Development Of Adverse Reactions Research Articles

Update 2014: advances to optimize 6-mercaptopurine and azathioprine to reduce toxicity and improve efficacy in the management of IBD.

The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine (AZA), remain as a mainstay therapy in inflammatory bowel disease (IBD). Differences in metabolism of these drugs lead to individual variation in thiopurine metabolite levels that can determine its therapeutic efficacy and development of adverse reactions. In this update, we will review thiopurine metabolic pathway along with the up-to-date approaches in administering thiopurine medications based on the current literature. A search of the PubMed database by 2 independent reviewers identifying 98 articles evaluating thiopurine metabolism and IBD management. Monitoring thiopurine metabolites can assist physicians in optimizing 6-MP and AZA therapy in treating patients with IBD. Of the dosing strategies reviewed, we found evidence for monitoring thiopurine metabolite level, use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of AZA or 6-MP to optimize thiopurine therapy and minimize adverse effects in IBD. Based on the currently available literature, various dosing strategies to improve therapeutic response and reduce adverse reactions can be considered, including use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of thiopurine.

Infliximab drug and antibody levels in patients with dermatological conditions.

In recent years, studies monitoring infliximab in rheumatoid arthritis and inflammatory bowel disease have confirmed the relationship between the clinical response and the infliximab and anti-infliximab antibodies serum levels. However, there is only limited evidence in the field of dermatology. The aim of this study was to establish the correlation between plasma infliximab levels, the presence of anti-infliximab antibodies and the clinical response in dermatological conditions. Retrospective observational study in a tertiary hospital (University Hospital of La Coruña, Spain). Patients with dermatological conditions being treated with infliximab (5 mg/kg/8 weeks after the induction dose) were included in the study. The concentrations of infliximab and anti-infliximab antibodies were quantified by two sandwich-type ELISA immunoassays. The patients were classified into three groups based on the efficacy: good, partial or non-efficacy at the time of each blood assessment. The development of adverse reactions was also evaluated. Plasma levels of infliximab and anti-infliximab antibodies, clinical response and infusion reactions. 17 patients (45 assessments) were included. The good/partial efficacy rate was significantly higher in the case of >0.05 than <0.05 μg/mL infliximab concentration (93.3 vs. 40.0 %, p < 0.001). Anti-infliximab antibodies were only detected in five samples. Their presence was associated with a higher frequency of infusion reactions and a lower efficacy rate in comparison with the group without antiinfliximab antibodies (100.0 vs. 0.0 %, p < 0.001 and 0.0 vs. 85.0 %, p < 0.001 respectively). The results obtained show that the presence of infliximab concentrations higher than 0.05 μg/mL are correlated with a good clinical response and the absence of toxicity. The incidence of anti-infliximab antibodies is low, although a correlation was observed between the presence of antibodies, absence of infliximab concentration, loss of clinical response and the development of infusion reactions.

Ultrasound-guided regional anesthesia for the pain management of elderly patients with hip fractures in the emergency department.

ObjectiveWe examined the pain-relieving effect of ultrasound-guided regional anesthesia performed by emergency physicians on elderly hip fracture patients.MethodsThis study is a prospective, non-randomized, case-control study. The subjects were patients older than 65 years who visited the emergency department with a hip fracture. After we obtained informed consent, two emergency physicians performed an ultrasound-guided three-in-one femoral block using 20 mL of 0.5% bupivacaine. The pain score was measured just before regional anesthesia, and 0.25, 0.5, 1, 2, 3, and 4 hours after the procedure. Another group of patients was given multiple doses of morphine to control the pain. We compared the change in pain score and the development of adverse reactions between the two groups.ResultsA total of 47 patients were enrolled in this study, of which 25 were given regional anesthesia. Successful pain control (pain score<4) was significantly higher in the regional anesthesia group (96.0% vs. 40.9%; P<0.001). The decrease in pain score was significantly higher in the regional anesthesia group (7 [interquartile range, 6 to 7] vs. 4 [interquartile range, 3 to 5]; P< 0.001). The only adverse reaction observed was mild nausea in 4 patients (1 out of 25 from the regional anesthesia group and 3 out of 22 from the morphine group).ConclusionUltrasound-guided regional anesthesia administered by emergency physicians treating elderly hip fracture patients provided faster pain relief and a larger decrease in pain than conventional intravenous injections of morphine.

Efficacy of laryngeal mask airway Guardian for airway management in patients requiring insertion of nasogastric tube before laparoscopic cholecystectomy

Objective To evaluate the efficacy of laryngeal mask airway(LMA)Guardian for airway management in the patients requiring insertion of nasogastric tube before laparoscopic cholecystectomy. Methods Sixty patients of both sexes, aged 26-64 yr, weighing 48-95 kg, of American Society of Anesthesiologists physical statusⅠ-Ⅲ, with Mallampati gradeⅠ-Ⅲ, scheduled for elective laparoscopic cholecystectomy under general anesthesia, were divided into groupⅠand groupⅡ(n=30 each)using a random number table.In group Ⅰ, the nasogastric tube was inserted through the drain tube of LMA Guardian.In group Ⅱ, the nasogastric tube was inserted through the nostril before operation, and after successful LMA Guardian placement, another nasogastric tube was inserted through the drain tube of LMA Guardian.The hemodynamic parameters, SpO2, end-tidal pressure of carbon dioxide and peak airway pressure(Ppeak)were monitored during operation.The fiberoptic laryngoscopy scores were assessed after successful LMA placement, and the nasogastric tube displacement was recorded.The LMA placement time, success rate of LMA placement at first attempt, airway sealing pressure, occurrence of air leakage of LMA and nasogastric tube drainage were recorded.The bloodstains and gastroesophageal reflux were observed after removal of the LMA.The pH values were tested at the tip of LMA and on the dorsal and ventral sides of the body of LMA using pH test papers.The development of adverse reactions in the oropharynx was recorded within 24 h after operation. Results The hemodynamics was stable, the SpO2 and Ppeak were within the normal range during operation, and Ppeak was lower than airway sealing pressure in the two groups(P>0.05), and there was no significant difference between the two groups.There was no significant difference between the two groups in the LMA placement time, success rate of LMA placement at first attempt, airway sealing pressure, score for exposure of oropharynx, development of adverse reactions in the oropharynx, consumption of anesthetics, development of bloodstains within the body of LMA and gastroesophageal reflux, and pH values at the tip of LMA and on the dorsal and ventral sides of the body of LMA(P>0.05). Nasogastric tube drainage: the rate of nasogastric tube drainage through the LMA Guardian was 67% in group I; the rate of nasogastric tube drainage through the nostril was 40%, and the rate of nasogastric tube drainage though the LMA Guardian was 50% in group Ⅱ.No nasogastric tube displacement was found after operation in group Ⅱ. Conclusion For the patients requiring insertion of nasogastric tube before laparoscopic cholecystectomy, insertion of LMA Guardian is easy, and LMA Guardian can assure good airway sealing and adequate ventilation and can be safely and effectively used for airway management in this type of patients. Key words: Laryngeal mask; Respiration, artificial; Intubation, gastrointestinal; Laparoscopy

English

OBJECTIVES: 1. To evaluate the efficacy of Immunotherapy in improvement of nasal symptoms in patients with Allergic Rhinitis. 2. To evaluate the adverse reactions of Immunotherapy in patients suffering with allergic rhinitis. MATERIALS AND METHODS: Study group included 138 patients with Allergic rhinitis, who presented in Department of ENT, during July 2011 to March 2014. Patients with clinical history of allergic rhinitis were screened with total serum IgE. Patients with elevated total serum IgE were investigated with skin prick test. Patients with positive skin reactions were treated with sub cutaneous immunotherapy. Development of adverse reactions during administration of immunotherapy was assessed. A follow up period of 18 months was considered for the study. A relief in clinical symptoms of allergic rhinitis at the end of 18 months was considered. CONCLUSION: Immunotherapy offers significant improvement in relief of clinical symptoms of allergic rhinitis with minimal adverse reactions over a long time. Total serum IgE forms an affective screening tool in diagnosis of allergic rhinitis. Immunotherapy appears as a safe alternative treatment for the management of allergic rhinitis.

Effect of external beam radiotherapy on patency of uncovered metallic stents in patients with inoperable bile duct cancer

Although biliary decompression with metallic stenting is the preferred treatment for inoperable bile duct cancer (BDC), maintenance of patency is still unsatisfactory. We tried to assess the effectiveness and safety of external beam radiotherapy (EBRT) for prolonging stent patency in patients having uncovered metallic stents. We retrospectively reviewed 50 patients who received endoscopic stenting, of whom 18 received EBRT (RT group) and 32 did not (non-RT group). No difference was found in baseline characteristics between the two groups. Although stent patency was longer in the RT group than that in the non-RT group (140.7+/-51.3 vs 136.4+/-34.9 days, P=0.94), the difference was not statistically significant. There were a lower rate of stent occlusion (27.8% vs 50.0% of patients, P=0.12) and a longer overall survival (420.1+/-73.2 vs 269.1+/-41.7 days, P=0.11) in the RT group than in the non-RT group, and the difference again was not statistically significant. The development of adverse reactions did not differ (55.6% vs 53.1% of patients, P=0.91). There was no serious adverse reaction in both groups (P=0.99). EBRT did not significantly improve stent patency in patients with inoperable BDC having uncovered metallic stents. However, EBRT was safe. Future trials with refined protocols for better efficacy are expected.

Hematopoietic SCT with cryopreserved grafts: adverse reactions after transplantation and cryoprotectant removal before infusion

Transplantation of hematopoietic stem cells (HSCs) has been successfully developed as a part of treatment protocols for a large number of clinical indications, and cryopreservation of both autologous and allogeneic sources of HSC grafts is increasingly being used to facilitate logistical challenges in coordinating the collection, processing, preparation, quality control testing and release of the final HSC product with delivery to the patient. Direct infusion of cryopreserved cell products into patients has been associated with the development of adverse reactions, ranging from relatively mild symptoms to much more serious, life-threatening complications, including allergic/gastrointestinal/cardiovascular/neurological complications, renal/hepatic dysfunctions, and so on. In many cases, the cryoprotective agent (CPA) used-which is typically dimethyl sulfoxide (DMSO)-is believed to be the main causal agent of these adverse reactions and thus many studies recommend depletion of DMSO before cell infusion. In this paper, we will briefly review the history of HSC cryopreservation, the side effects reported after transplantation, along with advances in strategies for reducing the adverse reactions, including methods and devices for removal of DMSO. Strategies to minimize adverse effects include medication before and after transplantation, optimizing the infusion procedure, reducing the DMSO concentration or using alternative CPAs for cryopreservation and removing DMSO before infusion. For DMSO removal, besides the traditional and widely applied method of centrifugation, new approaches have been explored in the past decade, such as filtration by spinning membrane, stepwise dilution-centrifugation using rotating syringe, diffusion-based DMSO extraction in microfluidic channels, dialysis and dilution-filtration through hollow-fiber dialyzers and some instruments (CytoMate, Sepax S-100, Cobe 2991, microfluidic channels, dilution-filtration system, etc.) as well. However, challenges still remain: development of the optimal (fast, safe, simple, automated, controllable, effective and low cost) methods and devices for CPA removal with minimum cell loss and damage remains an unfilled need.

Results of combined anesthesia application with the usage of non-narcotic analgesics in the surgical oncology practice

Aim. To evaluate the effectiveness of pre-, intra- and postoperative intravenous administration of paracetamol in combined anesthesia in patients undergoing surgical interventions in the surgical oncology practice. Methods. Examined were 35 patients aged from 43 to 75 years, operated on under combined anesthesia. During the operation and after its completion an infusion of liquid paracetamol at a dose of 3.3 mg/h was performed. Cardiac monitoring was conducted, the content of cortisol in the blood and the Bispectral Index were determined. The pain indices measured by visual analogue and digital rating scales were determined in the postoperative period. The control group included 35 patients in whom anesthesia was performed without the use of paracetamol. Results. During the infusion of paracetamol an adequate level of analgesia was achieved without development of adverse reactions on the part of the vital systems. The use of paracetamol in the early postoperative period contributed to the reduction of pain on digital rating and visual analogue scales compared to the group with basic anesthesia. Conclusion. The use of liquid paracetamol is a promising and safe method of additional analgesia.

Association of anti-IgA antibodies with adverse reactions to γ-globulin infusion

Association of anti-IgA antibodies with adverse reactions to γ-globulin infusion

Adverse event following immunization in a Nigerian tertiary health institution

Vaccine manufacturers develop products with the highest safety and effectiveness possible. But some very rare vaccine-related adverse events still occur. A descriptive retrospective study design was employed in this investigation. The investigation was limited to the four major health facilities in a metropolitan city that offer major immunization services to children. All cases of injection abscess or local reaction following vaccine administration from January 2004 to June 2006 were extracted from the records of each facility and included in the investigation. More than half of the cases reported were between 2 -4 months of age constituting 57.9% of all reported cases. The mean age of all reported cases was 4.368 ± 2.794 with a modal age of 2 months. Over half of all documented cases of adverse reactions following vaccine administration during the period under investigation were local swelling at site of injection (50.9%). About half of all cases documented (49.1%), were given DPT before development of adverse reactions. Almost all the cases of adverse reaction to vaccine administration (93%) were seen at the tertiary health facility. Cold chain equipment should be supplied and maintained at utmost working conditions at all health facilities to guarantee potency of vaccines.

Renal Function Following Fluorescein Angiography in Diabetic Patients With Chronic Kidney Disease

Intravenous fluorescein angiography has been widely used in evaluating diabetic retinopathy. Diabetic patients in whom fluorescein angiography is crucial are likely to have chronic kidney disease (CKD) because retinopathy and nephropathy usually progress in parallel. Although numerous reports have been published concerning the development of adverse reactions after fluorescein angiography (1–3), to the best of our knowledge, it has never been debated in the literature whether fluorescein (noniodinated contrast media) induces nephropathy as does iodinated radiocontrast. Therefore, we conducted this hospital-based retrospective cohort study to determine whether fluorescein angiography is associated with deterioration of renal function in diabetic patients with CKD. Among consecutive diabetic patients undergoing fluorescein angiography to assess retinopathy at the Department of Ophthalmology, …

HDL therapy for cardiovascular diseases: the road to HDL mimetics

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are currently the drug of choice for the clinical management of elevated low-density lipoprotein (LDL) cholesterol. Although statin treatment provides an overall improvement in outcomes, clinical trial data reveal a significant number of cardiac events despite reaching targeted LDL levels. A low serum high-density lipoprotein (HDL) cholesterol level is an independent predictor of cardiovascular risk. Accordingly, there has been interest in determining whether HDL elevation, in addition to LDL lowering, further reduces risk in patients with coronary artery disease. Several commonly prescribed lipid-lowering therapies modestly raise HDL, but their use may be limited by the development of adverse reactions. Emerging data suggest that HDL quality and function may also be significantly reduced by atherosclerosis and other inflammatory diseases. The goal of this review is to discuss the current status of HDL therapeutics, with emphasis on a novel class of agent, the apolipoprotein A-I mimetic peptides, which improve the functional properties of HDL cholesterol.

Neutrophil activation in ivermectin-treated onchocerciasis patients.

Ivermectin is a safe and effective drug for onchocerciasis treatment. In certain individuals, however, therapy is accompanied by adverse reactions. The mechanisms underlying these reactions are not yet known. The aim of the present study was to investigate whether neutrophils are involved in the development of these adverse reactions. Elastase and lactoferrin, two markers for the release of neutrophil azurophilic and specific granule contents respectively, were measured by radioimmunoassays in plasma of onchocerciasis patients with varying degrees of side effects, as well as in control subjects before and 1 and 2 days after ivermectin treatment. A considerable increase of elastase levels after treatment was observed, whereas lactoferrin levels did not change. The percentage of patients with elevated elastase levels was significantly correlated with the degree of side effects. These findings suggest that neutrophil activation may be involved in the development of adverse reactions in these patients.

Autologous bone marrow cells in the treatment of cirrhosis of the liver

The data characterizing tolerance and efficiency of autologous bone marrow cells in the treatment of patients with cirrhosis of the liver are presented. Injection of autologous bone marrow cells was not associated with the development of adverse reactions. Cell therapy of patients with compensated cirrhosis arrested asthenic syndrome, reduced cytolysis, increased the level of serum albumin and platelet count. Ultrasonic examination revealed reduction of portal hypertension (the area of the spleen and the portal vein lumen decreased). In patients with decompensated cirrhosis, a positive response presenting as reduction of the disease severity (by 1.9 points) was observed in 48.6% cases. Positive shifts in these patients were associated with a decrease of ALT and AST levels, reduction of laboratory signs of cirrhosis, increase in platelet count, and reduction of the asthenic syndrome. Hence, therapy with autologous bone marrow cells is safe and, according to preliminary results, can be regarded as a new approach to the treatment of patients with cirrhosis of the liver.

Higher maximal serum concentration of methotrexate predicts the incidence of adverse reactions in Japanese rheumatoid arthritis patients

Weekly pulsed low-dose methotrexate (MTX) is a standard regimen for rheumatoid arthritis (RA). Severe adverse reactions to MTX, such as pneumonia and cytopenia, sometimes occur; however, it is difficult to predict the development of these adverse reactions. In this article, we examine the serum concentrations of orally administered MTX of 69 Japanese patients with RA in the clinical setting. The maximum serum concentration (C (max)) after the first dose of the weekly administration and the time at which C (max) was obtained (T (max)) were analyzed. C (max) correlated with the administered dose before measurement. The average T (max) was 2.0 +/- 0.8 h, and none of the patients showed a T (max) of more than 4 h. In addition, we demonstrated that the weekly MTX dosage and the mean dosage of steroids were significantly higher in patients with adverse reactions than in those without them, and the C (max) after the first dose of the weekly administration particularly correlated with the incidence of adverse reactions (P < 0.001). In fact, the cut-off point of C (max) (0.16 micromol/l) was a sensitive predictor of the adverse reactions (sensitivity 81% and specificity 67%). We concluded that C (max) after the first dose of weekly administration is a useful parameter for predicting the development of adverse reactions to MTX.

Higher maximal serum concentration of methotrexate predicts the incidence of adverse reactions in Japanese rheumatoid arthritis patients

Weekly pulsed low-dose methotrexate (MTX) is a standard regimen for rheumatoid arthritis (RA). Severe adverse reactions to MTX, such as pneumonia and cytopenia, sometimes occur; however, it is difficult to predict the development of these adverse reactions. In this article, we examine the serum concentrations of orally administered MTX of 69 Japanese patients with RA in the clinical setting. The maximum serum concentration (Cmax) after the first dose of the weekly administration and the time at which Cmax was obtained (Tmax) were analyzed. Cmax correlated with the administered dose before measurement. The average Tmax was 2.0 ± 0.8 h, and none of the patients showed a Tmax of more than 4 h. In addition, we demonstrated that the weekly MTX dosage and the mean dosage of steroids were significantly higher in patients with adverse reactions than in those without them, and the Cmax after the first dose of the weekly administration particularly correlated with the incidence of adverse reactions (P < 0.001). In fact, the cut-off point of Cmax (0.16 µmol/l) was a sensitive predictor of the adverse reactions (sensitivity 81% and specificity 67%). We concluded that Cmax after the first dose of weekly administration is a useful parameter for predicting the development of adverse reactions to MTX.

Gene Expression Profiles in Mouse Lung Tissue after Administration of Two Cationic Polymers Used for Nonviral Gene Delivery

This study compared gene expression profiles in mouse lungs after administration of the cationic polymers polyethyleneimine (PEI) or chitosan alone or formulated with a luciferase reporter plasmid (PEI-pLuc, chitosan-pLuc). The polymers and formulations were administered intratracheally to Balb/c mice at doses judged to be nontoxic according to intracellular dehydrogenase activity and tissue morphology. RNA was isolated from the lungs 24 or 72 h after administration, and a dedicated stress and toxicology cDNA array was used to monitor the in vivo response to the gene delivery system in the lung tissue. The gene expression profiles differed between the PEI and chitosan groups with regard to both the total number and the type of expressed genes. Chitosan-pLuc upregulated genes that protect the cell from oxidative stress and inflammation, such as heme oxygenase-1 and catalase, whereas PEI-pLuc upregulated genes involved in inflammatory processes, such as the cyclooxygenases 1 and 2, indicating possible involvement in the development of adverse reactions. However, both polymers activated genes involved in reaction to stress, such as DNA damage repair. Furthermore, in the PEI group, chaperone genes and members of the p38 mitogen-activated protein kinase pathway were also upregulated, suggesting a possible explanation for the better performance of PEI in gene delivery systems. The results indicate that gene expression profiling is a useful and sensitive tool for the evaluation of tissue responses after administration of polymers or gene delivery systems. The results also suggest a possible explanation for the differences in gene delivery performance between the two polymers in gene delivery systems.

Constitutive mRNA expression of DNA repair-related genes as a biomarker for clinical radio-resistance: A pilot study in prostate cancer patients receiving radiotherapy

Purpose: Repair of radiation-induced DNA damage is believed to play a critical role in the development of adverse reactions in radiotherapy patients. Constitutive mRNA expression of repair genes was investigated in such patients to analyze whether expression patterns are predictive for therapy-related acute side effects.Materials and methods: Prostate cancer patients (n = 406) receiving intensity-modulated radiotherapy were recruited in a prospective epidemiological study. Adverse effects were monitored during therapy using common toxicity criteria. For expression analyses, samples from 58 patients were selected according to their observed grade of clinical side effects to radiotherapy. Expression profiles were generated from peripheral blood lymphocytes using customized cDNA-arrays which carried probes for 143 DNA repair or repair-related genes. In addition, expression of selected genes was confirmed by quantitative real-time reverse transcription PCR (RT-PCR). Constitutive mRNA expression profiles were analyzed for predicting acute clinical radiosensitivity or radio-resistance.Results: Cluster analysis identified 19 differentially expressed genes. Many of these genes are involved in DNA double strand break repair. Expression levels of these genes differed up to 7-fold from the mean of all patients whereas expression levels of housekeeping genes varied only up to 2-fold. High expression of the identified genes was associated with a lack of clinical radiation sensitivity thus indicating radio-resistance.Conclusions: Constitutive expression of DNA repair-related genes may affect the development of acute side effects in radiotherapy patients, and high expression levels of these genes seem to support protection from adverse reactions.

Association of transient dermal mastocytosis and elevated plasma tryptase levels with development of adverse reactions after treatment of onchocerciasis with ivermectin.

To investigate the role of mast cells in treatment-associated adverse reactions in patients with onchocerciasis, changes in plasma tryptase levels and skin mast cell counts were examined in 2 groups of Onchocerca volvulus-infected subjects after ivermectin treatment. After treatment, an increase in tryptase levels was observed concurrent with the onset of blood eosinopenia and preceding the appearance of plasma eosinophil-derived neurotoxin (EDN) and interleukin-5. Tryptase levels were correlated with development of peripheral eosinopenia and markers of eosinophil activation and degranulation. Dermal mast cell numbers increased transiently at 24 h after treatment, preceding the onset of dermal eosinophil infiltration and the development of clinically apparent inflammation. Local reactions were strongly correlated with levels of plasma tryptase and EDN, and the severity of systemic reactions was correlated with levels of tryptase, EDN, and interleukin-5. The data indicate that mast cells play a role in initiation of tissue inflammatory reactions after ivermectin treatment of onchocerciasis.

Stereotactic radiosurgery XIV: the role of the haemosiderin 'ring' in the development of adverse reactions following radiosurgery for intracranial cavernous malformations: a sustainable hypothesis

There are strong data suppor ting the clinical efficacy of ionizing radiation therapy in the treatment of extracranial cavernous angiomas; no unusual complications occur. There is no a priori reason to anticipate a high rate of complications following radiosurgery for brain cavernous angiomas and yet equivalent dose prescriptions (site, size and target volume) to those used for AVM are associated with a considerably higher complication rate. The observed sub-acute reactions sometimes recover with steroid therapy. Previous authors have not sought to define the aetiological basis of this observation. Haemosiderin staining of the fringe of normal brain tissue surrounding the cavernoma is a unique feature of these brain lesions and the potential radiosensitizing proper ties of this iron based substance, for which there is a considerable experimental and clinical observational basis for radiosensitization, are reviewed. These provide good support for the concept that this characteristic feature of brain cavernomas accounts for the higher post radiation reaction/complication rate. Treatment considerations, stemming from these observations, are suggested.