Trastornos somatomorfos y conversivos en otorrinolaringología pediátrica: revisión de la literatura

Resumen Los trastornos somatomorfos (TS) corresponden a un conjunto de entidades de expresión polimorfa cuya característica común es la relevancia de los síntomas somáticos asociados a un malestar psicológico significativo evidente o no, pero sin una base estructural delimitada. Si la sintomatología se asocia al sistema nervioso se denominan trastornos conversivos (TC). Su etiología tiene una naturaleza multicausal y compleja y se expresan en todos los sistemas del organismo. Los TS y los TC han sido poco estudiados en la otorrinolaringología pediátrica y su enseñanza es escasa en la formación médica. Se realizó una búsqueda sistemática sobre TS y TC en otorrinolaringología pediátrica en las bases de datos PubMed/Medline, SciELO y Cochrane Library. Se incluyeron 49 referencias, principalmente estudios observacionales y revisiones narrativas. Los cuadros clínicos descritos fueron el estridor funcional, la sordera psicógena, el trastorno facticio y el vértigo psicógeno. El proceso diagnóstico requiere de la evaluación otorrinolaringológica y psiquiátrica. En todos los estudios se reconoció que los participantes tenían alguna alteración afectiva prominente, aunque a veces oculta. El análisis del contexto social y escolar, además de los antecedentes familiares de TS, TC o cualquier desorden mental son elementos primordiales. La terapia es multidisciplinaria, incluyendo intervenciones otorrinolaringológicas, fonoaudiológicas, psicológicas y psicofarmacológicas. Sin embargo, la evidencia que sustenta a las intervenciones especializadas es escasa. Los niños, niñas y adolescentes con TS y TC presentan hallazgos clínicos y biológicos que no se presentan en los simuladores. Un adecuado diagnóstico y tratamiento se relacionan con un buen pronóstico.

Abstract Somatoform disorders (SD) make up a group of entities with polymorphic expression, characterized by the relevance of somatic symptoms associated to a significant psychological stress whether or not noticeable, but without a defined structural basis. When the symptomatology is related to the nervous system, they are known as conversion disorders (CD). Their etiology has a multicausal and complex nature, having expressions in all the body systems. SD and CD have been scarcely studied in pediatric otolaryngology and are poorly reviewed during medical training. We performed a systematic search on SD and CD in pediatric otolaryngology in PubMed/Medline, SciELO and Cochrane Library databases. We included 49 references, mostly observational studies and narrative reviews. The most described clinical pictures were functional stridor, psychogenic deafness, factitious disorder, and psychogenic vertigo. The diagnostic process requires otolaryngologic and psychiatric evaluations. All studies showed that participants had some relevant affective alteration, although sometimes unnoticeable. Thus, some essential elements are social and school context, family history of SD or CD or any mental disorder. Therapy involves a multidisciplinary approach, including otolaryngologic, audiological, psychological and psychopharmacological interventions. However, evidence supporting specialized interventions is still scarce. Children and adolescents who suffer from SD and CD show clinical and biological findings which are not found in malingering. Proper diagnosis and treatment are related to a good prognosis.

Characterization of invisible breast cancers in digital mammography and tomosynthesis: radio-pathological correlation. / Caracterización de cánceres de mama sintomáticos invisibles en mamografía digital y tomosíntesis: correlación radiopatológica.

OBJECTIVE: To review the radio-pathologic features of symptomatic breast cancers not detected at digital mammography (DM) and digital breast tomosynthesis (DBT). MATERIAL AND METHODS: Retrospective analysis of 169 lesions from symptomatic patients with breast cancer that were studied with DM, DBT, ultrasound (US) and magnetic resonance (MR). We identified occult lesions (true false negatives) in DM and DBT. Clinical data, density, US and MR findings were analyzed as well as histopathological results. RESULTS: We identified seven occult lesions in DM and DBT. 57% (4/7) of the lesions were identified in high-density breasts (type c and d), and the rest of them in breasts of density type b. Six carcinomas were identified at US and MR (BI-RADS 4 masses); the remaining lesion was only identified at MR. The tumor size was larger than 3cm at MRI in 57% of the lesions. All tumors were ductal infiltrating carcinomas, six of them with high stromal proportion. According to molecular classification, we found only one triple-negative breast cancer, the other lesions were luminal-type. We analyzed the tumor margins of two resected carcinomas that were not treated with neoadjuvant chemotherapy, both lesions presented margins that displaced the adjacent parenchyma without infiltrating it. CONCLUSION: Occult breast carcinomas in DM and DBT accounted for 4% of lesions detected in patients with symptoms. They were mostly masses, all of them presented the diagnosis of infiltrating ductal carcinoma (with predominance of the luminal immunophenotype) and were detected in breasts of density type b, c and d.

Cerámica 55S como sustrato para la regeneración de defectos óseos, estudio in vitro / Ceramic 55S as a substrate for the regeneration of bone defects; an in vitro study

Introducción. El objetivo de nuestro trabajo es evaluar in vitro el comportamiento y la capacidad inductora de la diferenciación osteoblástica de una vitrocerámica 55S (Vc) sobre una población de células madre mesenquimales adultas (del inglés mesenchymal stem cells [MSCs]) de conejo. Material y métodos. El material se obtuvo mediante el método sol-gel. Las células se obtuvieron de aspirado de médula ósea de conejo y se sembraron sobre la Vc y sobre el plástico (control). Las MSCs se cultivaron en dos medios de cultivo, uno estándar DMEM (medio de crecimiento [Mc]) y otro inductor del fenotipo osteoblástico compuesto por DMEM complementado con dexametasona, ß-glicerofosfáto y ácido ascórbico-2P (medio osteogénico [Mo]). Se evaluó la morfología de las células que crecieron mediante microscopía electrónica de barrido. Se usó el ensayo de reducción de sales de tetrazolio (XTT) para la evaluación del crecimiento celular. Para determinar la diferenciación celular se cuantificó la producción de osteocalcina y la pérdida del antígeno de superficie CD90, característico de las MSCs. Resultados. Durante el tiempo en cultivo las MSCs se adhirieron, proliferaron y formaron matriz extracelular mineralizada sobre la Vc, mostrando finalmente un fenotipo osteoblástico, produciendo osteocalcina y disminuyendo la expresión del antigeno CD90, independientemente del medio de cultivo utilizado. Conclusión. En base a estos resultados podemos afirmar que la Vc 55S se comportó como un material capaz de soportar la adhesión y el crecimiento de las MSCs y de inducir por sí misma la diferenciación de las MSCs a células de estirpe osteoblástica, mostrando por tanto, propiedades osteoconductoras y osteoinductoras (AU)

Introduction. The purpose of this work is to evaluate the in vitro behaviour and the capacity to induce osteoblastic differentiation of a 55S vitro-ceramic (Vc) on a population of adult rabbit mesenchymal stem-cells (MSCs). Material and methods. The material was obtained using the sol-gel method. The cells were obtained from rabbit bone-marrow aspirate and seeded over the Vc, and over plastic (control). The MSCs were cultivated in two culture media; one a standard DMEM (growth medium), and the other an osteoblastic phenotype inducer, composed of DMEM complemented with dexamethasone, ß-glycerophosphate and ascorbic acid-2-phosphate (osteogenic medium). The morphology of the cells that grew was assessed using a scanning electronic microscope. The tetrazolium salt reduction test was used for evaluating the cell growth. For cell differentiation, osteocalcin production and loss of CD90 bone surface antigen, characteristic of MSCs, were quantified. Results. During the culture time the MSCs adhered, proliferated and formed a mineralised extracellular matrix over the Vc. An osteoblastic phenotype finally being shown, producing osteocalcin and decreasing the expression of the CD90 antigen, regardless of the culture medium used. Conclusion. Based on these results we can state that Vc 55S behaved like a material capable of supporting adhesion and growth of MSCs and, in turn, inducing the differentiation of the MSCs to osteoblastic cell lines, thus showing osteoconduction and osteoinduction properties (AU)

[Ceramic 55S as a substrate for the regeneration of bone defects; an in vitro study]. / Cerámica 55S como sustrato para la regeneración de defectos óseos, estudio in vitro.

INTRODUCTION: The purpose of this work is to evaluate the in vitro behaviour and the capacity to induce osteoblastic differentiation of a 55S vitro-ceramic (Vc) on a population of adult rabbit mesenchymal stem-cells (MSCs). MATERIAL AND METHODS: The material was obtained using the sol-gel method. The cells were obtained from rabbit bone-marrow aspirate and seeded over the Vc, and over plastic (control). The MSCs were cultivated in two culture media; one a standard DMEM (growth medium), and the other an osteoblastic phenotype inducer, composed of DMEM complemented with dexamethasone, ß-glycerophosphate and ascorbic acid-2-phosphate (osteogenic medium). The morphology of the cells that grew was assessed using a scanning electronic microscope. The tetrazolium salt reduction test was used for evaluating the cell growth. For cell differentiation, osteocalcin production and loss of CD90 bone surface antigen, characteristic of MSCs, were quantified. RESULTS: During the culture time the MSCs adhered, proliferated and formed a mineralised extracellular matrix over the Vc. An osteoblastic phenotype finally being shown, producing osteocalcin and decreasing the expression of the CD90 antigen, regardless of the culture medium used. CONCLUSION: Based on these results we can state that Vc 55S behaved like a material capable of supporting adhesion and growth of MSCs and, in turn, inducing the differentiation of the MSCs to osteoblastic cell lines, thus showing osteoconduction and osteoinduction properties.

Granuloma mercurial en mano. A propósito de un caso / Mercury granuloma of the hand. Report of a case

Se presenta un caso de granuloma mercurial en dorso de la primera falange del tercer dedo mano izquierda tras rotura accidental de un termómetro convencional de mercurio. La paciente fue tratada durante 6 meses con crioterapia sin conseguir resolver el problema. Se practicó resección amplia en bloque de la lesión con cobertura del aparato extensor con injerto libre de piel total del pliegue de la muñeca. En la actualidad el resultado es satisfactorio no presentado recidiva al año de la intervención (AU)

A case is presented of mercury granuloma on the dorsal surface of the first phalanx of the middle finger of the left hand, secondary to accidental rupture of a conventional mercury thermometer. Six months of cryotherapy proved unable to solve the problem. Wide en bloc resection of the lesion was performed, covering the extensor unit with a full-thickness skin graft harvested from the fold of the wrist. The result is satisfactory, and there has been no recurrence after one year of follow-up (AU)

Plasticity of xyloglucan composition in bean (Phaseolus vulgaris)-cultured cells during habituation and dehabituation to lethal concentrations of dichlobenil.

Bean cells that have been habituated to grow in a lethal concentration (12 µM) of 2,6-dichlorobenzonitrile (dichlobenil or DCB, a cellulose biosynthesis inhibitor) are known to have decreased cellulose content in their cell walls. Xyloglucan, which is bound to cellulose and together with it forms the main loading network of plant cell walls, has also been described to decrease in habituated cells, but whether the change on cellulose affects the xyloglucan structure besides its abundance has not been analyzed. Fragmentation analysis with xyloglucan-specific endoglucanase (XEG) and endocellulase revealed that habituation to DCB caused a change in the fine structure of xyloglucan, namely a decrease in fucosyl residues attached to the galactosyl-xylosyl residues along the glucan backbone. After the removal of herbicide from the medium (dehabituated cells), xyloglucan recovered its fucosyl residues. In addition, some cello-oligosaccharides could be detected only in habituated cells' xyloglucan digested by XEG and endocellulase, corresponding to a glucan covalently bound or co-precipitated with the hemicelluloses. These results show that structural flexibility of cell walls relies in part on the plasticity of xyloglucan composition and opens up new perspectives to further research in this field.

Noninvasive assessment of fibrosis and steatosis in NASH and ASH.

NAFLD and alcoholic liver disease affect a substantial proportion of the population worldwide. Although presence and amount of steatosis can be determined with a good level of accuracy using noninvasive imaging techniques, currently, there is no available noninvasive tests to distinguish between simple steatosis from steatohepatitis or to stage fibrosis that had demonstrated to be simple, reproducible, and valid in patients who have NAFLD or alcoholic liver disease. Liver biopsy remains a useful tool to confirm the diagnosis and exclude other liver disease and remains the only investigation able to provide prognostic information by staging and grading these diseases. Noninvasive serum markers offer considerable promise in their ability to stage liver fibrosis. Routine liver tests may detect occult cirrhosis but are insensitive at predicting lesser stages of fibrosis. Several serum markers of collagen synthesis and degradation are not validated sufficiently and are not available in most medical centers to replace liver biopsy. These markers currently may assist in stratifying patients who are more likely to have advanced fibrosis and, therefore, may benefit from proceeding with liver biopsy. It is likely the more complex models, which include multiple serum markers, will be more accurate at predicting fibrosis. These currently have limited ability at predicting the full range of liver fibrosis, generally having the greatest diagnostic accuracy at predicting advanced fibrosis or absent fibrosis but not in-between. Measuring liver stiffness with different imaging techniques holds promise, but further carefully designed studies are necessary before they can be recommended in clinical practice.

The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years.

OBJECTIVES: The long-term prognosis of non-alcoholic fatty liver disease (NAFLD) in children remains uncertain. We aimed at determining the long-term outcomes and survival of children with NAFLD. DESIGN: Retrospective longitudinal hospital-based cohort study. PATIENTS: Sixty-six children with NAFLD (mean age 13.9 (SD 3.9) years) were followed up for up to 20 years with a total of 409.6 person-years of follow-up. RESULTS: The metabolic syndrome was present in 19 (29%) children at the time of NAFLD diagnosis with 55 (83%) presenting with at least one feature of the metabolic syndrome including obesity, hypertension, dyslipidaemia and/or hyperglycaemia. Four children with baseline normal fasting glucose developed type 2 diabetes 4-11 years after NAFLD diagnosis. A total of 13 liver biopsies were obtained from five patients over a mean of 41.4 (SD 28.8) months showing progression of fibrosis stage in four children. During follow-up, two children died and two underwent liver transplantation for decompensated cirrhosis. The observed survival free of liver transplantation was significantly shorter in the NAFLD cohort as compared to the expected survival in the general United States population of the same age and sex (log-rank test, p<0.00001), with a standardised mortality ratio of 13.6 (95% confidence interval, 3.8 to 34.8). NAFLD recurred in the allograft in the two cases transplanted, with one patient progressing to cirrhosis and requiring re-transplantation. CONCLUSIONS: Children with NAFLD may develop end-stage liver disease with the consequent need for liver transplantation. NAFLD in children seen in a tertiary care centre may be associated with a significantly shorter survival as compared to the general population.

GI epidemiology: nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common diagnosis in clinical practice. Insulin resistance and oxidative stress play an important role in NAFLD development and progression. AIM: To review the data available on the epidemiology and natural history of NAFLD as well as the risk factors for its development and the areas where future research is necessary. RESULTS /CONCLUSIONS: NAFLD may affect individuals of any age range and race/ethnicity. NAFLD affects one in three adults and one in ten children/adolescents in the United States. Mortality in patients with NAFLD is significantly higher than in the general population of same age and gender with liver-related complications being a common cause of death. Liver-related morbidity and mortality in NAFLD occurs when the disease has progressed to advanced fibrosis and cirrhosis. Further studies are necessary to determine the impact of NAFLD on health-related quality of life and resources utilization, and to the extent to which preventing the development of the metabolic syndrome would prevent NAFLD development and reduce liver-related morbidity and mortality. Lifestyle intervention may improve NAFLD, but medications that increase insulin sensitivity and the antioxidant defenses in the liver deserve evaluation in carefully controlled trials.

Increase in XET activity in bean (Phaseolus vulgaris L.) cells habituated to dichlobenil.

Bean (Phaseolus vulgaris L.) cells have been habituated to grow in lethal concentrations of dichlobenil (DCB), a specific inhibitor of cellulose biosynthesis. Bean callus cells were successively cultured in increasing DCB concentrations up to 2 microM. The 2-microM DCB habituated cells were impoverished in cellulose and xyloglucan, had an increased xyloglucan endotransglucosylase (XET; EC 2.4.1.207) activity, together with an increased growth rate and a decreased molecular size of xyloglucan. However, the application of lethal concentrations of two different cellulose-biosynthesis inhibitors (DCB and isoxaben) for a short period of time produced little effect on XET activity and xyloglucan molecular size. We propose that the weakening of plant cell wall provoked by decrease in cellulose content might promote the xyloglucan tethers and increase the ability of xyloglucan to bind to cellulose in order to give rigidity to the wall.

Treatment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is common and may progress to cirrhosis and its complications. The pathogenesis of steatosis and cellular injury is thought to be related mostly to insulin resistance and oxidative stress. Therefore, management entails identification and treatment of metabolic risk factors, improving insulin sensitivity, and increasing antioxidant defences in the liver. Weight loss and exercise improve insulin sensitivity. Bariatric surgery may improve liver histology in patients with morbid obesity. Insulin sensitising drugs showed promise in pilot trials as have a number of hepatoprotective agents. Further randomised, well controlled trials are required to determine the efficacy of these drugs.

Recent concepts in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is present in up to one-third of the general population and in the majority of patients with metabolic risk factors such as obesity and diabetes. Insulin resistance is a key pathogenic factor resulting in hepatic fat accumulation. Recent evidence demonstrates NAFLD in turn exacerbates hepatic insulin resistance and often precedes glucose intolerance. Once hepatic steatosis is established, other factors, including oxidative stress, mitochondrial dysfunction, gut-derived lipopolysaccharide and adipocytokines, may promote hepatocellular damage, inflammation and progressive liver disease. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies, however, staging the disease requires a liver biopsy. NAFLD is associated with an increased risk of all-cause death, probably because of complications of insulin resistance such as vascular disease, as well as cirrhosis and hepatocellular carcinoma, which occur in a minority of patients. NAFLD is also now recognized to account for a substantial proportion of patients previously diagnosed with 'cryptogenic cirrhosis'. Diabetes, obesity and the necroinflammatory form of NAFLD known as non-alcoholic steatohepatitis, are risk factors for progressive liver disease. Current treatment relies on weight loss and exercise, although various insulin-sensitizing medications appear promising. Further research is needed to identify which patients will achieve the most benefit from therapy.

Primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic syndrome of unknown etiology frequently associated with inflammatory bowel disease and characterized by diffuse inflammation and fibrosis of the intra and/or extrahepatic bile ducts. Recent studies seem to favor autoimmunity in the context of a genetic predisposition as the most likely underlying mechanism for the development of the disease, however our knowledge on the pathogenesis of PSC is still incomplete and further work is needed. The most common manifestations are fatigue, pruritus, jaundice and abdominal pain; however, the increasing use of invasive cholangiography has led to diagnosing this condition in a high proportion of asymptomatic patients. PSC usually follows a progressive course leading to biliary cirrhosis with complications of portal hypertension and hepatic failure. Patients with PSC also may develop a number of other complications, including bacterial cholangitis, dominant biliary strictures, conditions of chronic cholestasis, colorectal cancer and cholangiocarcinoma. Currently, no medical therapy aimed at disrupting disease progression is available, although high-dose ursodeoxycholic acid and other medicines are being evaluated in clinical trials. A better understanding of the pathogenesis of the disease will serve as a guide for evaluating new medical approaches. Liver transplantation is the only therapeutic alternative that improves survival in patients with end-stage PSC. Prognostic models are useful in determining the timing of liver transplantation.

Development of autoimmune hepatitis in the setting of long-standing primary biliary cirrhosis.

Primary biliary cirrhosis and autoimmune hepatitis, the most common autoimmune liver diseases in adults, are frequently easily differentiated by a combination of clinical, biochemical, and histological features along with the presence of highly sensitive and characteristic serum autoantibodies. Patients presenting with "overlapping" features of both conditions simultaneously are not uncommon. However, patients who switch over time from one disease to another have remained largely unrecognized. We report here two cases from the spectrum of autoimmune liver disease, patients who had well-defined primary biliary cirrhosis for a number of years and then developed the classic picture of superimposed autoimmune hepatitis. The importance of its recognition and the appropriate management modifications are discussed.

Incomplete response to ursodeoxycholic acid in primary biliary cirrhosis: is a double dosage worthwhile?

OBJECTIVE: The aim of this study was to assess the safety and efficacy of high-dose ursodeoxycholic acid (UDCA, 28-32 mg/kg/day) in patients with primary biliary cirrhosis (PBC) who had shown an incomplete response to the standard dose (13-15 mg/kg/day). METHODS: A total of 25 patients with PBC who had been on UDCA (13-15 mg/kg/day) therapy for 24-141 months and had shown persistent elevation of ALP activity at least two times the upper limit of normal were enrolled. The dose of UDCA was increased to 30 (28-32) mg/kg/day and given for 1 yr. RESULTS: A significant but marginal improvement in serum ALP activity (707+/-52 vs 571+/-32, p = 0.001) was noted at 1 yr of treatment with high-dose UDCA. However, levels of total bilirubin (1.1+/-0.2 vs 1.0+/-0.2, p = 0.1), AST (58+/-9 vs 54+/-1, p = 0.1), albumin (4.1+/-0.7 vs 4.0+/-0.08, p = 0.1), or Mayo risk score (4.13+/-0.3 vs 4.12+/-0.3, p = 0.2) remained essentially unchanged. Normalization of liver tests did not occur in any patient, and adverse events were not recorded in any case. CONCLUSIONS: Although UDCA at a dose of 28-32 mg/kg/day is well tolerated, this dosage does not seem to benefit most patients with PBC responding incompletely to a dose of 13-15 mg/kg/day. The results of this pilot study would seem to discourage further controlled trials of high-dose UDCA in suboptimal responders to the standard dose of UDCA.