Orthostatic hypotension in internal medicine wards

Objectives: Most studies of orthostatic hypotension (OH) have focused on community-dwelling and institutionalized patient populations. Less is known about OH in hospitalized patients. Moreover, a comprehensive review of OH in internal medicine wards has not been published in the English literature. Our purpose is to provide current information regarding OH in internal medicine inpatients.

Methods: A comprehensive search of medical databases was performed for potentially relevant articles, using the following keywords: postural or orthostatic hypotension, with the combination of hospitalization or internal medicine. Inclusion criteria were: population of patients hospitalized for acute disorders in internal medicine or geriatric wards with a sample size of ≥50 and publication as an original full-length article in the English language. Data from 14 selected studies are reviewed, including: pathophysiology, evaluation, prevalence, manifestations, risk factors, prognosis, and management.

Results: OH is a common and often symptomatic disorder in elderly internal medicine patients. The prevalence of OH in this population ranges from 22–75%. There are substantial discrepancies between the studies reviewed regarding definitions and means of evaluating OH. OH in internal medicine wards is largely non-neurogenic and multifactorial. The main predisposing factors for OH are prolonged bed rest, hypertension, and heart failure. OH in internal medicine wards is managed mainly with non-pharmacologic interventions, and is frequently reversible.

Conclusions: In internal medicine inpatients, OH warrants attention because this disorder is common, potentially dangerous, and treatable. In the hospital setting, OH should be routinely assessed on ambulation, following the current guidelines for OH definition and meaning.     

Contrasting associations of polymorphisms in FcγRIIa and DC-SIGN with the clinical presentation of dengue infection in a Mexican population

Dengue virus (DENV) causes a spectrum of illness from asymptomatic infection, to a mild febrile illness, to occasional more severe complications including hemorrhage and shock. Dengue is endemic in the state of Morelos, Mexico. Two single nucleotide polymorphisms (SNPs), rs1801274 of FcγRIIa and rs4804803 of DC-SIGN, have been associated with protection from or susceptibility to severe dengue infection. Both of these polymorphisms are located in genes for receptors with important roles in dengue pathogenesis, and their relationship with the clinical presentation of dengue infection in Mexican populations is unknown. In this study, real-time PCR was used to characterize the distribution of rs1801274 and rs4804803 in subjects with asymptomatic dengue infection (n = 145), uncomplicated dengue (n = 67), and severe dengue (n = 36) in Morelos. In contrast with previous studies, the histidine (A) variant of rs1801274 was associated with more mild infection: carrying the histidine allele (either homozygous or heterozygous) was associated with protection from symptomatic infection compared with asymptomatic (OR 0.51, p = 0.038). Histidine homozygotes were also less likely to present severe dengue (OR 0.34, p = 0.05). Logistic regression models confirm this association (OR 0.48, p = 0.04) and also indicate that the G allele of rs4804803 is associated with symptomatic dengue (OR 2.3, p = 0.08), after accounting for other biological factors including history of infection. This variant was rare in this study population, with a frequency of 5.4%. These findings reflect the complexity of influences on the development of severe dengue infection. The inclusion of asymptomatic infections and adjusted case definitions likely do not explain the entire disparity with previous findings. Interactions with other polymorphisms may explain why the association of rs1801274 is reversed in this population compared to others. This study demonstrates the importance of genetic association studies in multiple genetically distinct populations.     

The decline of butterflies in Europe: Problems,significance, and possible solutions

We review changes in the status of butterflies in Europe, focusing on long-running population data available for the United Kingdom, the Netherlands, and Belgium, based on standardized monitoring transects. In the United Kingdom, 8% of resident species have become extinct, and since 1976 overall numbers declined by around 50%. In the Netherlands, 20% of species have become extinct, and since 1990 overall numbers in the country declined by 50%. Distribution trends showed that butterfly distributions began decreasing long ago, and between 1890 and 1940, distributions declined by 80%. In Flanders (Belgium), 20 butterflies have become extinct (29%), and between 1992 and 2007 overall numbers declined by around 30%. A European Grassland Butterfly Indicator from 16 European countries shows there has been a 39% decline of grassland butterflies since 1990. The 2010 Red List of European butterflies listed 38 of the 482 European species (8%) as threatened and 44 species (10%) as near threatened (note that 47 species were not assessed). A country level analysis indicates that the average Red List rating is highest in central and mid-Western Europe and lowest in the far north of Europe and around the Mediterranean. The causes of the decline of butterflies are thought to be similar in most countries, mainly habitat loss and degradation and chemical pollution. Climate change is allowing many species to spread northward while bringing new threats to susceptible species. We describe examples of possible conservation solutions and a summary of policy changes needed to conserve butterflies and other insects.     

The metabolic syndrome predicts cardiovascular mortality: a 13-year follow-up study in elderly non-diabetic Finns.

AIMS: The metabolic syndrome (MetS) is defined as a clustering of cardiovascular risk factors characterized by insulin resistance. We investigated the relationship of the MetS and its single components, defined by all six different criteria, with coronary heart disease (CHD), cardiovascular disease (CVD), and all-cause mortality in a prospective population-based study. METHODS AND RESULTS: The MetS was defined according to the World Health Organization (WHO), the European Group for the Study of Insulin Resistance (EGIR), the National Cholesterol Education Program (NCEP), the American College of Endocrinology (ACE), the International Diabetes Federation (IDF), and the American Heart Association (updated NCEP) criteria. We investgated the relationship of the MetS defined by aforementioned six criteria with CHD, CVD, and all-cause mortality with Cox regression analyses in a non-diabetic Finnish population of 1025 subjects, aged 65-74 years, during the 13-year follow-up. The MetS defined by all aforementioned criteria was associated with a statistically significant risk for CVD mortality when adjusted for all confounding variables (Hazards Ratios, HRs from 1.31 to 1.51). The MetS defined by the WHO, ACE, and IDF criteria was associated with an increased risk of CHD mortality (HRs from 1.42 to 1.58). There was no association between the MetS by any criteria and all-cause mortality. Of the single components of the MetS, the following predicted CVD mortality in multivariable models: impaired fasting glucose by the WHO, NCEP, and ACE criteria (HR 1.34) and by the IDF and updated NCEP criteria (HR 1.29); impaired glucose tolerance by the WHO and ACE criteria (HR 1.55); low HDL cholesterol by the EGIR criteria (HR 1.50) and by the NCEP, IDF, and updated NCEP criteria (HR 1.29); and microalbuminuria according to the WHO definition (HR 1.86). CONCLUSION: The MetS defined by all six current criteria predicts CVD mortality in elderly subjects. However, of the single components of the MetS, IFG, IGT, low HDL cholesterol, and microalbuminuria predicted CVD mortality with equal or higher HRs when compared with the different definitions of the MetS. Therefore, our study suggests that the MetS is a marker of CVD risk, but not above and beyond the risk associated with its individual components.     

New legal requirements for submission of product information to poisons centres in EU member states

Introduction: In the past eight years, the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) has been intensively involved in a European Commission led process to develop EU legislation on the information of hazardous products that companies have to notify to EU Poisons Centres (or equivalent “appointed bodies”). As a result of this process, the Commission adopted Regulation (EU) No 2017/542, amending the CLP Regulation by adding an Annex on harmonised product submission requirements.

Harmonised mixture information requirements: Detailed and consistent information on the composition of the hazardous product will become available to EU Poisons Centres (PC). The information will be submitted by companies to PCs (or equivalent “appointed bodies”) using a web-based software application or in-house software. Two new important features are introduced. Firstly, to be able to rapidly identify the product formula, a Unique Formula Identifier (UFI) on the product label links to the submitted information. Secondly, for better comparability of reports on poisonings between EU member states, a harmonised Product Categorisation System will specify the intended use of a product. Rapid product identification and availability of detailed composition information will lead to timely and adequate medical intervention. This may lead to considerable reduction in healthcare costs.

Additionally, for companies trading across the EU, costs of submission of this information will be reduced significantly.

Next steps: From 2017, an implementation period has started, consisting of a three-year period for stakeholders to implement the new requirements, followed by a gradual applicability for consumer products (2020), professional products (2021) and industrial use-only products (2024). Technical tools to generate the electronic format and the UFI together with guidance documents are expected to be made available by the end of 2017 by the European Chemicals Agency (ECHA). Guidance on interpretation of legal text and ECHA helpdesk support are planned to be ready at the end of 2018.     

Suppression of pro-inflammatory cytokine release by selective inhibition of inducible nitric oxide synthase in mucosal explants from patients with ulcerative colitis

BACKGROUND: In ulcerative colitis (UC), inflammatory damage is associated with increased production of pro-inflammatory cytokines and nitric oxide through the inducible nitric oxide synthase (iNOS) pathway. In an animal model of acute experimental colitis we have previously shown amelioration of inflammation with the highly selective iNOS inhibitor 1400W. The aim of the present study was to investigate the effects of selective iNOS inhibition on the production of pro-inflammatory cytokines by the colon mucosa in UC. METHODS: Inflamed and uninflamed mucosa from patients with severe UC were incubated with a highly selective iNOS inhibitor N-[3-(aminomethyl)benzyl]acetamidine (1400W), with a relatively selective cNOS inhibitor N(G)-nitro-L-arginine-methyl-esther (L-NAME), or with an NO-donor, S-nitroso-acetylpenicillamine (SNAP). Cytokine concentrations in the incubation medium were quantitated with ELISA. RESULTS: Compared to uninflamed mucosa there was an increase in iNOS protein and nitrotyrosine levels in inflamed mucosal samples. Immunolocalization of iNOS and nitrotyrosine showed their expression in inflammatory cells in the lamina propria. Expression of iNOS was also found in the epithelial brush border. Selective inhibition of iNOS suppressed the release of tumour necrosis factor alpha (TNF-alpha, by 66%) and interleukin-6 (IL-6, by 27%). The NO-donor, SNAP, augmented the secretion of TNF-alpha, IL-6 and IL-1-beta (by 62%, 52% and 175%, respectively) and decreased the release of IL-1 receptor antagonist (IL-1Ra, by 34%) by the inflamed mucosa. Moreover, in uninflamed samples, 1400W suppressed the production of TNF-alpha (by 69%) and incubation with SNAP decreased IL-6 concentrations by 48%. The cNOS over iNOS selective inhibitor L-NAME had no significant effects on the accumulation of cytokines. CONCLUSION: Selective inhibition of iNOS suppresses mucosal TNF-alpha and IL-6 release in active UC, whereas NO seems to exacerbate the inflammatory response. These results suggest that selective iNOS inhibition may have therapeutic promise in the treatment of UC.     

Leuprolide acetate induces structural and functional recovery of injured spinal cord in rats

Gonadotropin-releasing hormone (GnRH) and its synthetic analog leuprolide acetate, a GnRH agonist, have neurotrophic properties. This study was designed to determine whether administration of leuprolide acetate can improve locomotor behavior, gait, micturition reflex, spinal cord morphology and the amount of microglia in the lesion epicenter after spinal cord injury in rats. Rats with spinal cord compression injury were administered leuprolide acetate or saline solution for 5 weeks. At the 5^th week, leuprolide acetate-treated rats showed locomotor activity recovery by 38%, had improvement in kinematic gait and exhibited voiding reflex recovery by 60%, as compared with the 1^st week. By contrast, saline solution-treated rats showed locomotor activity recovery only by 7%, but voiding reflex did not recover. More importantly, leuprolide acetate treatment reduced microglial immunological reaction and induced a trend towards greater area of white and gray matter in the spinal cord. Therefore, leuprolide acetate has great potential to repair spinal cord injury.