Role of adjuvants in regional anesthesia: A systematic review.

The combination of drugs and routes of administration produces a synergistic effect, and one of the most important components of multimodal analgesic strategies are, therefore, nerve blocks for pain management. The effect of a local anaesthetic can be prolonged by administering an adjuvant. In this systematic review, we included studies on adjuvants associated with local anaesthetics in peripheral nerve blocks published in the last 5 years in order to evaluate their effectiveness. The results were reported according to the PRISMA guidelines. The 79 studies selected using our criteria showed a clear prevalence of dexamethasone (n=24) and dexmedetomidine (n=33) over other adjuvants. Different meta-analyses comparing adjuvants suggest that dexamethasone administered perineurally achieves superior blockade with fewer side effects than dexmedetomidine. Based on the studies reviewed, we found moderate evidence to recommend the use of dexamethasone as an adjuvant to peripheral regional anaesthesia in surgeries that can cause moderate to severe pain.

Quadratus lumborum block. New approach for a chronic hip pain. Cases report. / Bloqueo del cuadrado lumbar: nueva vía de abordaje para el dolor crónico de cadera. Serie de casos.

Hip arthrosis is a frequent and difficult to manage disease. The generated pain supposes a great impact in the quality life of the patient. The goal of the treatment should be to reduce pain and to improve function. Based on the complex innervation of the hip, the minimally invasive thecniques have been increasing. In this context, we present the results obtained in four patients with a hip chronic pain due to arthrosis, to whom we performed a quadratus lumborum block type 2 (QL2) with levobupivacaine plus dexametasone as therapeutic option. The results have shown a significant decrease of the intensity of pain (NRS) for more than 6 months.

Serratus-intercostal interfascial block as an opioid-saving strategy in supra-umbilical open surgery. / Bloqueo interfascial serrato-intercostal como estrategia ahorradora de opioides en cirugía supraumbilical abierta.

INTRODUCTION: The administration of local anaesthetic in the serratus-intercostal space provides adequate analgesia in non-reconstructive breast surgery. The aim of this study was to evaluate whether the blockage of the last intercostal nerves (T7-T11) can lead to opioid savings in supra-umbilical open surgery procedures. MATERIAL AND METHODS: A prospective observational study was conducted on patients undergoing open supra-umbilical surgery under general anaesthesia and with a serratus-intercostal plane block [modified Blocking the bRanches of IntercostaL nerves in the Middle Axillary line (BRILMA)] as an associated analgesic strategy. Post-operative pain was assessed with the numerical verbal scale (NVS 0 to 10) on admission to the post-anAesthesia recovery unit, at 6, 12, 24, and 48h postintervention and by need for analgesic rescues with opioids (2mg iv of morphine, if values higher than 3 in NVS). Adverse events related to the technique were also recorded. The statistical package used in the analysis of the data was SPSS® for Windows. RESULTS: The study recruited 52 patients. Differences, with a p<.05, were found intra-operatively in the consumption of fentanyl: 400 + 80µg versus 110 + 50µg in patients who underwent pre-incisional blockade. In the first 24hours, only 3 cases (two gastrectomies and one cholecystectomy) required morphine (single bolus of 2mg). Between 24h and 48h it was necessary to administer several morphine boluses (8 + 2mg) in four patients (three gastrectomies and one cholecystectomy). Four patients presented with nausea and / or vomiting and there were no complications related to the analgesic technique. CONCLUSION: The intercostal nerves block (T7-T11) in the serratus-intercostal space may constitute an opioid-sparing analgesic strategy in open supra-umbilical surgery.

Schwannoma of the breast: an unexpected diagnosis by magnetic resonance. / Schwannoma mamario: un diagnóstico inesperado por resonancia magnética.

Schwannomas consist of benign tumors that arise from the nerves, however, they are not frequent in the breast. Our search criteria only found 28 cases described in Literature. We show the case about a 63 years old woman who underwent a breast magnetic resonance (MR) because of high risk for breast cancer, in which a lession on her left breast was found. Not only MR features seemed to be benign, but ultrasound and mamography features, too. The diagnosis of schwannoma was confirmed by ultrasound-guided biopsy. Findings in conventional radiology were correlated with those described in the reviewed literature. In our opinion, this case results valuable due to the inicial diagnosis by MR, which is not an imaging proof for bening tumors, innitially. According to the revised bibliography these features are pretty funny, as mamography and ultrasound, with histological findings, are the clues for the usual diagnosis.

Sevoflurane anaesthesia for nasal surgery in a patient with multiple chemical sensitivity. / Anestesia con sevoflurano para cirugía de senos paranasales en un paciente con sensibilidad química múltiple.

Multiple chemical sensitivity syndrome is a group of complex disorders that include psychiatric disorders, chronic fatigue and/or respiratory problems. This syndrome could be triggered by specific allergens and toxins that cause neurophysiological sensitization and the appearance of the clinical symptomatology. Anaesthesia for these patients always poses a challenge for the anaesthetist, because they need to find and use drugs that do not trigger or aggravate the symptoms of the disease. Therefore, sevoflurane in these circumstances might be "the ideal anaesthetic". Performing general anaesthesia with sevoflurane as the sole anaesthetic agent, together with a series of environmental measures formed the basis for successful anaesthesia and surgery in our patient with a multiple chemical sensitivity syndrome.

Levofloxacin versus azithromycin for treating legionella pneumonia: a propensity score analysis.

OBJECTIVES: Concerns have arisen regarding the equivalence of levofloxacin and some macrolides for treating community-acquired legionella pneumonia (LP). We aimed to compare the outcomes of current patients with LP treated with levofloxacin, azithromycin and clarithromycin. METHODS: Observational retrospective multicentre study of consecutive patients with LP requiring hospitalization (2000-2014) conducted in two hospitals. The primary outcome assessed was 30-day mortality. To control for confounding, therapy was assessed by multivariate analysis. RESULTS: We documented 446 patients with LP, of which 175 were treated with levofloxacin, 177 with azithromycin and 58 with clarithromycin. No significant differences in time to defervescence (2 (interquartile range (IQR) 1-4) versus 2 (IQR 1-3) days; p 0.453), time to achieve clinical stability (3 (2-5) versus 3 (2-5) days; p 0.486), length of intravenous therapy (3 (2-5.25) versus 4 (3-6) days; p 0.058) and length of hospital stay (7 (5-10) versus 6 (5-9) days; p 0.088) were found between patients treated with levofloxacin and those treated with azithromycin. Patients treated with clarithromycin had longer intravenous antibiotic treatment (3 (2-5.25) versus 5 (3-6.25) days; p 0.002) and longer hospital stay (7 (5-10) versus 9 (7-14) days; p 0.043) compared with those treated with levofloxacin. The overall mortality was 4.3% (19 patients). Neither univariate nor multivariate analysis showed a significant association of levofloxacin versus azithromycin on mortality (4 (2.3%) versus 9 (5.1%) deaths; p 0.164). The results did not change after incorporation of the propensity score into the models. CONCLUSIONS: In our study, no significant differences in most outcomes were found between patients treated with levofloxacin and those treated with azithromycin. Due to the small number of deaths, results regarding mortality should be interpreted with caution.

Patient satisfaction with the clinical pharmacist and prescribers during hepatitis C virus management.

WHAT IS KNOWN AND OBJECTIVES: Clinical pharmacists play an important role in the management of patients undergoing hepatitis C virus (HCV) treatment. No satisfaction surveys have been published on clinical pharmacist interventions in HCV management. The objective was to evaluate patient satisfaction with clinical pharmacist and prescriber services in the HCV patient population at an urban academic hepatology clinic. METHODS: An anonymous patient satisfaction survey was offered to patients who were initiating or receiving HCV treatment under the care of a clinical pharmacist. Survey items assessed demographics and satisfaction with HCV care. Satisfaction was assessed with 17 or 20 Likert-scale questions (1 = poor, 2 = fair, 3 = okay, 4 = good, 5 = great) and two or three open-ended questions. Survey results were analysed via comparative and descriptive statistics. A qualitative content analysis was used for the open-ended survey questions. RESULTS AND DISCUSSION: Sixty-four patients completed 77 (24 pharmacist and 53 prescriber) patient satisfaction surveys. The mean age was 53 (±9·72) years. Patients reported high levels of satisfaction with the pharmacist and prescribers. All 24 (100%) patients ranked overall satisfaction with services provided by pharmacists as 'great', and 36 (69%) of 52 patients ranked overall satisfaction with services provided by prescribers as 'great'. Patients supported the inclusion of a clinical pharmacist on health care teams for other disease states. WHAT IS NEW AND CONCLUSION: Patients reported high levels of satisfaction with the clinical pharmacist involved in HCV treatment management at an urban academic medical centre. Clinical pharmacist services were highly valued and recommended by the patients surveyed. The survey was able to identify areas in need of improvement in the clinic. Clinical pharmacists play an important role in the treatment and management of HCV. This survey may serve as a model for assessment of satisfaction in other pharmacist-run clinic settings.

ICRP Publication 131: Stem cell biology with respect to carcinogenesis aspects of radiological protection.

Current knowledge of stem cell characteristics, maintenance and renewal, evolution with age, location in 'niches', and radiosensitivity to acute and protracted exposures is reviewed regarding haematopoietic tissue, mammary gland, thyroid, digestive tract, lung, skin, and bone. The identity of the target cells for carcinogenesis continues to point to the more primitive and mostly quiescent stem cell population (able to accumulate the protracted sequence of mutations necessary to result in malignancy), and, in a few tissues, to daughter progenitor cells. Several biological processes could contribute to the protection of stem cells from mutation accumulation: (1) accurate DNA repair; (2) rapid induced death of injured stem cells; (3) retention of the intact parental strand during divisions in some tissues so that mutations are passed to the daughter differentiating cells; and (4) stem cell competition, whereby undamaged stem cells outcompete damaged stem cells for residence in the vital niche. DNA repair mainly operates within a few days of irradiation, while stem cell replications and competition require weeks or many months depending on the tissue type. This foundation is used to provide a biological insight to protection issues including the linear-non-threshold and relative risk models, differences in cancer risk between tissues, dose-rate effects, and changes in the risk of radiation carcinogenesis by age at exposure and attained age.

ICRP Publication 131: Stem Cell Biology with Respect to Carcinogenesis Aspects of Radiological Protection.

This report provides a review of stem cells/progenitor cells and their responses to ionising radiation in relation to issues relevant to stochastic effects of radiation that form a major part of the International Commission on Radiological Protection's system of radiological protection. Current information on stem cell characteristics, maintenance and renewal, evolution with age, location in stem cell 'niches', and radiosensitivity to acute and protracted exposures is presented in a series of substantial reviews as annexes concerning haematopoietic tissue, mammary gland, thyroid, digestive tract, lung, skin, and bone. This foundation of knowledge of stem cells is used in the main text of the report to provide a biological insight into issues such as the linear-no-threshold (LNT) model, cancer risk among tissues, dose-rate effects, and changes in the risk of radiation carcinogenesis by age at exposure and attained age. Knowledge of the biology and associated radiation biology of stem cells and progenitor cells is more developed in tissues that renew fairly rapidly, such as haematopoietic tissue, intestinal mucosa, and epidermis, although all the tissues considered here possess stem cell populations. Important features of stem cell maintenance, renewal, and response are the microenvironmental signals operating in the niche residence, for which a well-defined spatial location has been identified in some tissues. The identity of the target cell for carcinogenesis continues to point to the more primitive stem cell population that is mostly quiescent, and hence able to accumulate the protracted sequence of mutations necessary to result in malignancy. In addition, there is some potential for daughter progenitor cells to be target cells in particular cases, such as in haematopoietic tissue and in skin. Several biological processes could contribute to protecting stem cells from mutation accumulation: (a) accurate DNA repair; (b) rapidly induced death of injured stem cells; (c) retention of the DNA parental template strand during divisions in some tissue systems, so that mutations are passed to the daughter differentiating cells and not retained in the parental cell; and (d) stem cell competition, whereby undamaged stem cells outcompete damaged stem cells for residence in the niche. DNA repair mainly occurs within a few days of irradiation, while stem cell competition requires weeks or many months depending on the tissue type. The aforementioned processes may contribute to the differences in carcinogenic radiation risk values between tissues, and may help to explain why a rapidly replicating tissue such as small intestine is less prone to such risk. The processes also provide a mechanistic insight relevant to the LNT model, and the relative and absolute risk models. The radiobiological knowledge also provides a scientific insight into discussions of the dose and dose-rate effectiveness factor currently used in radiological protection guidelines. In addition, the biological information contributes potential reasons for the age-dependent sensitivity to radiation carcinogenesis, including the effects of in-utero exposure.

[Ultrasound-guided cutaneous intercostal branches nerves block: A good analgesic alternative for gallbladder open surgery]. / Bloqueo fascial ecoguiado de las ramas cutáneas de los nervios intercostales: una buena alternativa analgésica para la cirugía abierta de vesícula biliar.

Laparoscopic cholecystectomy has become the standard treatment for gallbladder diseases. However, there are still some patients for whom conversion to open surgery is required. This surgery can produce significant post-operative pain. Opioids drugs have traditionally been used to treat this pain, but side effects have led to seeking alternatives (plexus, nerve or fascia blocks or wound). The cases are presented of 4 patients subjected to ultrasound-guided intercostal branches blocks in the mid-axillary line from T6 to T12 with levobupivacaine as an analgesic alternative in open surgery of gallbladder, with satisfactory results.

Potential role of the gaseous mediator hydrogen sulphide (H2S) in inhibition of human colonic contractility.

BACKGROUND: Hydrogen sulphide (H2S) is an endogenous signalling molecule that might play a physiologically relevant role in gastrointestinal motility. Cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE) are two enzymes responsible for H2S production. d,l-Propargylglycine (PAG) is a CSE inhibitor whereas both aminooxyacetic acid (AOAA) and hydroxylamine (HA) are CBS inhibitors. The characterization of H2S responses and its mechanism of action are crucial to define H2S function. METHODS: Human colonic strips were used to investigate the role of H2S on contractility (muscle bath) and smooth muscle electrophysiology (microelectrodes). NaHS was used as a H2S donor. RESULTS: Combination of PAG and AOAA depolarized the smooth muscle (5-6mV, n=4) and elicited a transient increase in tone (260.5±92.8mg, n=12). No effect was observed on neural mediated inhibitory junction potential or relaxation. In the presence of tetrodotoxin 1µM, NaHS concentration-dependently inhibited spontaneous contractions (EC50=329.2µM, n=18). This effect was partially reduced by the guanylyl cyclase inhibitor ODQ 10µM (EC50=2.6µM, n=12) and by l-NNA 1mM (EC50=1.4mM, n=8). NaHS reversibly blocked neural mediated cholinergic (EC50=2mM) and tachykinergic (EC50=5.7mM) contractions. NaHS concentration-dependently reduced the increase in spontaneous mechanical activity (AUC) induced by carbachol (EC50=1.9mM) and NKA (EC50=1.7mM AUC). CONCLUSIONS: H2S might be an endogenous gasomediator regulating human colonic contractility. Its inhibitory effect is observed at high concentrations and could be mediated by a direct effect on smooth muscle with a possible synergistic effect with NO, as well as by an interaction with the cholinergic and tachykinergic neural mediated pathways.

EP2 and EP4 receptors mediate PGE2 induced relaxation in murine colonic circular muscle: pharmacological characterization.

BACKGROUND: Prostaglandin E2 (PGE2) is a regulator of gastrointestinal motility that might be involved in impaired motor function associated to gut inflammation. The aim of the present work is to pharmacologically characterize responses to exogenous and endogenous PGE2 in the mouse colon targeting EP2 and EP4 receptors. METHODS: Wild type (WT) and EP2 receptor knockout (EP2-KO) mice were used to characterize PGE2 and butaprost (EP2 receptor agonist) effects on smooth muscle resting membrane potential and myogenic contractility in circularly oriented colonic preparations. RESULTS: In WT animals, PGE2 and butaprost concentration-dependently inhibited spontaneous contractions and hyperpolarized smooth muscle cells. Combination of both EP2 (PF-04418948 0.1µM) and EP4 receptor antagonists (L-161,982 10µM) was needed to block both electrical and mechanical PGE2 responses. Butaprost inhibitory responses (both electrical and mechanical) were totally abolished by PF-04418948 0.1µM. In EP2-KO mice, PGE2 (but not butaprost) concentration-dependently inhibited spontaneous contractions and hyperpolarized smooth muscle cells. In EP2-KO mice, PGE2 inhibition of spontaneous contractility and hyperpolarization was fully antagonized by L-161,982 10µM. In WT animals, EP2 and EP4 receptor antagonists caused a smooth muscle depolarization and an increase in spontaneous mechanical activity. CONCLUSIONS: PGE2 responses in murine circular colonic layer are mediated by post-junctional EP2 and EP4 receptors. PF-04418948 and L-161,982 are selective EP2 and EP4 receptor antagonists that inhibit PGE2 responses. These antagonists might be useful pharmacological tools to limit prostaglandin effects associated to dismotility in gut inflammatory processes.

Effects of organic modifier and temperature on the enantiomeric separation of several azole drugs using supercritical fluid chromatography and the Chiralpak AD column.

The effects of organic modifier and temperature on the enantioseparation of 10 triazoles and eight imidazoles, using supercritical fluid chromatography with the Chiralpak AD column, have been investigated in this work. For this purpose four different organic modifiers (methanol, ethanol, 2-propanol and acetonitrile) were evaluated. Only in the case of two compounds could the enantiomeric separation not be achieved with any of the modifiers tested; the rest of compounds were baseline or partially resolved with at least one of the modifiers. The alcohol-type modifiers provided the best results in terms of retention time and resolution. In general, retention increased in the order methanol < ethanol < 2-propanol; moreover it was possible to establish a relationship between the retention and the number of aromatic rings and dioxolane groups in the molecule, that is, the higher the number is, the higher the retention time. From the study of the temperature effect, the enthalpy-entropy compensation was demonstrated for all the compounds, except for bifonazole using methanol and miconazole using acetonitrile. This suggested that both analytes are enantiomerically resolved through different mechanisms.

Development of SCAR Primers for PCR Assay to Detect Diplodia seriata.

The aim of this study was to develop primer pairs for Diplodia seriata identification, one of the most common fungal species associated with grapevine decline in Castilla y León (Spain). Genetic variability of selected isolates of D. seriata was estimated. A molecular marker was generated from a random amplified polymorphic DNA (RAPD) fragment. PCR products of around 1200 bp were obtained with OPE20 primer. The PCR products were cloned and sequenced. The sequences were compared and a fragment of 1207 bp was used to design primer pairs. Two primer pairs were selected (DS3.8 S3-DS3.8 R6 and DS3.8 S3-DS3.8 R4) that amplified a single DNA product of 634 bp and 233 bp, respectively, with D. seriata isolates. No amplification was obtained for any of the 57 isolates of other species. The designed SCAR primer pairs allowed a rapid detection of D. seriata, and were able to detect 0.1 pg of the target DNA. Detection was specific and sensitive for D. seriata. The established protocols detected these fungi in naturally infected grapevines after DNA purification. Diplodia seriata was detectable without DNA purification and isolation in 62.5% to 75% of reactions. The detection of this pathogen in wood samples has great potential for use in pathogen-free certification schemes.

Mechanisms of action of otilonium bromide (OB) in human cultured smooth muscle cells and rat colonic strips.

BACKGROUND: The pharmacological properties of otilonium bromide (OB) have been investigated using different experimental models, techniques, and conditions, and consequently, the results are not always easy to compare. The aim of the present work was to investigate the pharmacological properties of OB in human cultured colonic smooth muscle cells (HCSMCs), which is the main target of the drug 'in vivo'. Rat colonic strips were used to confirm the pharmacological properties. METHODS: Human cultured colonic smooth muscle cells were studied using the calcium imaging technique. Microelectrodes and muscle bath experiments were performed in rat colonic strips. KEY RESULTS: Otilonium bromide (OB) concentration dependently inhibited nifedipine-sensitive calcium transients induced by KCl (EC50  = 3.6 µM) and BayK8644 (EC50  = 4.0 µM). All the following experiments were performed in the presence of nifedipine. In HCSMC, carbachol-induced calcium transients were inhibited by OB (EC50  = 8.4 µM). Carbachol evoked 1-a smooth muscle depolarization (10 mV) that was antagonized by 100 µM OB; and 2-a contraction that was inhibited by OB (EC50  = 13.0 µM). 'Non-nitrergic (L-NNA 1 mM) non-purinergic (MRS2500 1 µM)' conditions were used to elicit endogenous excitatory responses. Electrical field stimulation caused 1-an atropine-sensitive excitatory junction potential that was inhibited by OB (EC50  = 8.9 µM) and 2-an atropine-sensitive contraction that was inhibited by OB (EC50  = 7.3 µM). In HCSMC, neurokinin A (NKA) and CaCl2 induced calcium transients that were inhibited by OB (NKA: EC50  = 11.7 µM; CaCl2 : EC50  = 17.5 µM). CONCLUSIONS & INFERENCES: Otilonium bromide causes inhibition of L-/T-type calcium channels, muscarinic, and tachykininergic responses that acting together explain the pharmacological properties of the compound.

P2Y(1) knockout mice lack purinergic neuromuscular transmission in the antrum and cecum.

BACKGROUND: Pharmacological studies using selective P2Y(1) antagonists, such as MRS2500, and studies with P2Y(1)(-/-) knockout mice have demonstrated that purinergic neuromuscular transmission is mediated by P2Y(1) receptors in the colon. The aim of the present study was to test whether P2Y(1) receptors are involved in purinergic neurotransmission in the antrum and cecum. METHODS: Microelectrode recordings were performed on strips from the antrum and cecum of wild type animals (WT) and P2Y(1)(-/-) mice. KEY RESULTS: In the antrum, no differences in resting membrane potential and slow wave activity were observed between groups. In WT animals, electrical field stimulation elicited a MRS2500-sensitive inhibitory junction potential (IJP). In P2Y(1)(-/-) mice, a nitrergic IJP (N(ω) -nitro-l-arginine-sensitive), but not a purinergic IJP was recorded. This IJP was equivalent to the response obtained in strips from WT animals previously incubated with MRS2500. Similar results were obtained in the cecum: 1- the purinergic IJP (MRS2500-sensitive) recorded in WT animals was absent in P2Y(1)(-/-) mice 2- nitrergic neurotransmission was preserved in both groups. Moreover, 1- spontaneous IJP (MRS2500-sensitive) could be recorded in WT, but not in P2Y(1)(-/-) mice 2- MRS2365 a P2Y(1) agonist caused smooth muscle hyperpolarization in WT, but not in P2Y(1) (-/-) animals, and 3- ß-NAD caused smooth muscle hyperpolarization both in WT and P2Y(1)(-/-) animals. CONCLUSIONS & INFERENCES: 1- P2Y(1) receptor is the general mechanism of purinergic inhibition in the gastrointestinal tract, 2- P2Y(1)(-/-) mouse is a useful animal model to study selective impairment of purinergic neurotransmission and 3- P2Y(1)(-/-) mouse might help in the identification of purinergic neurotransmitter(s).