Two Cases of H2-Receptor Antagonist Hypersensitivity and Cross-Reactivity

H2-receptor antagonists, such as cimetidine, ranitidine and famotidine, are some of the most commonly prescribed medications for gastric acid-related disorders. These compounds are generally well-tolerated and anaphylactic reactions to them are rare. Here, we report two cases of H2-receptor antagonist-induced anaphylactic reactions: the first presented with sudden dyspnea, sneezing, urticaria, and swelling of the eyelids after ranitidine intake. The second presented with sudden severe urticaria, facial swelling, chest discomfort, dizziness, and hypotension. Possible cross-reactivity with other H2-receptor antagonists was assessed by oral challenge and skin tests. To date, only a few reports addressing cross-reactivity among H2-receptor antagonists have been published. We review the literature and summarize the data available on drug cross-reactivity in H2-receptor antagonist hypersensitivity

Pneumopericardium as a Complication of Pericardiocentesis

Pneumopericardium is a rare complication of pericardiocentesis, occurring either as a result of direct pleuro-pericardial communication or a leaky drainage system. Air-fluid level surrounding the heart shadow within the pericardium on a chest X-ray is an early observation at diagnosis. This clinical measurement and process is variable, depending on the hemodynamic status of the patient. The development of a cardiac tamponade is a serious complication, necessitating prompt recognition and treatment. We recently observed a case of pneumopericardium after a therapeutic pericardiocentesis in a 20-year-old man with tuberculous pericardial effusion

Normative Values and Correlates of Mean Common Carotid Intima-Media Thickness in the Korean Rural Middle-aged Population: The Atherosclerosis RIsk of Rural Areas iN Korea General Population (ARIRANG) Study

Carotid intima-media thickness (CIMT) is considered as a surrogate marker for cardiovascular disease (CVD). We determined the normative value of CIMT and correlates of CVD risk factors and Framingham risk score (FRS) in Korean rural middle-aged population. We measured CIMT with a B-mode ultrasonography in 1,759 subjects, aged 40 to 70 yr, in a population-based cohort in Korea. A healthy reference sample (n = 433) without CVD, normal weight and normal metabolic parameters was selected to establish normative CIMT values. Correlates between CIMT and conventional CVD risk factors were assessed in the entire population. Mean values of CIMT (in mm) for healthy reference sample aged 40-49, 50-59, and 60-70 yr were 0.55, 0.59, and 0.66 for men and 0.48, 0.55, and 0.63 for women, respectively. In multivariate regression analysis, CIMT was correlated with older age, higher BMI, male gender, higher LDL-cholesterol level and history of diabetes mellitus. The mean CIMT was also correlated with FRS in both gender (r2 = 0.043, P < 0.01 for men; r2 = 0.142, P < 0.01 for women). We identified normative value of CIMT for the healthy Korean rural middle-aged population. The CIMT is associated with age, obesity, gender, LDL-cholesterol, diabetes mellitus and FRS

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Characterization of VRDN-001, a High Affinity and Potent Anti-IGF-1R Inhibitory Antibody in Development for the Treatment of Thyroid Eye Disease

VRDN-001 is an antagonist antibody to insulin-like growth factor-1 receptor (IGF-1R) under development by Viridian Therapeutics for Thyroid Eye Disease (TED). TED is characterized by recruitment of fibrocytes that express IGF-1R and TSHR into orbital tissues, where they mediate deposition of hyaluronan and expansion of orbital tissues. We evaluated the binding characteristics of VRDN-001 to IGF-1R and its potency for inhibition of IGF-1R phosphorylation

Mobile-Oriented Future Internet: Implementation and Experimentations over EU–Korea Testbed

Today’s mobility management (MM) architectures, such as Mobile Internet Protocol (IP) and Proxy Mobile IP, feature integration of data and control planes, as well as centralized mobility control. In the existing architecture, however, the tight integration of the data and control planes can induce a non-optimal routing path, because data packets are delivered via a central mobility agent, such as Home Agent and Local Mobility Anchor. Furthermore, the centralized mobility control mechanism tends to increase traffic overhead due to the processing of both data and control packets at a central agent. To address these problems, a new Internet architecture for the future mobile network was proposed, named Mobile-Oriented Future Internet (MOFI). The MOFI architecture was mainly designed as follows: (1) separation of data and control planes for getting an optimal data path; (2) distributed identifier–locator mapping control for alleviating traffic overhead at a central agent. In this article, we investigate the validity of the MOFI architecture through implementation and experimentations over the European Union (EU)–Korea testbed network. For this purpose, the MOFI architecture is implemented using OpenFlow and Click Modular Router over a Linux platform, and then it is evaluated over the locally and internationally configured EU–Korea testbed network. In particular, we operate two realistic communication scenarios over the EU–Korea testbed network. From the experimentation results, we can see that the proposed MOFI architecture can not only provide the mobility management efficiently, but also support the backward compatibility for the current IP version 6 (IPv6) applications and an Internet Protocol network

Noradrenaline inhibits pacemaker currents through stimulation of β(1)-adrenoceptors in cultured interstitial cells of Cajal from murine small intestine

1. Interstitial cells of Cajal (ICCs) are pacemaker cells that activate the periodic spontaneous inward currents (pacemaker currents) responsible for the production of slow waves in gastrointestinal smooth muscle. The effects of noradrenaline on the pacemaker currents in cultured ICCs from murine small intestine were investigated by using whole-cell patch-clamp techniques at 30°C. 2. Under current clamping, ICCs had a mean resting membrane potential of −58±5 mV and produced electrical slow waves. Under voltage clamping, ICCs produced pacemaker currents with a mean amplitude of −410±57 pA and a mean frequency of 16±2 cycles min(−1). 3. Under voltage clamping, noradrenaline inhibited the amplitude and frequency of pacemaker currents and increased resting currents in the outward direction in a dose-dependent manner. These effects were reduced by intracellular GDPβS. 4. Noradrenaline-induced effects were blocked by propranolol (β-adrenoceptor antagonist). However, neither prazosin (α(1)-adrenoceptor antagonist) nor yohimbine (α(2)-adrenoceptor antagonist) blocked the noradrenaline-induced effects. Phenylephrine (α(1)-adrenoceptor agonist) had no effect on the pacemaker currents, whereas isoprenaline (β-adrenoceptor agonist) mimicked the effect of noradrenaline. Atenolol (β(1)-adrenoceptor antagonist) blocked the noradrenaline-induced effects, but butoxamine (β(2)-adrenoceptor antagonist) did not. In addition, BRL37344 (β(3)-adrenoceptor agonist) had no effect on pacemaker currents. 5. 9-(Tetrahydro-2-furanyl)-9H-purine-6-amine (SQ-22536; adenylate cyclase inhibitor) and a myristoylated protein kinase A inhibitor did not inhibit the noradrenaline-induced effects and 8-bromo-cAMP had no effects on pacemaker currents. 8-Bromo-cGMP and SNAP inhibited pacemaker currents and these effects of SNAP were blocked by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a guanylate cyclase inhibitor). However, ODQ did not block the noradrenaline-induced effects. 6. Neither tetraethylammonium (a voltage-dependent K(+) channel blocker), apamin (a Ca(2+)-dependent K(+) channel blocker) nor glibenclamide (an ATP-sensitive K(+) channel blocker) blocked the noradrenaline-induced effects. 7. The results suggest that noradrenaline-induced stimulation of β(1)-adrenoceptors in the ICCs inhibits pacemaker currents, and that this is mediated by the activation of G-protein. Neither adenylate cyclase, guanylate cyclase nor a K(+) channel-dependent pathway are involved in this effect of noradrenaline

Deoxycholic acid inhibits pacemaker currents by activating ATP-dependent K(+) channels through prostaglandin E(2) in interstitial cells of Cajal from the murine small intestine

1. We investigated the role of deoxycholic acid in pacemaker currents using whole-cell patch-clamp techniques at 30°C in cultured interstitial cells of Cajal (ICC) from murine small intestine. 2. The treatment of ICC with deoxycholic acid resulted in a decrease in the frequency and amplitude of pacemaker currents and increases in resting outward currents. Also, under current clamping, deoxycholic acid produced the hyperpolarization of membrane potential and decreased the amplitude of the pacemaker potentials. 3. These observed effects of deoxycholic acid on pacemaker currents and pacemaker potentials were completely suppressed by glibenclamide, an ATP-sensitive K(+) channel blocker. 4. NS-398, a specific cyclooxygenase-2 (COX-2) inhibitor, significantly inhibited the deoxycholic acid-induced effects. The treatment with prostaglandin E(2) (PGE(2)) led to a decrease in the amplitude and frequency of pacemaker currents and to an increase in resting outward currents, and these observed effects of PGE(2) were blocked by glibenclamide. 5. We next examined the role of deoxycholic acid in the production of PGE(2) in ICC, and found that deoxycholic acid increased PGE(2) production through the induction of COX-2 enzyme activity and its gene expression. 6. The results suggest that deoxycholic acid inhibits the pacemaker currents of ICC by activating ATP-sensitive K(+) channels through the production of PGE(2)