[Moral judgment of physicians is insufficient as a framework for medical ethics]. / ¿Es suficiente la base moral de los médicos?

Physicians values are largely supported by a socio-cultural moral basis, also known as "classical utilitarianism". Technological advances and social questions to physicians show their paucity of an ethical conceptualization in medicine. A new way of approaching ethical conflicts in medicine should be constructed. Training should promote ethical reflection about these conflicts and about the actions of physicians. Ontogenetic and phylogenetic research on human nature, and the advances in moral psychology, could allow us to understand the construction of our judgment of values. An introspective emotional and rational effort to understand "how we are" and from there, to "how we act" lacks among physicians. This issue is even more complex in a political-social model which does not stimulate this type of analysis. The university space is a privileged opportunity to educate. The student must be envisioned as a human being whose professional acts should consider the needs of our society, aiming at a new ethical conceptualization in medicine.

[Thyroid hormone Levels in very preterm neonates and extremely preterm]. / Niveles de hormonas tiroideas en recién nacidos muy prematuros y prematuros extremos.

INTRODUCTION: The thyroid function of the pretern infant is altered by the relative immaturity of the hypothalamus-pituitary thyroid gland axis, along with other factors such as the incidence of diseases or the use of some drugs. Currently, there is controversy over normal levels of free thyroxine (FT4) in preterm infants. Our objective was to determine the distribution of FT4 and TSH values in newborn younger than 32 weeks or 1500 g of birth weight at 15 days of chronological age, in the neonatology service at Dr. Hernán Henríquez Aravena Hospital, Temuco. PATIENTS AND METHOD: Cross-sectional study; the results of FT4 and TSH from a database of 308 newborns, were analyzed, which were categorized into three gestational age ranges, 31-34, 28-30 and 23-27 weeks. It was used Pearson Chi-square for comparisons between categorical variables, and T-Test or ANOVA for categorical-variable ratios. RESULTS: Significant differences were observed between the average values of FT4 by gestatio nal age ranges (p = 0.000), these were 1.13 ng/dl for the range of 31 to 34 weeks, 1.03 ng/dl for the range of 28 to 30 weeks and 0.92 ng/dl for the range of 23 to 27 weeks; we did not observe significant differences in TSH levels by gestational age categories (p = 0.663). CONCLUSIONS: We established the distribution of FT4 and TSH levels in our population of very preterm and extremely preterm infants, finding differences with previous papers.

Implant Surface Design Regulates Mesenchymal Stem Cell Differentiation and Maturation.

Changes in dental implant materials, structural design, and surface properties can all affect biological response. While bulk properties are important for mechanical stability of the implant, surface design ultimately contributes to osseointegration. This article reviews the surface parameters of dental implant materials that contribute to improved cell response and osseointegration. In particular, we focus on how surface design affects mesenchymal cell response and differentiation into the osteoblast lineage. Surface roughness has been largely studied at the microscale, but recent studies have highlighted the importance of hierarchical micron/submicron/nanosurface roughness, as well as surface roughness in combination with surface wettability. Integrins are transmembrane receptors that recognize changes in the surface and mediate downstream signaling pathways. Specifically, the noncanonical Wnt5a pathway has been implicated in osteoblastic differentiation of cells on titanium implant surfaces. However, much remains to be elucidated. Only recently have studies been conducted on the differences in biological response to implants based on sex, age, and clinical factors; these all point toward differences that advocate for patient-specific implant design. Finally, challenges in implant surface characterization must be addressed to optimize and compare data across studies. An understanding of both the science and the biology of the materials is crucial for developing novel dental implant materials and surface modifications for improved osseointegration.

Functional analysis and in vitro correction of splicing FAH mutations causing tyrosinemia type I.

Hereditary tyrosinemia type I (HT1) is a rare disease caused by a deficiency of fumarylacetoacetate hydrolase (FAH) in the tyrosine catabolic pathway, resulting mainly in hepatic alterations due to accumulation of the toxic metabolites fumarylacetoacetate, maleylacetoacetate and succinylacetone. We have characterized using minigenes four splicing mutations affecting exonic or intronic nucleotides of the FAH gene identified in two HT1 patients. Two of the mutations are novel, c.82-1G>A and c.913G>C and the other two have been previously associated with a splicing defect (c.836A>G and c.1062+5G>A). All mutations were confirmed to affect splicing in minigenes, resulting in exon skipping or activation of a cryptic splice site. We have analyzed the effect of different compounds known to modulate splicing (valproic acid, phenyl butyrate, M344, EIPA, and resveratrol) and the overexpression of splice factors of the SR protein family on the transcriptional profile of the mutant minigenes. For the c.836A>G mutation, a partial recovery of the correctly spliced transcript was observed. These results confirm the relevance of performing functional studies for mutations potentially affecting the splicing process and open the possibility of supplementary therapeutic approaches to diseases caused by splicing defects.

Role of the N-terminal peptide of amelogenin on osteoblastic differentiation of human mesenchymal stem cells.

Porcine enamel matrix derivative (pEMD), a complex mixture of proteins and peptides including full-length amelogenin protein, splice variants, and proteolytic peptides, is used clinically with a carrier to regenerate supportive tissue around teeth. During application, pEMD self-assembles as nanospheres and precipitates as a three-dimensional matrix to facilitate cell migration and differentiation. Amelogenin, the primary constituent of pEMD, stimulates osteoblast differentiation, but it is unclear what specific roles other components of pEMD play in determining biological response. This study examined the potential of one constituent of pEMD, the N-terminal amelogenin peptide (NTAP), to promote osteoblastic differentiation of human mesenchymal stem cells (MSCs) and to elucidate possible signaling pathways involved. Effects of porcine NTAP on MSC cultures were compared to those of recombinant human amelogenin. While amelogenin induced MSC osteoblastic differentiation, a more robust osteoblastic response was seen after NTAP treatment. A phospho-kinase proteasome array measuring phosphorylation of 35 proteins indicated that protein kinase C (PKC), extracellular signal-regulated kinase 1/2 (ERK1/2), and ß-catenin were highly phosphorylated by NTAP. This was confirmed by measuring PKC activity and levels of phospho-ERK1/2 and ß-catenin. Both amelogenin and NTAP increased PKC, but NTAP induced higher phosho-ERK1/2 and phospho-ß-catenin than amelogenin. ERK1/2 inhibition blocked both amelogenin- and NTAP-induced increases in RUNX2, ALP, OCN, COL1, and BMP2. The results demonstrate that NTAP induces osteogenic differentiation of MSCs via PKC and ERK1/2 activation and ß-catenin degradation. NTAP may be an active bone regeneration component of amelogenin, and may play this role in pEMD-stimulated periodontal regeneration.

Bendamustine as salvage treatment for patients with relapsed or refractory mantle cell lymphoma patients: a retrospective study of the Spanish experience.

Patients with mantle cell lymphoma (MCL) have an adverse outcome after relapse. Bendamustine has demonstrated a good efficacy and toxicity profile in previously reported trials. In this study, we present a retrospective analysis of the Spanish experience in relapsed/refractory MCL treated with bendamustine in combination or alone with the objective of knowing the efficacy and toxicity profile of this treatment in our current clinical practice. Fifty eight patients were registered: 67 % male with median age of 71 years, and 2 is the median number of previous lines. The most frequent bendamustine regimen was bendamustine plus rituximab (83 %). The median number of cycles was 5 (range 1-8). The overall response rate was 84 % with 53 % of complete response/unconfirmed complete response (CR/uCR). Median progression-free survival (PFS) was 16 months (95 % confidence interval (CI) 13.3-18.8), and for patients who achieved CR/uCR, it was 33 months (95 % CI 11.1-54.2). Median overall survival (OS) was 30 months (95 % CI 25.6-34.9). For PFS, only blastoid histology and not achieving CR after bendamustine had a significant negative impact on the univariate and multivariate analyses (p < 0.05). Nevertheless, for OS, only an elevated lactate dehydrogenase (LDH) had negative impact on both, univariate and multivariate analyses (p < 0.05). Only one case of treatment-related mortality in a 79-year-old patient with very bad performance status was reported. In 280 cycles, 12 (4 %) hospitalizations for febrile neutropenia were reported. In our population, bendamustine has been a good salvage treatment with a favorable toxicity profile in a non selected and heavily pretreated population of patients with MCL.

Single-molecule magnet behavior and magnetocaloric effect in ferromagnetically coupled Ln(III)-Ni(II)-Ni(II)-Ln(III) (Ln(III) = Dy(III) and Gd(III)) linear complexes.

New types of linear tetranuclear Ln(III)-Ni(II)-Ni(II)-Ln(III) (Ln(III) = Dy (1), Gd (2)) complexes have been prepared using the multidentate ligand N,N'-bis(3-methoxysalicylidene)-1,3-diaminobenzene, which has two sets of NO and OO' coordination pockets that are able to selectively accommodate Ni(II) and Ln(III) ions, respectively. The X-ray structure analysis reveals that the Ni(II) ions are bridged by phenylenediimine groups forming a 12-membered metallacycle in the central body of the complex, whereas the Ln(III) ions are located at both sides of the metallacycle and linked to the Ni(II) ions by diphenoxo bridging groups. Phenylenediimine and diphenoxo bridging groups transmit ferromagnetic exchange interactions between the two Ni(II) ions and between the Ni(II) and the Ln(III) ions, respectively. Complex 1 shows slow relaxation of the magnetization at zero field and a thermal energy barrier Ueff = 7.4 K with HDC = 1000 Oe, whereas complex 2 exhibits an S = 9 ground state and significant magnetocaloric effect (-ΔSm = 18.5 J kg(-1) K(-1) at T = 3 K and ΔB = 5 T).

Effectiveness of 5-aminolevulinic acid photodynamic therapy in the treatment of hidradenitis suppurativa: a report of 5 cases.

Hidradenitis suppurativa has been described as a chronic, recurrent, and disabling inflammatory disease involving the entire hair follicle. Several treatments, including photodynamic therapy, have been used, but the results have been inconsistent and recurrence is high. In this prospective study, we evaluated disease severity, quality of life, and treatment tolerance in 5 patients with moderate to severe hidradenitis suppurativa treated with photodynamic therapy using 5-aminolevulinic acid and a 635-nm light source. Treatment effectiveness was evaluated using the Sartorius severity score, the Dermatology Life Quality Index, and a visual analog scale for pain and disease activity. Significant improvements were observed with all 3 instruments and the effects remained visible at 8 weeks. Our results suggest that photodynamic therapy with 5-aminolevulinic acid and a light wavelength of 635 nm could reduce disease severity and improve quality of life in patients with difficult-to-treat hidradenitis suppurativa.

Influence of exposure to tobacco cigarette smoke on the eosinophil count in the nasal mucosa of young patients with perennial allergic rhinitis.

BACKGROUND: To assess the influence of exposure to tobacco cigarette smoke on the eosinophil count and the frequency of apoptosis of eosinophils in the nasal mucosa of teenagers with perennial allergic rhinitis. METHODS: Fifty patients were evaluated (aged 10 to 19 years old): 25 patients with and 25 patients with no recent exposure to tobacco cigarette smoke, by means of The Global Youth Tobacco Survey and cotinine/creatinine ratio. After a clinical evaluation, all the patients replied to a validated questionnaire of the severity of nasal symptoms; then, a nasal sample was processed to identify the eosinophil count and the frequency of apoptosis of eosinophils. RESULTS: Patients with active exposure to tobacco cigarette smoke had higher eosinophil counts than patients with no exposure to the smoke. In the two groups, apoptosis of eosinophils in the nasal mucosa was scarce and no significant correlation was observed between the frequency/severity of the nasal symptoms and the eosinophil count. CONCLUSION: Teenagers with perennial allergic rhinitis and active exposure to tobacco cigarette smoke may show increased eosinophil counts in the nasal mucosa, which might not be related to apoptosis of eosinophils or to the frequency/severity of nasal symptoms.

Influence of topography and hydrophilicity on initial oral biofilm formation on microstructured titanium surfaces in vitro.

OBJECTIVES: The aim of this study was to analyse the influence of the microtopography and hydrophilicity of titanium (Ti) substrates on initial oral biofilm formation. MATERIALS AND METHODS: Nine bacterial species belonging to the normal oral microbiota, including: Aggregatibacter actinomycetemcomitans, Actinomyces israelii, Campylobacter rectus, Eikenella corrodens, Fusobacterium nucleatum, Parvimonas micra, Porphyromonas gingivalis, Prevotella intermedia, and Streptococcus sanguinis were tested on Ti surfaces: pretreatment (PT [R(a) <0.2 µm]), acid-etched (A [R(a) <0.8 µm]), A modified to be hydrophilic (modA), sand-blasted/acid-etched (SLA [R(a) =4 µm]), and hydrophilic SLA (modSLA). Disks were incubated for 24 h in anaerobic conditions using a normal culture medium (CM) or human saliva (HS). The total counts of bacteria and the proportion of each bacterial species were analysed by checkerboard DNA-DNA hybridization. RESULTS: Higher counts of bacteria were observed on all surfaces incubated with CM compared with the samples incubated with HS. PT, SLA, and modSLA exhibited higher numbers of attached bacteria in CM, whereas SLA and modSLA had a significant increase in bacterial adhesion in HS. The proportion of the species in the initial biofilms was also influenced by the surface properties and the media used: SLA and modSLA increased the proportion of species like A. actinomycetemcomitans and S. sanguinis in both media, while the adhesion of A. israelii and P. gingivalis on the same surfaces was affected in the presence of saliva. CONCLUSIONS: The initial biofilm formation and composition were affected by the microtopography and hydrophilicity of the surface and by the media used.

Integrin alpha2beta1 plays a critical role in osteoblast response to micron-scale surface structure and surface energy of titanium substrates.

Efforts to improve bone response to biomaterials have focused on ligands that bind alpha5beta1 integrins. However, antibodies to alpha5beta1 reduce osteoblast proliferation but do not affect differentiation when cells are grown on titanium (Ti). beta1-silencing blocks the differentiation stimulus of Ti microtopography, suggesting that other beta1 partners are important. Stably alpha2-silenced MG63 human osteoblast-like cells were used to test whether alpha2beta1 specifically mediates osteoblast response to Ti surface micron-scale structure and energy. WT and alpha2-silenced MG63 cells were cultured on tissue culture polystyrene (TCPS) and Ti disks with different surface microtopographies: machined pretreatment (PT) surfaces [mean peak to valley roughness (R(a)) < 0.02 microm], PT surfaces that were grit-blasted and acid-etched (SLA; R(a) = 4 microm), and SLA with high surface energy (modSLA). Alkaline phosphatase (ALP), alpha2 and beta1 mRNA, but not alpha5, alpha v, beta3, type-I collagen, or osteocalcin, increased on SLA and modSLA at 6 days. Alpha2 increased at 8 days on TCPS and PT, but remained unchanged on SLA and modSLA. Alpha2-protein was reduced 70% in alpha2-siRNA cells, whereas alpha5-mRNA and protein were unaffected. Alpha2-knockdown blocked surface-dependent increases in beta1 and osteocalcin and decreases in cell number and increases in ALP and local factors typical of MG63 cells grown on SLA and modSLA [e.g., prostaglandin E(2), osteoprotegerin, latent and active TGF-beta1, and stimulatory effects of 1alpha,25(OH)(2)D(3) on these parameters]. This finding indicates that alpha2beta1 signaling is required for osteoblastic differentiation caused by Ti microstructure and surface energy, suggesting that conclusions based on cell behavior on TCPS are not predictive of behavior on other substrates or the mechanisms involved.

Rhinomanometry in young patients with perennial allergic rhinitis with/without recent exposure to tobacco smoke.

OBJECTIVE: To assess the influence of environmental exposure to tobacco smoke on the nasal symptoms and nasal resistance of young patients with perennial allergic rhinitis. DESIGN: Cross-sectional study. SETTING: Tertiary referral centre. PARTICIPANTS: Fifty patients were evaluated (aged 10-19 years old): 25 patients with and 25 patients without recent exposure to tobacco smoke (confirmed by cotinine/creatinine ratio). MAIN OUTCOMES MEASURES: After a clinical evaluation, all the patients replied to a validated questionnaire of the severity of the nasal symptoms. Then total nasal airway resistance was recorded by active anterior rhinomanometry. RESULTS: Patients with exposure to tobacco smoke had a larger total resistance than patients without exposure (t-test, P < 0.01). No significant correlation was observed between the total score of the questionnaire of nasal symptoms and the nasal resistance. CONCLUSIONS: In young patients with perennial allergic rhinitis, exposure to tobacco smoke can be related to increased nasal resistance, which may not be recognised by the report of nasal symptoms.

Exploring the prevalence of substance-induced neurocognitive disorder among polysubstance users, adding subjective and objective evidence of cognitive impairment.

The objective of this study was to explore the prevalence of substance-induced neurocognitive disorder (NCD) in a sample of polysubstance users, adding both objective- and subjective cognitive impairment. METHOD: We collected cross-sectional data from 33 community-based residential facilities in Mexico City. Montreal Cognitive Assessment was used for measurement of objective cognitive impairment, and a DSM-5-based interview for subjective impairment. Years and days of recent use of alcohol, marijuana, cocaine and inhalants were collected for regression analyses. RESULTS: 753 participants were analyzed; from these, 50.5% show objective impairment, 71% and 58.5% self-reported any cognitive deficit and cognitive decline, respectively. Between 21.8%-36.5% would qualify for NCD when integrating both objective- and subjective impairment (deficit or decline). Significant weak associations were found between objective impairment and subjective deficits in all cognitive domains except social cognition. Regression models adding both objective- and subjective measures explained more variation in the years of alcohol, inhalant and cocaine use, and in recent marijuana use, than the objective measure alone, but associations were inconsistent. CONCLUSION: Though significant in proportion, the prevalence of NCD in this population can only be partially related to substance use. Further integrative approaches are needed to refine the epidemiology of this disorder.

Relationship of bispectral index to hemodynamic variables and alveolar concentration multiples of sevoflurane in puppies.

The relationships between bispectral index (BIS), cardiovascular variables and minimum alveolar concentration (MAC) multiples of sevoflurane in puppies were determined. Five puppies were anesthetized with sevoflurane on two occasions. First, the individual sevoflurane MAC values were determined for each puppy. Secondly, dogs were anesthetized with sevoflurane at each of 5 MAC multiples, 0.75, 1, 1.25, 1.5 and 1.75 MAC administered in random order. Hemodynamic parameters and BIS data were collected for 20min. Somatic stimulus was then applied and the same parameters and data were collected for 6min. Correlation between BIS and end tidal sevoflurane and between BIS and hemodynamic parameters were studied. We found positive significant correlation in both cases. BIS is lower in puppies that in adults at the same alveolar anesthetic concentrations and sevoflurane appears to be a safe anesthetic in puppies.

Characterization of mesenchymal stromal cells derived from full-term umbilical cord blood.

BACKGROUND: Multipotent mesenchymal stromal cells (MSC) are of interest for their potential to repair bone and cartilage, and also their immunosuppressive properties. Umbilical cord blood (UCB) is reported to contain MSC, and therefore may be a useful source of these cells for clinical applications. METHODS: We evaluated protocols for isolating MSC from UCB and characterized the surface phenotype, differentiation potential and immunoregulatory properties of the cells obtained. RESULTS: Ten of 25 UCB units processed yielded MSC-like colonies, with depletion of lineage+ cells providing a higher efficiency. Only two of the cultures could be expanded satisfactorily; the remainder failed to proliferate. One culture generated transformed lines that were grossly aneuploid, had up-regulated TERT transcripts and had lost CD90 expression and the capacity to differentiate. The two propagated UCB-MSC lines were similar to those from bone marrow but were not identical to each other, with differences seen in expression of surface markers and cytoskeletal proteins. Both underwent osteogenesis, but at different rates and to different degrees, while neither generated adipocytes. When added as a third party to a mixed lymphocyte culture, both suppressed proliferation. DISCUSSION: MSC-like cells can be isolated from UCB, but at low efficiencies, and they exhibit a variety of morphologies, growth rates and differentiation potentials and can transform in culture.

[Renal transplantation with living donors. A critical analysis of surgical procedures based on 40 years of experience]. / Transplante renal de donante vivo: un análisis crítico de estrategias quirúrgicas basado en 40 años de experiencia.

INTRODUCTION: Absolute priority in an LDKT programme are donnor safety and kidney optimal anatomical and functional preservation. Reduced donnor morbidities, both at short and long term, are important objectives. Excellent technical grafting is a must as are the strategies employed for facilitatig it. We revised the incidences of our whole LDKT programme (40 years 243 donors) to confirm if these exigences have been acomplished or a change to new surgical procedures is recommended. MATERIAL AND METHODS: Between 1968-2008 243 nephrectomies and grafting has been performed, a reduced number per year (A cadaver programme has been running simultaneously since 1964). For the nephrectomies a Turner-Warrick apprach was inititialy used and since 1973 a miniincisional, anterior, extraperitoneal approach of approximately 10 cm in length. The right kidney was removed in 75% of the cases and the right iliac area for the implant in 85% In adjacent opperating rooms, one team performs the nephrectomy while the other prepares and dissects free the grafting vessels. Most of the time the same senior surgeon performed both operatios: the nephrectomy and the implant. Peroperative and postoperative complications were evaluated by urologists and nephrologists in charge. RESULTS: No donors dead, organs lost or major complications in the donors have been documented. Minor complications such as intestinal paresia, wound infection, persistent incisional pain were common. Miniincisional abdominal approach reduced postoperative pain and hospital stay (4 days). At long term no incisional hernia or abdominal paresia have been documented. Simultaneous work reduces ischemia time (30-45 s warm: 30-45 min cold) and opperatig room occupation(patient preparation plus anesthesia plus operation) estimated in 90-120 min for the nephrectomy and 120-160 for the grafting. The responsibility of the senior surgeon in both procedures facilitates vessel selection for the grafting. CONCLUSIONS: No reasons have been found to reconvert our current nephrectomy procedure to laparoscopic or modify current surgical strategy. Superior safety of open surgery for donors and organs is confirmed. Pain and recovery time are reduced in laparoscopic surgery but not as much when compared with miniincisional approach. Open surgery permits optimal anatomical and functional organ extration facilitatig the quality of the implant. As numbers matter in laparoscopic surgery open nephrectomy is recommended for reduced LDKT programmes.

[The figure of the head of service (Chairman): what profile should have?]. / La figura del Jefe de Servicio: qué perfil debe de tener?

Great social-health care changes in the short term have been predicted that will seriously affect the departmental structure and care hierarchy of future hospital, universitary, public or private. The Spanish Association of Urology (AEU) wondered whether in these circumstances, in which the welfare and economic management of the hospital so-called "industrial" will dominate over other traditional aspects of the scientific hierarchy, social welfare and teaching of head Urology of service, will change his image, goals, functions, and ultimately its authority. Likewise which must be the attributes of this new generation of department heads. To this end the AEU call a roundtable requesting opinions and comments which are reflected in the enclosed text.

Polycystosis of the renal sinus or polycystic kidney disease Controversies, challenges and history of a shared discovery. / Poliquistosis del seno renal o hilioquistosis. Controversias, retos e historia de un descubrimiento compartido.

OBJECTIVE: To recall the history of the discovery of non-nephron cystic disease, detected simultaneously in 2 hospitals in Madrid, and the vicissitudes that the authors endured during the process of recognising this disease, while being ignored by the international scientific literature. MATERIAL AND METHOD: We analysed the authors' first publications and presentations, their correspondence relaying the difficulties in reporting the confusion with adult polycystic kidney disease (APKD) and the subsequent nosological identification of the process. We consulted with individuals who worked with the 2 authors to increase the accuracy and objectivity of the history report. RESULTS: We confirmed the authors' remarkable efforts in getting the process definitively recognised despite the notable difficulties. CONCLUSIONS: Rigorous clinical observation recognises processes ignored by the medical literature, and the correct application of the scientific method helps identify and reveal new nosological entities, confirming with this story's example that, in medicine, there are no exhausted issues.