Hemodynamic impact of isobaric levobupivacaine versus hyperbaric bupivacaine for subarachnoid anesthesia in patients aged 65 and older undergoing hip surgery

BackgroundThe altered hemodynamics, and therefore the arterial hypotension is the most prevalent adverse effect after subarachnoid anesthesia. The objective of the study was to determine the exact role of local anesthetic selection underlying spinal anesthesia-induced hypotension in the elderly patient. We conducted a descriptive, observational pilot study to assess the hemodynamic impact of subarachnoid anesthesia with isobaric levobupivacaine versus hyperbaric bupivacaine for hip fracture surgery.DescriptionHundred twenty ASA status I-IV patients aged 65 and older undergoing hip fracture surgery were enrolled. The primary objective of our study was to compare hemodynamic effects based on systolic blood pressure (SBP) and dyastolic blood pressure (DBP) values, heart rate (HR) and hemoglobin (Hb) and respiratory effects based on partial oxygen saturation (SpO2%) values. The secondary objective was to assess potential adverse events with the use of levobupivacaine versus bupivacaine. Assessments were performed preoperatively, at 30 minutes into surgery, at the end of anesthesia and at 48 hours and 6 months after surgery.Among intraoperative events, the incidence of hypotension was statistically significantly higher (p <0.05) in group BUPI (38.3%) compared to group LEVO (13.3%). There was a decrease (p <0.05) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at 30 minutes intraoperatively (19% in group BUPI versus 17% in group LEVO). SpO2% increased at 30 minutes after anesthesia onset (1% in group BUPI versus 1.5% in group LEVO). Heart rate (HR) decreased at 30 minutes after anesthesia onset (5% in group BUPI versus 9% in group L). Hemoglobin (Hb) decreased from time of operating room (OR) admission to the end of anesthesia (9.3% in group BUPI versus 12.5% in group LEVO). The incidence of red blood cell (RBC) transfusion was 13.3% in group BUPI versus 31.7% in group LEVO, this difference was statistically significant. Among postoperative events, the incidence of congestive heart failure (CHF) was significantly higher in group BUPI (8,3%). At 6 months after anesthesia, no differences were found.ConclusionsGiven the hemodynamic stability and lower incidence of intraoperative hypotension observed, levobupivacaine could be the agent of choice for subarachnoid anesthesia in elderly patients

Heteroreceptor complexes formed by dopamine D1, histamine H3 and N-methyl-D-aspartate glutamate receptors as targets to prevent neuronal death in Alzheimer's disease

Alzheimer’s disease (AD) is a neurodegenerative disorder causing progressive memory loss and cognitive dysfunction. Anti-AD strategies targeting cell receptors consider them as isolated units. However, many cell surface receptors cooperate and physically contact each other forming complexes having different biochemical properties than individual receptors. We here report the discovery of dopamine D , histamine H , and N-methylD-aspartate (NMDA) glutamate receptor heteromers in heterologous systems and in rodent brain cortex. Heteromers were detected by coimmunoprecipitation and in situ proximity ligation assays (PLA) in the rat cortex where H receptor agonists, via negative cross-talk, and H receptor antagonists, via cross-antagonism, decreased D receptor agonist signaling determined by ERK1/2 or Akt phosphorylation and counteracted D receptormediated excitotoxic cell death. Both D and H receptor antagonists also counteracted NMDA toxicity suggesting a complex interaction between NMDA receptors and D -H receptor heteromer function. Likely due to heteromerization, H receptors act as allosteric regulator for D and NMDA receptors. By bioluminescence resonance energy transfer (BRET), we demonstrated that D or H receptors form heteromers with NR1A/NR2B NMDA receptor subunits. D -H -NMDA receptor complexes were confirmed by BRET combined with fluorescence complementation. The endogenous expression of complexes in mouse cortex was determined by PLA and similar expression was observed in wild-type and APP/PS1 mice. Consistent with allosteric receptor-receptor interactions within the complex, H receptor antagonists reduced NMDA or D receptor-mediated excitotoxic cell death in cortical organotypic cultures. Moreover, H receptor antagonists reverted the toxicity induced by ß -amyloid peptide. Thus, histamine H receptors in D -H -NMDA heteroreceptor complexes arise as promising targets to prevent neurodegeneration

Molecular psychiatry of zebrafish

Due to their well-characterized neural development and high genetic homology to mammals, zebrafish (Danio rerio) have emerged as a powerful model organism in the field of biological psychiatry. Here, we discuss the molecular psychiatry of zebrafish, and its implications for translational neuroscience research and modeling central nervous system (CNS) disorders. In particular, we outline recent genetic and technological developments allowing for in vivo examinations, high-throughput screening and whole-brain analyses in larval and adult zebrafish. We also summarize the application of these molecular techniques to the understanding of neuropsychiatric disease, outlining the potential of zebrafish for modeling complex brain disorders, including attention-deficit/hyperactivity disorder (ADHD), aggression, post-traumatic stress and substance abuse. Critically evaluating the advantages and limitations of larval and adult fish tests, we suggest that zebrafish models become a rapidly emerging new field in modern molecular psychiatry research

Exercise and bone health across the lifespan

With ageing, bone tissue undergoes significant compositional, architectural and metabolic alterations potentially leading to osteoporosis. Osteoporosis is the most prevalent bone disorder, which is characterised by progressive bone weakening and an increased risk of fragility fractures. Although this metabolic disease is conventionally associated with ageing and menopause, the predisposing factors are thought to be established during childhood and adolescence. In light of this, exercise interventions implemented during maturation are likely to be highly beneficial as part of a long-term strategy to maximise peak bone mass and hence delay the onset of age- or menopause-related osteoporosis. This notion is supported by data on exercise interventions implemented during childhood and adolescence, which confirmed that weight-bearing activity, particularly if undertaken during peripubertal development, is capable of generating a significant osteogenic response leading to bone anabolism. Recent work on human ageing and epigenetics suggests that undertaking exercise after the fourth decade of life is still important, given the anti-ageing effect and health benefits provided, potentially occurring via a delay in telomere shortening and modification of DNA methylation patterns associated with ageing. Exercise is among the primary modifiable factors capable of influencing bone health by preserving bone mass and strength, preventing the death of bone cells and anti-ageing action provided

Development of a hypoallergenic recombinant parvalbumin for first-in-man subcutaneous immunotherapy of fish allergy.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.The FAST (food allergy-specific immunotherapy) project aims at developing safe and effective subcutaneous immunotherapy for fish allergy, using recombinant hypoallergenic carp parvalbumin, Cyp c 1.Preclinical characterization and good manufacturing practice (GMP) production of mutant Cyp (mCyp) c 1.Escherichia coli-produced mCyp c 1 was purified using standard chromatographic techniques. Physicochemical properties were investigated by gel electrophoresis, size exclusion chromatography, circular dichroism spectroscopy, reverse-phase high-performance liquid chromatography and mass spectrometry. Allergenicity was assessed by ImmunoCAP inhibition and basophil histamine release assay, immunogenicity by immunization of laboratory animals and stimulation of patients' peripheral blood mononuclear cells (PBMCs). Reference molecules were purified wild-type Cyp c 1 (natural and/or recombinant). GMP-compliant alum-adsorbed mCyp c 1 was tested for acute toxicity in mice and rabbits and for repeated-dose toxicity in mice. Accelerated and real-time protocols were used to evaluate stability of mCyp c 1 as drug substance and drug product.Purified mCyp c 1 behaves as a folded and stable molecule. Using sera of 26 double-blind placebo-controlled food-challenge-proven fish-allergic patients, reduction in allergenic activity ranged from 10- to 5,000-fold (1,000-fold on average), but with retained immunogenicity (immunization in mice/rabbits) and potency to stimulate human PBMCs. Toxicity studies revealed no toxic effects and real-time stability studies on the Al(OH)3-adsorbed drug product demonstrated at least 20 months of stability.The GMP drug product developed for treatment of fish allergy has the characteristics targeted for in FAST: i.e. hypoallergenicity with retained immunogenicity. These results have warranted first-in-man immunotherapy studies to evaluate the safety of this innovative vaccine.info:eu-repo/grantAgreement/EC/FP7/20187

Mortality and cause of death in hip fracture patients aged 65 or older - a population-based study

<p>Abstract</p> <p>Background</p> <p>The high mortality of hip fracture patients is well documented, but sex- and cause-specific mortality after hip fracture has not been extensively studied. The purpose of the present study was to evaluate mortality and cause of death in patients after hip fracture surgery and to compare their mortality and cause of death to those in the general population.</p> <p>Methods</p> <p>Records of 428 consecutive hip fracture patients were collected on a population-basis and data on the general population comprising all Finns 65 years of age or older were collected on a cohort-basis. Cause of death was classified as follows: malignant neoplasms, dementia, circulatory disease, respiratory disease, digestive system disease, and other.</p> <p>Results</p> <p>Mean follow-up was 3.7 years (range 0-9 years). Overall 1-year postoperative mortality was 27.3% and mortality after hip fracture at the end of the follow-up was 79.0%. During the follow-up, age-adjusted mortality after hip fracture surgery was higher in men than in women with hazard ratio (HR) 1.55 and 95% confidence interval (95% CI) 1.21-2.00. Among hip surgery patients, the most common causes of death were circulatory diseases, followed by dementia and Alzheimer's disease. After hip fracture, men were more likely than women to die from respiratory disease, malignant neoplasm, and circulatory disease. During the follow-up, all-cause age- and sex-standardized mortality after hip fracture was 3-fold higher than that of the general population and included every cause-of-death category.</p> <p>Conclusion</p> <p>During the study period, the risk of mortality in hip fracture patients was 3-fold higher than that in the general population and included every major cause of death.</p

Becoming a special educator – Finnish and Swedish students' views of their future profession

Peer reviewe

Impact of meteorological variation on hospital visits of patients with tree pollen allergy

<p>Abstract</p> <p>Background</p> <p>Climate change could affect allergic diseases, especially due to pollen. However, there has been no epidemiologic study to demonstrate the relationship between meteorological factors, pollen, and allergic patients. We aimed to investigate the association between meteorological variations and hospital visits of patients with tree pollen allergy.</p> <p>Methods</p> <p>The study subjects were adult patients who received skin prick tests between April and July from 1999 to 2008. We reviewed the medical records for the test results of 4,715 patients. Patients with tree pollen allergy were defined as those sensitized to more than 1 of 12 tree pollen allergens. We used monthly means of airborne tree pollen counts and meteorological factors: maximum/average/minimum temperature, relative humidity, and precipitation. We analyzed the correlations between meteorological variations, tree pollen counts, and the patient numbers. Multivariable logistic regression analyses were used to investigate the associations between meteorological factors and hospital visits of patients.</p> <p>Results</p> <p>The minimum temperature in March was significantly and positively correlated with tree pollen counts in March/April and patient numbers from April through July. Pollen counts in March/April were also correlated with patient numbers from April through July. After adjusting for confounders, including air pollutants, there was a positive association between the minimum temperature in March and hospital visits of patients with tree pollen allergy from April to July(odds ratio, 1.14; 95% CI 1.03 to 1.25).</p> <p>Conclusions</p> <p>Higher temperatures could increase tree pollen counts, affecting the symptoms of patients with tree pollen allergy, thereby increasing the number of patients visiting hospitals.</p

Temporomandibular joint dysfunction and orthognathic surgery: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Relations between maxillo-mandibular deformities and TMJ disorders have been the object of different studies in medical literature and there are various opinions concerning the alteration of TMJ dysfunction after orthognathic surgery. The purpose of the present study was to evaluate TMJ disorders changes before and after orthognathic surgery, and to assess the risk of creating new TMJ symptoms on asymptomatic patients.</p> <p>Methods</p> <p>A questionnaire was sent to 176 patients operated at the Maxillo-Facial Service of the Lille's 2 Universitary Hospital Center (Chairman Pr Joël Ferri) from 01.01.2006 to 01.01.2008. 57 patients (35 females and 22 males), age range from 16 to 65 years old, filled the questionnaire. The prevalence and the results on pain, sounds, clicking, joint locking, limited mouth opening, and tenseness were evaluated comparing different subgroups of patients.</p> <p>Results</p> <p>TMJ symptoms were significantly reduced after treatment for patients with pre-operative symptoms. The overall subjective treatment outcome was: improvement for 80.0% of patients, no change for 16.4% of patients, and an increase of symptoms for 3.6% of them. Thus, most patients were very satisfied with the results. However the appearance of new onset of TMJ symptoms is common. There was no statistical difference in the prevalence of preoperative TMJ symptoms and on postoperative results in class II compared to class III patients.</p> <p>Conclusions</p> <p>These observations demonstrate that: there is a high prevalence of TMJ disorders in dysgnathic patients; most of patients with preoperative TMJ signs and symptoms can improve TMJ dysfunction and pain levels can be reduced by orthognathic treatment; a percentage of dysgnathic patients who were preoperatively asymptomatic can develop TMJ disorders after surgery but this risk is low.</p