A tissue-bioengineering strategy for modeling rare human kidney diseases in vivo.

The lack of animal models for some human diseases precludes our understanding of disease mechanisms and our ability to test prospective therapies in vivo. Generation of kidney organoids from Tuberous Sclerosis Complex (TSC) patient-derived-hiPSCs allows us to recapitulate a rare kidney tumor called angiomyolipoma (AML). Organoids derived from TSC2-/- hiPSCs but not from isogenic TSC2+/- or TSC2+/+ hiPSCs share a common transcriptional signature and a myomelanocytic cell phenotype with kidney AMLs, and develop epithelial cysts, replicating two major TSC-associated kidney lesions driven by genetic mechanisms that cannot be consistently recapitulated with transgenic mice. Transplantation of multiple TSC2-/- renal organoids into the kidneys of immunodeficient rats allows us to model AML in vivo for the study of tumor mechanisms, and to test the efficacy of rapamycin-loaded nanoparticles as an approach to rapidly ablate AMLs. Collectively, our experimental approaches represent an innovative and scalable tissue-bioengineering strategy for modeling rare kidney disease in vivo.

Vía aérea fisiológicamente difícil: nuevo concepto a considerar: Caso clínico vía aérea difícil fisiológica / Physiologically difficult airway: new concept to consider: case report

Airway management in the ICU scenario is a real challenge due to instability imposed by illness severity. Some of these patients may also suffer from other diseases associated to difficult airway. Rheumatoid arthritis represents a special condition because not only can limit access to the hypopharynx, but also can hamper laryngoscopy. Among many options for difficult airway management, only a few can be safely applied to intubate the trachea while preserving physiologic stability in an emergency setting. We chose awake fiberoptic intubation as the first and safest approach for this combined difficult patient. This approach requires not only individual skills but also a plan in advance and a well coordinated team to be successful. A case is presented as an example of difficulties imposed by physiologic instability added to anatomic difficult.

El manejo de la vía aérea en la UCI representa un desafío debido a la inestabilidad derivada de la severidad de la patología. Además, algunos de estos pacientes pueden presentar condiciones preexistentes asociadas a vía aérea difícil. La artritis reumatoide representa una condición especial debido a que no sólo limita el acceso a la hipofaringe, sino que también puede dificultar la laringoscopía. Entre las diferentes opciones para manejar la vía aérea, sólo algunas pueden ser aplicadas para intubar la tráquea de manera segura y al mismo tiempo preservar la estabilidad fisiológica en un contexto de urgencia. Este abordaje requiere no sólo habilidades individuales, sino que también trabajo en equipo coordinado y planificación. Se presenta un caso como ejemplo de dificultades impuestas por la inestabilidad fisiológica agregada a dificultad anatómica.

Infecciones del tracto urinario bajo en adultos y embarazadas: consenso para el manejo empírico / Lower Urinary Tract Infections in Adults and Pregnant Women: A Consensus for Empirical Treatment

Introducción: La infección no complicada del tracto urinario bajo y la bacteriuria asintomática son causas frecuentes de consulta médica ambulatoria y en el servicio de urgencias en Colombia y el mundo. La falta de pautas y consenso para el manejo, así como la emergencia de resistencia a las múltiples opciones terapéuticas disponibles en los uropatógenos provenientes de la comunidad, hacen necesario elaborar unas recomendaciones que orienten al clínico sobre el abordaje óptimo de estas entidades. Objetivo: Definir un consenso sobre el manejo empírico de la bacteriuria asintomática y la infección del tracto urinario (ITU) bajo en adultos y mujeres embarazadas en Colombia. Metodología: Se lleva a cabo una metodología de consenso con expertos en urología, infectología, medicina interna, ginecología y microbiología basada en la revisión de las referencias bibliográficas disponibles en los términos de búsqueda relacionados, haciendo énfasis en estudios locales. Resultados: Se elaboró un algoritmo de manejo para el tratamiento empírico de la ITU baja no complicada en adultos con antisépticos urinarios como nitrofurantoína y fosfomicina trometamol como primera línea, con recomendaciones terapéuticas específicas para el tratamiento de la bacteriuria asintomática en mujeres embarazadas. Adicionalmente, se formuló un algoritmo de decisión para el procesamiento de cultivos de orina. La recurrencia o recaída frecuente justifica remisión a urología e infectología. Conclusiones: Se generan recomendaciones prácticas de fácil implementación en el diagnóstico y manejo de la ITU bajo en adultos y embarazadas, y de los casos donde es necesario tratar la bacteriuria asintomática, con opciones terapéuticas efectivas y de espectro reducido.

Background: Uncomplicated infection of the lower urinary tract and asymptomatic bacteriuria are frequent causes of visits to outpatient clinics and emergency departments in Colombia and worldwide. The lack of guidelines and a consensus for their management, and the emergence of resistance of community-based uropathogens to the available therapeutic options, make it necessary to develop recommendations to guide clinicians on the optimal approach to these entities. Objective: Define a consensus for the empiric management of asymptomatic bacteriuria and Urinary Tract Infection (UTI) in adults and pregnant women in Colombia. Methods: We carried out a consensus methodology with experts in urology, infectious diseases, internal medicine, gynecology and clinical microbiology; based on reviewing the available literature on the related terms, and emphasizing local studies. Results: We developed a management algorithm for the empirical treatment of uncomplicated lower UTI in adults with urinary antiseptics such as nitrofurantoin and fosfomycin trometamol as first line, with specific therapeutic recommendations for the treatment of asymptomatic bacteriuria in pregnant women. Additionally, we created a decision algorithm for processing urine cultures. Frequent recurrence or relapse justifies referral to urology and infectious disease professionals. Conclusions: We generated straightforward and easy-to-implement recommendations for the diagnosis and management of UTI in adults and pregnant women, and in cases where it is necessary to treat asymptomatic bacteriuria, with effective therapeutic and narrow spectrum options.

Significance of liquefaction degeneration in oral lichen planus: a study of its relationship with apoptosis and cell cycle arrest markers.

OBJECTIVE: To assess the utility of liquefaction degeneration as a marker of apoptosis in oral lichen planus (OLP). METHODS: TdT-mediated dUTP-biotin nick-end labelling (TUNEL) assay and immunohistochemical methods were used to detect p21 proteins and the active form of caspase 3 in 32 tissue samples of oral mucosa with OLP and 20 samples of normal oral mucosa. RESULTS: Liquefaction degeneration was moderate or intense in 27.5% (n=8) and slight in 72.4% (n=21) of OLP samples. There was low expression of apoptosis markers (TUNEL, active caspase 3 form), which was not significantly associated with liquefaction degeneration of the basal cell layer. Basal and suprabasal expression of p21 was significantly more frequent in samples with more intense liquefaction degeneration of basal cells (P<0.01). CONCLUSIONS: Our results demonstrate that liquefaction degeneration, as a morphological expression of T lymphocyte attack, does not unequivocally indicate apoptosis. Attacked basal cells more frequently respond with cell-cycle arrest or senescence than with apoptosis.

Oral cancer: experiences and diagnostic abilities elicited by dentists in North-western Spain.

BACKGROUND: Opinions, knowledge, behaviours and attitudes of general dental practitioners on oral cancer prevention and detection have been reported from many countries. However, experiences and skills of oral cancer detection have not been evaluated systematically. OBJECTIVE: To obtain information on behaviours of screening and ability to correctly detect oral cancer and precancer among general dentists (GDP) in North-western Spain. SUBJECTS AND METHODS: Thirty-two randomly selected GDPs completed questionnaires and then classified 50 projected images of clinical lesions, into cancer, precancer or benign lesions. RESULTS: 87.5% reported conducting routine oral examinations, 84.4% provided routine advice to their subjects for risk modifications and 84.4% claimed to biopsy a suspected oral mucosal lesion that they detected in practice. In a quasi research setting using clinical slides, the sensitivity of visual diagnosis of a cancerous lesion was 61.4% and precancer 59.5%. The diagnostic accuracy reported here is lower than what is already reported by evaluation of published screening programmes by dentists. CONCLUSIONS: Our data from Spain suggest a need for improving the diagnostic ability of GDPs in the visual detection of oral cancer/precancer by strengthening continuing professional education.

Apoptosis and cell cycle arrest in oral lichen planus Hypothesis on their possible influence on its malignant transformation.

The quantitative importance of cell cycle arrest and apoptosis mechanisms in oral lichen planus (OLP) was analysed in order to assess the cell response to T lymphocyte aggression and establish a hypothesis on the influence of these phenomena in the malignant transformation process. The TUNEL assay and immunohistochemical methods were used to detect caspase-3, bax, and p21 in 32 tissue samples of oral mucosa with OLP and in 20 samples of normal oral mucosa. Positivity for TUNEL, caspase-3 and p21 was significantly more frequent in cases than in controls (p<0.001). Both TUNEL and caspase-3 positivity was significantly greater in the basal versus suprabasal layer (p=0.004 and 0.052, respectively). The basal and suprabasal expression of p21 was significantly higher in cases with a more intense liquefaction degeneration (p<0.01). There was no significant difference in basal expression of bax between cases and controls. The quantitative importance of apoptosis was small in OLP. Epithelial cells attacked in OLP have a very low response to apoptosis and cell cycle arrest mechanisms, which may produce an epithelial substrate that favours malignant transformation.

Effects of irrigation deprivation during the harvest period on leaf persistence and function in mature almond trees.

In nut tree orchards in California, irrigation is typically withheld during the harvest period to reduce the likelihood of bark damage during mechanical shaking of the trees. The ensuing water stress, however, may result in premature defoliation and subsequent yield declines. Our objective was to establish and quantify the water stress resulting from irrigation deprivation and determine its impact on leaf function and persistence in mature almond trees (Prunus dulcis (Mill.) D.A. Webb cv. Nonpareil) during a 3-year field experiment. The severity of the water stress was characterized by measurements of predawn leaf (Psi(pd)) and midday stem (Psi(ms)) water potentials, stomatal conductance (gs), net CO2 assimilation rate (A) and leaf abscission. During 1995, Psi(ms) of fully irrigated (FI) trees was maintained above -1.0 MPa. In trees in the moderate- (MS) and severe-stress (SS) treatments, Psi(ms) was reduced to -1.4 to -2.0 MPa and -2.0 to -2.6 MPa, respectively. After 18 days of irrigation deprivation, A was reduced by 32 and 58% at midday and early afternoon, respectively, compared with morning values. A significant decrease in morning values of A only occurred after 30 days of irrigation deprivation. Water-use efficiency and A declined as evaporative demand increased from morning to afternoon. Assimilation also declined seasonally as leaves aged. Midday stem water potential was highly correlated with A, but less so with gs. The coefficient of determination between Psi(ms) and gs improved considerably when vapor pressure deficit and wind were multiply regressed with Psi(ms). Although A recovered rapidly when MS trees were irrigated, recovery in SS trees was slower and incomplete. Integrating the MS and SS effects for an extended period during 1995 resulted in 14 and 30% declines in A, and 6 and 20% declines in gs, respectively. The apparent Psi(ms) threshold for leaf abscission was -1.8 MPa. Daily canopy light interception declined with decreasing Psi(ms) as a result of premature defoliation (and perhaps altered leaf angles) from 67.9% in FI trees to 61.4 and 60.7% in MS and SS trees, respectively.

Effects of irrigation deprivation during the harvest period on yield determinants in mature almond trees.

Effects of irrigation deprivation during the harvest period on yield determinants in mature almond (Prunus dulcis (Mill.) D.A. Webb cv. Nonpareil) trees were investigated during a 3-year field experiment. Return bloom and fruit set were measured on 2185 individually tagged spurs. Water stress resulting from irrigation deprivation during the harvest period, which purportedly coincides with the time of flower initiation, had no effect on the percentage of spurs that flowered or set fruit during subsequent years. Although water stress had no apparent effect on spur mortality, 66% of the tagged spurs died within 3 years. In addition, many spurs were vegetative by the third year, indicating the importance of spur renewal for sustained fruit production. Reductions in nut yield were evident after two successive years of irrigation deprivation during the harvest period. Regression analysis indicated a loss in yield of 7.7 kg tree(-1) in response to each 1 MPa decrease in stem water potential below -1.2 MPa during the previous seasons. The number of fruiting positions per tree (estimated indirectly for whole trees based on weight of current-year shoots > 5 cm in length) was negatively associated with water stress. Yield reduction in response to water stress during harvest appears to be a compound, multiyear effect, associated with reduced annual growth and renewal of fruiting positions.

Effects of irrigation deprivation during the harvest period on nonstructural carbohydrate and nitrogen contents of dormant, mature almond trees.

Effect of irrigation deprivation during the harvest period on the nonstructural carbohydrate (NC) content of dormant, mature, field-grown almond (Prunus dulcis (Mill.) D.A. Webb cv. Nonpareil) trees was studied. Roots, trunk, branches, spurs and stems of 12 trees were subsampled in February 1997, across a gradient of irrigation treatments (FI = fully irrigated, MS = moderately stressed and SS = severely stressed) to relate NC concentration to the degree of water stress experienced by individual trees during the previous (1996) harvest period. To assess the effect of water stress on whole-tree NC content, three dormant FI trees and three dormant SS trees were excavated on December 10, 1997, and dry weights and NC and N concentrations of the tree components were determined. Whole-tree biomass did not differ significantly between FI and SS trees, although SS trees tended to have less total dry weight. Although roots constituted just 13% of tree biomass, they stored 36 and 44% of tree NC and N contents, respectively. There were negative relationships between the seasonal minimum values of both midday (Psi(ms)) and predawn (Psi(pd)) stem water potentials during the harvest period and root NC content of dormant trees. Severe water stress during the harvest period resulted in a 26% reduction in NC content and a 50% reduction in biomass of current-year stems (> 5 cm in length) per tree. The reduction in NC content is consistent with the previously reported late season reductions in leaf function and persistence. The SS trees exhibited a reduction in NC content but not in N content per tree, indicating that late season accumulation of NC and N were uncoupled in trees subjected to severe harvest-period water stress.

Influence of canopy light environment and nitrogen availability on leaf photosynthetic characteristics and photosynthetic nitrogen-use efficiency of field-grown nectarine trees.

Relationships between CO(2) assimilation at light saturation (A(max)), nitrogen (N) content and weight per unit area (W(A)) were studied in leaves grown with contrasting irradiances (outer canopy versus inner canopy) and N supply rates in field-grown nectarine trees Prunus persica L. Batsch. cv. Fantasia. Both A(max) and N content per unit leaf area (N(A)) were linearly correlated to W(A), but leaves in the high-N treatment had higher N(A) and A(max) for the same value of W(A) than leaves in the low-N treatment. The curvilinear relationship between photosynthesis and total leaf N was independent of treatments, both when expressed per unit leaf area A(maxA) and N(A)) and per unit leaf weight (A(maxW) and N(W)), but the relationship was stronger when data were expressed on a leaf area basis. Both A(maxA) and N(A) were higher for outer canopy leaves than for inner canopy leaves and A(maxW) and N(W) were higher for leaves in the high-N treatment than for leaves in the low-N treatment. The relationship between A(max) and N resulted in a similar photosynthetic nitrogen-use efficiency at light saturation (A(max)NUE) for both N and light treatments. Photosynthetic nitrogen-use efficiency was similar among treatments throughout the whole light response curve of photosynthesis. Leaves developed in shade conditions did not show higher N-use efficiency at low irradiance. At any intercellular CO(2) partial pressure (C(i)), photosynthetic CO(2) response curves were higher for outer canopy leaves and, within each light treatment, were higher for the high-N treatments than for the low-N treatments. Consequently, most of the differences among treatments disappeared when photosynthesis was expressed per unit N. However, slightly higher assimilation rates per unit N were found for outer canopy leaves compared with inner canopy leaves, in both N treatments. Because higher daily irradiance within the canopies of the low-N trees more than compensated for the lower photosynthetic performances of these leaves compared to the leaves of high-N trees, daily carbon gain (and N-use efficiency on a daily assimilation basis) per leaf was higher for the low-N treatment than for the high-N treatment in both outer and inner canopy leaves.

Assessment of dental students' ability to recognise precancerous lesions and conditions.

The role of dentists in both primary (promoting a healthier lifestyle) and secondary (early diagnosis) prevention of oral cancer is undeniable, and becomes particularly important as oral cancer is thought to be preceded by premalignant lesions or conditions in about one half of the cases. In these situations, there is the possibility for an early diagnosis which will definitively influence the survival rate. Thus, it is an undergraduate educational objective related to secondary prevention of oral cancer to increase the efficacy of screening of precancerous lesions/conditions. A questionnaire with 38 clinical cases including 16 benign lesions, 9 malignant lesions and 13 precancerous lesions or conditions was applied voluntarily to 3rd, 4th and 5th year University of Santiago de Compostela dental students on April 1996. The participation rate was 90% of the 3rd-year students, 60% in 4th-year class, and 50% of the 5th-year group. The agreement in the diagnosis with a panel of experts reached 81.45% for 5th-year students. Students of 3rd- and 4th-year scored lower percentages, probably due to the rarity of some of the conditions in our area. 5th-year students scored significantly higher values than 3rd- and 4th-year students.

[Conceptual review of Behçet's syndrome. Diagnostic and therapeutic criteria]. / Revisión conceptual del sindrome de Behçet. Criterios diagnósticos yterapéuticos.

A review of the literature on clinical, diagnostic and therapeutic aspects on Behcet Syndrom is done.

[Macroglossia in a case of amyloidosis and hypothyroidism]. / Macroglosia en un caso den amiloidosis e hipotiroidismo.

It is reported a case of macroglossia with neoplasic-like ulcer in the tongue, in a patient with amyloidosis and hypothyroidism.

La planeación hospitalaria en México / Hospital planning in Mexico

Mostra en forma panoramica, los antecedentes de planeación hospitalaria en Mexico y posteriormente, la situaçón actual en ese sentido y el desglose de un programa médico-arquitectónico. (AU)