The effect of beta adrenergic blockade on bronchial sensitivity to acetyl-beta-methacholine in normal and allergic rhinitis subjects.

The effect of propranolol inhalation on sensitivity to methacholine inhalation was studied in normal and allergic rhinitis subjects to determine whether beta adrenergic blockade alters sensitivity to mediators in nonasthmatic atopic individuals. A partial beta adrenergic blockade is suggested as being instrumental in asthma. Hay fever patients studied showed similar effects and also developed asthma for the first time.     

Cytotoxicity of ionophore A23187 for basophils and other human blood cells.

The calcium ionophore A23187(A23) at concentrations exceeding 1 microgram/ml has been shown to be progressively cytotoxic for human blood basophils, neutrophils, lymphocytes, and erythrocytes. Toxicity to basophils was considered to be manifested by the increasing inability of 2-deoxyglucose (2DG) to inhibit histamine release (HR) at increasing concentrations of A23. The toxicity to neutrophils and lymphocytes was demonstrated by decreased lactate production (LP) after incubation with A23 of Ficoll-Hypaque fractions greatly enriched in each respective cell type. Red cells present in dextran-sedimented leukocytes were increasingly susceptible to lysis during washing subsequent to exposure to increasing concentrations of A23. A concentration of 4 microgram A23/ml, which is cytotoxic at 37 degrees C, produced optimal and noncytotoxic HR at 22 degrees C. It was possible to reduce A23 concentrations required for optimal HR by increasing Ca++ from 0.6 to 3 mM.     

Endogenous brain angiotensin II disrupts passive avoidance behavior in rats

The presence of angiotensinogen, the precursor of angiotensin II (ANG II), in brain tissue and in cerebrospinal fluid (CSF) allows stimulation of endogenous brain ANG II by renin. Passive avoidance tests were performed in female Wistar rats. The animals received an electrical shock after entering a black box on the first experimental day. Avoidance was tested every 24 h for 5 consecutive days. Renin in doses of 0.01 and 0.1 units was injected once into the lateral brain ventricles 2 min before the first test. CSF ANG II increased from 40 to 4547 and 5152 fmol per ml (means), respectively. A dose-dependent disruption of avoidance learning was observed, the frequency to enter the black box increasing from 11% (control) to 29% and 46%, and the latency decreasing from 165 (control) to 143 and 116 sec, respectively. These effects were statistically significant (P less than 0.001) for more than 24 h and returned to control levels after 48 to 120 h. Administration of the converting-enzyme inhibitor SQ 14225 i.v.t. prior to renin injections abolished the renin effects. Injections of renin given 22 h after learning were without effect.     

Molecular epidemiological and clinical aspects of hepatitis D virus in a unique triple hepatitis viruses (B,C, D) endemic community in Taiwan

The molecular epidemiological and clinical aspects of hepatitis D virus (HDV) in a unique HBV, HCV, and HDV triple virus endemic community in southern Taiwan were investigated. A total of 2,909 residents aged 45 or older were screened for hepatitis B surface antigen (HBsAg), anti-HCV antibody, and anti-HDV antibody (specifically for HBsAg-positive carriers). Factors that might be associated with HDV infection, viral nucleic acid detection, and genotyping of HBV, HCV, and HDV were investigated. The prevalence of HBsAg and anti-HCV were 12.6% (366/2,909) and 41.6% (1,227/2,909), respectively. For HBsAg carriers, 15.3% (56/366) were positive for anti-HDV assay. Living in a higher endemic district of HCV infection (odds ratio [OR] = 3.2; 95% confidence interval [CI] = 1.7-6.3), male gender (OR = 1.9; 95% CI = 1.1-3.6) and co-infection with HCV (OR = 1.8; 95% CI = 1.0-3.3) were significantly independent factors associated with HDV infection. The detection rate of HDV RNA among anti-HDV-positive patients was only 12.7% (7/55). The mean HBV titer of triple infection group was significantly lower than in the HBV/HDV co-infection group (2.23 vs 3.05 in log(10), copies/ml, P = 0.046). HCV RNA detection among the triple infection group showed 47.4% (9/19) viremia rate and viral loads of 579,121 IU/ml in median (16,803-1,551,190 IU/ml). The prevalent genotype of HBV was type B (23/25); HCV was 1b (7/9) and HDV was IIa/IIb (4/4). Only the presence of HCV RNA predicted the presence of elevated ALT significantly (OR = 25.0; 95% CI = 3.39-184.6). In conclusion, the geographical aggregation of HDV infection paralleled that of HCV infection in this community. HCV suppressed the replication of HBV among triple vital infection patients. HBV and HDV lapsed into a remission or nonreplicative phase in most cases, and HCV acted as a dominant factor in triple viral-infected individuals. Only the presence of HCV RNA was associated with elevated ALT values, but not HBV or HDV.     

Involvement of the open-source community in combating the worldwide COVID-19 pandemic: a review

Abstract

The ongoing COVID-19 pandemic is unprecedented in the modern age both due to its scale and its disruption to daily life throughout the world. Widespread social isolation and restrictions in the age of modern communicative technology, coupled with some early successes for makers, have united the open-source community towards a common goal in a way not previously seen. Local hospitals and care facilities are turning to makers to print essential consumable parts, such as simple visors, while in the hardest hit areas, critical pieces of medical technology are being fabricated. While important and effective innovations are appearing almost daily, there are also some worrying trends towards hobbyists attempting manufacture of complex medical devices with little understanding of the clinical or scientific rationale behind their design. The nature of the open-source community, an area of intensive innovation, fluidity, and experimentation, jars with the exacting standards of medical device regulation. Here, we review the involvement of rapid prototyping and the open-source community in the key areas of personal protective equipment (PPE), diagnostics, critical care technology, and information acquisition and sharing, highlighting where makers and hackers have clashed with medical device regulations, and areas where the system has worked well to facilitate change.     

Leukocyte histamine release in Hymenoptera-allergic patients. Correlation with skin test reactivity and changes following hyposensitization therapy

We have studied 46 Hymenoptera-allergic patients and 11 nonallergic controls by grading the severity of their sting reaction, determining their skin test reactivity, and performing human leukocyte histamine release with a commercial mixed stinging insect extract. A significant correlation was found between increasing severity of sting reaction and increasing skin test reactivity (p < 0.001). In $\text{41}\text{46}$ allergic patients from 15 to 100 per cent release of total cellular histamine occurred, whereas in the 11 nonallergic controls no greater than 10 per cent release of total cellular histamine was observed. Skin test reactivity correlated significantly with cell sensitivity in the allergic patients (p < 0.001). Following hyposensitization therapy, cell sensitivity generally did not change, but significant increases in antigen-neutralizing capacity (A.N.C.) of allergic serum did occur in $\text{11}\text{15}$ Hymenoptera-allergic patients.     

Bronchocentric granulomatosis: a complication of allergic bronchopulmonary aspergillosis.

Hypersensitivity to the fungal antigens of Aspergillus fumigatus may result in a spectrum of immune injury collectively known as allergic bronchopulmonary aspergillosis (ABPA). This report describes a 14-yr-old boy who presented clinical findings consistent with ABPA,including a history of asthma, blood eosinophilia, serum precipitins, and IgE antibodies to Aspergillus fumigatus. Sputum Aspergillus, pulmonary infiltrates, and dual types I and III skin reactions to Aspergillus fumigatus were observed also. Pathology of the resected right upper lobe revealed severe bronchial destruction with the findings of bronchocentric granulomatosis. Noninvasive septate fungal hyphae compatible with Aspergillus were identified. Cultures from sputum and surgical specimens grew Aspergillus and Mycobacterium intracellulare avium. The PPD-B (purified protein derivative-Batty) intradermal skin test produced a 6 mm induration (PPD-S was negative). The patient's condition has been well controlled with prednisone and several antituberculous drugs. In addition, inflammatory and immunologic parameters have begun to return to normal. The relationship between ABa and the atypical mycobacterial infection is not clear. The association of ABPA with the severe bronchial destruction seen in bronchocentric granulomatosis is emphasized to alert physicans to this serious sequelae of ABa seen in the asthmatic.     

Plasma steroid concentrations during alternate-day treatment with prednisone

Plasma steroid concentrations were measured in asthmatic children 24 and 48 hours after administration of alternate-day treatment with prednisone, and the results were compared with those of control patients who did not receive corticosteroid treatment as well as those of patients who were treated with prednisone each day. It was found that 24 hours after administration of prednisone in any dose, plasma steroid concentrations were significantly lower than those of the control group. The degree of suppression in plasma steroid concentration was less marked in patients who received treatment on alternate days than in those who received the same doses of prednisone each day. Within 48 hours after administration of alternate-day treatment, plasma steroid concentrations approached the values observed in the control group and were independent of the magnitude of the prednisone dose. Although alternateday steroid treatment was associated with transient and incomplete suppression of pituitary-adrenal function, patients whose therapy was changed from a daily to an alternate-day regimen sometimes exhibited prolonged suppression of adrenal cortical function.     

Interaction of human lung surfactant proteins A and D with mite (Dermatophagoides pteronyssinus) allergens

Human lung surfactant proteins A (SP-A) and D (SP-D) are both collagenous C-type lectins which appear to mediate antimicrobial activity by binding to carbohydrates on micro-organisms and to receptors on phagocytic cells. Purified native SP-A and SP-D, isolated from human bronchoalveolar lavage fluid, were found to bind to whole mite extracts (Dermatophagoides pteronyssinus) and the purified allergen Der p I, in a carbohydrate-specific and calcium-dependent manner. Binding was inhibited by ethylenediamine tetra-acetic acid (EDTA) as well as by maltose in the case of SP-D, or mannose in the case of SP-A. A recombinant polypeptide, which trimerized to form the neck region and carbohydrate recognition domains of SP-D, also inhibited the binding of native SP-D to the whole mite extract and Der p I. Both SP-A and SP-D did not bind to deglycosylated whole mite extracts or to recombinant Der p proteins, which lacked carbohydrate residues. These results suggest that the ability of surfactant proteins to bind certain allergens is mediated through their carbohydrate-recognition domains (CRDs) interacting with carbohydrate residues on the allergens. Moreover, SP-A and SP-D were found to inhibit allergen-specific IgE binding to the mite extracts either via steric hindrance or competitive binding. It is therefore possible that SP-A and SP-D may be involved in the modulation of allergen sensitization and/or the development of allergic reactions.