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.

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.

Functional interplay between p63 and p53 controls RUNX1 function in the transition from proliferation to differentiation in human keratinocytes.

The interfollicular epidermis is continuously renewed, thanks to a regulated balance between proliferation and differentiation. The ΔNp63 transcription factor has a key role in the control of this process. It has been shown that ΔNp63 directly regulates Runt-related transcription factor 1 (RUNX1) transcription factor expression in mouse keratinocytes. The present study showed for the first time that RUNX1 is expressed in normal human interfollicular epidermis and that its expression is tightly regulated during the transition from proliferation to differentiation. It demonstrated that ΔNp63 directly binds two different RUNX1 regulatory DNA sequences and modulates RUNX1 expression differentially in proliferative or differentiated human keratinocytes. It also showed that the regulation of RUNX1 expression by ΔNp63 is dependent on p53 and that this coregulation relies on differential binding and activation of RUNX1 regulatory sequences by ΔNp63 and p53. We also found that RUNX1 inhibits keratinocyte proliferation and activates directly the expression of KRT1, a critical actor in early keratinocyte differentiation. Finally, we described that RUNX1 expression, similar to ΔNp63 and p53, was strongly expressed and downregulated in basal cell carcinomas and squamous cell carcinomas respectively. Taken together, these data shed light on the importance of tight control of the functional interplay between ΔNp63 and p53 in regulating RUNX1 transcription factor expression for proper regulation of interfollicular epidermal homeostasis.

[Myotonic dystrophy. 18 years experience in a neuropaediatric clinic]. / Distrofia miotónica. Nuestra experiencia de 18 años en consulta de Neuropediatría.

INTRODUCTION: Myotonic dystrophy is a highly variable autosomic dominant inherited multisystemic disease. We review our 18 years experience with patients suffering from this disease. RESULTS: Eleven patients were identified following a molecular genetic study: 2 patients died, 5 are still under control, 2 are being controlled in another Centre, and 3 dropped out. Three of them were relatives. Seven newborns started with hypotonic symptoms in the neonatal period, with hypotonic symptoms, of which 4 had foetal suffering. One child was diagnosed at age of 3 due to her father being affected. One girl was seen at age of 10 due to stiffness and tightening of her hands for years. One boy, aged 5, was examined due to abnormal hands posture, and a 4 year old child due to psychomotor delay. Associated disorders: 7 children with psychomotor delay, 2 cases of cataracts, 1 case of diabetes type I, 3 cases of hypercholesterolemia, 1 abdominal sarcoma, 1 case of femur and hip fracture, 2 cases of interatrial communication. The diagnostic was made in 5 cases by a clinic due to mother-son relation phenotype, in 3 cases after the family diagnosis and in another 3 cases non-congenital symptoms exclusively in the child's clinic. DISCUSSION: In our experience, myotonic dystrophy is uncommon; it is often congenital, and is associated with perinatal suffering. Genetics can identify or exclude the process. This must be done on newborns who are hypotonic for an unknown reason. It should be suspected in a child who presents with motor abnormalities in the fingers and hands.

Behavior and preservation of an in vitro collection of European aspen in Spain

An in vitro collection has been Established with selected European aspen from Palencia province (Spain). Currently, this collection includes 32 high quality clones, selected for their good bearing and healthy state. Most of them belong to different discrete local populations. Populus tremula L. was propagated in proliferation Aspen Culture Medium; they required subculture every 3 months. The purpose of this study was, therefore, to select a medium which allows the maintenance of 32 clones for a period longer than 3 months without subculture and to observe the behavior of those clones in 15 different culture medium compositions. Seven nodal cutting stem explants from each clone were cultured in parallel in the different media. One and three months after setting on the stem explants, the number and the size of shoots, the root size, the presence or absence of callus and the survival, were evaluated. The survival was monthly recorded during 8 months. Taking into account the explant development, four media were proposed for collection preservation. One of them, Ga, with a reduction of salts, sucrose, 6-benzoaminopurine, omitting adenine sulphate and 1-naphthalene acetic acid, is the most economical. Behavior observations of the 32 clones in the 15 medium compositions showed the influence of the genotype of the clones.

LC-ESI-MSD fast determination of residual mitomycin C in hen aqueous humour after corneal refractive surgery.

A simple, fast and reliable method has been developed for the assay of traces of mitomycin C (MMC) in hen aqueous humour samples. The determination was carried out by high-performance liquid chromatography with electrospray ionization mass spectrometric detection. In isocratic elution analysis, the mobile phase was a mixture of water-acetonitrile (78:22, v/v) and the chromatographic column was C(18) at 35 degrees C. The method has been validated over a range from 0.1 to 250 microg L(-1) in hen aqueous humour with correlation coefficients higher than 0.999. Limit of detection and limit of quantification for MMC based in signal to noise ratio of 3 and 10, respectively, were 20 and 71 ng L(-1). The developed method allows the analysis of MMC in hen aqueous humour samples obtained at different times and conditions in order to evaluate and compare the efficacy of the drug administration.

Capillary gas chromatography with mass spectrometric and atomic emission detection for characterization and monitoring chlordimeform degradation in honey.

Capillary gas chromatography-mass spectrometry and capillary gas chromatography-atomic emission detection have been successfully used to identify and monitor the main degradation products of chlordimeform when this compound is initially present in honey. The analysis of laboratory-spiked honey samples over 28 weeks revealed the occurrence of two degradation products: 4-chloro-o-toluidine (I) and N-formyl-4-chloro-o-toluidine (III). During this period the concentration of chlordimeform decreased to 7.5% of its initial value; the concentration of compound I increased gradually whereas compound III was present in a larger proportion and reached a maximum around the 14th week.

Use of a particle beam interface combined with mass spectrometry/negative chemical ionization to determine polar herbicide residues in soil by liquid chromatography.

The use of mass spectrometry/negative chemical ionization (MS/NCI), in combination with selected-ion monitoring, allows sensitive and selective determination of polar and thermally unstable herbicide residues by liquid chromatography coupled to a particle beam interface. The method has been applied to the analysis of soil samples for herbicide residues, using various procedures for their extraction and employing matrix-standard calibration to avoid quantitative errors due to transfer of matter through the interface. Data for the fragment ions found in the MS/NCI procedure and chromatograms from analyses of real samples are also presented.

An open-label pilot study of low-dose thalidomide in chronically active, steroid-dependent Crohn's disease.

BACKGROUND & AIMS: Thalidomide decreases production of tumor necrosis factor alpha, a proinflammatory cytokine associated with Crohn's disease (CD). In this study the safety, tolerance, and efficacy of low-dose thalidomide were evaluated for treatment of moderate-to-severe, steroid-dependent CD. METHODS: Twelve adult male patients with Crohn's Disease Activity Index (CDAI) scores of > or = 250 and < or = 500 despite > or = 20 mg prednisone/day were enrolled. The first 6 patients received 50 mg thalidomide every night, the next 6 received 100 mg every night. Steroid doses were stable during the first 4 weeks of treatment, then tapered during weeks 5-12. CDAI was used to assess response. RESULTS: (1) Disease activity improved consistently in all patients during weeks 1-4: 58% response, 17% remission. (2) Clinical improvement was generally maintained despite steroid taper during weeks 5-12. All patients were able to reduce steroids by >/=50%. Forty-four percent discontinued steroids entirely. In weeks 5-12, 70% of patients responded and 20% achieved remission. (3) Side effects were mild and mostly transient, with the most common being drowsiness, peripheral neuropathy, edema, and dermatitis. CONCLUSIONS: Low-dose thalidomide appears to be well tolerated and effective over a 12-week period. Results of this pilot study support the need for controlled multicenter trials of thalidomide for treatment of CD.

Pyrrolidinoindoline alkaloids from Psychotria oleoides and Psychotria lyciiflora.

The chemical study of two Rubiaceae from New Caledonia, Psychotria lyciiflora and Psychotria oleoides, led to the isolation of several pyrrolidinoindoline alkaloids. Two dimers, the known meso-chimonanthine (9) and the new Nb-desmethyl-meso-chimonanthine (5), and a known trimer, hodgkinsine (1), have been isolated from P. lyciiflora. Hodgkinsine (1), quadrigemine C (2), isopsychotridine B (3), psychotridine (4), and three new alkaloids, quadrigemine I (6), oleoidine (7), and caledonine (8), have been isolated from P. oleoides. Structural assignments of the compounds were based on mass spectra analysis and 2D NMR experiments. A tentative stereochemical determination is made from 2D NMR experiments, circular dichroism study and chemical correlations. Some of these compounds are functional antagonists of somatostatine (SRIH).

Cytotoxic 3,4-secoapotirucallanes from Aaglaia argentea bark.

Nine 3,4-secoapotirucallanes, argentinic acids A-I, were isolated from the bark of Aglaia argentea and transformed to their methyl esters 1-9. The structures were determined by spectral and chemical means. Compounds 1-8 showed moderate cytotoxic activity against KB cells (IC50 1.0-3.5 microg/mL).

Mitogen-activated protein kinase kinase kinase 1 activates androgen receptor-dependent transcription and apoptosis in prostate cancer.

Mitogen-activated protein (MAP) kinases phosphorylate the estrogen receptor and activate transcription from estrogen receptor-regulated genes. Here we examine potential interactions between the MAP kinase cascade and androgen receptor-mediated gene regulation. Specifically, we have studied the biological effects of mitogen-activated protein kinase kinase kinase 1 (MEKK1) expression in prostate cancer cells. Our findings demonstrate that expression of constitutively active MEKK1 induces apoptosis in androgen receptor-positive but not in androgen receptor-negative prostate cancer cells. Reconstitution of the androgen receptor signaling pathway in androgen receptor-negative prostate cancer cells restores MEKK1-induced apoptosis. MEKK1 also stimulates the transcriptional activity of the androgen receptor in the presence or absence of ligand, whereas a dominant negative mutant of MEKK1 impairs activation of the androgen receptor by androgen. These studies demonstrate an unanticipated link between MEKK1 and hormone receptor signaling and have implications for the molecular basis of hormone-independent prostate cancer growth.