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Asthma is a common respiratory disorder in Canada for which biologics may be prescribed for poorly controlled illness. Treatment with biologics, however, is sometimes inappropriately discontinued due to misconceptions regarding their potential immunologic effects, and concerns surrounding their continued use in severe asthma during the COVID-19 pandemic continue to propagate. Biologics can still be administered in a majority of health and treatment conditions. With regard to cardiac-related issues such as hypertension or cardiovascular disease (CVD), there is no solid evidence that suggests biologics should be withheld, as the benefits of treatment outweigh the risks. Asthmatic patients on biologic treatment should also continue treatment if they have, or are currently being treated for, a respiratory infection, including COVID-19. Evidence also indicates the importance of maintaining asthma control to reduce the risk of severe COVID-19 infection. Biologic treatment can be administered in severe asthmatic patients with bronchiectasis, though further evidence is needed to better understand the benefits. Biologic treatment should be continued postsurgery to reduce postoperative respiratory complications, as well as throughout the course of pregnancy. Regarding concerns over vaccine administration, nearly all vaccines can be given without interruption of biologic treatment in patients with severe asthma or allergic conditions. Appropriate screening for respiratory illnesses, such as COVID-19, continues to be warranted in clinical practices to reduce the risk of transmission. As recommendations from public health and regulatory agencies have been lacking, this guidance document addresses the administration of biologics in different health circumstances and respiratory illness screening during the COVID-19 pandemic., Competing Interests: Dr. Dorscheid is on faculty at the University of British Columbia and is supported by the following grants: Canadian Institutes of Health Research, British Columbia Lung Association, and Michael Smith Foundation for Health Research. In addition, he has received speaking fees, travel grants, unrestricted project grants, and writing fees and is a paid consultant for pharmaceutical companies, including Sanofi Regeneron, Novartis Canada, AstraZeneca, GSK, and Valeo Pharma. He is an active member of the Canadian Thoracic Society, American Thoracic Society, European Respiratory Society, and the Allergen Research Network. Dr. Dorscheid does not believe that any of the disclosed potential conflicts represent true conflicts with respect to the information and recommendations included in this manuscript. Dr. Jason K Lee is supported by the following grants: AstraZeneca, GSK, Novartis, Genentech, Regeneron, and Sanofi. In addition, he is a paid consultant to the following pharmaceutical companies: Sanofi, Regeneron, AstraZeneca, and GSK and has received speaking fees/travel grants/writing fees from Sanofi, Regeneron, GSK, AstraZeneca, and Novartis. He owns stock in Moderna. He is an active member of the American Academy of Allergy, Asthma & Immunology, the American College of Allergy, Asthma and Immunology, and the Canadian Society of Allergy and Clinical Immunology. He regularly provides consultation globally for the aforementioned organizations. Dr. Lee does not believe that any of the disclosed potential conflicts represent true conflicts with respect to the information and recommendations included in this manuscript. Dr. Ramesh is an employee of the Royal Alexandra Hospital and Edmonton Respiratory Consultants and has received speaking fees for continuing medical education events and from GSK, AstraZeneca, and Novartis. He also reports participation in advisory committees for GSK, AstraZeneca, and Sanofi. Dr. Ramesh does not believe that any of his disclosed potential conflicts represent true conflicts with respect to the information and recommendations included in this manuscript. Dr. Greenwald is an Associate Professor at Queen's University and University of Toronto and Attending Physician at Humber Regional Hospital. He also conducts a private practice dealing with allergy, asthma, and immunology. He is an active member of provincial, national, and international professional bodies in allergy and immunology. He maintains his specialist certification with the Royal College of Physicians and Surgeons of Canada. He is a consultant/speaker/advisory board member for various pharmaceutical companies, specifically relevant are AstraZeneca, Merck, Novartis, AmerisourceBergen, and Genentech. Dr. Greenwald states that none of his disclosed conflicts represent known conflicts of interest relevant to the submitted manuscript. Dr. Del Carpio is an Associate Professor of Medicine at McGill University and an Attending Physician at the McGill University Health Center Department of Allergy and Immunology and practices in his own private clinic in downtown Montreal. In addition, he is a PI/consultant/speaker and has been part of advisory boards for Stallergenes Greer, Novartis, Merck, AstraZeneca, GSK, Genentech, Circassia, Tribute/Aralez, Teva, ALK, Mylan, Pediapharm, and Covis Pharma Canada. He is an active member of the European Academy of Allergy and Clinical Immunology, American College of Allergy and Immunology, Association of Allergists and Immunologists of Quebec, Canadian Society of Allergy and Clinical Immunology, and Royal College of Physicians. Dr. Del Carpio does not believe that any of the disclosed potential conflicts represent true conflicts with respect to the information and recommendations included in this manuscript., (Copyright © 2022 Delbert R. Dorscheid et al.)

Background: Models developed to predict hospital-acquired acute kidney injury (HA-AKI) in non-critically ill patients have a low sensitivity, do not include dynamic changes of risk factors and do not allow the establishment of a time relationship between exposure to risk factors and AKI. We developed and externally validated a predictive model of HA-AKI integrating electronic health databases and recording the exposure to risk factors prior to the detection of AKI., Methods: The study set was 36 852 non-critically ill hospitalized patients admitted from January to December 2017. Using stepwise logistic analyses, including demography, chronic comorbidities and exposure to risk factors prior to AKI detection, we developed a multivariate model to predict HA-AKI. This model was then externally validated in 21 545 non-critical patients admitted to the validation centre in the period from June 2017 to December 2018., Results: The incidence of AKI in the study set was 3.9%. Among chronic comorbidities, the highest odds ratios (ORs) were conferred by chronic kidney disease, urologic disease and liver disease. Among acute complications, the highest ORs were associated with acute respiratory failure, anaemia, systemic inflammatory response syndrome, circulatory shock and major surgery. The model showed an area under the curve (AUC) of 0.907 [95% confidence interval (CI) 0.902-0.908), a sensitivity of 82.7 (95% CI 80.7-84.6) and a specificity of 84.2 (95% CI 83.9-84.6) to predict HA-AKI, with an adequate goodness-of-fit for all risk categories (χ 2 = 6.02, P = 0.64). In the validation set, the prevalence of AKI was 3.2%. The model showed an AUC of 0.905 (95% CI 0.904-0.910), a sensitivity of 81.2 (95% CI 79.2-83.1) and a specificity of 82.5 (95% CI 82.2-83) to predict HA-AKI and had an adequate goodness-of-fit for all risk categories (χ 2 = 4.2, P = 0.83). An online tool (predaki.amalfianalytics.com) is available to calculate the risk of AKI in other hospital environments., Conclusions: By using electronic health data records, our study provides a model that can be used in clinical practice to obtain an accurate dynamic and updated assessment of the individual risk of HA-AKI during the hospital admission period in non-critically ill patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: The Madrid Acute Kidney Injury Prediction Score (MAKIPS) is a recently described tool capable of performing automatic calculations of the risk of hospital-acquired acute kidney injury (HA-AKI) using data from from electronic clinical records that could be easily implemented in clinical practice. However, to date, it has not been externally validated. The aim of our study was to perform an external validation of the MAKIPS in a hospital with different characteristics and variable case mix., Methods: This external validation cohort study of the MAKIPS was conducted in patients admitted to a single tertiary hospital between April 2018 and September 2019. Performance was assessed by discrimination using the area under the receiver operating characteristics curve and calibration plots., Results: A total of 5.3% of the external validation cohort had HA-AKI. When compared with the MAKIPS cohort, the validation cohort showed a higher percentage of men as well as a higher prevalence of diabetes, hypertension, cardiovascular disease, cerebrovascular disease, anaemia, congestive heart failure, chronic pulmonary disease, connective tissue diseases and renal disease, whereas the prevalence of peptic ulcer disease, liver disease, malignancy, metastatic solid tumours and acquired immune deficiency syndrome was significantly lower. In the validation cohort, the MAKIPS showed an area under the curve of 0.798 (95% confidence interval 0.788-0.809). Calibration plots showed that there was a tendency for the MAKIPS to overestimate the risk of HA-AKI at probability rates ˂0.19 and to underestimate at probability rates between 0.22 and 0.67., Conclusions: The MAKIPS can be a useful tool, using data that are easily obtainable from electronic records, to predict the risk of HA-AKI in hospitals with different case mix characteristics., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Background and Objective: To investigate the effects of antiangiogenic drugs on the transcription profile of acetylation genes in immortalized human retinal pigment epithelium cells (ARPE-19) in vitro., Materials and Methods: This in vitro study evaluated the effect of antiangiogenic drugs on the expression of histone acetylation genes on immortalized ARPE-19 cell cultures. ARPE-19 cells were cultured, plated, and treated for 24 hours with aflibercept (Eylea; Regeneron, Tarrytown, NY), ranibizumab (Lucentis; Genentech, South San Francisco, CA), or bevacizumab (Avastin; Genentech, South San Francisco, CA) at one (1×) or two times (2×) the concentrations of the clinical intravitreal dose. Untreated cells were used as controls. RNA was isolated, and real-time quantitative reverse transcription polymerase chain reaction analysis was performed on individual samples to quantify expression levels of genes associated with epigenetic acetylation pathways: histone acetyltransferase 1 (HAT1) and histone deacetylases 1, 6, and 11 (HDAC1, HDAC6, and HDAC11). Differences in cycle thresholds (ΔΔCts) were obtained, and folds were calculated using the formula 2 ^ΔΔCt . Main outcome measures were expression levels of candidate genes in treated versus untreated samples., Results: Compared with untreated cells, 1× ranibizumab-treated cells expressed higher levels of HDAC6, and 2× ranibizumab-treated cells expressed higher HDAC11 levels. Bevacizumab-treated (1×) cells had significant change in HDAC1, HDAC6, and HDAC11. In cultures treated with 2× bevacizumab, only HDAC11 expression levels were significantly affected compared with controls. Aflibercept-treated (1×) cells had changes in expression of HDAC1, HDAC6, and HDAC11. At 2× concentration, only HDAC11 was significantly changed., Conclusion: Our results show that antiangiogenic drugs can affect the transcription profile of genes regulating the histone acetylation status in ARPE-19 cells in vitro. This finding may have an implication in differential patient response to anti-vascular endothelial growth factor therapy by means of possible interactions between treatment and patient's epigenomic profile. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:S29-S33.]., (Copyright 2018, SLACK Incorporated.)

Mitochondrial (mt) DNA haplogroups, defined by specific single nucleotide polymorphism (SNP) patterns, represent populations of diverse geographic origins and have been associated with increased risk or protection of many diseases. The H haplogroup is the most common European haplogroup while the K haplogroup is highly associated with the Ashkenazi Jewish population. Transmitochondrial cybrids (cell lines with identical nuclei, but mtDNA from either H (n=8) or K (n=8) subjects) were analyzed by the Seahorse flux analyzer, quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry (IHC). Cybrids were treated with amyloid-β peptides and cell viabilities were measured. Other cybrids were demethylated with 5-aza-2'-deoxycytidine (5-aza-dC) and expression levels for APOE and NFkB2 were measured. Results show K cybrids have (a) significantly lower mtDNA copy numbers, (b) higher expression levels for MT-DNA encoded genes critical for oxidative phosphorylation, (c) lower Spare Respiratory Capacity, (d) increased expression of inhibitors of the complement pathway and important inflammasome-related genes; and (e) significantly higher levels of APOE transcription that were independent of methylation status. After exposure to amyloid-β1-42 peptides (active form), H haplogroup cybrids demonstrated decreased cell viability compared to those treated with amyloid-β42-1 (inactive form) (p<0.0001), while this was not observed in the K cybrids (p=0.2). K cybrids had significantly higher total global methylation levels and differences in expression levels for two acetylation genes and four methylation genes. Demethylation with 5-aza-dC altered expression levels for NFkB2, while APOE transcription patterns were unchanged. Our findings support the hypothesis that mtDNA-nuclear retrograde signaling may mediate expression levels of APOE, a key factor in many age-related diseases. Future studies will focus on identification of the mitochondrial-nuclear retrograde signaling mechanism(s) contributing to these mtDNA-mediated differences., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Brimonidine is a selective alpha-2 adrenergic agonist used to reduce intraocular pressure and it has been shown to have some neuroprotective effects. Hydroquinone (HQ) is a toxicant present in cigarette smoke, and other sources. In this study, we investigated the cyto-protective effects in vitro of Brimonidine on human retinal pigment epithelium cells (ARPE-19) and human retinal Müller cells (MIO-M1) that had been treated with HQ., Methods: Cells were pretreated for 6 h with different doses of Brimonidine tartrate 0.1% (1/2×, 1×, 5×, 10×), followed by a 24-h exposure to 100 μM of HQ, while the Brimonidine was still present. Assays were used to measure cell viability, mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS) production, and lactate dehydrogenase (LDH) release., Results: Brimonidine increased the cell viability at all concentrations studied in both cell lines studied. ΔΨm also improved at all Brimonidine doses in ARPE-19 cells and in the 5× and 10× dosages MIO-M1 cells. The ROS levels decreased at 1×, 5×, and 10× doses of Brimonidine in ARPE-19 but only at 10× on MIO-M1 cells. The 10×-Brimonidine ARPE-19 cells had decreased LDH release, but no LDH changes were observed on MIO-M1 cells., Conclusion: HQ-induced toxicity is mediated through mitochondrial damaging, oxidative stress-related and necrosis-related pathways; Brimonidine significantly prevented the mitochondrial damaging and oxidative stress-related effects but had little effect on blocking the necrosis component of HQ-toxicity. Brimonidine protective effects differ between the different retinal cell types and high concentrations of Brimonidine (10×) have minimal damaging effects on human retinal cells.

CKD and CKD-related mineral and bone disorders (CKD-MBDs) are associated with high cardiovascular and mortality risks. In randomized clinical trials (RCTs), no single drug intervention has been shown to reduce the high mortality risk in dialysis patients, but several robust secondary analyses point toward important potential beneficial effects of controlling CKD-MBD-related factors and secondary hyperparathyroidism. The advent of cinacalcet, which has a unique mode of action at the calcium-sensing receptor, represented an important step forward in controlling CKD-MBD. In addition, new RCTs have conclusively shown that cinacalcet improves achievement of target levels for all of the metabolic abnormalities associated with CKD-MBD and may also attenuate the progression of vascular and valvular calcifications in dialysis patients. However, a final conclusion on the effect of cinacalcet on hard outcomes remains elusive. Tolerance of cinacalcet is limited by frequent secondary side effects such as nausea, vomiting, hypocalcemia and oversuppression of parathyroid hormone, which may cause some management difficulties, especially for those lacking experience with the drug. Against this background, this review aims to summarize the results of studies on cinacalcet, up to and including the publication of the recent ADVANCE and EVOLVE RCTs, as well as recent post hoc analyses, and to offer practical guidance on how to improve the clinical management of the most frequent adverse events associated with cinacalcet, based on both currently available information and personal experience. In addition, attention is drawn to less common secondary effects of cinacalcet treatment and advisable precautions., (Copyright © 2016 by the American Society of Nephrology.)

Steroids have been extensively used to treat macular edema due to diabetic retinopathy, venous occlusive disease, ocular inflammation and, to a lesser extent, also in some cases of choroidal neovascularization. The various intraocular steroids that have been employed include dexamethasone, triamcinolone and fluocinolone. During the past few years, new drug delivery methods for corticosteroids have been developed and are now part of our therapeutic armamentarium. This chapter provides a brief description of the pharmacology, efficacy and adverse effects associated with the use of steroids in various retinal diseases., (© 2016 S. Karger AG, Basel.)

Background: The aim of this study is to evaluate the safety profile of Brilliant Blue G (BBG) with and without exposure to light (L) on three different retinal cell lines., Method: ARPE-19, R28 and MIO-M1 cells were treated with BBG: 0.125 mg/mL (0.5x clinical concentration), 0.25 mg/mL (1x) or 0.5 mg/mL (2x) with or without surgical illumination of halogen light exposure for 10 min, 15 min or 30 min. Cells were further cultured after 24 h and then analysed for cell viability, late stages of apoptosis and mitochondrial damage associated with early apoptosis using assays that measure trypan blue dye exclusion, increases in caspase-3/7 activity or changes in mitochondrial membrane potential (ΔΨm), respectively., Result: All three cell lines that were exposed to BBG in the presence or absence of light exposure for 30 min were found to have cell viability and caspase-3/7 activity levels similar to the untreated cultures. The mitochondrial membrane potential (ΔΨm) was decreased significantly at the 2x + L dose and 2x dose in all three retinal cell lines compared to their respective untreated control cells. At the lower doses of BBG, with or without exposure to light, the ΔΨm values were similar to the untreated control cultures., Conclusion: Exposure to BBG dye concentrations that are used clinically (0.125 mg/mL and 0.25 mg/mL) in the presence up to 30 min of surgically equivalent light intensity is safe for retinal cells., (© 2015 Royal Australian and New Zealand College of Ophthalmologists.)

Mitochondrial (mt) DNA can be classified into haplogroups representing different geographic and/or racial origins of populations. The H haplogroup is protective against age-related macular degeneration (AMD), while the J haplogroup is high risk for AMD. In the present study, we performed comparison analyses of human retinal cell cybrids, which possess identical nuclei, but mtDNA from subjects with either the H or J haplogroups, and demonstrate differences in total global methylation, and expression patterns for two genes related to acetylation and five genes related to methylation. Analyses revealed that untreated-H and -J cybrids have different expression levels for nuclear genes (CFH, EFEMP1, VEGFA and NFkB2). However, expression levels for these genes become equivalent after treatment with a methylation inhibitor, 5-aza-2'-deoxycytidine. Moreover, sequencing of the entire mtDNA suggests that differences in epigenetic status found in cybrids are likely due to single nucleotide polymorphisms (SNPs) within the haplogroup profiles rather than rare variants or private SNPs. In conclusion, our findings indicate that mtDNA variants can mediate methylation profiles and transcription for inflammation, angiogenesis and various signaling pathways, which are important in several common diseases., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Chagas disease vector control campaigns are being conducted in Latin America, but little is known about medium-term or long-term effectiveness of these efforts, especially in urban areas. After analyzing entomologic data for 56,491 households during the treatment phase of a Triatoma infestans bug control campaign in Arequipa, Peru, during 2003-2011, we estimated that 97.1% of residual infestations are attributable to untreated households. Multivariate models for the surveillance phase of the campaign obtained during 2009-2012 confirm that nonparticipation in the initial treatment phase is a major risk factor (odds ratio [OR] 21.5, 95% CI 3.35-138). Infestation during surveillance also increased over time (OR 1.55, 95% CI 1.15-2.09 per year). In addition, we observed a negative interaction between nonparticipation and time (OR 0.73, 95% CI 0.53-0.99), suggesting that recolonization by vectors progressively dilutes risk associated with nonparticipation. Although the treatment phase was effective, recolonization in untreated households threatens the long-term success of vector control.

Background: It has been recognized that cells do not respond equally to ultraviolet (UV) radiation but it is not clear whether this is due to genetic, biochemical or structural differences of the cells. We have a novel cybrid (cytoplasmic hybrids) model that allows us to analyze the contribution of mitochondrial DNA (mtDNA) to cellular response after exposure to sub-lethal dose of UV. mtDNA can be classified into haplogroups as defined by accumulations of specific single nucleotide polymorphisms (SNPs). Recent studies have shown that J haplogroup is high risk for age-related macular degeneration while the H haplogroup is protective. This study investigates gene expression responses in J cybrids versus H cybrids after exposure to sub-lethal doses of UV-radiation., Methodology/principal Findings: Cybrids were created by fusing platelets isolated from subjects with either H (n = 3) or J (n = 3) haplogroups with mitochondria-free (Rho0) ARPE-19 cells. The H and J cybrids were cultured for 24 hours, treated with 10 mJ of UV-radiation and cultured for an additional 120 hours. Untreated and treated cybrids were analyzed for growth rates and gene expression profiles. The UV-treated and untreated J cybrids had higher growth rates compared to H cybrids. Before treatment, J cybrids showed lower expression levels for CFH, CD55, IL-33, TGF-A, EFEMP-1, RARA, BCL2L13 and BBC3. At 120 hours after UV-treatment, the J cybrids had decreased CFH, RARA and BBC3 levels but increased CD55, IL-33 and EFEMP-1 compared to UV-treated H cybrids., Conclusion/significance: In cells with identical nuclei, the cellular response to sub-lethal UV-radiation is mediated in part by the mtDNA haplogroup. This supports the hypothesis that differences in growth rates and expression levels of complement, inflammation and apoptosis genes may result from population-specific, hereditary SNP variations in mtDNA. Therefore, when analyzing UV-induced damage in tissues, the mtDNA haplogroup background may be important to consider.

Purpose: To compare the safety profiles of antivascular endothelial growth factor (VEGF) drugs ranibizumab, bevacizumab, aflibercept and ziv-aflibercept on retinal pigment epithelium cells in culture., Methods: Human retinal pigment epithelium cells (ARPE-19) were exposed for 24 h to four anti-VEGF drugs at 1/2×, 1×, 2× and 10× clinical concentrations. Cell viability and mitochondrial membrane potential assay were performed to evaluate early apoptotic changes and rate of overall cell death., Results: Cell viability decreased at 10× concentrations in bevacizumab (82.38%, p=0.0001), aflibercept (82.68%, p=0.0002) and ziv-aflibercept (77.25%, p<0.0001), but not at lower concentrations. However, no changes were seen in cell viability in ranibizumab-treated cells at all concentrations including 10×. Mitochondrial membrane potential was slightly decreased in 10× ranibizumab-treated cells (89.61%, p=0.0006) and 2× and 10× aflibercept-treated cells (88.76%, 81.46%; p<0.01, respectively). A larger reduction in mitochondrial membrane potential was seen at 1×, 2× and 10× concentrations of bevacizumab (86.53%, 74.38%, 66.67%; p<0.01) and ziv-aflibercept (73.50%, 64.83% and 49.65% p<0.01) suggestive of early apoptosis at lower doses, including the clinical doses., Conclusions: At clinical doses, neither ranibizumab nor aflibercept produced evidence of mitochondrial toxicity or cell death. However, bevacizumab and ziv-aflibercept showed mild mitochondrial toxicity at clinically relevant doses., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: Determine hemoglobin levels and prevalence of anemia in pregnant women seen in health care centers of the Ministry of Health at national level., Materials and Methods: Cross-cut study where the database of the Information System on the Nutritional Health of Children under 5 and Pregnant Women (SIEN) were analyzed. 287 691 records of pregnant women examined at the health care centers of the Peruvian Ministry of Health in 2011 were included, hemoglobin levels corrected by height, age, gestational age, altitude and prevalence of anemia (light, moderate and serious) were analyzed. Descriptive statistics and the chi-square method were used., Results: Nationwide prevalence of anemia in pregnant women was 28.0%, with mild anemia being at 25.1%, moderate anemia at 2.6% and severe anemia at 0.2%. Hemoglobin levels are higher in older and younger women during the first months of pregnancy, prevalence of anemia decreases with altitude. Furthermore, prevalence is higher in the Highland regions. Huancavelica was the region with higher prevalence of anemia (53.6%), followed by Puno with 51.0%., Conclusions: Hemoglobin levels get higher as the mother gets older, and they go down in keeping with the gestation trimester and altitude. Huancavelica has the highest prevalence of anemia in pregnant women.

Background: Sublingual swallow immunotherapy has been increasingly recognized as a safe and efficacious alternative to parenteral specific immunotherapy., Objective: To determine the safety and efficacy of sublingual swallow immunotherapy ragweed allergen extract for rhinoconjunctivitis treatment starting just before and continuing through the ragweed pollen season., Methods: This randomized, double-blind, placebo-controlled study was performed in children and adults with a documented history of allergic rhinoconjunctivitis during ragweed season at 9 Canadian allergy centers. Active treatment was standardized extract of ragweed allergen administered as sublingual swallow drops at increasing doses starting shortly before the pollen season and maintenance doses continued daily during the season. Primary efficacy variables were symptom and medication scores, and secondary variables included global evaluation of efficacy and immunologic measurements., Results: Eighty-three patients were included in the safety analysis; 76 patients were included in the intent-to-treat analysis. Nine placebo recipients and 1 treatment recipient withdrew for lack of efficacy (P = .004). Nine patients in the treatment group withdrew because of adverse events, none serious (P = .003). Investigator evaluation of efficacy showed that significantly more patients improved and fewer deteriorated in the treatment group vs the placebo group (P = .047). Ragweed IgE and IgG4 levels increased significantly in treatment recipients vs placebo users (P < .001). Sneezing and nasal pruritus approached significant improvement in the treatment group vs the placebo group (P = .09 and .06, respectively). Quebec City experienced low pollen counts. Excluding Quebec City, significant improvement was seen for these 2 symptoms (P = .04)., Conclusion: Sublingual swallow immunotherapy seems to be safe and efficacious for ragweed rhinoconjunctivitis even when started immediately before the ragweed pollen season.

In a double-blind study, 185 patients with seasonal allergic rhinitis were randomly assigned to receive 10 mg of loratadine or placebo once daily for three days. On day 1 of treatment, the onset of relief of symptoms within 30 minutes of drug administration was reported by 13% of the loratadine-treated patients and by 4% of the placebo patients (P less than 0.05). At two hours after drug administration, 65% of the loratadine-treated patients and 48% of the placebo patients reported symptom relief. On day 3, the loratadine-treated patients reported a significantly greater relief of symptoms, and according to both physician and patient evaluations, the treatment response was significantly superior in the loratadine-treated than in the placebo patients. The incidence of sedation was 2% in the loratadine group and 1% in the placebo group.

Noberastine (NOB), a new histamine H1 antagonist, has potent and specific peripheral antihistaminic activity. To evaluate the efficacy and safety of NOB in ragweed seasonal allergic rhinitis, 250 eligible patients were randomized to one of four parallel, double-blind treatment groups: NOB, 10, 20, and 30 mg, or placebo, each administered once daily for 3 weeks. Rescue medication was prohibited. Efficacy parameters included global response rate (percentage of responders), physician visit, patient-diary symptom scores, and onset of action. Efficacy analyses used alpha = 0.0167 (adjusted for multiple comparisons). Efficacy parameters demonstrated universal superiority of NOB therapy over placebo therapy with statistical significance achieved frequently; no statistically or clinically significant separation was demonstrated among NOB-treated groups. Global-response rates for all active-treatment groups (range, 62.7% to 71.1%) were statistically significantly greater than rates for the placebo-treated group (39.6%). Median time to first relief of symptoms was within 2 to 4 hours for NOB-treated groups versus 72 hours for the placebo-treated group. No significant abnormalities in safety parameters were ascribed to NOB treatment. Incidence and severity of adverse experiences of NOB-treated groups were comparable in incidence and severity to placebo treatment. NOB treatment did not appear to cause weight gain or sedation. Once-daily NOB, 10, 20, and 30 mg, is equally and highly effective and safe in the symptomatic management of seasonal allergic rhinitis compared to placebo.

A total of 317 patients received loratadine, 10 mg once daily, terfenadine 60 mg twice daily, or placebo in a 14-day, double-blind, randomized study in seasonal allergic rhinitis. Four nasal and four nonnasal symptoms were evaluated. At the end point evaluation, mean total scores of combined nasal and nonnasal symptoms decreased from baseline (improved) 46%, 44%, and 35%, respectively, for loratadine, terfenadine, and placebo. The difference between loratadine and placebo treatment was significant (p = 0.03). Loratadine was particularly effective compared with placebo in relieving nasal discharge, sneezing, and itching/burning eyes. Therapeutic response to treatment was good or excellent in 66 (64%) of 103 loratadine-treated patients, 58 (56%) of 104 terfenadine-treated patients, and 48 (47%) of 102 placebo-treated patients. Adverse experiences reported during the study were usually mild or moderate and were not significantly different among the three treatment groups. Sedation (somnolence) was reported by 10 loratadine-treated patients, seven terfenadine-treated patients, and eight placebo-treated patients. Loratadine, 10 mg once daily, was comparable to terfenadine, 60 mg twice daily, and significantly superior to placebo in the symptomatic relief of seasonal allergic rhinitis.

A patient with biopsy-proven lymphomatoid granulomatosis of the brain as the sole manifestation of the disease is described. During 14 months of follow-up since surgical excision of the cerebral mass, no evidence of recurrent brain involvement or of extracranial lesions has been found. This case is unusual in the confinement of the disease to the central nervous system and in the favorable outcome following surgical treatment alone.

In a patient with classical rheumatoid arthritis and pericardial involvement, accelerated restriction of cardiac filling resulting from pericardial constriction developed. Pericardiectomy was necessary to relieve this condition. Examination of the synovial and pericardial fluid showed noteworthy decreases in total hemolytic complement (CH50) and C3 levels, while these were normal in the serum. Immunofluorescence staining of the pericardium showed plasma cell infiltration and immune deposit staining of pericardial vessels with IgG, IgM, IgA, or C3. These findings suggest that immune complexes deposition plays an important role in the pathogenesis of this condition.

A 52-year-old woman suffered an acute anaphylactic reaction to topically applied bacitracin. An investigation disclosed the presence of concurrent type I and IV hypersensitivity to bacitracin. We review five other cases of anaphylactic reactions to topical medications and describe the clinical characteristics common to all six cases.

Dexchlorpheniramine maleate 6 mg b.i.d. was compared with Terfenadine 60 mg b.i.d. for efficacy in controlling Ragweed Hay Fever symptoms, as well as tolerance and occurrence of adverse reactions. The study was a randomized, multicentric, parallel group, blind evaluator design which involved 174 patients equally divided, eighty-seven receiving dexchlorpheniramine and eighty-seven terfenadine, for a period of 2 weeks during the latter half of August and the first half of September 1983. The study indicated that dexchlorpheniramine at the doses tested, was significantly more effective in controlling hay fever symptoms than terfenadine.