Hypersensitivity-like Reactions Research Articles

Development of a Screening Algorithm for Lung Disease in Systemic Juvenile Idiopathic Arthritis.

Lung disease (LD) is an increasingly recognized complication of systemic juvenile idiopathic arthritis (sJIA). As there are no currently available guidelines for pulmonary screening in sJIA, we sought to develop such an algorithm at our institution. A multidisciplinary workgroup was convened, including members representing rheumatology, pulmonary, stem cell transplantation, and patient families. The workgroup leaders drafted an initial algorithm based on published literature and experience at our center. A modified Delphi approach was used to achieve agreement through three rounds of anonymous, asynchronous voting and a consensus meeting. Statements approved by the workgroup were rated as appropriate with moderate or high levels of consensus. These statements were organized into the final approved screening algorithm for LD in sJIA. The workgroup ultimately rated 20 statements as appropriate with a moderate or high level of consensus. The approved algorithm recommends pulmonary screening for newly diagnosed patients with sJIA with clinical features that the workgroup agreed may confer increased risk for LD. These "red flag features" include baseline characteristics (young age of sJIA onset, human leukocyte antigen type, trisomy 21), high disease activity (macrophage activation syndrome [MAS], sJIA-related ICU admission, elevated MAS biomarkers), respiratory symptoms or abnormal pulmonary examination findings, and features of drug hypersensitivity-like reactions (eosinophilia, atypical rash, anaphylaxis). The workgroup achieved consensus on the recommended pulmonary work-up and monitoring guidelines. We developed a pulmonary screening algorithm for sJIA-LD through a multidisciplinary consensus-building process, which will be revised as our understanding of sJIA-LD continues to evolve.

The Conundrum of Lung Disease and Drug Hypersensitivity-like Reactions in Systemic Juvenile Idiopathic Arthritis.

An unusual form of lung disease has begun to affect some children with systemic juvenile idiopathic arthritis (JIA), coincident with increasing utilization of interleukin-1 (IL-1) and IL-6 antagonists. Many children with systemic JIA-associated lung disease (SJIA-LD) have a history of clinical and laboratory features resembling drug reaction with eosinophilia and systemic symptoms (DRESS), a presentation now convincingly associated with HLA-DRB1*15. Treatment of DRESS typically requires drug discontinuation, a daunting prospect for clinicians and families who rely upon these agents. Here we review SJIA-LD and its associated DRESS-like phenotype. We suggest an alternative explanation, the cytokine plasticity hypothesis, proposing that IL-1 and IL-6 blockers modulate the milieu in which T cells develop, leading to a pathologic immune response triggered through exposure to common microbes, or to other exogenous or endogenous antigens, rather than to the drugs themselves. This hypothesis differs from DRESS in mechanism but also in clinical implications, predicting that control of pathogenic T cells could permit continued use of IL-1 and IL-6 antagonists in some individuals. The spectrum posed by these two hypotheses provides a conceptual framework that will guide investigation into the pathogenesis of SJIA-LD and may open up new therapeutic avenues for patients with systemic JIA.

Plant induced resistance in Solanacearum lycopersicum species against root knot nematodes

The impact of root-knot nematodes of the tomato, Solanacearum lycopersicum, has resulted in severe damage and reduction in crop yields of both temperate and tropical agriculture systems. Keeping in mind the economic significance of the plant, the parasitic nematodes have not only been a burden for plant production but also cause for global agricultural economy depletion. At present, various countries have banned the nematicides after analyzing their consequence on environment and humans thereby making it an imperative to find an alternative method for the inhibition of nematodes against S. lycopersicum. With the plant root comprising of several bioactive secondary metabolites, a self-defense mechanism can be initiated against the infecting parasites. Not with standing, limited research has been carried out to understand the efficacy of induced resistance between or within the same species. Hence, the current review, we summarize on how hypersensitivity-like reactions can enhance plant resistance inducers in solanaceous species and their effects of various root metabolisms, chemical compounds which can act as repellents, hatching stimulants, attractant, or as inhibitors. The review focuses on the objective of understanding the mechanistic intricacies of how RNA interference acts on a root-knot nematode.

Adverse drug reactions of local anesthetics used in dentistry

The objects of the study were 122 notification forms about LA ADR recorded in the regional base (Register) of spontaneous reports called ARCADe (Adverse Reactions in Crimea, Autonomic Database). In most cases, ADR was associated with the use of amide LA Lidocaine - 69 cases (56.55% of the total number of cases for LA ADR), less often, ADR was caused by combinations containing Articaine (34 cases, 27.87%). Rare cases of ADR were reported for Novocaine/Procaine (9 cases, 7.38%), Bupivacaine (8 cases, 6.56%) and Mepivacaine (2 cases, 1.64%). The main clinical manifestations of reactions were hypersensitivity-like reactions (38 cases), cardiac and vascular disorders (29 cases) and central nervous system disorders (19 cases). Lack of effectiveness of LA occurred in 13 cases (10.66%). A study of the outcome of ADR revealed a high incidence of life-threatening conditions associated with LA use - 31 cases (25.4%), which indicates the severity of the event and the need to cancel the suspected drug and prescribe additional medications for correction. The need for hospitalization or prolongation of hospitalization was necessary in 7 cases (5.8%), and temporary disability of patients was revealed in 5 cases (4.1%). Of particular interest are 2 cases (1.6%) of the development of a fatal outcome as a result of the suspected anaphylactic shock (1 case) and disorders of the central nervous system (convulsions, development of respiratory failure). The high frequency and severity of unwanted effects resulted from the use of LA requires healthcare professionals to make rational choices and strictly monitor patient safety.

Liposomes with cyclic RGD peptide motif triggers acute immune response in mice

Liposomes with peptides motifs have been widely applied for targeted delivery of anticancer drugs. However, few studies have questioned whether peptide modification on liposomes may induce serious toxicity associated with immune stimulation. Here, we report that display of a tumor targeting cyclic RGD peptide (e.g. c(RGDyK) and c(RGDfK) on the surface of liposomes can be a potent inducer of lethal hypersensitivity-like reactions in mice upon re-administration, with the main symptom a sudden drop in body temperature. The hypothermia usually abates within 4 h but is sometimes lethal with death happening within 30 min post injection. This reaction has been proven to be IgE-independent acute systemic anaphylaxis, which may due to IgG immune complex triggered complement activation, anaphylatoxin and cytokine release, etc., leading to acute conspicuous organ damage. Results from an exploration of influence factors showed that the immunotoxicity of c(RGDyK)-liposomes could not be eliminated by minimizing the c(RGDyK) motif ratio, or by decreasing injection doses in the normal dose range, or by increasing the mPEG-DSPE motif ratio. However, encapsulation of a strong cytotoxic drug completely shut off this unwanted immune response. Investigation with a series of peptides containing the RGD sequence suggested that the lethal immunotoxicity of the cyclic RGD peptide was RGD sequence and peptide cyclization dependent. This study provides a valuable alert for the utilization of peptide modified liposomes in drug delivery, especially when carrying low-toxicity drugs.

Cutaneous Hypersensitivity-Like Reactions Associated With Breast Implants: A Review.

Breast implantation is an increasingly common procedure for both cosmesis and reconstruction. Risk of cutaneous reactions to breast implants is low and typically described in postsurgical settings. Adverse skin hypersensitivity-like reactions to implants have also been reported but are not well described. To review the scientific literature on cutaneous hypersensitivity-like reactions to breast implants. A systematic literature review was conducted using PubMed. Articles pertaining to breast implants and cutaneous hypersensitivity-like reactions in humans were included. In total, 10 studies on hypersensitivity-like reactions from breast implants were included in the review. Potential allergenic compounds in breast implants include silicone, polyurethane texturing, and acellular dermal matrix. Perivascular lymphocytic infiltrate was a common finding on histopathology. Patch testing and preoperative silicone cube implantation were used to determine sensitivity. Attempted treatments included topical and oral corticosteroids, montelukast and antibiotics. Most cases required implant removal for resolution of symptoms. Cutaneous hypersensitivity-like reactions to breast implants seem to be rare complications, sometimes necessitating implant removal. Future studies are needed to establish their incidence and etiology, and the diagnostic role of patch testing and preoperative screening.

Iron nanomedicines induce Toll-like receptor activation, cytokine production and complement activation.

Approximately a dozen of intravenous iron nanomedicines gained marketing authorization in the last two decades. These products are generally considered as safe, but have been associated with an increased risk for hypersensitivity-like reactions of which the underlying mechanisms are unknown. We hypothesized that iron nanomedicines can trigger the innate immune system. We hereto investigated the physico-chemical properties of ferric gluconate, iron sucrose, ferric carboxymaltose and iron isomaltoside 1000 and comparatively studied their interaction with Toll-like receptors, the complement system and peripheral blood mononuclear cells. Two out of four formulations appeared as aggregates by Scanning Transmission Electron Microscopy analysis and were actively taken up by HEK293T- and peripheral blood mononuclear cells in a cholesterol-dependent manner. These formulations triggered invitro activation of intracellular Toll-like receptors 3, -7 and -9 in a dose- and serum-dependent manner. In parallel experiments, we determined that these compounds activated the complement system. Finally, we found that uptake of aggregation-prone iron nanomedicines by peripheral blood mononuclear cells in whole blood induced production of the proinflammatory cytokine IL-1β, but not IL-6.

Immunomodulatory impression of anti and pro-inflammatory cytokines in relation to humoral immunity in human scabies.

The chief manifestations of scabies are mediated through hypersensitivity-like reactions and immune responses which are so far not well understood and remain poorly characterized. The aim of this study is to investigate the role of inflammatory cytokines in relation to humoral immunity in patients with scabies. Serum levels of total IgE, specific IgG, IL-10, IL-6, INF-γ, and TNF-α were investigated in a cross-sectional study including 37 patients with manifestations suggestive of scabies and serologically positive for anti-Sarcoptes IgG, in addition to 20 healthy controls. The median value of total IgE was 209 (range, 17-1219 IU/mL), reflecting its wide range within cases. IL-10 showed significant higher levels (287 ±: 139) in cases than in controls (17.4 ± 11.32). A positive correlation was reported between total IgE and severity of manifestations (r = 0.429, P <0.005). A significant positive correlation was observed between total IgE and both IgG and IL-6. On the contrary, a negative correlation was recorded between IL-6 and TNF-α which makes us suggested anti-inflammatory rather than pro-inflammatory effect of IL-6. Moreover, a negative correlation was noticed between the anti-inflammatory cytokine IL-10 and severity of manifestations, specific IgG, total IgE, and INF-γ. Therefore, the current study theorized a regulatory role of IL-10 in inflammatory responses of scabietic patients suggesting further future analysis of its therapeutic potential.

Targeting Leukocytes in Immune Glomerular Diseases

The glomerulonephritides are a collection of separate diseases with differing pathogeneses that collectively are common and important causes of renal disease. Effective, non-toxic immunomodulatory treatments for glomerulonephritis are lacking. This review will focus on our understanding of the role of leukocytes in immune glomerular disease, specifically in severe and rapidly progressive forms of glomerulonephritis, and provide examples of potential therapeutic targets. The glomerulus is a high flow, high pressure capillary plexus bounded by arterioles that is vulnerable to a variety of immune or inflammatory insults. The variety in the pathogenesis of different forms of glomerulonephritis, together with the capacity of both humoral and cellular effector arms to induce injury, means that understanding the pathogenesis of glomerulonephritis is necessary to effectively apply new treatments. Leukocytes are involved in the pathogenesis of glomerulonephritis at several levels, including the loss of tolerance, adaptive immune responses directed by T cells, cellular effectors inducing injury in delayed type hypersensitivity-like reactions, and by macrophage/neutrophil recruitment via the deposition of circulating immune complexes or in situ immune complexes. Evidence is emerging that anti-neutrophil cytoplasmic antibodies activate neutrophils, leading to glomerular capillaritis. Some therapeutic options limit local inflammation, while others modify the underlying pathogenetic immune response. Areas of current interest include the relationship between infiltrating and local cells, limiting effector cell activation, particularly macrophages; as well as understanding and targeting leukocyte recruitment to this unique vasculature. Modifying pathogenetic T or B cells also is a promising strategy in both systemic autoimmunity affecting the kidney and organ specific autoimmunity.

Hypersensitivity Cases Associated With Drug-Eluting Coronary Stents: A Review of Available Cases From the Research on Adverse Drug Events and Reports (RADAR) Project

We undertook the review of all available cases of hypersensitivity reactions after placement of a drug-eluting stent (DES) and classified potential causes. Six months after the approval of the first DES, the Food and Drug Administration (FDA) reported 50 hypersensitivity reactions after stent placement but later concluded these were due to concomitantly prescribed medications such as clopidogrel. Nevertheless, the FDA continued to receive reports of hypersensitivity. Reports available from April 2003 through December 2004 for hypersensitivity-like reactions associated with the sirolimus-eluting stent (CYPHER, Cordis Corp., Miami Lakes, Florida) and paclitaxel-eluting stent (TAXUS, Boston Scientific Corp., Natick, Massachusetts) were reviewed. Sources of reports included the FDA's adverse-device-event database, the published literature, and investigators from the Research on Adverse Drug/Device events And Reports (RADAR) project. Causality was assessed using standardized World Health Organization criteria. Of 5,783 reports identified for the DES in the FDA database, 262 unique events included hypersensitivity symptoms. Of these reports, 2 were certainly and 39 unlikely caused by clopidogrel and 1 was certainly, 9 probably, and 13 unlikely caused by the DES. From all sources, we identified 17 distinct cases that were probably or certainly caused by the stent, of which 9 had symptoms that lasted longer than four weeks. Four autopsies confirmed intrastent eosinophilic inflammation, thrombosis, and lack of intimal healing. The FDA reports and autopsy findings suggest that DES may be a cause of systemic and intrastent hypersensitivity reactions that, in some cases, have been associated with late thrombosis and death.

A pilot trial of chronic low-dosegranulocyte-macrophage colony-stimulating factor therapy in patients with intensively pretreated breast or female genital tract cancer

2537 Background: Prolonged low-dose (PLD) granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment which stimulates dendritic cell differentiation has been successfully used in patients (pts) with stage III-IV melanoma. However, data of PLD GM-CSF therapy in other tumors are still lacking. This pilot trial was thus initiated in order to evaluate both the efficacy and tolerabilty of PLD GM-CSF in pts with various heavily pretreated solid malignancies. Methods: 16 pts failing 2–7 prior (median, 4) chemotherapies were included with: metastatic breast cancer (MBC), n=6; recurrent ovarian carcinoma (ROC), n=8; metastatic endometrial carcinoma (MEC), n=1; recurrent cervical cancer (RCC, n=1). PLD GM-CSF (Leukine®) was delivered subcutaneously at a daily starting dose of 125 μg. The treatment was monitored by weekly whole blood cell counts (WBC). GM-CSF was increased at 25 μg increments until a maximum of 200 μg or when mild leukocytosis (i. e. 10–20 G/l) was achieved. Therapy was continued until progression or refusal by the pts. Response was assessed using either the common ECOG score (in 13 pts with measurable disease) or the Rustin criteria for CA 125-positive ROC (n=3). Results: All pts are evaluable for toxicity which was generally mild. In 2 pts, temporary dose-reduction was necessary due to mild skin reactions, which recovered spontaneously. Mild to moderate leucytosis was obvious in 7 pts. Hypersensitivity-like reactions did not occur nor did any pt require hospitalization to other life-threatening side effects. The objective response rate was 38% with 1 CR, 5 PR, 3 SD, and 7 PD. Response-duration ranged between 2 and 13 months, respectively. Until today, 8 pts are still alive. Notably, 5 of 6 responders but only 1 of 7 pts with PD developed leukocytosis during therapy. Conclusion: PLD GM-CSF exhibits substantial activity in heavily pretreated patients with either MBC or female genital tract cancer with mild leukocytosis being a potential predictor of response. Large-scaled clinical trials are now warranted to define the exact clinical value of this promising new strategy. No significant financial relationships to disclose.

Infliximab heals intestinal inflammatory lesions and restores growth in children with Crohn’s disease

Background. Infliximab has recently emerged as an efficacious agent for patients with severe Crohn’s disease. There are only few studies on the use of infliximab in children with Crohn’s disease: most of them are retrospective and deal only with the clinical response to the drug. Aim. We aimed at assessing the efficacy of infliximab in children and adolescents with severe Crohn’s disease recruited consecutively and followed up prospectively at a single centre. Clinical response, intestinal inflammation and growth pattern were evaluated. Patients. Eighteen patients entered into the trial (median age: 13 years, range: 6–18). They were referred because of severe symptoms with unsatisfactory response to conventional drugs. Methods. All patients received a baseline schedule of three intravenous infusions of infliximab (0, 2 and 6 weeks), 5 mg/kg. Paediatric Crohn’s Disease Activity Index, nutritional and activity serum variables, and ileocolonoscopy (with histology) were evaluated before and 8 weeks after beginning the therapy. All patients had long-term administration of azathioprine (2 mg/kg per day). After the baseline schedule, eight patients had a retreatment infusion of infliximab (5 mg/kg) every 8 weeks. Weight and height Z scores were measured before starting the baseline infusion programme and after 6 months. Results. After 8 weeks of therapy, there was a dramatic improvement in Paediatric Crohn’s Disease Activity Index, in nutritional and activity blood parameters, as well as in endoscopic and histological scores; 10 patients had a clinical remission ( Paediatric Crohn’s Disease Activity Index ≤10) , 12 patients had an inflammatory remission (decrease in both endoscopic and histological scores for ≥50% as compared to baseline values). In all patients corticosteroids were stopped within 4 weeks after beginning infliximab therapy. After 6 months of therapy, Paediatric Crohn’s Disease Activity Index was markedly lower than the pre-treatment value; however, it was significantly lower in patients on retreatment than in those who received only three infusions of infliximab. Furthermore, a significant increase in both weight and height Z scores was observed 6 months after beginning of the baseline infusion programme. Moreover, weight and height gain was significantly higher in patients on retreatment rather than in those treated only with three baseline infusions of infliximab. Mild infusion reactions controlled by slowing infusion rate were observed in four patients. No delayed hypersensitivity-like reactions were seen. Conclusions. In children with severe Crohn’s disease, infliximab is a safe and valuable treatment in inducing remission, in healing inflammatory lesions of the gut, as documented by endoscopy and histology, and in promoting growth. Retreatment infusions of infliximab may be suggested in childhood-onset Crohn’s disease to maintain remission and reverse growth failure.

Infliximab in the treatment of Crohn's disease: a user's guide for clinicians.

Induction therapy with infliximab is indicated for treatment of signs and symptoms, and induction and maintenance of remission in patients with moderate to severely active inflammatory Crohn's disease with an inadequate response to conventional therapy, and for reduction in the number of draining fistulas in patients with fistulizing Crohn's disease. Emerging indications for infliximab therapy in patients with Crohn's disease include maintenance of fistula improvement (reduction in the number of draining perianal or enterocutaneous fistulas) and complete fistula response (no draining fistulas) in patients with fistulizing Crohn's disease, steroid sparing in steroid-treated patients, early use in hospitalized patients who have not failed conventional medical therapy where there is either a severe clinical presentation or a rapid onset of action is desired, and in a variety of unusual and extra-intestinal manifestations of Crohn's disease. An infliximab dose of 5 mg/kg is recommended initally, but some patients who require maintenance dosing may benefit from increasing the infliximab dose over a range of 5-10 mg/kg. An induction regimen of 3 doses at 0, 2, and 6 weeks is the preferred dosing strategy for inducing remission. The optimal dosing interval for patients who require retreatment appears to be every 8 weeks for most patients. Concomitant immunosuppressive therapy with azathioprine, 6-mercaptopurine, or methotrexate may result in improved outcomes due to a reduction in the frequency of human anti-chimeric antibody formation, acute infusion reactions, and a reduced risk of delayed hypersensitivity-like reactions and formation of antinuclear antibodies. Pretreatment with diphenhydramine (and in selected cases of acetaminophen and, rarely, corticosteroids) is recommended in patients with a history of infusion reactions and patients at risk for delayed hypersensitivity-like reactions. Patients with evidence of active infection should not receive infliximab until the infection is adequately treated, and all patients should be screened for tuberculosis prior to initiating infliximab therapy.

Epidermal cells of a symbiosis-defective mutant of Lotus japonicus show altered cytoskeleton organisation in the presence of a mycorrhizal fungus.

The influence of the mycorrhizal fungus Gigaspora margarita on cytoskeleton organisation in epidermal cells of Lotus japonicus roots was compared between plants of the wild type Gifu and the mutant Ljsym4-2, in which the fungus is confined to the epidermal cells. Immunofluorescence labelling of plant microtubules and microfilaments showed only limited alterations in the peripheral cytoskeleton of epidermal cells during early stages of fungal interaction with the wild type. Later, microtubules and microfilaments enveloped the growing hypha, while the host cell nucleus moved close to the fungus. In contrast, epidermal cells of the mutant responded with disorganisation and disassembly of microtubules and microfilaments before and during fungal penetration attempts. The fungus penetrated only as far as to epidermal cells, whose cytoplasm became devoid of tubulin and actin, suggesting cell death. The close relationship between host cytoskeleton organisation and compatibility with the fungus suggests that a functional Ljsym4 gene is necessary for correct reorganisation of the epidermal cell cytoskeleton in the presence of the fungus and for avoiding hypersensitivity-like reactions.

The role of biological therapy in inflammatory bowel disease.

Substantial evidence suggests a central role for TNF-alpha in the pathogenesis of IBD. This molecular observation has been supported by clinical trials with anti-TNF therapies. The most extensively investigated among the various anti-TNF agents is infliximab. Clinical trials to date have demonstrated its efficacy in inducing remission in patients with moderately active, refractory Crohn's disease (CD) and in managing patients with CD complicated by fistulas. One advantage of infliximab is its rapid onset of action. However, as expected with most medications used to treat patients with IBD, the effect of infliximab is of limited duration, with the response lasting 2-3 months in most patients. The efficacy of repeated infusions of infliximab in maintaining remission in patients with inflammatory CD has been demonstrated in one trial to date. The results from the ACCENT I trial should soon be available. Many other important questions regarding the use of infliximab remain unanswered. These include the optimal schedules of infusions, the effect of concomitant therapy with aminosalicylates, immunomodulators and antibiotics, and the timing and indication of using infliximab in the general management algorithm of a patient with CD. Certainly, the efficacy of infliximab in the treatment of ulcerative colitis (UC) remains to be further explored in a controlled fashion, though preliminary uncontrolled data suggests efficacy. As experience with infliximab use accumulates, more data will become available regarding its safety with either short-term or long-term use. A large body of evidence exists regarding the short-term safety of infliximab. The concern of increased risk of hypersensitivity-like reactions with longer interval between treatments will also need to be addressed. The currently available data supports that infliximab is safe and well tolerated. Other anti-TNF therapies will also need to be investigated with the same rigor before widespread use can be advocated. In addition to these agents, advances in molecular engineering techniques have further expanded the array of biologic therapies available to treat IBD. These newer therapies hold promise in targeting specific pathways of the pathogenesis of IBD that may be different from all prior therapies. Certainly, the anti-TNF therapies and others aforementioned have taken the field of IBD into a new and exciting generation, the biological era. (c) 2001 Prous Science. All rights reserved.

Allergic reaction to a highly purified urinary follicle stimulating hormone preparation in controlled ovarian hyperstimulation for in vitro fertilization

We report a case of general hypersensitivity-like allergic reactions to intramuscular injections of highly purified urinary follicle stimulating hormone (uFSH-HP) successfully managed by using intramuscular recombinant FSH (rFSH).The patient underwent a first cycle of in vitro fertilization (IVF) and controlled ovarian hyperstimulation (COH) was achieved with a combination of gonadotropin releasing hormone against (GnRH-a) and uFSH-HP. Because, after oocyte recovery, no fertilization occurred, the couple subsequently entered an intracytoplasmic sperm injection (ICSI) program. During the COH, the woman developed general hypersensitivity-like allergic reactions with itching, redness and swelling. Although there was regular follicular growth, the allergic symptoms worsened and, on day 8 of COH, the stimulation cycle was suspended. A few months later, the patient entered a new ICSI cycle. COH was achieved by using a combination of GnRH-a and rFSH. The cycle was completed and the patient did not report any allergic reaction.To avoid allergic reaction to the protein components of the urine-derived FSH preparations, the use of rFSH is suggested in those patients who present local and/or general hypersensitivity-like allergic reactions.

Assessing the Role of the Biomaterial Aquavene in Patient Reactions to Landmark Midline Catheters

Landmark midline catheters (Menlo Care, Inc., Palo Alto, CA) provide peripheral venous access for the infusion of medications or fluids. They are constructed of an inner layer of polyurethane and an outer layer of the biomaterial Aquavene, a blend of polyurethane and polyethylene oxide to which butylated hyroxyanisole (BHA), butylated hydroxytoluene (BHT), and triallyl-s-triazine trione (TTT) are added. Once inside the vein, the Aquavene material becomes hydrated and the catheter swells resulting in minimal trauma to the vein. It is well recognized that some patients experience reactions to catheterization. Recent reports of hypersensitivity-like reactions in some patients catheterized with Landmark catheters have prompted the manufacturer to reexamine biocompatibility data and clinical data to assess whether Aquavene was the source of the patient responses. None of the biocompatibility studies provided by Menlo Care in support of U.S. registration and marketing of Aquavene-based catheters demonstrated any tendency for Aquavene or material extracted from Aquavene to invoke an immunological or toxicological response. Examination of potential catheter residuals revealed that significant amounts of BHA and BHT were unlikely to be released from the catheters during expected use. The amounts of polyethylene oxide and TTT expected to be released during the first few minutes after catheter insertion (when most of the patient reactions were reported) are almost 92,500 and 270,000 times lower, respectively, than nontoxic animal exposures. These analyses do not support chemically mediated toxicity as an explanation for the adverse events experienced by some patients. A review of the postmarket surveillance data on Aquavene-based catheters revealed that the reported events were not consistent with a hypersensitivity (immunogenic) response to the biomaterial. The rare reported adverse events tend to occur quickly, most often after flushing of the catheter, and resolve quickly, even when the catheter remains in place. Determining the frequency and severity of adverse events reported in association with the use of Landmark catheters will ultimately require a controlled prospective study, preferably one with a concurrent control group using alternative products.

OZONE-INDUCED IMPAIRMENT OF PULMONARY TYPE IV HYPERSENSITIVITY AND AIRWAY HYPERRESPONSIVENESS IN MICE

It is evident that exposure to ozone has toxic effects and can lead to lung function disturbances. Individuals suffering from COPD or asthma are groups especially at risk with respect to the effects of ozone. The majority of studies dealing with ozone effects on pulmonary allergy are restricted to immunoglobulin E (IgE) mediated allergy (type I allergy). It has been demonstrated that ozone can potentiate the induction as well as the effector phase of allergic asthma. Recently it has been demonstrated in animal models that in nonIgE-mediated "asthma," T cells may play a role also. It has been demonstrated in mice that low-molecular-weight compounds can induce pulmonary delayed-type hypersensitivitylike reactions that are Th-1 dependent. For this reason it might be suggested that in certain non-IgE-mediated pulmonary diseases Th-1 cells are involved. This in contrast to the classical allergic immune response in asthma where Th-2 cells are thought to be crucial. Effects of ozone on non-IgE-mediated pulmonary allergy induced by, for example, lowmolecular-weight compounds such as toluene diisocyanate, nickel, and trimellitic anhydride have never been studied. In this study we demonstrated that acute ozone exposure can inhibit pulmonary delayed-type hypersensitivity induced by low-molecular-weight compounds in the mouse. The inflammatory component and the hyperresponsiveness of the trachea that is induced by this type of hypersensitivity reaction are significantly inhibited by ambient ozone levels. As is true for the effects on type I allergy, this type of hypersensitivity can also be affected in the induction as well as the effector phase. The results of this study are in general opposite to the effect on type I allergic reactions. The effect, that is, suppression of type IV hypersensitivity, may be due to activation of Th-2 celldependent reactions that may be potentiated by ozone. This potentiation might lead to a downregulation of Th-1-mediated immunity because Th-1 and Th-2 cells modulate each other's activity. On the other hand, it can also be suggested that ozone has a direct effect on Th-1 cells or other cell types that are crucial for delayed-type hypersensitivity and related airway hyperresponsiveness in this animal model.

Ethanol metabolite acetic acid as causative agent for type-I hypersensitivity-like reactions to alcoholic beverages

Ethanol metabolite acetic acid as causative agent for type-I hypersensitivity-like reactions to alcoholic beverages

Ethanol metabolite acetic acid as causative agent for type‐I hypersensitivity‐like reactions to alcohohc beverages

Adverse reactions to alcoholic beverages are common and more frequently mediated by immunological mechanisms than previously thought. To elucidate relevant allergens in this context we studied patients with an informative medical history. This report describes a comprehensive allergological approach in a patient exhibiting type-I hypersensitivity-like reactions towards beverages and medication containing alcohol, and salad dressings with acetic acid. The ethanol metabolite acetic acid was found to yield positive prick test results in concentrations not eliciting reactions in healthy and atopic controls. Among other ethanol metabolites, acetic acid is a potential allergen in the context of hypersensitivity towards alcoholic beverages.