scholarly journals Early Introduction of Multi-Allergen Mixture for Prevention of Food Allergy

Author(s):  
A. Zoe Quake ◽  
Taryn Audrey Liu ◽  
Rachel D’Souza ◽  
Katherine G Jackson ◽  
Margie Woch ◽  
...  

The incidence and prevalence of food allergy (FA) are increasing. While several studies have established the safety and efficacy of early introduction of single allergens in infants for the prevention of FA, the exact dose, frequency, and number of allergens that can be safely introduced to infants particularly in those at high or low risk of atopy are still unclear. This 1-year study evaluated the safety of early introduction of single foods (milk, egg, or peanut), vs. two foods (milk/egg, egg/peanut, milk/peanut), vs. multiple foods (milk/egg/peanut/cashew/almond/shrimp/walnut/wheat/fish/soy at low, medium, or high doses) vs no early introduction in infants between 4-6 months of age. At the end of the study, they were evaluated for plasma biomarkers associated with food reactivity with standardized blood tests. Two to four years after the start of the study, participants were evaluated by standardized food challenges. The serving sizes for the single, double, and low dose mixtures were 300 mg total protein per day. The serving sizes for the medium and high dose mixture was 900 mg and 3000 mg total protein, respectively. Equal parts of each protein were used for double or mixture foods. All infants were breastfed until at least 6 months of age. Results demonstrate that infants at either high or low risk for atopy were able to tolerate early introduction of multiple allergenic foods with no increases in any safety issues, including eczema, FA, or food protein induced enterocolitis. The mixtures of foods at either low, medium, or high doses demonstrated trends for improvement in food challenge reactivity and plasma biomarkers compared to single and double food introductions. The results of this study suggest that early introduction of foods, particularly simultaneous mixtures of many allergenic foods is efficacious for preventing FA and can occur safely.

2020 ◽  
Vol 41 (1) ◽  
pp. e11-e18 ◽  
Author(s):  
Pınar Gur Cetinkaya ◽  
Melike Kahveci ◽  
Betül Karaatmaca ◽  
Saliha Esenboga ◽  
Umit Murat Sahiner ◽  
...  

Background: Food protein-induced allergic proctocolitis (FPIAP) is a non‐immunoglobulin E (IgE) mediated food allergy that typically presents with blood-mixed mucoid stool. Objective: To identify the predictors that affect the tolerance development in infants with FPAIP and laboratory as well as clinical differences between patients with early and with late tolerance. Methods: A total of 185 infants with FPIAP were included. The patients were grouped and analyzed based on laboratory tests and clinical characteristics. Results: The median (interquartile range [IQR]) age of onset of symptoms was 2.0 months (1.0‐3.0 months). Symptoms began in severe cases in patients (n = 23) at a younger median (IQR) age (1.5 months [0.7‐2.0 months]) than the group with nonsevere presentation (median 2.0 months [IQR 1.5‐3.0 months]) (p < 0.001). The frequency of neutropenia (<1500/mm3) (p = 0.045) and eosinophilia (450 mm3) (p = 0.018) was increased in severe cases. Concomitant IgE-related food allergy (odds ratio [OR] 3.595 [95% confidence interval {CI}, 1.096‐11.788], p = 0.035), non‐IgE-mediated multiple food allergy (OR 3.577 [95% CI, 1.595‐8.018], p = 0.002), feeding with cow's milk‐based formula (at least once during infancy) (OR 2.517 [95% CI, 1.188‐5.333], p = 0.016), and late complementary feeding (OR 5.438 [95% CI, 2.693‐10.981], p < 0.001) were the predictors for late tolerance development. The estimated optimal cutoff value for introduction of complementary foods for the resolution of allergy was 5.5 months, with 69.4% sensitivity, 74.4% specificity, and an area under the curve of 0.737 (95% CI, 0.626‐0.812) (p < 0.001). Conclusion: This study showed that the early introduction of complementary feeding accelerates tolerance development in FPAIP. A longer duration of an elimination diet has no impact on the resolution of allergy. Physicians should consider conservative avoidance measures and earlier introduction of complementary feeding in FPIAP.


1958 ◽  
Vol 02 (01/02) ◽  
pp. 111-124 ◽  
Author(s):  
E Deutsch ◽  
K Martiny

Summary1. Normal platelets are necessary for induction of normal clot retraction.2. Serotonin does not induce retraction in human platelet-free plasma-clots or enhance clot firmness as measured in the coagulogram.3. Serotonin does not improve clot retraction or firmness in plasma clots with sub-optimal platelet counts.4. Methylserotonin inhibits clot retraction of platelet-rich plasma to a certain extent in moderate doses, whereas, high doses are ineffective. BOL 148 has a similar, but less significant action. There is a possibility that these effects are specific antiserotonin-effects.5. LSD 25 was ineffective in all concentrations used.6. Largactil and reserpin inhibit retraction in high doses. There seems to be a non specific effect caused by the high dose.7. Reserpine does not release a retraction-inducing agent from the platelets, which could be detected in the centrifuged platelet-free plasma used for the incubation.8. Serotonin does not replace the retraction-cofactor of Hartert, or the dialyzable factor of Lüscher in synthetic clotting substrates.9. Serotonin is of no essential value in inducing normal retraction of human plasma clots.


2019 ◽  
Vol 40 (6) ◽  
pp. 450-452 ◽  
Author(s):  
Ashley L. Devonshire ◽  
Rachel Glick Robison

Primary prevention and secondary prevention in the context of food allergy refer to prevention of the development of sensitization (i.e., the presence of food-specific immunoglobulin E (IgE) as measured by skin-prick testing and/or laboratory testing) and sensitization plus the clinical manifestations of food allergy, respectively. Until recently, interventions that target the prevention of food allergy have been limited. Although exclusive breast-feeding for the first 6 months of life has been a long-standing recommendation due to associated health benefits, recommendations regarding complementary feeding in infancy have significantly changed over the past 20 years. There now is evidence to support early introduction of peanut into the diet of infants with egg allergy, severe atopic dermatitis, or both diagnoses, defined as high risk for peanut allergy, to try to prevent development of peanut allergy. Although guideline-based recommendations are not available for early introduction of additional allergenic foods, this topic is being actively studied. There is no evidence to support additional dietary modification of the maternal or infant diet for the prevention of food allergy. Similarly, there is no conclusive evidence to support maternal avoidance diets for the prevention of food allergy.


Author(s):  
Mona Aslani ◽  
Arman Ahmadzadeh ◽  
Zahra Aghazadeh ◽  
Majid Zaki-Dizaji ◽  
Laleh Sharifi ◽  
...  

Background: : Based on the encouraging results of phase III clinical trial of β-D-mannuronic acid (M2000) (as a new anti-inflammatory drug) in patients with RA, in this study, we aimed to evaluate the effects of this drug on the expression of chemokines and their receptors in PBMCs of RA patients. Methods:: PBMCs of RA patients and healthy controls were separated and the patients' cells were treated with low, moderate and high doses (5, 25 and 50 μg/mL) of M2000 and optimum dose (1 μg/mL) of diclofenac, as a control in RPMI-1640 medium. Real-time PCR was used for evaluating the mRNA expression of CXCR3, CXCR4, CCR2, CCR5 and CCL2/MCP-1. Cell surface expression of CCR2 was investigated using flow cytometry. Results:: CCR5 mRNA expression reduced significantly, after treatment of the patients' cells with all three doses of M2000 and optimum dose of diclofenac. CXCR3 mRNA expression down-regulated significantly followed by treatment of these cells with moderate and high doses of M2000 and optimum dose of diclofenac. CXCR4 mRNA expression declined significantly after treatment of these cells with moderate and high doses of M2000. CCL2 mRNA expression significantly reduced only followed by treatment of these cells with high dose of M2000, whereas, mRNA and cell surface expressions of CCR2 diminished significantly followed by treatment of these cells with high dose of M2000 and optimum dose of diclofenac. Conclusion:: According to our results, M2000 through the down-regulation of chemokines and their receptors may restrict the infiltration of immune cells into the synovium.


Author(s):  
Riitta Niinimäki ◽  
Henri Aarnivala ◽  
Joanna Banerjee ◽  
Tytti Pokka ◽  
Kaisa Vepsäläinen ◽  
...  

Abstract Purpose Low doses of folinic acid (FA) rescue after high-dose methotrexate (HD-MTX) have been associated with increased toxicity, whereas high doses may be related to a decreased antileukemic effect. The optimal dosage and duration of FA rescue remain controversial. This study was designed to investigate, whether a shorter duration of FA rescue in the setting of rapid HD-MTX clearance is associated with increased toxicity. Methods We reviewed the files of 44 children receiving a total of 350 HD-MTX courses during treatment for acute lymphoblastic leukemia according to the NOPHO ALL-2000 protocol. Following a 5 g/m2 HD-MTX infusion, pharmacokinetically guided FA rescue commenced at hour 42. As per local guidelines, the patients received only one or two 15 mg/m2 doses of FA in the case of rapid MTX clearance (serum MTX ≤ 0.2 μmol/L at hour 42 or hour 48, respectively). Data on MTX clearance, FA dosing, inpatient time, and toxicities were collected. Results Rapid MTX clearance was observed in 181 courses (51.7%). There was no difference in the steady-state MTX concentration, nephrotoxicity, hepatotoxicity, neutropenic fever, or neurotoxicity between courses followed by rapid MTX clearance and those without. One or two doses of FA after rapid MTX clearance resulted in a 7.8-h shorter inpatient time than if a minimum of three doses of FA would have been given. Conclusion A pharmacokinetically guided FA rescue of one or two 15 mg/m2 doses of FA following HD-MTX courses with rapid MTX clearance results in a shorter hospitalization without an increase in toxic effects.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1597.1-1597
Author(s):  
E. Treppo ◽  
M. Infantino ◽  
M. Benucci ◽  
V. Ravagnani ◽  
B. Palterer ◽  
...  

Background:Anti-3-hydroxy-3-methylglutaryl-coenzime A reductase (HMGCR) myopathy is a new entity, which has been clearly associated to statin use, even if it can be diagnosed in patients without a history of exposure to statin or even in the childhood (1).Objectives:The aim of the study is to describe the efficacy of a triple therapy regimen consisting in high-doses of intravenous immunoglobulins (IVIG), methotrexate (MTX), and glucocorticoids (GC) in 16 patients with Anti-HMGCR myopathy enrolled in 6 specialized centres.Methods:A total of 16 patients with anti-HMGCR myopathy (7 females; 9 males) were collected. Mean (±standard deviation) age at the onset of disease was 72.4±10.3 years old. All patients were diagnosed having anti-HMGCR myopathy [anti-HMGCR antibodies were measured by chemiluminescence assay (BioFlash, Inova, CA)] (2). Median follow-up was 29.5 months (interquartile range: 15.75-60 months). Anti-HMGCR antibodies were available in the follow-up in 8/16 patients.Results:Thirteen out of 16 patients (81.3%) had been exposed to statin (1/13 to red rice), 3/16 (18.7%) were not exposed. As induction therapy, 11/16 patients have been treated with triple therapy (high-dose IVIG, MTX and GC), 2/16 with double therapy (high-dose IVIG and GC), 2/16 have been treated with GC alone, the patient exposed to red rice resolved only with red rice suspension. Clinical remission and normalization of CPK values within month +24 were obtained in all the patients. All the patients were in remission at the last follow-up. Gradual improvement started soon from the first month, and among the 13 patients treated with an aggressive immunosuppresssive therapy including IVIG (13/13), GC (13/13) and methotrexate (11/13), 9/13 normalized the CPK value within 6 months. Clinical and laboratory response was accompanied by significant decrease or normalization of the anti-HMGCR antibody titer. All the patients were either not taking GC (56.3%), or were taking low doses of GC (43.7%) at the last follow-up. Four patients had stopped GC within 6 months. No serious side effects were recorded. After persistent remission, a maintenance immunosuppressive therapy was then administered. Only 3 relapses in 3 different cases were recorded, all of them during drug-free remission in long-term follow-up. Reinduction was again effective in all.Conclusion:Anti-HMGCR myopathy is a rare and serious myopathy which usually affects older people during statin treatment. After statin suspension, a rapid and sustained remission can be achieved by induction with a triple aggressive therapy consisting in medium-to high doses of GC, high-dose IVIG, and MTX (3). GC should be tapered as soon as possible. Relapse appears infrequent during maintenance treatment. Monitoring anti-HMGCR antibody titer may be clinically relevant.References:[1]AL Mammen et al. N Engl J Med. 2016;374:664-9[2]Musset L et al. Autoimmun Rev. 2016;15:983-93.[3]Aggarwal A et al. Scand J Rheumatol. 2019; 1-7.Acknowledgments:We thank MD Francesca Grosso and MD Valentina Mecheri from the University of Florence, MD Angela Zuppa and MD Chiara De Michelis, from San Martino Hospital, Genova, for their valued collaboration in data collectionDisclosure of Interests:Elena Treppo: None declared, Maria Infantino: None declared, Maurizio Benucci: None declared, Viviana Ravagnani: None declared, Boaz Palterer: None declared, Marina Grandis: None declared, Martina Fabris: None declared, Paola Tomietto: None declared, Mariangela Manfredi: None declared, Arianna Sonaglia: None declared, Maria Grazia Giudizi: None declared, Francesca Ligobbi: None declared, Daniele Cammelli: None declared, Paola Parronchi: None declared, Salvatore De Vita Consultant of: Roche, GSK, Speakers bureau: Roche, GSK, Novartis, Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer


1999 ◽  
Vol 90 (5) ◽  
pp. 1354-1362 ◽  
Author(s):  
Marc De Kock ◽  
Philippe Gautier ◽  
Athanassia Pavlopoulou ◽  
Marc Jonniaux ◽  
Patricia Lavand'homme

Background The rationale of this study was to compare high-dose epidural clonidine with a more commonly used agent, such as bupivacaine. This was performed to give a more objective idea of the relative analgesic potency of epidural clonidine. Methods Sixty patients undergoing intestinal surgery during propofol anesthesia were studied. At induction, the patients received epidurally a dose of 10 micrograms/kg [corrected] clonidine in 7 ml saline followed by an infusion of 6 micrograms [corrected] x kg(-1) x h(-1) (7 ml/h) (group 1, n = 20), a dose of 7 ml bupivacaine, 0.5%, followed by 7 ml/h bupivacaine, 0.25% (group 2, n = 20), or a dose of 7 ml bupivacaine, 0.25%, followed by 7 ml/h bupivacaine, 0.125% (group 3, n = 20). Intraoperatively, increases in arterial blood pressure or heart rate not responding to propofol (0.5 mg/kg) were treated with intravenous alfentanil (0.05 mg/kg). Additional doses of propofol were given to maintain an adequate bispectral index. The epidural infusions were maintained for 12 h. In cases of subjective visual analogue pain scores up to 5 cm at rest or up to 8 cm during coughing, the patients were given access to a patient-controlled analgesia device. Results During anesthesia, patients in group 1 required less propofol than those in groups 2 and 3 (78 [36-142] mg vs. 229 [184-252] mg and 362 [295-458] mg; P &lt; 0.05) and less alfentanil than patients in group 3 (0 [0-0] mg vs. 11 [6-20] mg; P &lt; 0.05). Analgesia lasted 380 min (range, 180-645 min) in group 1 versus 30 min (range, 25-40 min) in group 2 and 22 min (range, 12.5-42 min) in group 3 (P &lt; 0.05). There was no suggestion of a hemodynamic difference among the three groups except for heart rates that were significantly reduced in patients in group 1. Sedation scores were significantly higher in this group during the first 2 h postoperatively. Conclusion Our results show that high doses of epidural clonidine potentiate general anesthetics and provide more efficient postoperative analgesia than the two bupivacaine dosage regimens investigated.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Joe Schofield ◽  
Deborah Steven ◽  
Rebecca Foster ◽  
Catriona Matheson ◽  
Alexander Baldacchino ◽  
...  

Abstract Background Opioid prescribing for a range of health issues is increasing globally. The risk of fatal and non-fatal overdose is increased among people prescribed strong opioids: in high doses in the context of polypharmacy (the use of multiple medications at the same time), especially with other sedatives; and among people with multiple morbidities including cardiorespiratory, hepatic and renal conditions. This study described and quantified the prescribing of strong opioids, comorbidities and other overdose risk factors among those prescribed strong opioids, and factors associated with high/very high opioid dosage in a regional health authority in Scotland as part of a wider service improvement exercise. Methods Participating practices ran searches to identify patients prescribed strong opioids and their characteristics, polypharmacy, and other overdose risk factors. Data were anonymised before being analysed at practice and patient-level. Morphine Equivalent Doses were calculated for patients based on drug/dose information and classed as Low/Medium/High/Very High. Descriptive statistics were generated on the strong opioid patient population and overdose risk factors. The relationship between the prescribing of strong opioids and practice/patient-level factors was investigated using linear and logistic regression models. Results Eighty-five percent (46/54) of GP practices participated. 12.4% (42,382/341,240) of individuals in participating practices were prescribed opioids and, of these, one third (14,079/42,382) were prescribed strong opioids. The most common comorbidities and overdose risk factors among strong opioid recipients were pain (67.2%), cardiovascular disease (43.2%), and mental health problems (39.3%). There was a positive significant relationship between level of social deprivation among practice caseload and level of strong opioid prescribing (p < 0.001). People prescribed strong opioids tended to be older (mean 59.7 years) and female (8638, 61.4%) and, among a subset of patients, age, gender and opioid drug class were significantly associated with prescribing of High/Very High doses. Conclusions Our findings have identified a large population at potential risk of prescription opioid overdose. There is a need to explore pragmatic models of tailored interventions which may reduce the risk of overdose within this group and clinical practice may need to be tightened to minimise overdose risk for individuals prescribed high dose opioids.


1998 ◽  
Vol 4 (2) ◽  
pp. 63-69 ◽  
Author(s):  
O A Khan ◽  
H Jiang ◽  
P S Subramaniam ◽  
H M Johnson ◽  
S S Dhib-Jalbut

The interferons (IFN) are a family of complex proteins possessing antiviral, antiproliferative, and immunomodulatory activities. Two type 1 recombinant human IFN have been recently approved for the treatment of multiple sclerosis (MS). However, use of high dose type 1 IFN treatment in MS patients has been limited by dose-related toxicity. Ovine IFNt is a unique type 1 interferon discovered for its role in the animal reproductive cycle. It differs from other type 1 IFNs in that it is remarkably less toxic even at high concentrations, is able to cross species barriers, and is not inducible by viral infection. Ovine IFNt has been shown to be very effective in the treatment of animal models of MS. In this study, we examined the toxicity of OvIFNt on human T-cells at high doses and its immunregulatory properties at equivalent doses. Our experiments confirmed the remarkably non-toxic nature of OvIFNt on human cells at high concentrations as well as immunomodulating properties consistent with other type 1 IFNs including an antilymphoproliferative effect and inhibition of IFNg-induced HLA class II expression. These results suggest that OvIFNt could be developed into a potentially less toxic therapeutic option for immune-mediated disorders including MS.


2017 ◽  
Vol 7 (1) ◽  
pp. 171
Author(s):  
Hamid Reza Adeli Bhroz ◽  
Kazem Parivar ◽  
Iraj Amiri ◽  
Nasim Hayati Roodbari

Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism.Materials and Methods: In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).


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