Impact of the pericapsular nerve group (PENG) block on postoperative analgesia and functional recovery following total hip arthroplasty: a randomised, observer-masked, controlled trial.

The pericapsular nerve group (PENG) block is a novel regional anaesthesia technique that aims to provide hip analgesia with preservation of motor function, although evidence is currently lacking. In this single-centre, observer-masked, randomised controlled trial, patients undergoing total hip arthroplasty received pericapsular nerve group block or no block (control group). Primary outcome measure was maximum pain scores (0-10 numeric rating scale) measured in the first 48 h after surgery. Secondary outcomes included postoperative opioid consumption; patient mobilisation assessments; and length of hospital stay. Sixty patients were randomly allocated equally between groups. The maximum pain score of patients receiving the pericapsular nerve group block was significantly lower than in the control group at all time-points, with a median (IQR [range]) of 2.5 (2.0-3.7 [0-7]) vs. 5.5 (5.0-7.0 [2-8]) at 12 h; 3 (2.0-4.0 [0-7]) vs. 6 (5.0-6.0 [2-8]) at 24 h; and 2.0 (2.0-4.0 [0-5]) vs. 3.0 (2.0-4.7 [0-6]) at 48 h; all p < 0.001. Moreover, the pericapsular nerve group showed a significant reduction in opioid consumption, better range of hip motion and shorter time to ambulation. Although no significant difference in hospital length of stay was detected, our results suggest improved postoperative functional recovery following total hip arthroplasty in patients who received pericapsular nerve group block.

Expression and distribution of key proteins of the endocannabinoid system in the human seminal vesicles.

The endocannabinoid system (ECS), comprising the cannabinoid receptors (CBR), their ligands, and enzymes controlling the turnover of endocannabinoids, has been suggested to be involved in male reproductive function. As information is scarce on the expression of the ECS in human male reproductive tissues, this study aimed to investigate by means of molecular biology (RT-PCR) and immunohistochemistry/immunofluorescence the expression and distribution of CB1 and CB2, GPR55 (an orphan G protein-coupled receptor that recognises cannabinoid ligands) and FAAH (isoforms 1 and 2) in the human seminal vesicles (SV). The specimens expressed PCR products corresponding to CB1 (66 bp), CB2 (141 bp), GPR55 (112 bp), FAAH1 (260 bp) and FAAH2 (387 bp). Immumohistochemistry revealed dense expression of CB1, CB2 and GPR55 located to the pseudo-stratified columnar epithelium and varicose nerves (also characterised by the expression of vasoactive intestinal polypeptide and calcitonin gene-related peptide). Cytosolic staining for FAAH1 and FAAH2 was seen in cuboidal cells of all layers of the epithelium. No immunoreactivity was detected in the smooth musculature or nerve fibres. CB1, CB2, GPR55, FAAH1 and FAAH2 are highly expressed in the human SV. Considering their localisation, the ECS may be involved in epithelial homeostasis, secretory function or autonomic mechano-afferent signalling.

Equine hepacivirus persistent infection in a horse with chronic wasting.

Equine hepacivirus is the closest homologue of hepatitis C virus. Limited data on the clinical features of this infection are available. We report the identification of a horse with high-titre viremia by equine hepacivirus. Over a 15-month follow-up, the clinical signs and the viremic status persisted, suggesting a chronic evolution.

Does anticholinergics drug burden relate to global neuro-disability outcome measures and length of hospital stay?

PRIMARY OBJECTIVE: To assess the relationship between disability, length of stay (LOS) and anticholinergic burden (ACB) with people following acquired brain or spinal cord injury. RESEARCH DESIGN: A retrospective case note review assessed total rehabilitation unit admission. METHODS AND PROCEDURES: Assessment of 52 consecutive patients with acquired brain/spinal injury and neuropathy in an in-patient neuro-rehabilitation unit of a UK university hospital. Data analysed included: Northwick Park Dependency Score (NPDS), Rehabilitation complexity Scale (RCS), Functional Independence Measure and Functional Assessment Measure FIM-FAM (UK version 2.2), LOS and ACB. Outcome was different in RCS, NPDS and FIM-FAM between admission and discharge. MAIN OUTCOMES AND RESULTS: A positive change was reported in ACB results in a positive change in NPDS, with no significant effect on FIM-FAM, either Motor or Cognitive, or on the RCS. Change in ACB correlated to the length of hospital stay (regression correlation = -6.64; SE = 3.89). There was a significant harmful impact of increase in ACB score during hospital stay, from low to high ACB on NPDS (OR = 9.65; 95% CI = 1.36-68.64) and FIM-FAM Total scores (OR = 0.03; 95% CI = 0.002-0.35). CONCLUSIONS: There was a statistically significant correlation of ACB and neuro-disability measures and LOS amongst this patient cohort.

Analysis of candidate genes for morphine preference quantitative trait locus Mop2.

Compared to DBA/2J (D2), C57BL/6J (B6) inbred mice exhibit strong morphine preference when tested using a two-bottle choice drinking paradigm. A morphine preference quantitative trait locus (QTL), Mop2, was originally mapped to proximal chromosome (Chr) 10 using a B6xD2 F2 intercross population, confirmed with reciprocal congenic strains and fine mapped with recombinant congenic strains. These efforts identified a ∼ 10-Million base pair (Mbp) interval, underlying Mop2, containing 35 genes. To further reduce the interval, mice from the D2.B6-Mop2-P1 congenic strain were backcrossed to parental D2 mice and two new recombinant strains of interest were generated: D2.B6-Mop2-P1.pD.dB and D2.B6-Mop2-P1.pD.dD. Results obtained from testing these strains in the two-bottle choice drinking paradigm suggest that the gene(s) responsible for the Mop2 QTL is one or more of 22 remaining within the newly defined interval (∼ 7.6 Mbp) which includes Oprm1 and several other genes related to opioid pharmacology. Real-time qRT-PCR analysis of Oprm1 and opioid-related genes Rgs17, Ppp1r14c, Vip, and Iyd revealed both between-strain and within-strain expression differences in comparisons of saline- and morphine-treated B6 and D2 mice. Analysis of Rgs17 protein levels also revealed both between-strain and within-strain differences in comparisons of saline- and morphine-treated B6 and D2 mice. Results suggest that the Mop2 QTL represents the combined influence of multiple genetic variants on morphine preference in these two strains. Relative contributions of each variant remain to be determined.

Effects by silodosin on the partially obstructed rat ureter in vivo and on human and rat isolated ureters.

BACKGROUND AND PURPOSE: α1 -adrenoceptor (-AR) antagonists may facilitate ureter stone passage in humans. We aimed to study effects by the α1 A -AR selective antagonist silodosin (compared to tamsulosin and prazosin) on ureter pressures in a rat model of ureter obstruction, and on contractions of human and rat isolated ureters. EXPERIMENTAL APPROACH: After ethical approval, ureters of male rats were cannulated beneath the kidney pelvis for in vivo ureteral intraluminal recording of autonomous peristaltic pressure waves. A partial ureter obstruction was applied to the distal ureter. Mean arterial blood pressure (MAP) was recorded. Approximate clinical and triple clinical doses of the α1 -AR antagonists were given intravenously. Effects by the α1 -AR antagonists on isolated human and rat ureters were studied in organ baths. KEY RESULTS: Intravenous silodosin (0.1-0.3 mg kg(-1) ) or prazosin (0.03-0.1 mg kg(-1) ) reduced obstruction-induced increases in intraluminal ureter pressures by 21-37% or 18-40% respectively. Corresponding effects by tamsulosin (0.01 or 0.03 mg kg(-1) ) were 9-20%. Silodosin, prazosin and tamsulosin reduced MAP by 10-12%, 25-26% (P < 0.05), or 18-25% (P < 0.05) respectively. When effects by the α1 A -AR antagonists on obstruction-induced ureter pressures were expressed as a function of MAP, silodosin had six- to eightfold and 2.5- to eightfold better efficacy than tamsulosin or prazosin respectively. Silodosin effectively reduced contractions of both human and rat isolated ureters. CONCLUSIONS AND IMPLICATIONS: Silodosin inhibits contractions of the rat and human isolated ureters and has excellent functional selectivity in vivo to relieve pressure-load of the rat obstructed ureter. Silodosin as pharmacological ureter stone expulsive therapy should be clinically further explored.

Quantitative trait loci for electrical seizure threshold mapped in C57BLKS/J and C57BL/10SnJ mice.

We mapped the quantitative trait loci (QTL) that contribute to the robust difference in maximal electroshock seizure threshold (MEST) between C57BLKS/J (BKS) and C57BL10S/J (B10S) mice. BKS, B10S, BKS × B10S F1 and BKS × B10S F2 intercross mice were tested for MEST at 8-9 weeks of age. Results of F2 testing showed that, in this cross, MEST is a continuously distributed trait determined by polygenic inheritance. Mice from the extremes of the trait distribution were genotyped using microarray technology. MEST correlated significantly with body weight and sex; however, because of the high correlation between these factors, the QTL mapping was conditioned on sex alone. A sequential series of statistical analyses was used to map QTLs including single-point, multipoint and multilocus methods. Two QTLs reached genome-wide levels of significance based upon an empirically determined permutation threshold: chromosome 6 (LOD = 6.0 at ∼69 cM) and chromosome 8 (LOD = 5.7 at ∼27 cM). Two additional QTLs were retained in a multilocus regression model: chromosome 3 (LOD = 2.1 at ∼68 cM) and chromosome 5 (LOD = 2.7 at ∼73 cM). Together the four QTLs explain one third of the total phenotypic variance in the mapping population. Lack of overlap between the major MEST QTLs mapped here in BKS and B10S mice and those mapped previously in C57BL/6J and DBA/2J mice (strains that are closely related to BKS and B10S) suggest that BKS and B10S represent a new polygenic mouse model for investigating susceptibility to seizures.

Chronic asymptomatic hyperamylasemia unrelated to pancreatic diseases.

PURPOSE: This study was addressed to assess the clinical characteristics of patients presenting with chronic hyperamylasemia unrelated to pancreatic diseases (CHUPD). Almost all patients presenting with chronic hyperamylasemia undergo expensive, long, difficult, and often unnecessarily repeated diagnostic procedures. This is in conjunction with the poor knowledge of the fact that besides hyperenzymemia secondary to pancreatic diseases and systemic illnesses, various non-pathological forms of chronic hyperamylasemia without relevant pathologic consequence can occur in clinical practice. MATERIAL AND METHODS: Data of all patients with CHUPD were retrospectively reviewed (June 1997-December 2009). Fifty one patients were included in the study; median follow up was 48 months (range 8-112 months). Their pre-enrolment diagnoses were: chronic pancreatitis in 31 cases (60.7%) and recurrent pancreatitis in 13 cases (25.4%); the remaining 7 patients (13.7%) were without a specific diagnosis. RESULTS: Our observations, supported by diagnostic procedures (Ca19-9 serum levels, abdominal ultrasonography, computed tomography and magnetic resonance, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasonography) revealed that CHUPD was secondary to: a) benign pancreatic hyperamylasemia, 20 patients (39.2%); b) macroamylasemia, 18 patients (35.2 %) and c) salivary hyperamylasemia, 13 patients (25.4%). CONCLUSIONS: Due to the poor familiarity with CHUPD, the occurrence of this condition quite frequently leads to unnecessarily repeated diagnostic procedures.

Confirmation of multiple seizure susceptibility QTLs on chromosome 15 in C57BL/6J and DBA/2J inbred mice.

To confirm seizure susceptibility (SZS) quantitative trait loci (QTLs) on chromosome (chr) 15 identified previously using C57BL/6J (B6) and DBA/2J (D2) mice and to refine their genomic map position, we studied a set of three congenic strains in which overlapping segments of chr 15 from D2 were transferred onto the B6 background. We measured thresholds for generalized electroshock seizure (GEST) and maximal electroshock seizure (MEST) in congenic strains and B6-like littermates and also tested their responses to kainic acid (KA) and pentylenetetrazol (PTZ). Results document that MEST is significantly lower in strains 15M and 15D, which harbor medial and distal (telomeric) segments of chr 15 (respectively) from D2, compared with strain 15P, which harbors the proximal (acromeric) segment of chr 15 from D2, and with control littermates. Congenic strains 15P and 15M exhibited greater KA SZS compared with strain 15D and B6-like controls. All congenic strains were similar to controls with regard to PTZ SZS. Taken together, results suggest there are multiple SZS QTLs on chr 15 and that two QTLs harbor gene variants that affect MEST and KA SZS independently. The MEST QTL is refined to a 19 Mb region flanked by rs13482630 and D15Mit159. This interval contains 350 genes, 183 of which reside in areas where the polymorphism rate between B6 and D2 is high. The KA QTL interval spans a 65 Mb region flanked by markers D15Mit13 and rs31271969. It harbors 83 genes in highly polymorphic areas, 310 genes in all. Complete dissection of these loci will lead to identification of genetic variants that influence SZS in mice and provide a better understanding of seizure biology.

Indications and results of videocapillaroscopy in clinical practice.

Nailfold videocapillaroscopy (NVC) is one of the best diagnostic non-invasive imaging techniques to evaluate microcirculation in vivo and is increasingly employed in the field of rheumatology. Indeed, at present, the most important utility of NVC is in the identification of microvascular involvement in many rheumatic diseases, particularly in systemic sclerosis. More recently, this technique has been shown to be applicable to the study of many other extra-rheumatic diseases, such as arterial hypertension, diabetes mellitus, acromegaly, hyperthyroidism, cardiac syndrome X, primary biliary cirrhosis, Crohn's disease, psoriasis, familial Mediterranean fever. This article sets down the methodology of examination and normal pattern of capillary vessels and reviews the applications of NVC in clinical practice and its results in rheumatic and non-rheumatic diseases.

Leflunomide in psoriatic arthritis: a retrospective study of discontinuation rate in daily clinical practice compared with methotrexate.

OBJECTIVE: To assess the safety profile of leflunomide (LEF) in a two-year retrospective analysis of psoriatic arthritis (PsA) patients (pts) treated in daily clinical practice compared with methotrexate (MTX). PATIENTS: Fourty-two PsA patients with polyarticular involvement or asymmetrical oligoarticular arthritis, satisfying ESSG criteria for the spondyloarthropathies, treated with LEF monotherapy (10-20mg/die without loading dose) between September, 2004 and August, 2006 were reviewed. They were compared with MTX (7.5-15mg/week) users (44 cases). The adverse events (AEs) and the causes of withdrawal were evaluated. RESULTS: At 24 months, cumulative survival rate of pts remaining on drugs was 54.9% in LEF users and 57.0% in MTX users (p > 0.05). The discontinuation rate (DR) for toxicity was higher in LEF group (29.2%) than in MTX group (10.8%) (p = 0.07). The occurrence of AEs was more frequently registered in the first year in both groups. LEF monotherapy showed a significant higher crude incidence for any AEs (38.7 events x100 person-years) compared to MTX (14.3 events x100 person-years) (p < 0.001). The cumulative DR for inefficacy was greater but not statistically significant in MTX group than LEF (28.6% vs. 12.6% respectively; p = 0.056). Finally, DR for other causes accounted for 8.7% vs. 11.0% respectively (p > 0.05). CONCLUSIONS: Our data showed, in a setting of clinical practice, that the rate of PsA pts remaining on drug was comparable between LEF and MTX, and a manageable LEF safety profile during a 24 months of follow-up, even if a greater incidence of DR for AEs was registered than in MTX users.

[Safety of methotrexate in rheumatoid arthritis: a retrospective cohort study in clinical practice]. / Profilo di tollerabilità del methotrexate nell'artrite reumatoide: analisi retrospettiva su una coorte di pazienti ambulatoriali.

OBJECTIVE: To evaluate the treatment duration with MTX monotherapy or in association with DMARDs or TNFalpha inhibitors and the incidence and typology of adverse events (AE) occurred in rheumatoid arthritis (RA) patients. METHODS: A retrospective large cohort study of RA outpatients, consecutively seen from January 2000 to June 2005 was performed. Study group were RA patients classified according to the 1984 ACR criteria for the classification of rheumatoid arthritis. The patients were divided in 3 groups according to the treatment regimen: MTX monotherapy, MTX in combination with DMARD or with anti TNFalpha agents. We analyzed 348 therapeutic cycles, 177 of whom using MTX monotherapy. RESULTS: The 224 RA patients accumulated 800 person-years of follow up. Follow up for each of the groups was: MTX monotherapy 479.4 person-years, MTX in combination with DMARDs 244.5, or with TNFalpha inhibitors, 75.7 person-years. From the Kaplan-Meier analysis, the probability of patients remaining on treatment 5 years was 58.5 after starting MTX. The incidence of any AE was 8.87 per 100 person-years. From all, 69 (97.2%) AE were no severe. Among those, more frequently were observed at gastrointestinal tract (31%), liver (19.7%), skin (15.5%). Incidence of severe AE (lung adenocarcinoma, 1 case; pancreatitis, 1 case) was 0.25 per 100 person-years, occurring in patients taking MTX monotherapy or MTX in combination with DMARDs, respectively. CONCLUSIONS: These data confirm that methotrexate is well tolerated in clinical practice in the medium-long term. Nevertheless, the occurrence of severe AE require an accurate vigilance for methotrexate toxicity.

Alternative transcripts and evidence of imprinting of GNAL on 18p11.2.

Genetic studies implicating the region of human chromosome 18p11.2 in susceptibility to bipolar disorder and schizophrenia have observed parent-of-origin effects that may be explained by genomic imprinting. We have identified a transcriptional variant of the GNAL gene in this region, employing an alternative first exon that is 5' to the originally identified start site. This alternative GNAL transcript encodes a longer functional variant of the stimulatory G-protein alpha subunit, Golf. The isoforms of Golf display different expression patterns in the CNS and functionally couple to the dopamine D1 receptor when heterologously expressed in Sf9 cells. In addition, there are CpG islands in the vicinity of both first exons that are differentially methylated, a hallmark of genomic imprinting. These results suggest that GNAL, and possibly other genes in the region, is subject to epigenetic regulation and strengthen the case for a susceptibility gene in this region.

Effect of Gaviscon Infant on gastro-oesophageal reflux in infants assessed by combined intraluminal impedance/pH.

BACKGROUND: Gaviscon Infant (GI) has been recommended for gastro-oesophageal reflux (GOR) in infants. Its efficacy has not been examined with a physiologically appropriate denominator to define the degree of GOR. AIM: To investigate the influence of Gaviscon Infant on GOR in infants using combined pH and intraluminal impedance measurement. METHODS: Twenty infants (mean age 163.5 days, range 34-319 days) exclusively bottle fed, with symptoms clinically suggestive of GOR, underwent 24 hour studies of intra-oesophageal 6 channel impedance and dual channel pH monitoring, during which six random administrations (3+3) of Gaviscon Infant (625 mg in 225 ml milk) or placebo (mannitol and Solvito N, 625 mg in 225 ml milk) were given in a double blind fashion. Impedance/pH reflux data were recorded and analysed blind by one observer. RESULTS: The median number of reflux events/hour (1.58 v 1.68), acid reflux events/hour (0.26 v 0.43), minimum distal or proximal pH, total acid clearance time per hour (time with pH below pH 4), and total reflux duration per hour were not significantly different after GI than after placebo. Reflux height was marginally lower after GI (median 66.6% v 77.3% oesophageal length) compared with placebo. CONCLUSIONS: Results showed a marginal but significant difference between Gaviscon Infant and placebo in average reflux height, and raises questions regarding any perceived clinical benefit of its use.