites.

  6. Adverse Childhood Experiences, Commitment Offense, and Race/Ethnicity: Are the Effects Crime-, Race-, and Ethnicity-Specific?

    PubMed Central

    DeLisi, Matt; Alcala, Justin; Kusow, Abdi; Hochstetler, Andy; Heirigs, Mark H.; Caudill, Jonathan W.; Trulson, Chad R.; Baglivio, Michael T.

    2017-01-01

    Adverse childhood experiences are associated with an array of health, psychiatric, and behavioral problems including antisocial behavior. Criminologists have recently utilized adverse childhood experiences as an organizing research framework and shown that adverse childhood experiences are associated with delinquency, violence, and more chronic/severe criminal careers. However, much less is known about adverse childhood experiences vis-à-vis specific forms of crime and whether the effects vary across race and ethnicity. Using a sample of 2520 male confined juvenile delinquents, the current study used epidemiological tables of odds (both unadjusted and adjusted for onset, total adjudications, and total out of home placements) to evaluate the significance of the number of adverse childhood experiences on commitment for homicide, sexual assault, and serious persons/property offending. The effects of adverse childhood experiences vary considerably across racial and ethnic groups and across offense types. Adverse childhood experiences are strongly and positively associated with sexual offending, but negatively associated with homicide and serious person/property offending. Differential effects of adverse childhood experiences were also seen among African Americans, Hispanics, and whites. Suggestions for future research to clarify the mechanisms by which adverse childhood experiences manifest in specific forms of criminal behavior are offered. PMID:28327508

  7. Adverse Childhood Experiences, Commitment Offense, and Race/Ethnicity: Are the Effects Crime-, Race-, and Ethnicity-Specific?

    PubMed

    DeLisi, Matt; Alcala, Justin; Kusow, Abdi; Hochstetler, Andy; Heirigs, Mark H; Caudill, Jonathan W; Trulson, Chad R; Baglivio, Michael T

    2017-03-22

    Adverse childhood experiences are associated with an array of health, psychiatric, and behavioral problems including antisocial behavior. Criminologists have recently utilized adverse childhood experiences as an organizing research framework and shown that adverse childhood experiences are associated with delinquency, violence, and more chronic/severe criminal careers. However, much less is known about adverse childhood experiences vis-à-vis specific forms of crime and whether the effects vary across race and ethnicity. Using a sample of 2520 male confined juvenile delinquents, the current study used epidemiological tables of odds (both unadjusted and adjusted for onset, total adjudications, and total out of home placements) to evaluate the significance of the number of adverse childhood experiences on commitment for homicide, sexual assault, and serious persons/property offending. The effects of adverse childhood experiences vary considerably across racial and ethnic groups and across offense types. Adverse childhood experiences are strongly and positively associated with sexual offending, but negatively associated with homicide and serious person/property offending. Differential effects of adverse childhood experiences were also seen among African Americans, Hispanics, and whites. Suggestions for future research to clarify the mechanisms by which adverse childhood experiences manifest in specific forms of criminal behavior are offered.

  8. Parent Report of Antidepressant, Anxiolytic, and Antipsychotic Medication Use in Individuals with Williams Syndrome: Effectiveness and Adverse Effects

    ERIC Educational Resources Information Center

    Martens, Marilee A.; Seyfer, Daisha L.; Andridge, Rebecca R.; Foster, Jessica E. A.; Chowdhury, Monali; McClure, Kelsey E.; Coury, Daniel L.

    2012-01-01

    Williams syndrome (WS) is a neurodevelopmental genetic disorder characterized in part by anxiety and behavioral difficulties. We examine the effectiveness and adverse effects of antidepressant, anxiolytic, and antipsychotic medications in individuals with WS. A total of 513 parents/caregivers completed a survey of psychotropic medication usage…

  9. Inhaled diesel emissions generated with cerium oxide nanoparticle fuel additive induce adverse pulmonary and systemic effects.

    PubMed

    Snow, Samantha J; McGee, John; Miller, Desinia B; Bass, Virginia; Schladweiler, Mette C; Thomas, Ronald F; Krantz, Todd; King, Charly; Ledbetter, Allen D; Richards, Judy; Weinstein, Jason P; Conner, Teri; Willis, Robert; Linak, William P; Nash, David; Wood, Charles E; Elmore, Susan A; Morrison, James P; Johnson, Crystal L; Gilmour, Matthew Ian; Kodavanti, Urmila P

    2014-12-01

    Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe results in greater adverse pulmonary effects compared with DE. Male Sprague Dawley rats were exposed to filtered air, DE, or DECe for 5 h/day for 2 days. N-acetyl glucosaminidase activity was increased in bronchial alveolar lavage fluid (BALF) of rats exposed to DECe but not DE. There were also marginal but insignificant increases in several other lung injury biomarkers in both exposure groups (DECe > DE for all). To further characterize DECe toxicity, rats in a second study were exposed to filtered air or DECe for 5 h/day for 2 days or 4 weeks. Tissue analysis indicated a concentration- and time-dependent accumulation of lung and liver cerium followed by a delayed clearance. The gas-phase and high concentration of DECe increased lung inflammation at the 2-day time point, indicating that gas-phase components, in addition to particles, contribute to pulmonary toxicity. This effect was reduced at 4 weeks except for a sustained increase in BALF γ-glutamyl transferase activity. Histopathology and transmission electron microscopy revealed increased alveolar septa thickness due to edema and increased numbers of pigmented macrophages after DECe exposure. Collectively, these findings indicate that DECe induces more adverse pulmonary effects on a mass basis than DE. In addition, lung accumulation of cerium, systemic translocation to the liver, and delayed clearance are added concerns to existing health effects of DECe.

  10. Inhaled Diesel Emissions Generated with Cerium Oxide Nanoparticle Fuel Additive Induce Adverse Pulmonary and Systemic Effects

    PubMed Central

    Snow, Samantha J.; McGee, John; Miller, Desinia B.; Bass, Virginia; Schladweiler, Mette C.; Thomas, Ronald F.; Krantz, Todd; King, Charly; Ledbetter, Allen D.; Richards, Judy; Weinstein, Jason P.; Conner, Teri; Willis, Robert; Linak, William P.; Nash, David; Wood, Charles E.; Elmore, Susan A.; Morrison, James P.; Johnson, Crystal L.; Gilmour, Matthew Ian; Kodavanti, Urmila P.

    2014-01-01

    Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe results in greater adverse pulmonary effects compared with DE. Male Sprague Dawley rats were exposed to filtered air, DE, or DECe for 5 h/day for 2 days. N-acetyl glucosaminidase activity was increased in bronchial alveolar lavage fluid (BALF) of rats exposed to DECe but not DE. There were also marginal but insignificant increases in several other lung injury biomarkers in both exposure groups (DECe > DE for all). To further characterize DECe toxicity, rats in a second study were exposed to filtered air or DECe for 5 h/day for 2 days or 4 weeks. Tissue analysis indicated a concentration- and time-dependent accumulation of lung and liver cerium followed by a delayed clearance. The gas-phase and high concentration of DECe increased lung inflammation at the 2-day time point, indicating that gas-phase components, in addition to particles, contribute to pulmonary toxicity. This effect was reduced at 4 weeks except for a sustained increase in BALF γ-glutamyl transferase activity. Histopathology and transmission electron microscopy revealed increased alveolar septa thickness due to edema and increased numbers of pigmented macrophages after DECe exposure. Collectively, these findings indicate that DECe induces more adverse pulmonary effects on a mass basis than DE. In addition, lung accumulation of cerium, systemic translocation to the liver, and delayed clearance are added concerns to existing health effects of DECe. PMID:25239632

  11. Scientific and Regulatory Policy Committee: Recommended ("Best") Practices for Determining, Communicating, and Using Adverse Effect Data from Nonclinical Studies.

    PubMed

    Kerlin, Roy; Bolon, Brad; Burkhardt, John; Francke, Sabine; Greaves, Peter; Meador, Vince; Popp, James

    2016-02-01

    Recommendations (best practices) are provided by the Society of Toxicologic Pathology's Adversity Working Group for making consistent interpretations of test article-related effects as "adverse" and assigning a "no observed adverse effect level" (NOAEL) in nonclinical toxicity studies. Adverse is a term indicating "harm" to the test animal, while nonadverse indicates lack of harm. Adverse findings in the study reports should be defined in relation to effects on the test species used and within the context of the given study. Test article-related effects should be described on their own merits, and decisions to consider them as adverse or nonadverse should be justified. Related effects may be discussed together; in particular, markers of toxicity that are not in and of themselves adverse ideally should be discussed in conjunction with the causal toxicity to determine adversity. Adverse findings should be identified in subreports (clinical data, pathology data, etc.) if sufficient information is available, and/or in the final study report as individual or grouped findings, but study NOAELs should be established at the level of the overall study report. Interpretations such as "not biologically relevant" or "not toxicologically important" should be avoided unless defined and supported by scientific rationale. Decisions defining adverse findings and the NOAEL in final study reports should combine the expertise of all contributing scientific disciplines. Where possible, use of NOAELs in data tables should be linked to explanatory text that places them in context. Ideally, in nonclinical summary documents, NOAELs from multiple studies are considered together in defining the most important adverse responses in the most sensitive species. These responses are then considered along with an understanding of their likely mechanisms, as well as other information such as variability in species sensitivity, comparative pathology, reversibility and progression, kinetics, and

  12. Adverse effects of citrate/gold nanoparticles on human dermal fibroblasts.

    PubMed

    Pernodet, Nadine; Fang, Xiaohua; Sun, Yuan; Bakhtina, Asya; Ramakrishnan, Aditi; Sokolov, Jonathan; Ulman, Abraham; Rafailovich, Miriam

    2006-06-01

    Nanoscale engineering is one of the most dynamically growing areas at the interface between electronics, physics, biology, and medicine. As there are no safety regulations yet, concerns about future health problems are rising. We investigated the effects of citrate/gold nanoparticles at different concentrations and exposure times on human dermal fibroblasts. We found that, as a result of intracellular nanoparticle presence, actin stress fibers disappeared, thereby inducing major adverse effects on cell viability. Thus, properties such as cell spreading and adhesion, cell growth, and protein synthesis to form the extracellular matrix were altered dramatically. These results suggest that the internal cell activities have been damaged.

  13. Generalized intense pruritus during canagliflozin treatment: Is it an adverse drug reaction?

    PubMed

    Vasapollo, Piero; Cione, Erika; Luciani, Filippo; Gallelli, Luca

    2016-04-05

    Selective agents able to locate and identify unique targets represent a crucial aspect of modern pharmacology. The exclusive location of sodium-glucose co-transporter-2 (SGLUT2) on kidneys prompt companies to develop SGLT2 inhibitors that today are the latest class of drugs for diabetes treatment. In particular, canagliflozin blocks the re-absorption of glucose in the kidney lowering blood glucose levels by increasing glucose excretion. We report a 61-year old woman who developed an intense and severe pruritus during the treatment with canagliflozin. Clinical and laboratory findings excluded the presence of systemic or skin diseases able to induce pruritus. The discontinuation of canagliflozin and the treatment with pioglitazone/metformin fixed combination induced a remission of pruritus. This case emphasizes the need to consider pruritus as a differential diagnosis during the treatment with canagliflozin.

  14. Adverse events risk associated with anti-VEGFR agents in the treatment of advanced nonsmall-cell lung cancer

    PubMed Central

    Gu, Biao; Gao, WenChuang; Chu, HongJun; Gao, Jian; Fu, Zhi; Ding, Hui; Lv, JunJie; Wu, QingQuan

    2016-01-01

    Abstract To perform this meta-analysis, we investigated the risk of the most clinically relevant adverse events related to antivascular endothelial growth factor receptor (VEGFR) agents in advanced nonsmall-cell lung cancer (NSCLC). A comprehensive literature search for studies published up to October 2015 was performed. Prospective randomized controlled phase II/III clinical trials that comparing therapy with or without anti-VEGFR agents for advanced NSCLC were included for analysis. Summary relative risk (RR) and 95% confidence intervals (CIs) were calculated using random effects or fixed effects according to the heterogeneity among included trials. A total of 11,701 patients from 18 clinical trials were included for analysis. Pooled RR showed that the use of anti-VEGFR agents significantly increased the risk of developing hypertension (RR 4.71, 95% CI 3.29–6.73, P < 0.001) and fatal adverse events (RR 1.33, 95% CI 1.12–1.58, P = 0.001). No statistically significant differences were found for gastrointestinal (GI) perforation (P = 0.41), arterial or venous thromboembolic events (P = 0.49 and P = 0.16, respectively), or hemorrhagic events (P = 0.81). Sensitive analysis indicated that the significance estimate of pooled RR of fatal adverse event (FAEs) was not significantly influenced by omitting any single study. The use of anti-VEGFR agents in advanced NSCLC does significantly increase the risk of hypertension and fatal adverse events, but not for arterial or venous thromboembolic events, GI perforation, or hemorrhagic events. PMID:27902583

  15. Adverse reproductive effects of maternal low-dose melamine exposure during pregnancy in rats.

    PubMed

    Chu, Ching Yan; Tang, Ling Ying; Li, Lu; Shum, Alisa Sau Wun; Fung, Kwok Pui; Wang, Chi Chiu

    2017-01-01

    Melamine is a heterocyclic, aromatic amine and nitrogen-enriched environmental toxicant, found in not only adulterated foodstuffs but also industrial household tableware and paints. Previous studies demonstrated adverse effects of high-dose melamine on human infants and pregnant animals, but effects of low-dose melamine on pregnancy have not been reported. In this study, reproductive effects of low-dose melamine were investigated in pregnant rats. Melamine in the range of 12.5-50 mg/kg was administered to pregnant rats at different gestational stages. Maternal weight gain was not significantly affected, and other maternal morbidity was not observed. Low-dose melamine exposure during pregnancy increased fetal size but reduced somite number in gastrulation (GD8.5-GD10.5) and organogenesis (GD10.5-GD16.5) periods, and increased incidence of stillbirth in whole gestational period (GD0.5 to delivery). Embryotoxicity of melamine was further confirmed by whole embryo culture in vitro that melamine retarded embryonic growth, impaired development of brain and heart, and induced open neural tube and atrioventricular defects with increased apoptosis. In conclusion, adverse reproductive effects of low-dose melamine during pregnancy were identified in the developing rat embryos and the perinatal effects of melamine were gestational and developmental stage dependent. Detailed hazard and risk assessment of melamine in reproduction system are warrant. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 131-138, 2017.

  16. Time-Dependent Effects in Algae for Chemicals with Different Adverse Outcome Pathways: A Novel Approach.

    PubMed

    Vogs, Carolina; Altenburger, Rolf

    2016-07-19

    Chemicals affect unicellular algae as a result of toxicokinetic and toxicodynamic processes. The internal concentration of chemicals in algae cells typically reaches equilibrium within minutes, while damage cumulatively increases over hours. The time gap between the steady state of internal exposure and damage development is thus suspected to span up to hours, mainly due to toxicodynamic processes. The quantification of rate-limited toxicodynamic processes, aggregated as a progressive effect from an initiating molecular event through biological key events toward the adverse outcome on algae growth inhibition, might discriminate between different adverse outcome pathways (AOPs). To support our hypothesis, we selected six chemicals according to different physicochemical properties and three distinctly dissimilar AOPs. The time courses of internal concentrations were linked to the observed affected Scenedesmus vacuolatus growth using toxicokinetic-toxicodynamic modeling. Effects on cell growth were explained by effect progression and not by the time to reach internal equilibrium concentration. Effect progression rates ranged over 6 orders of magnitude for all chemicals but varied by less than 1 order of magnitude within similar AOP (photosystem II inhibitors > reactive chemicals > lipid biosynthesis inhibitors), meaning that inhibitors of photosystem II advance an effect toward algae growth fastest compared to reactive chemicals and inhibitors of lipid biosynthesis.

  17. Novel Associations between FAAH Genetic Variants and Postoperative Central Opioid related Adverse Effects

    PubMed Central

    Sadhasivam, Senthilkumar; Zhang, Xue; Chidambaran, Vidya; Mavi, Jagroop; Pilipenko, Valentina; Mersha, Tesfaye B.; Meller, Jaroslaw; Kaufman, Kenneth M.; Martin, Lisa J.; McAuliffe, John

    2014-01-01

    Opioid effects are potentiated by cannabinoid agonists including anandamide, an endocannabinoid. Inter-individual variability in responses to opioids is a major clinical problem. Multiple deaths and anoxic brain injuries occur every year in due to opioid induced respiratory depression in surgical patients and drug abusers of opioids and cannabinoids. This study aimed to determine specific associations between genetic variants of fatty acid amide hydrolase (FAAH) and postoperative central opioid adverse effects in children undergoing tonsillectomy. This is a prospective genotype blinded observational study 259 healthy children between 6 and 15 years that received standard perioperative care with a standard anesthetic and an intraoperative dose of morphine were enrolled. Associations between frequent polymorphisms of FAAH and central postoperative opioid adverse effects including, respiratory depression (RD), postoperative nausea and vomiting (PONV) and prolonged stay in Post Anesthesia Recovery Room (PACU) due to RD and PONV were analyzed. Five specific FAAH SNPs had significant associations with more than 2 fold increased risk for refractory PONV (adjusted p<0.0018), and nominal associations (p<0.05) with RD and prolonged PACU stay in white children undergoing tonsillectomy. FAAH SNP, rs324420 is a missense mutation with altered FAAH function and it is linked with other FAAH SNPs associated with PONV and RD in our cohort; association between PONV and rs324420 was confirmed in our extended cohort with additional 66 white children. Specific FAAH polymorphisms are associated with refractory PONV, opioid-related respiratory depression, and prolonged PACU stay due to opioid adverse effects in white children undergoing tonsillectomy. PMID:25558980

  18. Novel associations between FAAH genetic variants and postoperative central opioid-related adverse effects.

    PubMed

    Sadhasivam, S; Zhang, X; Chidambaran, V; Mavi, J; Pilipenko, V; Mersha, T B; Meller, J; Kaufman, K M; Martin, L J; McAuliffe, J

    2015-10-01

    Opioid effects are potentiated by cannabinoid agonists including anandamide, an endocannabinoid. Inter-individual variability in responses to opioids is a major clinical problem. Multiple deaths and anoxic brain injuries occur every year because of opioid-induced respiratory depression (RD) in surgical patients and drug abusers of opioids and cannabinoids. This study aimed to determine specific associations between genetic variants of fatty acid amide hydrolase (FAAH) and postoperative central opioid adverse effects in children undergoing tonsillectomy. This is a prospective genotype-blinded observational study in which 259 healthy children between 6 and 15 years of age who received standard perioperative care with a standard anesthetic and an intraoperative dose of morphine were enrolled. Associations between frequent polymorphisms of FAAH and central postoperative opioid adverse effects including, RD, postoperative nausea and vomiting (PONV) and prolonged stay in Post Anesthesia Recovery Room (postoperative anesthesia care unit, PACU) due to RD and PONV were analyzed. Five specific FAAH single nucleotide polymorphisms (SNPs) had significant associations with more than twofold increased risk for refractory PONV (adjusted P<0.0018), and nominal associations (P<0.05) with RD and prolonged PACU stay in white children undergoing tonsillectomy. The FAAH SNP, rs324420, is a missense mutation with altered FAAH function and it is linked with other FAAH SNPs associated with PONV and RD in our cohort; association between PONV and rs324420 was confirmed in our extended cohort with additional 66 white children. Specific FAAH polymorphisms are associated with refractory PONV, opioid-related RD, and prolonged PACU stay due to opioid adverse effects in white children undergoing tonsillectomy.

  19. Assessment on the adverse effects of Aminoglycosides and Flouroquinolone on sperm parameters and male reproductive tissue: A systematic review

    PubMed Central

    Khaki, Arash

    2015-01-01

    Background: Antibiotic therapies used in treatment of many diseases have adverse effects on fertility. This review analyzes previous comparative studies that surveyed the effects of two common groups of antibiotics on male fertility. Objective: To evaluate histo-pathological effects of fluoroquinolones and aminoglycosides on sperm parameters and male reproductive tissue. Materials and Methods: Articles about the effects of aminoglycosides and fluoroquinolones on male infertility, sperm parameters, male reproductive tissue, and spermatogenesis in English and Persian languages published on Google Scholar and PubMed databases from January 2000 to December 2013 were assessed. Randomized controlled trials (RCTs) assessing the effects of aminoglycosides or fluoroquinolones on sperm parameters, artificial insemination, and male reproductive tract or RCTs comparing aminoglycosides vs. fluoroquinolones were eligible for inclusion. For ascertaining the reliability of study, data were extracted independently and in duplicate by two investigators. Results: Sperm viability was decreased significantly with streptomycin, gentamicin, and neomycin (p<0.001). Sperm motility was decreased significantly with gentamicin and neomycin (p<0.05). Total sperm count was significantly decreased with ofloxacin, gentamicin, streptomycin, and neomycin (p<0.022). There was significant decrease in post-thawing motility with low dose and high dose of ciprofloxacin. Testis weight was decreased with gentamicin and ofloxacin significantly (p<0.011). There was significant decrease in seminal vesicle weight with gentamicin, neomycin, and ofloxacin (p<0.022). Furthermore, changes in epididymis weight, percentage of total apoptotic cells, and diameter of seminiferous tubule were significant with all drugs including streptomycin, gentamicin, neomycin, and ofloxacin (p<0.05). Conclusion: Streptomycin has less negative effects on cell’s apoptosis and sperm parameters as compared to other drugs. Gentamicin

  20. Impact of schizophrenia and schizophrenia treatment-related adverse events on quality of life: direct utility elicitation

    PubMed Central

    Briggs, Andrew; Wild, Diane; Lees, Michael; Reaney, Matthew; Dursun, Serdar; Parry, David; Mukherjee, Jayanti

    2008-01-01

    Objective To examine the impact of schizophrenia, its treatment and treatment-related adverse events related to antipsychotics, on quality of life from the perspective of schizophrenia patients and laypersons. Methods Health state descriptions for stable schizophrenia, extra pyramidal symptoms (EPS), hyperprolactinemia, diabetes, weight gain and relapse were developed based on a review of the literature and expert opinion. The quality of life impact of each health state was elicited using a time trade-off instrument administered by interview to 49 stable schizophrenia patients and 75 laypersons. Regression techniques were employed to examine the importance of subject characteristics on health-related utility scores. Results Patients and laypersons completed the interview in similar times. Stable schizophrenia had the highest mean utility (0.87 and 0.92 for laypersons and patients respectively), while relapse (0.48 and 0.60) had the lowest mean utility. Of the treatment-related adverse events, EPS had the lowest mean utility (0.57 and 0.72, respectively). Age, gender and PANSS score did not influence the utility results independently of health state. On average, patient utilities are 0.077 points higher than utilities derived from laypersons, although the ranking was similar between the two groups. Conclusion Events associated with schizophrenia and treatment of schizophrenia can bring about a significant detriment in patient quality of life, with relapse having the largest negative impact. Results indicate that patients with stable schizophrenia are less willing to trade years of life to avoid schizophrenia-related symptoms compared to laypersons. Both sets of respondents showed equal ability to complete the questionnaire. PMID:19040721

  1. Designing Interventions Informed by Scientific Knowledge About Effects of Early Adversity: A Translational Neuroscience Agenda for Next Generation Addictions Research

    PubMed Central

    Fisher, Philip A.; Berkman, Elliot T.

    2015-01-01

    In spite of extensive scientific knowledge about the neurobiological systems and neural pathways underlying addictions, only limited progress has been made to reduce the population-level incidence of addictions by using prevention and treatment programs. In this area of research the translation of basic neuroscience of causal mechanisms to effective interventions has not been fully realized. In this article we describe how an understanding of the effects of early adverse experiences on brain and biological development may provide new opportunities to achieve impact at scale with respect to reduction of addictions. We propose four categories of new knowledge that translational neuroscience investigations of addictions should incorporate to be successful. We then describe a translational neuroscience-informed smoking cessation intervention based on this model. PMID:26985399

  2. Putative Kappa Opioid Heteromers As Targets for Developing Analgesics Free of Adverse Effects

    PubMed Central

    2015-01-01

    It is now generally recognized that upon activation by an agonist, β-arrestin associates with G protein-coupled receptors and acts as a scaffold in creating a diverse signaling network that could lead to adverse effects. As an approach to reducing side effects associated with κ opioid agonists, a series of β-naltrexamides 3–10 was synthesized in an effort to selectively target putative κ opioid heteromers without recruiting β-arrestin upon activation. The most potent derivative 3 (INTA) strongly activated KOR-DOR and KOR-MOR heteromers in HEK293 cells. In vivo studies revealed 3 to produce potent antinociception, which, when taken together with antagonism data, was consistent with the activation of both heteromers. 3 was devoid of tolerance, dependence, and showed no aversive effect in the conditioned place preference assay. As immunofluorescence studies indicated no recruitment of β-arrestin2 to membranes in coexpressed KOR-DOR cells, this study suggests that targeting of specific putative heteromers has the potential to identify leads for analgesics devoid of adverse effects. PMID:24978316

  3. Injected nanoparticles: the combination of experimental systems to assess cardiovascular adverse effects.

    PubMed

    Vlasova, Maria A; Tarasova, Olga S; Riikonen, Joakim; Raula, Janne; Lobach, Anatoly S; Borzykh, Anna A; Smirin, Boris V; Kauppinen, Esko I; Eletskii, Alexander V; Herzig, Karl-Heinz; Salonen, Jarno; Tavi, Pasi; Lehto, Vesa-Pekka; Järvinen, Kristiina

    2014-05-01

    When nanocarriers are used for drug delivery they can often achieve superior therapeutic outcomes over standard drug formulations. However, concerns about their adverse effects are growing due to the association between exposure to certain nanosized particles and cardiovascular events. Here we examine the impact of intravenously injected drug-free nanocarriers on the cardiovasculature at both the systemic and organ levels. We combine in vivo and in vitro methods to enable monitoring of hemodynamic parameters in conscious rats, assessments of the function of the vessels after sub-chronic systemic exposure to nanocarriers and evaluation of the direct effect of nanocarriers on vascular tone. We demonstrate that nanocarriers can decrease blood pressure and increase heart rate in vivo via various mechanisms. Depending on the type, nanocarriers induce the dilation of the resistance arteries and/or change the responses induced by vasoconstrictor or vasodilator drugs. No direct correlation between physicochemical properties and cardiovascular effects of nanoparticles was observed. The proposed combination of methods empowers the studies of cardiovascular adverse effects of the nanocarriers.

  4. Diesel exhaust: current knowledge of adverse effects and underlying cellular mechanisms.

    PubMed

    Steiner, Sandro; Bisig, Christoph; Petri-Fink, Alke; Rothen-Rutishauser, Barbara

    2016-07-01

    Diesel engine emissions are among the most prevalent anthropogenic pollutants worldwide, and with the growing popularity of diesel-fueled engines in the private transportation sector, they are becoming increasingly widespread in densely populated urban regions. However, a large number of toxicological studies clearly show that diesel engine emissions profoundly affect human health. Thus the interest in the molecular and cellular mechanisms underlying these effects is large, especially concerning the nature of the components of diesel exhaust responsible for the effects and how they could be eliminated from the exhaust. This review describes the fundamental properties of diesel exhaust as well as the human respiratory tract and concludes that adverse health effects of diesel exhaust not only emerge from its chemical composition, but also from the interplay between its physical properties, the physiological and cellular properties, and function of the human respiratory tract. Furthermore, the primary molecular and cellular mechanisms triggered by diesel exhaust exposure, as well as the fundamentals of the methods for toxicological testing of diesel exhaust toxicity, are described. The key aspects of adverse effects induced by diesel exhaust exposure described herein will be important for regulators to support or ban certain technologies or to legitimate incentives for the development of promising new technologies such as catalytic diesel particle filters.

  5. Putative kappa opioid heteromers as targets for developing analgesics free of adverse effects.

    PubMed

    Le Naour, Morgan; Lunzer, Mary M; Powers, Michael D; Kalyuzhny, Alexander E; Benneyworth, Michael A; Thomas, Mark J; Portoghese, Philip S

    2014-08-14

    It is now generally recognized that upon activation by an agonist, β-arrestin associates with G protein-coupled receptors and acts as a scaffold in creating a diverse signaling network that could lead to adverse effects. As an approach to reducing side effects associated with κ opioid agonists, a series of β-naltrexamides 3-10 was synthesized in an effort to selectively target putative κ opioid heteromers without recruiting β-arrestin upon activation. The most potent derivative 3 (INTA) strongly activated KOR-DOR and KOR-MOR heteromers in HEK293 cells. In vivo studies revealed 3 to produce potent antinociception, which, when taken together with antagonism data, was consistent with the activation of both heteromers. 3 was devoid of tolerance, dependence, and showed no aversive effect in the conditioned place preference assay. As immunofluorescence studies indicated no recruitment of β-arrestin2 to membranes in coexpressed KOR-DOR cells, this study suggests that targeting of specific putative heteromers has the potential to identify leads for analgesics devoid of adverse effects.

  6. Risk, mercury levels, and birds: relating adverse laboratory effects to field biomonitoring.

    PubMed

    Burger, J; Gochfeld, M

    1997-11-01

    There is an abundance of field data on levels of mercury in a variety of organisms and there are a number of studies that demonstrate the adverse effects of mercury on laboratory animals, but few studies examine the relationship between the two. Thus it is often difficult to determine the ecological relevance of mercury concentrations found in nature, or to predict the ecosystem consequences of current levels. In this paper we review the levels in tissues that are associated with adverse effects in birds from laboratory studies and compare these with levels found in wild bird populations in the New York Bight to provide a basis for interpreting values in avian populations. We use feathers from fledgling birds which would have been fed on locally obtained food to eliminate the problem of where toxic burdens were acquired by more mobile adult birds. Laboratory studies indicate that in some species mercury levels of 1.5 ppm in eggs and/or 5 to 40 ppm in the feathers of birds are associated with adverse effects, including impaired reproduction. We report egg levels in birds that range as high as 3.8 ppm and feather levels that range as high as 10.3 ppm, although means are much lower. The levels in eggs of some wild birds in the New York Bight are within the range known to lower hatchability, embryo and chick survival, and chick weight, all variables that reduce reproductive success. Species with high egg levels include Forster's tern (Sterna forsteri) and black skimmer (Rynchops niger). Levels in feathers of some young wild birds from the New York Bight are within the range associated with reduced hatchability of eggs, behavioral abnormalities of adults, and infertility. Species with dangerously elevated mercury levels in feathers include great egret (Ardea [=Egretta] alba), snowy egret [Egretta thula), and black skimmers.

  7. Epigenetics and transcriptomics to detect adverse drug effects in model systems of human development.

    PubMed

    Balmer, Nina V; Leist, Marcel

    2014-07-01

    Prenatal exposure to environmental chemicals or drugs has been associated with functional or structural deficits and the development of diseases in later life. For example, developmental neurotoxicity (DNT) is triggered by lead, and this compound may predispose to neurodegenerative diseases in later life. The molecular memory for such late consequences of early exposure is not known, but epigenetic mechanisms (modification of the chromatin structure) could take this role. Examples and underlying mechanisms have been compiled here for the field of DNT. Moreover, we addressed the question as to what readout is suitable for addressing drug memory effects. We summarize how complex developmental processes can be modelled in vitro by using the differentiation of human stem cells. Although cellular models can never replicate the final human DNT phenotype, they can model the adverse effect that a chemical has on key biological processes essential for organ formation and function. Highly information-rich transcriptomics data may inform on these changes and form the bridge from in vitro models to human prediction. We compiled data showing that transcriptome analysis can indicate toxicity patterns of drugs. A crucial question to be answered in our systems is when and how transcriptome changes indicate adversity (as opposed to transient adaptive responses), and how drug-induced changes are perpetuated over time even after washout of the drug. We present evidence for the hypothesis that changes in the histone methylation pattern could represent the persistence detector of an early insult that is transformed to an adverse effect at later time-points in life.

  8. PANCREATIC TOXICITY AS AN ADVERSE EFFECT INDUCED BY MEGLUMINE ANTIMONIATE THERAPY IN A CLINICAL TRIAL FOR CUTANEOUS LEISHMANIASIS.

    PubMed

    Lyra, Marcelo Rosandiski; Passos, Sonia Regina Lambert; Pimentel, Maria Inês Fernandes; Bedoya-Pacheco, Sandro Javier; Valete-Rosalino, Cláudia Maria; Vasconcellos, Erica Camargo Ferreira; Antonio, Liliane Fatima; Saheki, Mauricio Naoto; Salgueiro, Mariza Mattos; Santos, Ginelza Peres Lima; Ribeiro, Madelon Noato; Conceição-Silva, Fatima; Madeira, Maria Fatima; Silva, Jorge Luiz Nunes; Fagundes, Aline; Schubach, Armando Oliveria

    2016-09-22

    American tegumentary leishmaniasis is an infectious disease caused by a protozoan of the genus Leishmania. Pentavalent antimonials are the first choice drugs for cutaneous leishmaniasis (CL), although doses are controversial. In a clinical trial for CL we investigated the occurrence of pancreatic toxicity with different schedules of treatment with meglumine antimoniate (MA). Seventy-two patients were allocated in two different therapeutic groups: 20 or 5 mg of pentavalent antimony (Sb5+)/kg/day for 20 or 30 days, respectively. Looking for adverse effects, patients were asked about abdominal pain, nausea, vomiting or anorexia in each medical visit. We performed physical examinations and collected blood to evaluate serum amylase and lipase in the pre-treatment period, and every 10 days during treatment and one month post-treatment. Hyperlipasemia occurred in 54.8% and hyperamylasemia in 19.4% patients. Patients treated with MA 20 mg Sb5+ presented a higher risk of hyperlipasemia (p = 0.023). Besides, higher MA doses were associated with a 2.05 higher risk ratio (p = 0.003) of developing more serious (moderate to severe) hyperlipasemia. The attributable fraction was 51% in this group. Thirty-six patients presented abdominal pain, nausea, vomiting or anorexia but only 47.2% of those had hyperlipasemia and/ or hyperamylasemia. These findings suggest the importance of the search for less toxic therapeutic regimens for the treatment of CL.

  9. PANCREATIC TOXICITY AS AN ADVERSE EFFECT INDUCED BY MEGLUMINE ANTIMONIATE THERAPY IN A CLINICAL TRIAL FOR CUTANEOUS LEISHMANIASIS

    PubMed Central

    LYRA, Marcelo Rosandiski; PASSOS, Sonia Regina Lambert; PIMENTEL, Maria Inês Fernandes; BEDOYA-PACHECO, Sandro Javier; VALETE-ROSALINO, Cláudia Maria; VASCONCELLOS, Erica Camargo Ferreira; ANTONIO, Liliane Fatima; SAHEKI, Mauricio Naoto; SALGUEIRO, Mariza Mattos; SANTOS, Ginelza Peres Lima; RIBEIRO, Madelon Noato; CONCEIÇÃO-SILVA, Fatima; MADEIRA, Maria Fatima; SILVA, Jorge Luiz Nunes; FAGUNDES, Aline; SCHUBACH, Armando Oliveria

    2016-01-01

    SUMMARY American tegumentary leishmaniasis is an infectious disease caused by a protozoan of the genus Leishmania. Pentavalent antimonials are the first choice drugs for cutaneous leishmaniasis (CL), although doses are controversial. In a clinical trial for CL we investigated the occurrence of pancreatic toxicity with different schedules of treatment with meglumine antimoniate (MA). Seventy-two patients were allocated in two different therapeutic groups: 20 or 5 mg of pentavalent antimony (Sb5+)/kg/day for 20 or 30 days, respectively. Looking for adverse effects, patients were asked about abdominal pain, nausea, vomiting or anorexia in each medical visit. We performed physical examinations and collected blood to evaluate serum amylase and lipase in the pre-treatment period, and every 10 days during treatment and one month post-treatment. Hyperlipasemia occurred in 54.8% and hyperamylasemia in 19.4% patients. Patients treated with MA 20 mg Sb5+ presented a higher risk of hyperlipasemia (p = 0.023). Besides, higher MA doses were associated with a 2.05 higher risk ratio (p = 0.003) of developing more serious (moderate to severe) hyperlipasemia. The attributable fraction was 51% in this group. Thirty-six patients presented abdominal pain, nausea, vomiting or anorexia but only 47.2% of those had hyperlipasemia and/ or hyperamylasemia. These findings suggest the importance of the search for less toxic therapeutic regimens for the treatment of CL. PMID:27680173

  10. Safe Oral Triiodo-L-Thyronine Therapy Protects from Post-Infarct Cardiac Dysfunction and Arrhythmias without Cardiovascular Adverse Effects

    PubMed Central

    Rajagopalan, Viswanathan; Zhang, Youhua; Ojamaa, Kaie; Chen, Yue-feng; Pingitore, Alessandro; Pol, Christine J.; Saunders, Debra; Balasubramanian, Krithika; Towner, Rheal A.; Gerdes, A. Martin

    2016-01-01

    Background A large body of evidence suggests that thyroid hormones (THs) are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3) treatment in myocardial infarction (MI) rats increased left ventricular (LV) contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI. Methods and Results Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 μg/kg/day) was available in drinking water ad libitum immediately following MI and continuing for 2 month(s) (mo). Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy. Conclusions Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans. PMID:26981865

  11. Dose-Effect Relationships for Adverse Events After Cranial Radiation Therapy in Long-term Childhood Cancer Survivors

    SciTech Connect

    Dijk, Irma W.E.M. van; Cardous-Ubbink, Mathilde C.; Pal, Helena J.H. van der; Oldenburger, Foppe; Os, Rob M. van; Ronckers, Cécile M.; Schouten–van Meeteren, Antoinette Y.N.; Kremer, Leontien C.M.

    2013-03-01

    Purpose: To evaluate the prevalence and severity of clinical adverse events (AEs) and treatment-related risk factors in childhood cancer survivors treated with cranial radiation therapy (CRT), with the aim of assessing dose-effect relationships. Methods and Materials: The retrospective study cohort consisted of 1362 Dutch childhood cancer survivors, of whom 285 were treated with CRT delivered as brain irradiation (BI), as part of craniospinal irradiation (CSI), and as total body irradiation (TBI). Individual CRT doses were converted into the equivalent dose in 2-Gy fractions (EQD{sub 2}). Survivors had received their diagnoses between 1966 and 1996 and survived at least 5 years after diagnosis. A complete inventory of Common Terminology Criteria for Adverse Events grade 3.0 AEs was available from our hospital-based late-effect follow-up program. We used multivariable logistic and Cox regression analyses to examine the EQD{sub 2} in relation to the prevalence and severity of AEs, correcting for sex, age at diagnosis, follow-up time, and the treatment-related risk factors surgery and chemotherapy. Results: There was a high prevalence of AEs in the CRT group; over 80% of survivors had more than 1 AE, and almost half had at least 5 AEs, both representing significant increases in number of AEs compared with survivors not treated with CRT. Additionally, the proportion of severe, life-threatening, or disabling AEs was significantly higher in the CRT group. The most frequent AEs were alopecia and cognitive, endocrine, metabolic, and neurologic events. Using the EQD{sub 2}, we found significant dose-effect relationships for these and other AEs. Conclusion: Our results confirm that CRT increases the prevalence and severity of AEs in childhood cancer survivors. Furthermore, analyzing dose-effect relationships with the cumulative EQD{sub 2} instead of total physical dose connects the knowledge from radiation therapy and radiobiology with the clinical experience.

  12. Oral adverse effects of gastrointestinal drugs and considerations for dental management in patients with gastrointestinal disorders

    PubMed Central

    Karthik, Ramya; Karthik, K. S.; David, Chaya; Ameerunnisa; Keerthi, G.

    2012-01-01

    Gastrointestinal disease is associated with alterations in the mouth or influence the course of the dental diseases, and the dental health care workers are expected to recognize, diagnose, and treat oral conditions associated with gastrointestinal diseases and also provide safe and appropriate dental care for afflicted individuals. Drugs used in the management of these diseases result in oral adverse effects and also are known to interact with those prescribed during dental care. Hence, this article has reviewed the drug considerations and guidelines for drug use during dental management of patients with gastrointestinal diseases. PMID:23066260

  13. [Antivaccine misinformation about rate of adverse effects and toxicity of vaccines].

    PubMed

    Mats, A N; Gol'dshteĭn, A V

    2010-01-01

    Two widely known antivaccine inventions are discussed: "vaccination is accompanied by adverse effects, which exceeded complications of respective infections on frequency and severity" and "vaccines represent appalling conglomerate of toxic substances, which is unnaturally to administer to children". Informational and psychological nature of dissemination of these inventions is analyzed. On the basis of recent literature data conclusion was made about the absence of real toxicity (including neurotoxicity), carcinogenicity, allergenicity and autopathogenicity of phenol, folmaldehyde, aluminium hydroxide, Twin 80, squalen (MF59) and ethylmercury in concentrations found in vaccines of national immunization schedule.

  14. Varenicline for smoking cessation: a narrative review of efficacy, adverse effects, use in at-risk populations, and adherence

    PubMed Central

    Burke, Michael V; Hays, J Taylor; Ebbert, Jon O

    2016-01-01

    Treating tobacco dependence is the most effective way to reduce tobacco-related death and disability. Counseling and pharmacotherapy have been shown to increase tobacco abstinence rates among smokers. Varenicline is the most effective monotherapy treatment for tobacco dependence; however, it is prescribed less often than indicated, and adherence is less than optimal. We conducted a literature review of the development, efficacy, safety, contraindications, and adverse effects of varenicline; including reviewing data regarding combination therapy, extended duration, and patient adherence. Varenicline was developed to work specifically on the factors that underlie nicotine addiction. Phase II and Phase III trials established dosing, safety profiles, and efficacy. Postmarketing research raised concerns about neuropsychiatric and cardiac effects, resulting in warning labels being added and modified to encourage discussions with patients weighing the risks and benefits. While more research is needed, evidence is strong that varenicline is safe and effective in treating tobacco dependence among people who are at higher risk for neuropsychiatric symptoms and cardiovascular disease. The effectiveness of varenicline can be improved by taking it in combination with other medications, enhancing patient adherence and extending the duration of treatment. PMID:27099479

  15. Are adverse effects of antiepileptic drugs different in symptomatic partial and idiopathic generalized epilepsies? The Portuguese-Brazilian validation of the Liverpool Adverse Events Profile.

    PubMed

    Martins, H H; Alonso, N B; Vidal-Dourado, M; Carbonel, T D; de Araújo Filho, G M; Caboclo, L O; Yacubian, E M; Guilhoto, L M

    2011-11-01

    We report the results of administration of the Portuguese-Brazilian translation of the Liverpool Adverse Events Profile (LAEP) to 100 patients (mean age=34.5, SD=12.12; 56 females), 61 with symptomatic partial epilepsy (SPE) and 39 with idiopathic generalized epilepsy (IGE) (ILAE, 1989) who were on a stable antiepileptic drug (AED) regimen and being treated in a Brazilian tertiary epilepsy center. Carbamazepine was the most commonly used AED (43.0%), followed by valproic acid (32.0%). Two or more AEDs were used by 69.0% of patients. The mean LAEP score (19 questions) was 37.6 (SD=13.35). The most common adverse effects were sleepiness (35.0%), memory problems (35.0%), and difficulty in concentrating (25.0%). Higher LAEP scores were associated with polytherapy with three or more AEDs (P=0.005), female gender (P<0.001), older age (P<0.001), and uncontrolled seizures (P=0.045). The intraclass coefficient (test-retest reliability) for LAEP overall score was 0.848 (95% CI=0.782-0.895), with a range from 0.370 (unsteadiness) to 0.750 (memory problems). Cronbach's α coefficient (internal consistency) was 0.903. The LAEP was highly correlated with Quality of Life in Epilepsy-31 inventory (r=-0.804, P>0.001) and Hospital Anxiety and Depression Scale (Depression: r=0.637, P<0.001; Anxiety: r=0.621, P<0.001) dimensions. LAEP overall scores were similar in people with SPE and IGE and were not helpful in differentiating adverse effects in these two groups. Clinical variables that influenced global LAEP were seizure frequency (P=0.050) and generalized tonic-clonic seizures in the last month (P=0.031) in the IGE group, and polytherapy with three or more AEDs (P=0.003 and P=0.003) in both IGE and SPE groups.

  16. Adverse Psychosexual Impact Related to the Treatment of Genital Warts and Cervical Intraepithelial Neoplasia

    PubMed Central

    Campaner, Adriana Bittencourt; Vespa Junior, Nelson; Giraldo, Paulo César; Leal Passos, Mauro Romero

    2013-01-01

    Objective. To compare the psychosexual impact related to the treatment of genital warts and cervical intraepithelial neoplasia (CIN) in women. Methods. 75 patients presenting with HPV-induced genital lesions, belonging to one of two patient groups, were included in the study: 29 individuals with genital warts (GWs) and 46 individuals with CIN grades 2 or 3 (CIN 2/3). Initially, medical charts of each woman were examined for extraction of data on the type of HPV-induced infection and treatment administered. Subjects were interviewed to collect sociodemographic data as well as personal, gynecologic, obstetric, and sexual history. After this initial anamnesis, the Sexual Quotient-Female Version (SQ-F) questionnaire was applied to assess sexual function. After application of the questionnaire, patients answered specific questions produced by the researchers, aimed at assessing the impact of the disease and its treatment on their sexual lives. Results. It is noteworthy that patients with CIN 2/3 had statistically similar classification of sexual quotient to patients with GWs (P = 0.115). However, patients with GWs more frequently gave positive answers to the specific questions compared to patients with CIN 2/3. Conclusion. Based on these findings, it is clear that GWs have a greater impact on sexual behavior compared to CIN 2/3. PMID:26316956

  17. Atelocollagen-mediated Systemic Delivery Prevents Immunostimulatory Adverse Effects of siRNA in Mammals

    PubMed Central

    Inaba, Shinichiro; Nagahara, Shunji; Makita, Naoki; Tarumi, Yuzo; Ishimoto, Takuji; Matsuo, Seiichi; Kadomatsu, Kenji; Takei, Yoshifumi

    2012-01-01

    Short interfering RNA (siRNA) is a potent activator of the mammalian innate immune system. When considering possible clinical applications of siRNA for humans, the adverse immunostimulatory effects must also be taken into account. Here, we show that atelocollagen-mediated systemic delivery of siRNA without chemical modifications did not cause any immunostimulation in both animals and human peripheral blood mononuclear cells (PBMCs), even if the siRNA harbored an interferon (IFN)-inducible sequence. In contrast, systemic delivery of immunostimulatory RNA (isRNA)-mediated by a cationic lipid (such as Invivofectamine) induced potent type-I IFNs and inflammatory cytokines. Regarding the mechanism by which the isRNA/atelocollagen complex avoided adverse effects on immunostimulation, we revealed that this complex was not incorporated into PBMCs. On the other hand, Invivofectamine delivered isRNA into PBMCs. The use of either atelocollagen or Invivofectamine as a vehicle elicited significant and undistinguishable therapeutic effects in a contact hypersensitivity (CHS) inflammatory model mouse, when we intravenously injected the siRNA targeting monocyte chemoattractant protein-1 as the complex. For the goal of realizing siRNA-based medicines for humans, atelocollagen is an excellent and promising delivery vehicle, and it has the useful advantage of evading detection by the “radar” of innate immunity. PMID:22031237

  18. Uncertainty quantification of adverse human health effects from continuously released contaminant sources in groundwater systems

    NASA Astrophysics Data System (ADS)

    Zarlenga, Antonio; de Barros, Felipe P. J.; Fiori, Aldo

    2016-10-01

    We propose a computationally efficient probabilistic modeling methodology to estimate the adverse effects on humans of exposure to contaminated groundwater. Our work is aligned with the standard suggested by the regulatory agencies and allows to propagate uncertainty from hydrogeological, toxicological and behavioral parameters to the final health risk endpoint. The problem under consideration consists of a contaminated aquifer supplying water to a population. Contamination stems from a continuous source that feeds a steady plume which constitutes the hazard source. This scenario is particularly suited for NAPL pollutants. The erratic displacement of the contaminant plume in groundwater, due to the spatial variability of hydraulic conductivity, is characterized within the Lagrangian stochastic framework which enables the complete probabilistic characterization of the contaminant concentration at an environmentally sensitive location. Following the probabilistic characterization of flow and transport, we quantify the adverse health effects on humans. The dose response assessment involves the estimation of the uncertain effects of the exposure to a given contaminant while accounting for the exposed individual's metabolism. The model integrates groundwater transport, exposure and human metabolism in a comprehensive probabilistic framework which allows the assessment of the risk probability through a novel simple analytical solution. Aside from its computational efficiency, the analytical features of the framework allows the assessment of uncertainty arising from the hydrogeological parameters.

  19. Effect of RAAS blockers on adverse clinical outcomes in high CVD risk subjects with atrial fibrillation

    PubMed Central

    Chaugai, Sandip; Sherpa, Lhamo Yanchang; Sepehry, Amir A.; Arima, Hisatomi; Wang, Dao Wen

    2016-01-01

    Abstract Recent studies have demonstrated that atrial fibrillation significantly increases the risk of adverse clinical outcomes in high cardiovascular disease risk subjects. Application of renin–angiotensin–aldosterone system blockers for prevention of recurrence of atrial fibrillation and adverse clinical outcomes in subjects with atrial fibrillation is a theoretically appealing concept. However, results of clinical trials evaluating the effect of renin–angiotensin–aldosterone blockers on adverse clinical outcomes in high cardiovascular disease risk subjects with atrial fibrillation remain inconclusive. A pooled study of 6 randomized controlled trials assessing the efficacy of renin–angiotensin–aldosterone blockers on subjects with atrial fibrillation was performed. A total of 6 randomized controlled trials enrolled a total of 53,510 patients followed for 1 to 5 years. RAAS blockade therapy was associated with 14% reduction in the incidence of heart failure (OR: 0.86, [95%CI: 0.76– 0.97], P=0.018) and 17% reduction in the incidence of CVE (OR: 0.83, [95%CI: 0.70–0.99], P = 0.038). The corresponding decline in absolute risk against heart failure (ARR: 1.4%, [95%CI: 0.2–2.6%], P = 0.018) and CVE (ARR: 3.5%, [95%CI: 0.0–6.9%], P = 0.045) in the AF group was much higher than the non-AF group for heart failure (ARR: 0.4%, [95%CI: 0.0–0.7%], P = 0.057) and CVE (ARR: 1.6%, [95%CI: –0.1% to 3.3%], P = 0.071). No significant effect was noted on all-cause or cardiovascular mortality, stroke, or myocardial infarction. This study suggests that RAAS blockade offers protection against heart failure and cardiovascular events in high cardiovascular disease risk subjects with atrial fibrillation. PMID:27368043

  20. Adverse neuropsychological effects associated with cumulative doses of corticosteroids to treat childhood acute lymphoblastic leukemia: A literature review.

    PubMed

    Pépin, A J; Cloutier-Bergeron, A; Malboeuf-Hurtubise, C; Achille, M; Krajinovic, M; Laverdière, C; Lippé, S; Marcoux, S; Sinnett, D; Sultan, S

    2016-11-01

    Corticosteroids (CS) are an essential component of childhood acute lymphoblastic leukemia treatments (cALL). Although there is evidence that daily doses of CS can have neuropsychological effects, few studies have investigated the role of cumulative doses of CS in short- and long-term neuropsychological effects in cALL. The aims of this review were to identify the measures used for documenting adverse neuropsychological effects (ANEs) of CS treatment and to study the association between cumulative doses of CS and the presence of ANEs. Twenty-two articles met the inclusion criteria. A variety of measures were used to evaluate outcomes in the domains of emotion, behaviour, neurocognition, and fatigue/sleep. The results suggest that we cannot conclude in favour of an association between the cumulative dosage of CS and ANEs. Yet, several factors including the heterogeneity of measures used to evaluate outcomes and reporting biases may limit the scope of the results. We offer several recommendations that could help improve the future published evidence on ANEs in relation to CS treatment in cALL.

  1. Global Association of Cold Spells and Adverse Health Effects: A Systematic Review and Meta-Analysis

    PubMed Central

    Ryti, Niilo R.I.; Guo, Yuming; Jaakkola, Jouni J.K.

    2015-01-01

    Background There is substantial evidence that mortality increases in low temperatures. Less is known about the role of prolonged cold periods denoted as cold spells. Objective We conducted the first systematic review and meta-analysis to summarize the evidence on the adverse health effects of cold spells in varying climates. Data sources and extraction Four databases (Ovid Medline, PubMed, Scopus, Web of Science) were searched for all years and languages available. “Cold spell” was defined as an event below a temperature threshold lasting for a minimum duration of 2 days. Of 1,527 identified articles, 26 satisfied our eligibility criteria for the systematic review, and 9 were eligible for meta-analyses. The articles were grouped by the three main study questions into Overall-effect Group, Added-effect Group, and Temperature-change-effect Group. Data synthesis Based on random-effects models in the meta-analyses, cold spells were associated with increased mortality from all or all nonaccidental causes (summary rate ratio = 1.10; 95% CI: 1.04, 1.17 based on 9 estimates from five studies), cardiovascular diseases (1.11; 95% CI: 1.03, 1.19; 12 estimates from eight studies), and respiratory diseases (1.21; 95% CI: 0.97, 1.51; 8 estimates from four studies). Estimated associations were stronger for people ≥ 65 years of age (1.06; 95% CI: 1.00, 1.12) than for people 0–64 years of age (1.01; 95% CI: 1.00, 1.03). Study-specific effect estimates from a limited number of studies suggested an increased morbidity related to cold spells, but it was not possible to quantitatively summarize the evidence. Conclusions Cold spells are associated with increased mortality rates in populations around the world. The body of evidence suggests that cold spells also have other adverse health effects. There was substantial heterogeneity among the studies, which should be taken into account in the interpretation of the results. Citation Ryti NR, Guo Y, Jaakkola JJ. 2016. Global

  2. Delta-9-tetrahydrocannabinol accumulation, metabolism and cell-type-specific adverse effects in aggregating brain cell cultures

    SciTech Connect

    Monnet-Tschudi, Florianne Hazekamp, Arno; Perret, Nicolas; Zurich, Marie-Gabrielle; Mangin, Patrice; Giroud, Christian; Honegger, Paul

    2008-04-01

    Despite the widespread use of Cannabis as recreational drug or as medicine, little is known about its toxicity. The accumulation, metabolism and toxicity of THC were analyzed 10 days after a single treatment, and after repeated exposures during 10 days. Mixed-cell aggregate cultures of fetal rat telencephalon were used as in vitro model, as well as aggregates enriched either in neurons or in glial cells. It was found that THC accumulated preferentially in neurons, and that glia-neuron interactions decreased THC accumulation. The quantification of 11-OH-THC and of THC-COOH showed that brain aggregates were capable of THC metabolism. No cell-type difference was found for the metabolite 11-OH-THC, whereas the THC-COOH content was higher in mixed-cell cultures. No cell death was found at THC concentrations of 2 {mu}M in single treatment and of 1 {mu}M and 2 {mu}M in repeated treatments. Neurons, and particularly GABAergic neurons, were most sensitive to THC. Only the GABAergic marker was affected after the single treatment, whereas the GABAergic, cholinergic and astrocytic markers were decreased after the repeated treatments. JWH 015, a CB2 receptor agonist, showed effects similar to THC, whereas ACEA, a CB1 receptor agonist, had no effect. The expression of the cytokine IL-6 was upregulated 48 h after the single treatment with 5 {mu}M of THC or JWH 015, whereas the expression of TNF-{alpha} remained unchanged. These results suggest that the adverse effects of THC were related either to THC accumulation or to cannabinoid receptor activation and associated with IL-6 upregulation.

  3. Delta-9-tetrahydrocannabinol accumulation, metabolism and cell-type-specific adverse effects in aggregating brain cell cultures.

    PubMed

    Monnet-Tschudi, Florianne; Hazekamp, Arno; Perret, Nicolas; Zurich, Marie-Gabrielle; Mangin, Patrice; Giroud, Christian; Honegger, Paul

    2008-04-01

    Despite the widespread use of Cannabis as recreational drug or as medicine, little is known about its toxicity. The accumulation, metabolism and toxicity of THC were analyzed 10 days after a single treatment, and after repeated exposures during 10 days. Mixed-cell aggregate cultures of fetal rat telencephalon were used as in vitro model, as well as aggregates enriched either in neurons or in glial cells. It was found that THC accumulated preferentially in neurons, and that glia-neuron interactions decreased THC accumulation. The quantification of 11-OH-THC and of THC-COOH showed that brain aggregates were capable of THC metabolism. No cell-type difference was found for the metabolite 11-OH-THC, whereas the THC-COOH content was higher in mixed-cell cultures. No cell death was found at THC concentrations of 2 microM in single treatment and of 1 microM and 2 microM in repeated treatments. Neurons, and particularly GABAergic neurons, were most sensitive to THC. Only the GABAergic marker was affected after the single treatment, whereas the GABAergic, cholinergic and astrocytic markers were decreased after the repeated treatments. JWH 015, a CB2 receptor agonist, showed effects similar to THC, whereas ACEA, a CB1 receptor agonist, had no effect. The expression of the cytokine IL-6 was upregulated 48 h after the single treatment with 5 microM of THC or JWH 015, whereas the expression of TNF-alpha remained unchanged. These results suggest that the adverse effects of THC were related either to THC accumulation or to cannabinoid receptor activation and associated with IL-6 upregulation.

  4. Peripubertal aromatase inhibition in male rats has adverse long-term effects on bone strength and growth and induces prostatic hyperplasia.

    PubMed

    Bajpai, Anurag; Simm, Peter J; McPherson, Stephen J; Russo, Vincenzo C; Azar, Walid J; Wark, John D; Risbridger, Gail P; Werther, George A

    2010-10-01

    Aromatase inhibitors have been increasingly used in boys with growth retardation to prolong the duration of growth and increase final height. Multiple important roles of oestrogen in males point to potential adverse effects of this strategy. Although the deleterious effects of aromatase deficiency in early childhood and adulthood are well documented, there is limited information about the potential long-term adverse effects of peripubertal aromatase inhibition. To address this issue, we evaluated short-term and long-term effects of peripubertal aromatase inhibition in an animal model. Peripubertal male Wistar rats were treated with aromatase inhibitor letrozole or placebo and followed until adulthood. Letrozole treatment caused sustained reduction in bone strength and alteration in skeletal geometry, lowering of IGF1 levels, inhibition of growth resulting in significantly lower weight and length of treated animals and development of focal prostatic hyperplasia. Our observation of adverse long-term effects after peripubertal male rats were exposed to aromatase inhibitors highlights the need for further characterisation of long-term adverse effects of aromatase inhibitors in peripubertal boys before further widespread use is accepted. Furthermore, this suggests the need to develop more selective oestrogen inhibition strategies in order to inhibit oestrogen action on the growth plate, while beneficial effects in other tissues are preserved.

  5. Combustion-derived nanoparticulate induces the adverse vascular effects of diesel exhaust inhalation

    PubMed Central

    Mills, Nicholas L.; Miller, Mark R.; Lucking, Andrew J.; Beveridge, Jon; Flint, Laura; Boere, A. John F.; Fokkens, Paul H.; Boon, Nicholas A.; Sandstrom, Thomas; Blomberg, Anders; Duffin, Rodger; Donaldson, Ken; Hadoke, Patrick W.F.; Cassee, Flemming R.; Newby, David E.

    2011-01-01

    Aim Exposure to road traffic and air pollution may be a trigger of acute myocardial infarction, but the individual pollutants responsible for this effect have not been established. We assess the role of combustion-derived-nanoparticles in mediating the adverse cardiovascular effects of air pollution. Methods and results To determine the in vivo effects of inhalation of diesel exhaust components, 16 healthy volunteers were exposed to (i) dilute diesel exhaust, (ii) pure carbon nanoparticulate, (iii) filtered diesel exhaust, or (iv) filtered air, in a randomized double blind cross-over study. Following each exposure, forearm blood flow was measured during intra-brachial bradykinin, acetylcholine, sodium nitroprusside, and verapamil infusions. Compared with filtered air, inhalation of diesel exhaust increased systolic blood pressure (145 ± 4 vs. 133 ± 3 mmHg, P< 0.05) and attenuated vasodilatation to bradykinin (P= 0.005), acetylcholine (P= 0.008), and sodium nitroprusside (P< 0.001). Exposure to pure carbon nanoparticulate or filtered exhaust had no effect on endothelium-dependent or -independent vasodilatation. To determine the direct vascular effects of nanoparticulate, isolated rat aortic rings (n= 6–9 per group) were assessed in vitro by wire myography and exposed to diesel exhaust particulate, pure carbon nanoparticulate and vehicle. Compared with vehicle, diesel exhaust particulate (but not pure carbon nanoparticulate) attenuated both acetylcholine (P< 0.001) and sodium-nitroprusside (P= 0.019)-induced vasorelaxation. These effects were partially attributable to both soluble and insoluble components of the particulate. Conclusion Combustion-derived nanoparticulate appears to predominately mediate the adverse vascular effects of diesel exhaust inhalation. This provides a rationale for testing environmental health interventions targeted at reducing traffic-derived particulate emissions. PMID:21753226

  6. Neurosyphilis presenting with dementia, chronic chorioretinitis and adverse reactions to treatment: a case report

    PubMed Central

    Raycheva, Margarita Radoslavova; Petrova, Elena Petrova; Tsankov, Nikolay Konstantinov; Traykov, Latchezar Dintchov

    2009-01-01

    Neurosyphilis results from infection of the brain, meninges or spinal cord by Treponema pallidum and develops in about 25%-40% of persons who are not treated for syphilis. This article reports a rare case of active neurosyphilis with mild dementia, chronic chorioretinitis, and hearing loss. During the treatment with Penicillin, a rare combination of complications such as Jarisch-Herxheimer and Hoigné reactions were observed. The clinical feature is characterized by a slow progressive cognitive decline and behavior changes for the last 2 years. Neuropsychological examination revealed mild dementia (MMSE = 23) with impaired memory and attention and executive function. Left sided chronic chorioretinitis and hearing loss were documented. High dose intravenous penicillin therapy was complicated by Jarisch-Herxheimer and Hoigne reactions. During the follow up examinations at 6 and 12 months, the clinical signs, neuropsychological examination, and cerebrospinal fluid (CFS) samples showed improvement of dementia, CSF findings, and hydrocephalus. In conclusion, this atypical presentation of neurosyphilis in combination with rare complications of treatment is worthy of attention. Neurosyphilis should be part of the differential diagnosis of each patient showing cognitive deterioration and behaviour disturbances. PMID:19918420

  7. Association of acute adverse effects with high local SAR induced in the brain from prolonged RF head and neck hyperthermia

    NASA Astrophysics Data System (ADS)

    Adibzadeh, F.; Verhaart, R. F.; Verduijn, G. M.; Fortunati, V.; Rijnen, Z.; Franckena, M.; van Rhoon, G. C.; Paulides, M. M.

    2015-02-01

    To provide an adequate level of protection for humans from exposure to radio-frequency (RF) electromagnetic fields (EMF) and to assure that any adverse health effects are avoided. The basic restrictions in terms of the specific energy absorption rate (SAR) were prescribed by IEEE and ICNIRP. An example of a therapeutic application of non-ionizing EMF is hyperthermia (HT), in which intense RF energy is focused at a target region. Deep HT in the head and neck (H&N) region involves inducing energy at 434 MHz for 60 min on target. Still, stray exposure of the brain is considerable, but to date only very limited side-effects were observed. The objective of this study is to investigate the stringency of the current basic restrictions by relating the induced EM dose in the brain of patients treated with deep head and neck (H&N) HT to the scored acute health effects. We performed a simulation study to calculate the induced peak 10 g spatial-averaged SAR (psSAR10g) in the brains of 16 selected H&N patients who received the highest SAR exposure in the brain, i.e. who had the minimum brain-target distance and received high forwarded power during treatment. The results show that the maximum induced SAR in the brain of the patients can exceed the current basic restrictions (IEEE and ICNIRP) on psSAR10g for occupational environments by 14 times. Even considering the high local SAR in the brain, evaluation of acute effects by the common toxicity criteria (CTC) scores revealed no indication of a serious acute neurological effect. In addition, this study provides pioneering quantitative human data on the association between maximum brain SAR level and acute adverse effects when brains are exposed to prolonged RF EMF.

  8. Anxiolytic activity and evaluation of potentially adverse effects of a bradykinin-related peptide isolated from a social wasp venom.

    PubMed

    dos Anjos, Lilian Carneiro; Gomes, Flávia Maria Medeiros; do Couto, Lucianna Lopes; Mourão, Cecília Alves; Moreira, Karla Graziela; Silva, Luciano Paulino; Mortari, Márcia Renata

    2016-03-15

    Anxiety disorders are major health problems in terms of costs stemming from sick leave, disabilities, healthcare and premature mortality. Despite the availability of classic anxiolytics, some anxiety disorders are still resistant to treatment, with higher rates of adverse effects. In this respect, several toxins isolated from arthropod venoms are useful in identifying new compounds to treat neurological disorders, particularly pathological anxiety. Thus, the aims of this study were to identify and characterize an anxiolytic peptide isolated from the venom of the social wasp Polybia paulista. The peptide was identified as Polisteskinin R, with nominal molecular mass [M+H](+)=1301Da and primary structure consisting of Ala-Arg-Arg-Pro-Pro-Gly-Phe-Thr-Pro-Phe-Arg-OH. The anxiolytic effect was tested using the elevated plus maze test. Moreover, adverse effects on the spontaneous behavior and motor coordination of animals were assessed using the open field and rotarod tests. Polisteskinin R induced a dose-dependent anxiolytic effect. Animals treated with the peptide and diazepam spent significantly more time into the open arms when compared to the groups treated with the vehicle and pentylenetetrazole. No significant differences in spontaneous behavior or motor coordination were observed between the groups, showing that the peptide was well tolerated. The interaction by agonists in both known BK receptors induces a variability of physiological effects; Polisteskinin R can act on these receptors, inducing modulatory activity and thus, attenuating anxiety behaviors. The results of this study demonstrated that the compound Polisteskinin R exerted potent anxiolytic effects and its analogues are promising candidates for experimental pharmacology.

  9. Frequency, severity, and costs of adverse reactions following mass treatment for lymphatic filariasis using diethylcarbamazine and albendazole in Leogane, Haiti, 2000.

    PubMed

    McLaughlin, Steven I; Radday, Jeanne; Michel, Marie Carmel; Addiss, David G; Beach, Michael J; Lammie, Patrick J; Lammie, John; Rheingans, Richard; Lafontant, Jack

    2003-05-01

    In October 2000, 71,187 persons were treated for lymphatic filariasis using albendazole and diethylcarbamazine (DEC) or DEC alone in Leogane, Haiti. We documented the frequency of adverse reactions, severity and cost of treatment. Adverse reactions were classified as minor, moderate, or severe. Overall, 24% (17,421) of the treated persons reported one or more adverse reactions. There were 15,916 (91%) minor and 1502 (9%) moderate adverse reaction reports. Men outnumbered women 2:1 in reporting moderate problems. Three patients, representing roughly one in 25,000 persons treated, were hospitalized with severe adverse reactions judged to be treatment-associated by physician review. The cost per person treated for adverse reactions was more than twice the cost per person treated for lymphatic filariasis (dollar 1.60 versus dollar 0.71). Severe adverse reactions to lymphatic filariasis treatment using DEC with or without albendazole are uncommon. Minor and moderate reactions are more commonly reported and their management represents a challenge to lymphatic filariasis elimination programs.

  10. Adverse Effects Associated with Protein Intake above the Recommended Dietary Allowance for Adults.

    PubMed

    Delimaris, Ioannis

    2013-01-01

    Background. While high-protein consumption-above the current recommended dietary allowance for adults (RDA: 0.8 g protein/kg body weight/day)-is increasing in popularity, there is a lack of data on its potential adverse effects. Objective. To determine the potential disease risks due to high protein/high meat intake obtained from diet and/or nutritional supplements in humans. Design. Review. Subjects. Healthy adult male and female subjects. Method. In order to identify relevant studies, the electronic databases, Medline and Google Scholar, were searched using the terms:"high protein diet," "protein overconsumption," "protein overuse," and "high meat diet." Papers not in English were excluded. Further studies were identified by citations in retrieved papers. Results. 32 studies (21 experimental human studies and 11 reviews) were identified. The adverse effects associated with long-term high protein/high meat intake in humans were (a) disorders of bone and calcium homeostasis, (b) disorders of renal function, (c) increased cancer risk, (d) disorders of liver function, and (e) precipitated progression of coronary artery disease. Conclusions. The findings of the present study suggest that there is currently no reasonable scientific basis in the literature to recommend protein consumption above the current RDA (high protein diet) for healthy adults due to its potential disease risks. Further research needs to be carried out in this area, including large randomized controlled trials.

  11. Organophosphate pesticides exposure among farmworkers: pathways and risk of adverse health effects.

    PubMed

    Suratman, Suratman; Edwards, John William; Babina, Kateryna

    2015-01-01

    Organophosphate (OP) compounds are the most widely used pesticides with more than 100 OP compounds in use around the world. The high-intensity use of OP pesticides contributes to morbidity and mortality in farmworkers and their families through acute or chronic pesticides-related illnesses. Many factors contributing to adverse health effects have been investigated by researchers to determine pathways of OP-pesticide exposure among farmers in developed and developing countries. Factors like wind/agricultural pesticide drift, mixing and spraying pesticides, use of personal protective equipment (PPE), knowledge, perceptions, washing hands, taking a shower, wearing contaminated clothes, eating, drinking, smoking, and hot weather are common in both groups of countries. Factors including low socioeconomic status areas, workplace conditions, duration of exposure, pesticide safety training, frequency of applying pesticides, spraying against the wind, and reuse of pesticide containers for storage are specific contributors in developing countries, whereas housing conditions, social contextual factors, and mechanical equipment were specific pathways in developed countries. This paper compares existing research in environmental and behavioural exposure modifying factors and biological monitoring between developing and developed countries. The main objective of this review is to explore the current depth of understanding of exposure pathways and factors increasing the risk of exposure potentially leading to adverse health effects specific to each group of countries.

  12. Noise monitoring and adverse health effects in residents in different functional areas of Luzhou, China.

    PubMed

    Han, Zhi-Xia; Lei, Zhang-Heng; Zhang, Chun-Lian; Xiong, Wei; Gan, Zhong-Lin; Hu, Ping; Zhang, Qing-Bi

    2015-03-01

    The purpose of the study was to investigate the noise pollution situation and the resulting adverse effect on residents' health in Luzhou, China, to provide data for noise pollution prevention policies and interventions. Four different functional areas (commercial, construction, residential, and transportation hub areas) were chosen to monitor noise level for 3 months. The survey was performed by questionnaire on the spot on randomly selected individuals; it collected data on the impact of noise on residents' health (quality of sleep, high blood pressure, subjective feeling of nervous system damage, and attention) as well as the knowledge of noise-induced health damage, the degree of adaptation to noise, and their solutions. The noise levels of residential, commercial, transportation, and construction areas exceeded the national standards (P < .001). Sleep quality, prevalence of hypertension, and attention in transportation hub areas were significantly different from those in the other 3 areas (P < .05); only 24.46% of people knew the health hazards associated with noise; 64.57% of residents have adapted to the current noise environment. Most of them have to close the doors and windows to reduce noise. The noise pollution situation in Luzhou, China, is serious, especially the traffic noise pollution. Residents pay less attention to it and adopt single measures to reduce the noise. We should work toward the prevention and control of traffic noise and improve the residents' awareness to reduce the adverse health effects of noise.

  13. Wood combustion particles induce adverse effects to normal and diseased airway epithelia.

    PubMed

    Krapf, Manuel; Künzi, Lisa; Allenbach, Sandrine; Bruns, Emily A; Gavarini, Ilaria; El-Haddad, Imad; Slowik, Jay G; Prévôt, André S H; Drinovec, Luka; Močnik, Griša; Dümbgen, Lutz; Salathe, Matthias; Baumlin, Nathalie; Sioutas, Constantinos; Baltensperger, Urs; Dommen, Josef; Geiser, Marianne

    2017-02-27

    Residential wood burning is a major source of poorly characterized, deleterious particulate matter, whose composition and toxicity may vary with wood type, burning condition and photochemical age. The causative link between ambient wood particle constituents and observed adverse health effects is currently lacking. Here we investigate the relationship between chemical properties of primary and atmospherically aged wood combustion particles and acute toxicity in human airway epithelial cells. Emissions from a log wood burner were diluted and injected into a smog chamber for photochemical aging. After concentration-enrichment and removal of oxidizing gases, directly emitted and atmospherically aged particles were deposited on cell cultures at the air-liquid interface for 2 hours in an aerosol deposition chamber mimicking physiological conditions in lungs. Cell models were fully differentiated normal and diseased (cystic fibrosis and asthma) human bronchial epithelia (HBE) and the bronchial epithelial cell line BEAS-2B. Cell responses were assessed at 24 hours after aerosol exposure. Atmospherically relevant doses of wood combustion particles significantly increased cell death in all but the asthma cell model. Expression of oxidative stress markers increased in HBE from all donors. Increased cell death and inflammatory responses could not be assigned to a single chemical fraction of the particles. Exposure to primary and aged wood combustion particles caused adverse effects to airway epithelia, apparently induced by several interacting components.

  14. Comparison of gastrointestinal adverse effects of ketoprofen between adult and young cats.

    PubMed

    Takata, Kenji; Hikasa, Yoshiaki; Satoh, Hiroshi

    2012-12-01

    This study elucidated differences in predisposition to the gastrointestinal adverse effects of ketoprofen between young and adult cats. Ketoprofen was administered subcutaneously (2.0 mg/kg, s.c.) once a day for 3 days. The animals were sacrificed 24 hr after final injection to allow examination of gastrointestinal mucosal lesions. Ketoprofen caused gastric lesions in adult cats (>6 months) but not in young cats (<3 months). Ketoprofen caused more severe small intestinal lesions in adult cats than in young cats. In the study of prevention of lipopolysaccharide (LPS)-induced hyperthermia using ketoprofen, young and adult cats of both sexes were administered LPS (0.3 μg/kg, intravenously), and body temperature was measured 24 hr later. Ketoprofen was administered subcutaneously 30 min before LPS injection. LPS-induced hyperthermia was almost completely inhibited by pretreatment with ketoprofen in both adult and young cats. In the pharmacokinetics of ketoprofen, plasma concentrations were analyzed by high-performance liquid chromatography. No significant differences were observed in plasma concentrations of two mirror-image R(-) and S(+) ketoprofen between young and adult cats from 0.5-4 hr after injection. As observed in a previous study using flunixin, the degree of gastrointestinal damage was unrelated to plasma concentrations of ketoprofen. The results of this study demonstrated that ketoprofen is safer for use in young cats than in adult cats from the viewpoint of gastrointestinal adverse effects.

  15. HPV vaccines: their pathology-based discovery, benefits, and adverse effects.

    PubMed

    Nicol, Alcina F; de Andrade, Cecilia V; Russomano, Fabio B; Rodrigues, Luana S L; Oliveira, Nathalia S; Provance, David William; Nuovo, Gerard J

    2015-12-01

    The discovery of the human papillomavirus (HPV) vaccine illustrates the power of in situ-based pathologic analysis in better understanding and curing diseases. The 2 available HPV vaccines have markedly reduced the incidence of cervical intraepithelial neoplasias, genital warts, and cervical cancer throughout the world. Concerns about HPV vaccine safety have led some physicians, health care officials, and parents to refuse providing the recommended vaccination to the target population. The aims of the study were to discuss the discovery of HPV vaccine and review scientific data related to measurable outcomes from the use of HPV vaccines. The strong type-specific immunity against HPV in humans has been known for more than 25 years. Multiple studies confirm the positive risk benefit of HPV vaccination with minimal documented adverse effects. The most common adverse effect, injection site pain, occurred in about 10% of girls and was less than the rate reported for other vaccines. Use of HPV vaccine should be expanded into more diverse populations, mainly in low-resource settings.

  16. Registered Nurses' Knowledge about Adverse Effects of Analgesics when Treating Postoperative Pain in Patients with Dementia.

    PubMed

    Rantala, Maija; Hartikainen, Sirpa; Kvist, Tarja; Kankkunen, Päivi

    2015-08-01

    Registered nurses (RNs) play a pivotal role in treating pain and preventing and recognizing the adverse effects (AEs) of analgesics in patients with dementia. The purpose of this study was to determine RNs' knowledge of potentially clinically relevant AEs of analgesics. A descriptive, cross-sectional study design was used. In all, 267 RNs treating orthopedic patients, including patients with dementia, in 7 university hospitals and 10 central hospitals in Finland, completed a questionnaire. Analgesics were defined according to the Anatomic Therapeutic Classification as strong opioids, weak opioids, nonsteroidal anti-inflammatory analgesics (NSAIDs), and paracetamol. Definitions of AEs were based on the literature. Logistic regression analysis was applied to analyze which variables predicted nurses' knowledge. The RNs had a clear understanding of the AEs of paracetamol and strong opioids. However, the AEs of NSAIDs, especially renal and cardiovascular AEs, were less well known. The median percentage of correct answers was 87% when asked about strong opioids, 73% for weak opioids, and 60% for NSAIDs. Younger RNs had better knowledge of opioid-related AEs (odds ratio [OR] per 1-year increase, 0.97; 95% confidence interval [CI], 0.94-1.00) and weak opioids (OR, 0.96; 95% CI, 0.93-0.99). This study provides evidence of a deficiency in RNs' knowledge, especially regarding the adverse renal and cardiovascular effects of NSAIDs. Such lack of knowledge indicates that hospitals may need to update the knowledge of older RNs, especially those who treat vulnerable patients with dementia.

  17. Investigating clandestine drug laboratories: adverse medical effects in law enforcement personnel.

    PubMed

    Burgess, J L; Barnhart, S; Checkoway, H

    1996-10-01

    A retrospective cohort study was conducted among an international group of 46 law enforcement chemists and 13 Washington State clandestine drug laboratory investigation team members with more than 2,800 combined investigations. Each participant completed a questionnaire concerning previous drug laboratory investigations and adverse health effects during response activities. Methamphetamine laboratories accounted for 81-97% of all responses. Total illness incident rates varied between 0.75-3.4% of responses. Most exposures were through inhalation, and many occurred in the years prior to use of personal protective equipment. Symptoms were primarily those of headache and respiratory, mucous membrane, and skin irritation. Most illness episodes occurred during the processing phase of laboratory responses, and none occurred during the entry phase. A majority of illness episodes occurred in laboratories with leak/spills, fire/explosion, or uncontrolled reactions. Responding to an active laboratory was associated with a 7 to 15-fold risk of becoming ill as compared with setup, in-transit, or former (equipment removed) laboratory responses. No other laboratories characteristics were consistently associated with a significantly elevated relative risk of adverse health effects.

  18. Gratitude buffers the adverse effect of viewing the thin ideal on body dissatisfaction.

    PubMed

    Homan, Kristin J; Sedlak, Brittany L; Boyd, Elizabeth A

    2014-06-01

    Gratitude has robust associations with multiple aspects of well-being. However, little research has explored whether the psychological benefits of gratitude extend to body image. We used a repeated measures experimental design to test whether a brief period of grateful reflection would buffer the adverse effect of exposure to thin-ideal media. Female undergraduates (N=67) completed three sessions one week apart. The conditions were specifically designed to isolate (a) the effects of viewing thin models on body dissatisfaction and (b) the moderating effect of grateful contemplation. Results showed that body dissatisfaction scores were lower for women who engaged in a brief period of grateful contemplation before viewing photographs of thin models than for women who reflected upon life hassles before viewing the same photographs. The magnitude of this decrease depended on BMI. Gratitude offers an innovative direction for future research directed toward helping women to accept their bodies.

  19. Adverse effects of fullerenes (nC60) spiked to sediments on Lumbriculus variegatus (Oligochaeta).

    PubMed

    Pakarinen, K; Petersen, E J; Leppänen, M T; Akkanen, J; Kukkonen, J V K

    2011-12-01

    Effects of fullerene-spiked sediment on a benthic organism, Lumbriculus variegatus (Oligochaeta), were investigated. Survival, growth, reproduction, and feeding rates were measured to assess possible adverse effects of fullerene agglomerates produced by water stirring and then spiked to a natural sediment. L. variegatus were exposed to 10 and 50 mg fullerenes/kg sediment dry mass for 28 d. These concentrations did not impact worm survival or reproduction compared to the control. Feeding activities were slightly decreased for both concentrations indicating fullerenes' disruptive effect on feeding. Depuration efficiency decreased in the high concentration only. Electron and light microscopy and extraction of the worm fecal pellets revealed fullerene agglomerates in the gut tract but not absorption into gut epithelial cells. Micrographs also indicated that 16% of the epidermal cuticle fibers of the worms were not present in the 50 mg/kg exposures, which may make worms susceptible to other contaminants.

  20. Economic Adversity and Children’s Sleep Problems: Multiple Indicators and Moderation of Effects

    PubMed Central

    El-Sheikh, Mona; Bagley, Erika J.; Keiley, Margaret; Elmore-Staton, Lori; Chen, Edith; Buckhalt, Joseph A.

    2014-01-01

    Objective Toward explicating relations between economic adversity and children’s sleep, we examined associations between multiple indicators of socioeconomic status (SES)/adversity and children’s objectively and subjectively derived sleep parameters; ethnicity was examined as potential moderator. Methods Participants were 276 third- and fourth-grade children and their families (133 girls; M age = 9.44 years; SD = .71): 66% European American (EA) and 34% African American (AA). Four SES indicators were used: income-to-needs ratio, perceived economic well-being, maternal education, and community poverty. Children wore actigraphs for 7 nights and completed a self-report measure to assess sleep problems. Results Objectively and subjectively assessed sleep parameters were related to different SES indicators, and overall worse sleep was evident for children from lower SES homes. Specifically, children from homes with lower income-to-needs ratios had higher levels of reported sleep/wake problems. Parental perceived economic well-being was associated with shorter sleep minutes and greater variability in sleep onset for children. Lower mother’s education was associated with lower sleep efficiency. Children who attended Title 1 schools had shorter sleep minutes. Ethnicity was a significant moderator of effects in the link between some SES indicators and children’s sleep. AA children’s sleep was more negatively affected by income-to-needs ratio and mother’s education than was the sleep of EA children. Conclusions The results advocate for the importance of specifying particular SES and sleep variables used because they may affect the ability to detect associations between sleep and economic adversity. PMID:23148451

  1. Identifying adverse effects of area-based health policy: An ethnographic study of a deprived neighbourhood in England.

    PubMed

    Williams, Oli

    2017-03-17

    Health interventions commonly have adverse effects. Addressing these could significantly improve health outcomes. This paper addresses an adverse effect common in the promotion of health behaviours: exacerbation of health inequalities between low- and high-socioeconomic groups. Health behaviours - particularly, physical activity - are positioned within the context of social inequality and the inequitable spatial distribution of resources. Area-based health policy that targets deprived areas is assessed for its capacity to promote health behaviours without exacerbating inequality. Data are derived from a 16-month ethnography in a deprived English neighbourhood that was the target of area-based intervention that prioritised the promotion of physical activity. Findings provide evidence of adverse intervention effects that further disadvantaged the low-socioeconomic population. Analysis demonstrates how this was ultimately the outcome of localised policy drifting away from initial commitments to equitable service access. These findings increase understanding of the processes through which adverse intervention effects arise and how they can be mitigated.

  2. Developmental exposure to a mixture of two mechanistically distinct antiandrogens results in cumulative adverse reproductive effects in adult male rats

    EPA Science Inventory

    Typically, toxicological studies have focused on the adverse effects from exposure to single chemicals. However, endocrine disrupting chemicals (EDCs) are detected in the environment as mixtures. Empirical evidence suggests that mixtures of EDCs with the same mechanism of action...

  3. Dynamic Treatment Effects

    PubMed Central

    Heckman, James J.; Humphries, John Eric; Veramendi, Gregory

    2016-01-01

    This paper develops robust models for estimating and interpreting treatment effects arising from both ordered and unordered multistage decision problems. Identification is secured through instrumental variables and/or conditional independence (matching) assumptions. We decompose treatment effects into direct effects and continuation values associated with moving to the next stage of a decision problem. Using our framework, we decompose the IV estimator, showing that IV generally does not estimate economically interpretable or policy relevant parameters in prototypical dynamic discrete choice models, unless policy variables are instruments. Continuation values are an empirically important component of estimated total treatment effects of education. We use our analysis to estimate the components of what LATE estimates in a dynamic discrete choice model. PMID:27041793

  4. Dynamic Treatment Effects.

    PubMed

    Heckman, James J; Humphries, John Eric; Veramendi, Gregory

    2016-02-01

    This paper develops robust models for estimating and interpreting treatment effects arising from both ordered and unordered multistage decision problems. Identification is secured through instrumental variables and/or conditional independence (matching) assumptions. We decompose treatment effects into direct effects and continuation values associated with moving to the next stage of a decision problem. Using our framework, we decompose the IV estimator, showing that IV generally does not estimate economically interpretable or policy relevant parameters in prototypical dynamic discrete choice models, unless policy variables are instruments. Continuation values are an empirically important component of estimated total treatment effects of education. We use our analysis to estimate the components of what LATE estimates in a dynamic discrete choice model.

  5. Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects.

    PubMed

    Mathes, C; Melero, A; Conrad, P; Vogt, T; Rigo, L; Selzer, D; Prado, W A; De Rossi, C; Garrigues, T M; Hansen, S; Guterres, S S; Pohlmann, A R; Beck, R C R; Lehr, C-M; Schaefer, U F

    2016-02-10

    The treatment of various hair disorders has become a central focus of good dermatologic patient care as it affects men and women all over the world. For many inflammatory-based scalp diseases, glucocorticoids are an essential part of treatment, even though they are known to cause systemic as well as local adverse effects when applied topically. Therefore, efficient targeting and avoidance of these side effects are of utmost importance. Optimizing the balance between drug release, interfollicular permeation, and follicular uptake may allow minimizing these adverse events and simultaneously improve drug delivery, given that one succeeds in targeting a sustained release formulation to the hair follicle. To test this hypothesis, three types of polymeric nanocarriers (nanospheres, nanocapsules, lipid-core nanocapsules) for the potent glucocorticoid clobetasol propionate (CP) were prepared. They all exhibited a sustained release of drug, as was desired. The particles were formulated as a dispersion and hydrogel and (partially) labeled with Rhodamin B for quantification purposes. Follicular uptake was investigated using the Differential Stripping method and was found highest for nanocapsules in dispersion after application of massage. Moreover, the active ingredient (CP) as well as the nanocarrier (Rhodamin B labeled polymer) recovered in the hair follicle were measured simultaneously, revealing an equivalent uptake of both. In contrast, only negligible amounts of CP could be detected in the hair follicle when applied as free drug in solution or hydrogel, regardless of any massage. Skin permeation experiments using heat-separated human epidermis mounted in Franz Diffusion cells revealed equivalent reduced transdermal permeability for all nanocarriers in comparison to application of the free drug. Combining these results, nanocapsules formulated as an aqueous dispersion and applied by massage appeare to be a good candidate to maximize follicular targeting and minimize drug

  6. Treatment related toxicity in BRCA1-associated epithelial ovarian cancer – is DNA repairing impairment associated with more adverse events?

    PubMed Central

    Budryk, Magdalena; Nowara, Elżbieta; Starzyczny-Słota, Danuta

    2016-01-01

    Aim of the study The presence of BRCA germline mutations in patients with ovarian cancer has been shown to have predictive and prognostic significance, including increased platinum-sensitivity. The aim of the study was to evaluate if patients with BRCA1-associated ovarian cancer have more treatment related adverse events and, if so, does it have impact on chemotherapy outcomes. Material and methods We conducted a retrospective analysis of medical records of 172 patients with newly diagnosed epithelial ovarian cancer, treated in Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch between 2007 and 2013. Ninety-six of these patients have known BRCA mutation status – 21 patients were BRCA1(+) and 75 BRCA1(–). Analysed treatment related adverse events (AE’s) were: haematological toxicity, nausea/vomiting, neuropathy and mucositis. Results Grade 3–4 haematological AE’s were significantly more common among BRCA1(+) patients (OR = 3.86; 95% CI: 1.14–13.23; p = 0.02). There was no association between BRCA1 mutation status and neuropathy (p = 0.73) or nausea/vomiting (p = 0.91). Occurrence of above mentioned AE’s has no significant association with PFS (p = 0.75, 0.64, 0.97 respectively) and OS (p = 0.64, 0.69, 0.73 respectively). Conclusions Among patients with BRCA1-associated epithelial ovarian cancer we observed significantly more grade 3–4 haematological complications after chemotherapy. However, occurrence of AE’s did not correlate with better outcomes in this subgroup.

  7. Te Inclusions in CZT Detectors: New Method for Correcting Their Adverse Effects

    SciTech Connect

    Bolotnikov, A.E.; Babalola, S.; Camarda, G.S.; Cui, Y.; Egarievwe, S.U.; Hawrami, R.; Hossain, A.; Yang, G.; James, R.B.

    2009-10-25

    Both Te inclusions and point defects can trap the charge carriers generated by ionizing particles in CdZnTe (CZT) detectors. The amount of charge trapped by point defects is proportional to the carriers’ drift time and can be corrected electronically. In the case of Te inclusions, the charge loss depends upon their random locations with respect to the electron cloud. Consequently, inclusions introduce fluctuations in the charge signals, which cannot be easily corrected. In this paper, we describe direct measurements of the cumulative effect of Te inclusions and its influence on the response of CZT detectors of different thicknesses and different sizes and concentrations of Te inclusions. We also discuss a means of partially correcting their adverse effects.

  8. Air pollution and adverse cardiac remodeling: clinical effects and basic mechanisms

    PubMed Central

    Liu, Yonggang; Goodson, Jamie M.; Zhang, Bo; Chin, Michael T.

    2015-01-01

    Exposure to air pollution has long been known to trigger cardiovascular events, primarily through activation of local and systemic inflammatory pathways that affect the vasculature. Detrimental effects of air pollution exposure on heart failure and cardiac remodeling have also been described in human populations. Recent studies in both human subjects and animal models have provided insights into the basic physiological, cellular and molecular mechanisms that play a role in adverse cardiac remodeling. This review will give a brief overview of the relationship between air pollution and cardiovascular disease, describe the clinical effects of air pollution exposure on cardiac remodeling, describe the basic mechanisms that affect remodeling as described in human and animal systems and will discuss future areas of investigation. PMID:26042051

  9. Review for carrageenan-based pharmaceutical biomaterials: favourable physical features versus adverse biological effects.

    PubMed

    Liu, Jingjing; Zhan, Xiudan; Wan, Jianbo; Wang, Yitao; Wang, Chunming

    2015-05-05

    Carrageenan (CRG) is a family of natural polysaccharides derived from seaweeds and has widely been used as food additives. In the past decade, owing to its attractive physicochemical properties, CRG has been developed into versatile biomaterials vehicles for drug delivery. Nevertheless, studies also emerged to reveal its adverse effects on the biological system. In this review, we critically appraise the latest literature (two thirds since 2008) on the development of CRG-based pharmaceutical vehicles and the perspective of using CRG for broader biomedical applications. We focus on how current strategies exploit the unique gelling mechanisms, strong water absorption and abundant functional groups of the three major CRG varieties. Notably, CRG-based matrices are demonstrated to increase drug loading and drug solubility, enabling release of orally administrated drugs in zero-order or in a significantly prolonged period. Other amazing features, such as pH-sensitivity and adhesive property, of CRG-based formulations are also introduced. Finally, we discuss the adverse influence of CRG on the human body and then suggest some future directions for the development of CRG-based biomaterials for broader applications in biomedicine.

  10. Duration of Internet use and adverse psychosocial effects among European adolescents.

    PubMed

    Secades-Villa, Roberto; Calafat, Amador; Fernández-Hermida, José Ramón; Juan, Montse; Duch, Mariangels; Skärstrand, Eva; Becoña, Elisardo; Talic, Sanela

    2014-01-01

    Despite the significant contributions from previous studies about the prevalence of problematic Internet use (PIU) among adolescents in Europe, important questions remain regarding adverse consequences of PIU. This study aims to assess the relation between duration of Internet use and adverse psychosocial effects among adolescents from six European countries. The final sample included 7,351 adolescents (50.8% male and 49.2% female; mean age: 14.6±1.90) recruited from randomly selected schools within the six study sites. Results showed that 12.9% of adolescents used Internet more than 20 hours per week. There was a significant relationship between duration of Internet use and frequency of alcohol, tobacco, cannabis and other illegal drug use. Duration of Internet use is also significantly associated with school problems, with use of slot machines and with other psychosocial problems. These findings highlight the need to strengthen preventive efforts for reducing PIU and related consequences among adolescents. Key Words: Internet, adolescents, psychosocial problems.

  11. PERSYVE - Design and validation of a questionnaire about adverse effects of antihypertensive drugs

    PubMed Central

    Duarte-Silva, Daniela; Figueiras, Adolfo; Herdeiro, Maria T.; Teixeira Rodrigues, António; Silva Branco, Fábio; Polónia, Jorge; Figueiredo, Isabel V.

    2013-01-01

    Objective The aim of this study was to design and validate a questionnaire to measure perceived symptoms associated with antihypertensive drugs (PERSYVE). Methods The PERSYVE development and validation included four stages: 1) item development (bibliographic review and questionnaire elaboration); 2) face and content validation; 3) field testing (pre-test); and 4) test-retest validation, assessment of internal consistency (Cronbach’s alpha) and reproducibility over time (intraclass correlation coefficient and Cohen’s kappa coefficient). Results PERSYVE is divided into six sections according to results obtained from the literature review: (1) drug adherence, (2) perceived symptoms and how they affect quality of life (five-point Likert scale), (3) communication with health professionals, (4) perception of symptoms as adverse reactions, (5) influence on therapy compliance, and (6) adoption of non-pharmacological methods for blood pressure control. Content and face validation of the questionnaire led to some vocabulary changes and the introduction of section 2.1. Field-testing (n=26) revealed high comprehensibility of the questions. The Cronbach's alpha, calculated for section 2 (five-point Likert scale) was 0.850. PERSYVE was reproducible (n=167): kappa values presented fair to substantial reproducibility and, in section 2, ICC values resulted in good to excellent reproducibility. Conclusion Results showed that PERSYVE is a well-structured, objective, patient-friendly, valid and reliable questionnaire. PERSYVE can be a very useful instrument in hypertensive patients’ monitoring and in the screening of adverse effects. PMID:25035716

  12. Mediators and Adverse Effects of Child Poverty in the United States.

    PubMed

    Pascoe, John M; Wood, David L; Duffee, James H; Kuo, Alice

    2016-04-01

    The link between poverty and children's health is well recognized. Even temporary poverty may have an adverse effect on children's health, and data consistently support the observation that poverty in childhood continues to have a negative effect on health into adulthood. In addition to childhood morbidity being related to child poverty, epidemiologic studies have documented a mortality gradient for children aged 1 to 15 years (and adults), with poor children experiencing a higher mortality rate than children from higher-income families. The global great recession is only now very slowly abating for millions of America's children and their families. At this difficult time in the history of our nation's families and immediately after the 50th anniversary year of President Lyndon Johnson's War on Poverty, it is particularly germane for the American Academy of Pediatrics, which is "dedicated to the health of all children," to publish a research-supported technical report that examines the mediators associated with the long-recognized adverse effects of child poverty on children and their families. This technical report draws on research from a number of disciplines, including physiology, sociology, psychology, economics, and epidemiology, to describe the present state of knowledge regarding poverty's negative impact on children's health and development. Children inherit not only their parents' genes but also the family ecology and its social milieu. Thus, parenting skills, housing, neighborhood, schools, and other factors (eg, medical care) all have complex relations to each other and influence how each child's genetic canvas is expressed. Accompanying this technical report is a policy statement that describes specific actions that pediatricians and other child advocates can take to attenuate the negative effects of the mediators identified in this technical report and improve the well-being of our nation's children and their families.

  13. Differential effects of grape juice on gastric emptying and renal function from cisplatin-induced acute adverse toxicity.

    PubMed

    Ko, J-L; Tsai, C-H; Liu, T-C; Lin, M-Y; Lin, H-L; Ou, C-C

    2016-08-01

    Grape skin and seeds contain large amounts of phytochemicals such as polyphenols, resveratrol, and proanthocyanidins, which possess antioxidant activities. Cisplatin is widely used in the treatment of cancer. High doses of cisplatin have also been known to produce acute adverse effects. The aim of this study was to investigate the protective effects of antioxidant properties of whole grape juice (with skin and seeds) on cisplatin-induced acute gastrointestinal tract disorders and nephrotoxicity in Wistar rats. Gastric emptying is significantly increased in whole grape juice-pretreated rats when compared to cisplatin treatment alone. The expression of ghrelin mRNA of stomach is increased in rats with whole grape juice. However, pretreatment with whole grape juice did not reduce renal function markers in acute renal toxicity. No significant changes were recorded in the oxidative stress/antioxidant status parameters of any study group. In contrast, pretreatment with whole grape juice slightly improved tubular cell vacuolization, tubular dilatation, and cast formation in renal tubules. These results show that consumption of whole grape juice induces somewhat beneficial effects in preventing cisplatin-mediated dyspepsia but does not offer protection against cisplatin-induced acute renal toxicity.

  14. Efficacy and Adverse Events Associated With Use of OnabotulinumtoxinA for Treatment of Neurogenic Detrusor Overactivity: A Meta-Analysis

    PubMed Central

    2017-01-01

    Purpose OnabotulinumtoxinA is used widely for the treatment of neurogenic detrusor overactivity. We conducted a systematic review and meta-analysis to assess its efficacy and safety for neurogenic detrusor overactivity treatment. Methods A systematic literature review was performed to identify all published randomized double-blind, placebo-controlled trials of onabotulinumtoxinA for neurogenic detrusor overactivity treatment. MEDLINE, Embase, and the CENTRAL were employed. Reference lists of retrieved studies were reviewed carefully. Results Six publications involving 871 patients, which compared onabotulinumtoxinA with a placebo were analyzed. Efficacy of onabotulinumtoxinA treatment was shown as a reduction of the mean number of urinary incontinence episodes per day (mean difference, -1.41; 95% confidence interval [CI], -1.70 to -1.12; P<0.00001), maximum cystometric capacity (135.48; 95% CI, 118.22–152.75; P<0.00001), and maximum detrusor pressure (-32.98; 95% CI, -37.33 to -28.62; P<0.00001). Assessment of adverse events revealed that complications due to onabotulinumtoxinA injection were localized primarily to the urinary tract. Conclusions This meta-analysis suggests that onabotulinumtoxinA is an effective treatment for neurogenic detrusor overactivity with localized advent events. PMID:28361515

  15. Adverse drug effects attributed to phenylpropanolamine: a review of 142 case reports.

    PubMed

    Lake, C R; Gallant, S; Masson, E; Miller, P

    1990-08-01

    Phenylpropanolamine (PPA) is contained in about 106 products, over half of which are available over-the-counter (OTC). Most are cough/cold remedies; nine are OTC diet aids. More than nine million Americans were using OTC diet aids in 1981, making PPA the fifth most used drug in the United States, responsible for over $200 million in revenues. The safety of PPA remains controversial. Although most controlled studies indicate minimal pressor effects with recommended doses, adverse drug reactions (ADRs) continue to be documented. Since 1965, 142 ADRs have been reported in 85 studies, 69% of these in North America. Many such cases may go unrecognized. About two thirds of all ADRs occurred in females and in patients under 30. Of ADRs attributed to legitimately sold PPA products, 85% occurred after consumption of OTC products versus only 15% after prescription drugs. The PPA product often contained combination ingredients, or PPA was consumed along with additional drugs. An overdose of PPA was taken in about a third of the cases. After ingestion of non-overdose amounts, 82% of the ADRs were severe. The most frequent side effects involved symptoms compatible with acute hypertension, with severe headache the most common complaint. Twenty-four intracranial hemorrhages, eight seizures, and eight deaths (most due to stroke) were associated with PPA ingestion. We have summarized these data in an effort to alert clinicians to the prevalence of usage of PPA products and the potential for adverse effects. In patients who present with elevated blood pressure or signs of acute hypertension, especially hypertensive encephalopathy of undetermined origin, we recommend inquiry about recent ingestion of PPA-containing diet aids and cough/cold products and suggest having such patients remain upright rather than supine.

  16. Protective effects of phyllanthus emblica leaf extract on sodium arsenite-mediated adverse effects in mice.

    PubMed

    Sayed, Sadia; Ahsan, Nazmul; Kato, Masashi; Ohgami, Nobutaka; Rashid, Abdur; Akhand, Anwarul Azim

    2015-02-01

    Groundwater contamination of arsenic is the major cause of a serious health hazard in Bangladesh. No specific treatment is yet available to manage the large number of individuals exposed to arsenic. In this study, we evaluated the protective effects of Phyllanthus emblica (Indian gooseberry or Amla) leaf extract (PLE) on arsenic-mediated toxicity in experimental mice. Male Swiss albino mice were divided into three different groups (n=6/group). 'Control' mice received arsenic free water together with normal feed. Mice in the remaining two groups designated 'SA' and 'SA+PLE' were exposed to sodium arsenite (SA, 10 µg/g body weight/day) through drinking water in addition to receiving normal feed and PLE-supplemented feed, respectively. The weight gain of SA-exposed mice was decreased compared with the controls; however, this decrease in body weight gain was prevented when the feed was supplemented with PLE. A secondary effect of arsenic was enlargement of the liver, kidney and spleen of SA-group mice. Deposition of arsenic in those organs was demonstrated by ICP-MS. When PLE was supplemented in the feed the enlargement of the organs was minimized; however, the deposition of arsenic was not significantly reduced. These results indicated that PLE may not block arsenic deposition in tissue directly but rather may play a protective role to reduce arsenic-induced toxicity. Therefore, co-administration of PLE in arsenic-exposed animals might have a future therapeutic application for protecting against arsenic-mediated toxicity.

  17. Ground experiments for finding principles and working out methods for preventing adverse effects of weightlessness on the human organism

    NASA Technical Reports Server (NTRS)

    Kakurin, L. I.; Gregoryev, A. I.; Mikhailov, V. M.; Tishler, V. A.

    1980-01-01

    A comparative assessment of the effectiveness of different prophylactic procedures to prevent the adverse effects of weightlessness is presented. It is concluded that: physical training is most effective but no single method by itself produces the full effect, and an adjustment of regimes to one another enhances the effect. The approved complex of prophylactic procedures affected basic changes occurring in hypokinesia: deficit of muscular activity, no or reduced BP hydrostatic component, reduced volume of blood circulation, reduced hydration level, and the application of various prophylactic complexes during 49 day antiorthostatic hypodynamia eliminated or reduced the adverse effects of weightlessness in simulation.

  18. An in-flight simulation of approach and landing of a STOL transport with adverse ground effect

    NASA Technical Reports Server (NTRS)

    Ellis, D. R.

    1976-01-01

    The results of an in-flight simulation program undertaken to study the problems of landing a representative STOL transport in the presence of adverse ground effects are presented. Landings were performed with variations in ground effect magnitude, ground effect lag, and thrust response. Other variations covered the effects of augmented lift response, SAS-failures, turbulence, segmented approach, and flare warning. The basic STOL airplane required coordinated use of both stick and throttle for consistently acceptable landings, and the presence of adverse ground effects made the task significantly more difficult. Ground effect lag and good engine response gave noticeable improvement, as did augmented lift response.

  19. Interleaved programming of subthalamic deep brain stimulation to avoid adverse effects and preserve motor benefit in Parkinson's disease.

    PubMed

    Ramirez-Zamora, Adolfo; Kahn, Max; Campbell, Joannalee; DeLaCruz, Priscilla; Pilitsis, Julie G

    2015-03-01

    Subthalamic nucleus (STN) deep brain stimulation (DBS) is the most common surgical treatment for managing motor complications in Parkinson's disease (PD). Ultimately, outcomes depend on a variety of factors including lead location, access and expertize in programming and PD medical management. Nevertheless, achieving ideal programming settings can be difficult in certain patients, leading to suboptimal control of symptoms and stimulation-induced side effects, notably dysarthria and dyskinesia. Interleaved stimulation (ILS) is a newer programming technique that attempts to optimize the stimulation field, improving control of symptoms while minimizing stimulation-induced adverse effects. A retrospective chart review was performed on PD patients receiving STN DBS over the past 12 months. Clinical and demographic data were collected from patients identified as having received ILS. The rationale and clinical efficacy of ILS was analyzed. Nine patients received ILS due to incomplete PD symptom control or stimulation-induced side effects after attempting multiple programming options. Appropriate lead location was confirmed with postoperative MRI except in one case. Following ILS, patients reported improvement in symptoms and resolution of side effects, while preserving adequate control in Parkinsonism with a mean improvement in UPDRS-MOTOR scores of 51.2 %. ILS continues to emerge as a safe and effective programming strategy for maximizing symptom control in PD while diminishing stimulation-induced side effects.

  20. Adverse Renal, Endocrine, Hepatic, and Metabolic Events during Maintenance Mood Stabilizer Treatment for Bipolar Disorder: A Population-Based Cohort Study

    PubMed Central

    Marston, Louise; Walters, Kate; Geddes, John R.; King, Michael; Osborn, David P. J.

    2016-01-01

    0.73; p = 0.013) were also reduced relative to lithium. However, rates of greater than 15% weight gain on valproate, olanzapine, and quetiapine were higher (valproate HR 1.62; 95% CI 1.31–2.01; p < 0.001, olanzapine HR 1.84; 95% CI 1.47–2.30; p < 0.001, quetiapine HR 1.67; 95% CI 1.24–2.20; p < 0.001) than in individuals prescribed lithium, as were rates of hypertension in the olanzapine treated group (HR 1.41, 95% CI 1.06–1.87; p = 0.017). We found no significant difference in rates of chronic kidney disease stage 4 or more severe, type 2 diabetes mellitus, cardiovascular disease, or hepatotoxicity. Despite estimates being robust following sensitivity analyses, limitations include the potential for residual confounding and ascertainment bias and an inability to examine dosage effects. Conclusions Lithium use is associated with more renal and endocrine adverse events but less weight gain than commonly used alternative mood stabilizers. Risks need to be offset with the effectiveness and anti-suicidal benefits of lithium and the potential metabolic side effects of alternative treatment options. PMID:27483368

  1. Do shrubs reduce the adverse effects of grazing on soil properties?

    USGS Publications Warehouse

    Eldridge, David J.; Beecham, Genevieve; Grace, James B.

    2015-01-01

    Increases in the density of woody plants are a global phenomenon in drylands, and large aggregations of shrubs, in particular, are regarded as being indicative of dysfunctional ecosystems. There is increasing evidence that overgrazing by livestock reduces ecosystem functions in shrublands, but that shrubs may buffer the negative effects of increasing grazing. We examined changes in water infiltration and nutrient concentrations in soils under shrubs and in their interspaces in shrublands in eastern Australia that varied in the intensity of livestock grazing. We used structural equation modelling to test whether shrubs might reduce the negative effects of overgrazing on infiltration and soil carbon and nitrogen (henceforth ‘soil nutrients’). Soils under shrubs and subject to low levels of grazing were more stable and had greater levels of soil nutrients. Shrubs had a direct positive effect on soil nutrients; but, grazing negatively affected nutrients by increasing soil bulk density. Structural equation modelling showed that shrubs had a direct positive effect on water flow under ponded conditions but also enhanced water flow, indirectly, through increased litter cover. Any positive effects of shrubs on water flow under low levels of grazing waned at high levels of grazing. Our results indicate that shrubs may reduce the adverse effects of grazing on soil properties. Specifically, shrubs could restrict access to livestock and therefore protect soils and plants beneath their canopies. Low levels of grazing are likely to ensure the retention of soil water and soil carbon and nitrogen in shrubland soils.

  2. Excess dietary cholesterol may have an adverse effect on growth performance of early post-larval Litopenaeus vannamei.

    PubMed

    Niu, Jin; Chen, Peng-Fei; Tian, Li-Xia; Liu, Yong-Jian; Lin, Hei-Zhao; Yang, Hui-Jun; Liang, Gui-Ying

    2012-06-25

    One experiment was conducted to determine the nutritive value of cholesterol for post-larval shrimp, Litopenaeus vannamei. Four isoenergetic and isonitrogenous diets supplemented with four levels of cholesterol (D1, D2, D3 and D4 with 0, 0.5%, 1% and 2% cholesterol, respectively) were fed to triplicate groups of L. vannamei shrimp (mean initial wet weight 0.8 mg) for 27 days. After the trial, shrimp fed the D1 diet had the best growth performance (final body weights: FBW; weight gain: WG; specific growth rate: SGR), while there was no significant difference between diet treatments with respect to survival. The whole body crude protein level in the shrimp decreased with the increase in dietary cholesterol levels, while the whole body crude lipid level in shrimps in the D4 diet treatment was significantly higher (P < 0.05) than in other diet treatments. Dietary analysis indicated that the D1 diet contained 0.92% cholesterol prior to supplementation, which may have satisfied the dietary cholesterol requirement of post-larval L. vannamei; excess dietary cholesterol may thus lead to adverse effects on the growth performance of post-larval shrimp.

  3. Evidence for the adverse effect of starvation on bone quality: a review of the literature.

    PubMed

    Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E

    2015-01-01

    Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200-800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality.

  4. CORAL: binary classifications (active/inactive) for Liver-Related Adverse Effects of Drugs.

    PubMed

    Toropov, Andrey A; Toropova, Alla P; Rasulev, Bakhtiyor F; Benfenati, Emilio; Gini, Giuseppina; Leszczynska, Danuta; Leszczynski, Jerzy

    2012-09-01

    Classification data related to the Liver-Related Adverse Effects of Drugs have been studied with the CORAL software (http://www.insilico.eu/coral). Two datasets which contain compounds with two serum enzyme markers of liver toxicity: alanine aminotransferase (ALT, n=187) and aspartate aminotransferase (AST, n=209) are analyzed. Statistical quality of the prediction for ALT activity is n=35, Sensitivity = 0.5556, Specificity = 0.8077, and Accuracy = 0.7429. In the case of AST activity the prediction is characterized by n=42, Sensitivity = 0.6875, Specificity = 0.7692, and Accuracy = 0.7381. A number of structural alerts which can be related to the studied activities are revealed. It is the first attempt to build up the classification QSAR model by means of the Monte Carlo technique based on representation of the molecular structure by SMILES using the CORAL software.

  5. Propolis: a review of properties, applications, chemical composition, contact allergy, and other adverse effects.

    PubMed

    de Groot, Anton C

    2013-01-01

    Propolis (bee glue) is the resinous substance that bees collect from living plants for the construction and adaptation of their nests. It has antibacterial, antifungal, and antiviral properties and may have a wide range of other beneficial biological activities. Propolis is available as a dietary supplement, in products for the protection of health and prevention of diseases, in biopharmaceuticals, and as a constituent of (bio)cosmetics. In this article, the following aspects of propolis are reviewed: the nature and chemical composition, its biological properties and applications, contact allergy and allergic contact dermatitis (sensitizing potential, products causing contact allergy, clinical picture, frequency of sensitization, coreactivity and cross-reactivity, the allergens in propolis), and other adverse effects.

  6. Diagnostic criteria for adverse health effects in the environs of wind turbines.

    PubMed

    McMurtry, Robert Y; Krogh, Carmen Me

    2014-10-01

    In an effort to address climate change, governments have pursued policies that seek to reduce greenhouse gases. Alternative energy, including wind power, has been proposed by some as the preferred approach. Few would debate the need to reduce air pollution, but the means of achieving this reduction is important not only for efficiency but also for health protection. The topic of adverse health effects in the environs of industrial wind turbines (AHE/IWT) has proven to be controversial and can present physicians with challenges regarding the management of an exposure to IWT. Rural physicians in particular must be aware of the possibility of people presenting to their practices with a variety of sometimes confusing complaints. An earlier version of the diagnostic criteria for AHE/IWT was published in August 2011. A revised case definition and a model for a study to establish a confirmed diagnosis is proposed.

  7. Diagnostic criteria for adverse health effects in the environs of wind turbines

    PubMed Central

    Krogh, Carmen ME

    2014-01-01

    Summary In an effort to address climate change, governments have pursued policies that seek to reduce greenhouse gases. Alternative energy, including wind power, has been proposed by some as the preferred approach. Few would debate the need to reduce air pollution, but the means of achieving this reduction is important not only for efficiency but also for health protection. The topic of adverse health effects in the environs of industrial wind turbines (AHE/IWT) has proven to be controversial and can present physicians with challenges regarding the management of an exposure to IWT. Rural physicians in particular must be aware of the possibility of people presenting to their practices with a variety of sometimes confusing complaints. An earlier version of the diagnostic criteria for AHE/IWT was published in August 2011. A revised case definition and a model for a study to establish a confirmed diagnosis is proposed. PMID:25383200

  8. The forensic nursing in sexual assaults: the immunochemical diagnosis and prevention of its adverse effects.

    PubMed

    Vitale, Elsa

    2012-04-01

    Sexual assault was a ubiquitous and serious problem in our society. The world's care centers and forensic associations, which were at the forefront of scientific research in sexual assaults, discussed the role of the Forensic Nursing in their early diagnosis and their prevention, but little has been written in literature regarding their appropriate management. This article focuses on the immunochemical laboratory investigation in diagnosis and prevention of its adverse effects in sexual assaults and the role of the Forensic Nursing played in this task. After a careful reading of all the material received from many of the care centers and the associations contacted, a Forensic Nursing Examination Program, with specific immunochemical address, is identified.

  9. Evidence for the Adverse Effect of Starvation on Bone Quality: A Review of the Literature

    PubMed Central

    Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E.

    2015-01-01

    Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200–800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality. PMID:25810719

  10. Glaucoma-related adverse events in the first five years after unilateral cataract removal in the Infant Aphakia Treatment Study

    PubMed Central

    Freedman, Sharon F.; Lynn, Michael J.; Beck, Allen D.; Bothun, Erick D.; Orge, Faruk H.; Lambert, Scott R.

    2015-01-01

    Importance Glaucoma-related adverse events constitute major sight-threatening complications of cataract removal in infancy, yet their relationship to aphakia versus primary intraocular lens (IOL) implantation remains unsettled. Objective To identify and characterize cases of glaucoma and glaucoma-related adverse events (glaucoma+glaucoma suspect) among children in the Infant Aphakia Treatment Study (IATS) by the age of five years. Design, Setting, and Participants A multicenter randomized controlled trial of 114 infants with unilateral congenital cataract who were between age 1–6 months at surgery. Interventions Participants were randomized at cataract surgery to either primary IOL, or no IOL implantation (contact lens [CL]). Standardized definitions of glaucoma and glaucoma suspect were created for IATS and applied for surveillance and diagnosis. Main Outcome Measures Development of glaucoma and glaucoma+glaucoma suspect in operated eyes up to age five years, plus intraocular pressure, visual acuity, and axial length at age five years. Results Product limit estimates of the risk of glaucoma and glaucoma+glaucoma suspect at 4.8 years after surgery were 17% (95%CI=11%–25%) and 31% (95%CI=24%–41%), respectively. The CL and IOL groups were not significantly different for either outcome: glaucoma (hazard ratio(HR)=0.8[95%CI=0.3–2.0],p=0.62); glaucoma+glaucoma suspect: (HR=1.3[95%CI=0.6–2.5],p=0.58). Younger (versus older) age at surgery conferred increased risk of glaucoma (26% versus 9%, respectively at 4.8 years after surgery (HR=3.2[95%CI=1.2–8.3]), and smaller (versus larger) corneal diameter showed increased risk for glaucoma+glaucoma suspect (HR=2.5[95%CI=1.3–5.0]). Age and corneal diameter were significantly positively correlated. Glaucoma was predominantly open angle (19/20 cases, 95%), most eyes received medication (19/20, 95%), and 8/20 (40%) eyes had surgery. Conclusions and Relevance These results suggest that glaucoma-related adverse events

  11. Reversible Ototoxicity: A Rare Adverse Reaction of Liposomal Amphotericin-B Used for the Treatment of Antimony-Resist