Recuperación laboral clínica y funcional a 3 meses del alta en pacientes hospitalizados por neumonía por SARS-CoV-2: relación con la terapia recibida / Clinical and functional recovery and return to work 3 months after discharge in patients hospitalized for SARS-CoV-2 pneumonia: relationship with the therapy received

Resumen Introducción: La presentación clínica de neumonía por COVID-19 ha sido bien documentada; sin embargo, sus repercusiones a largo plazo son aún motivo de investigación. Objetivo: Evaluar la recuperación laboral, clínica y funcional respiratoria, a 3 meses del egreso de pacientes hospitalizados por neumonía por SARS-CoV-2, en relación con la terapia ventilatoria recibida. Pacientes y Métodos: Se analizó una cohorte prospectiva de 116 pacientes con neumonía por COVID-19 del Hospital Naval Almirante Nef de Viña del Mar, con seguimiento clínico y funcional respiratorio 3 meses después de su alta. Resultados: Mediana del seguimiento: 100 días. Constitución de la cohorte: 75 hombres, mediana de edad 60 años, 50% obesos, 34,5% fumadores y 13,8% con comorbilidad respiratoria. 16% recibió rehabilitación. Se reportó disnea en 48,3% y fatigabilidad en 33,6%. Solo 54,8% retornó al trabajo. El 65,2% que utilizó oxigenoterapia (O2) volvió a trabajar comparado con 44% que utilizó cánula nasal de alto flujo (CNAF) y 33,3% con ventilación mecánica invasiva (VMI). Mayoritariamente el grupo de O2 volvió a la vida normal en comparación con CNAF y VMI (71,4 versus 17,5% y 11,1% respectivamente). La función pulmonar fue normal en 39 pacientes (33,6%). La serie que volvió a vida normal tuvo mayor porcentaje de DLCO y test de caminata de 6 minutos normales. En comparación con la serie O2, la serie CNAF tuvo mayor frecuencia de alteración de DLCO (OR = 5) seguido por la serie VMI (OR = 3,6). Conclusión: A 3 meses de seguimiento, se evidenció ausentismo laboral, persistencia de síntomas y alteración funcional respiratoria (DLCO), especialmente en quienes recibieron soporte ventilatorio adicional a oxigenoterapia.

Introduction: The clinical presentation of COVID-19 pneumonia has been well documented; however, its long-term repercussions are still a matter of investigation. Objective: to evaluate the occupational, clinical and functional respiratory recovery, 3 months after the discharge of patients hospitalized for SARS-CoV-2 pneumonia, in relation to the ventilatory therapy received. Patients and Methods: A prospective cohort of 116 patients with COVID-19 pneumonia from Hospital Naval Almirante Nef (Viña del Mar, Chile) was analyzed, with clinical and functional respiratory follow-up at 3 months after being discharged. Results: Median follow-up: 100 days. Composition of the cohort: 75 men, median age 60 years-old, 50% obese, 34.5% smokers and 13.8% with respiratory comorbidity. 16% received rehabilitation. Dyspnea was reported in 48.3% and fatigue in 33.6%. Only 54.8% returned to work. 65.2% who used oxygen therapy (O2) returned to work compared to 44% who used high-flow nasal cannula (HFNC) and 33.3% with invasive mechanical ventilation (IMV). Mostly the O2 group returned to normal life compared to HFNC and VMI (71.4 versus 17.5% and 11.1% respectively). Lung function was normal in 39 patients (33.6%). The series that returned to normal life had higher percentage of normal DLCO and six-minute walk test. Compared to the O2 series, the CNAF series had a higher frequency of DLCO alteration (OR = 5) followed by the VMI series (OR = 3.6). Conclusion: At 3 months of follow-up, absenteeism from work, persistence of symptoms and respiratory functional alteration (DLCO) were evident, especially in those who received ventilatory support in addition to oxygen therapy.

Multivariable prediction models for difficult direct laryngoscopy: Systematic review and literature metasynthesis.

CONTEXT: The difficult airway is an important scenario in anaesthesia due to the impact of its potential complications, and the difficulty in predicting its presence in current clinical practice. METHODS: Systematic review of articles in English and Spanish retrieved from MEDLINE (Ovid), LILACS and EMBASE up to March 2018. The search strategy was defined by the authors. The reviewers uploaded the studies to specially designed tables in order to qualitatively analyse the results of each paper. RESULTS: A total of 3602 studies were identified. Thirty-four of these were included in the qualitative review. The most commonly used definition of difficulty was the Cormack-Lehane 3 or 4 classification, with a weighted mean incidence of 7.23%. The most relevant finding was the methodological weaknesses in obtaining these scales. CONCLUSIONS: Available prediction models show limited discrimination, and weaknesses were detected in the methodology used to develop these prediction rules.

Modelos de predicción multivariables para intubación orotraqueal difícil empleando laringoscopia directa: revisión sistemática y metasíntesis de la literatura / Multivariable prediction models for difficult direct laryngoscopy: Systematic review and literature metasynthesis

Contexto: La vía aérea difícil es un escenario relevante en anestesia por el impacto de sus consecuencias negativas. Además, persisten limitaciones en la capacidad de predicción en la práctica clínica actual. Métodos: Revisión sistemática de artículos en inglés y en español usando MEDLINE (Ovid), LILACS y Embase hasta marzo del 2018. Se empleó una estrategia de búsqueda definida por los autores: los estudios identificados fueron organizados de manera paralela por los revisores en tablas previamente elaboradas para analizar cualitativamente los resultados de cada uno de ellos. Resultados: Se identificaron 3.602 referencias, y 34 de ellas se incluyeron en la revisión cualitativa. La definición más empleada de dificultad fue la clasificación de Cormack-Lehane3 o 4. Esta gradación tuvo una incidencia media ponderada del 7,23%. El hallazgo más relevante fueron las debilidades metodológicas en la obtención de estas escalas. Conclusiones: Los modelos de predicción disponibles presentan discriminación limitada. Hay debilidades en la metodología que se ha empleado para el desarrollo de estas reglas de predicción.(AU)

Context: The difficult airway is an important scenario in anaesthesia due to the impact of its potential complications, and the difficulty in predicting its presence in current clinical practice. Methods: Systematic review of articles in English and Spanish retrieved from MEDLINE (Ovid), LILACS and Embase up to March 2018. The search strategy was defined by the authors. The reviewers uploaded the studies to specially designed tables in order to qualitatively analyse the results of each paper. Results: A total of 3602 studies were identified. Thirty-four of these were included in the qualitative review. The most commonly used definition of difficulty was the Cormack-Lehane3 or 4 classification, with a weighted mean incidence of 7.23%. The most relevant finding was the methodological weaknesses in obtaining these scales. Conclusions: Available prediction models show limited discrimination, and weaknesses were detected in the methodology used to develop these prediction rules.(AU)

Primary versus secondary tracheoesophageal puncture for voice rehabilitation in laryngectomy patients: A systematic review.

BACKGROUND: Among voice restoration options following laryngectomy, tracheoesophageal puncture (TEP) appears to be the most common. Currently, there is no consensus that exists with regard to the timing of performing TEP and the decision to perform a primary or secondary TEP has mostly been based on physician preference and expert opinion rather than data. OBJECTIVE OF REVIEW: The objective of this study was to compare primary and secondary tracheoesophageal puncture (TEP) for voice rehabilitation in laryngectomy patients in terms of success and complication rates. TYPE OF REVIEW: A systematic review of studies in the English literature was conducted for studies that directly compared primary and secondary TEP. SEARCH STRATEGY: A comprehensive search of MEDLINE (January 1948-15 July 2016), EMBASE (January 1974-15 July 2016) and Web of Science (January 1970-15 July 2016) was performed. EVALUATION METHOD: Two authors (KL/BAC) independently reviewed titles and abstracts, read full-text papers, extracted data and assessed quality. Disagreements were resolved via consensus. A third author (DV) resolved disagreements between reviewers when consensus was not possible. RESULTS: Eleven retrospective clinical cohort studies were included. No randomised controlled trials were identified. Newcastle-Ottawa score for assessment of quality ranged from 5 to 7. Success rate was defined differently across most studies. Two studies found higher success with primary TEP compared to secondary TEP; nine studies found no difference. Voice outcomes were inconsistently measured; no difference between groups was found in 4 studies. Complication rates were divided into TEP site related, infectious and stenosis. No difference between primary and secondary TEP was found in all but one study which showed a higher rate of pharyngocutaneous fistula in the primary TEP group in salvage laryngectomy patients. CONCLUSIONS: There is no robust evidence to suggest that primary TEP is associated with poorer outcomes compared to secondary TEP. A well-designed randomised controlled trial is required to appropriately answer this question.

El rol de la hipertensión pulmonar en la displasia broncopulmonar / The role of pulmonary hypertension on bronchopulmonary dysplasia

Resumen Hace 50 años Northway describió la Displasia Broncopulmonar (DBP), en nacidos de pretérmino expuestos a ventilación mecánica. Desde entonces, ha aumentado la sobrevida de ellos; sin embar go, ha aparecido una "nueva DBP" y la incidencia de esta no ha disminuido. Una de las caracte rísticas de esta patología es la remodelación vascular anómala, que en su expresión más severa se conoce como Hipertensión Pulmonar (HP); con una incidencia de 17%, que es proporcional a la severidad de la DBP (33% en DBP severa); y como un factor de mortalidad (hasta un 48% mortali dad a 2 años con HP por DBP). Debido a esto resulta importante conocer los métodos diagnósticos y alternativas terapéuticas, tema que se discute en esta revisión. Considerando la alta mortalidad de la asociación HP-DBP, adquiere importancia una estrategia de tamizaje en la población de riesgo. El gold standard para el diagnóstico de HP es el cateterismo cardíaco, sin embargo, el ecocardio-grama transtorácico es una herramienta útil para el tamizaje y diagnóstico de HP en pacientes dis-plásicos, con mediciones cuantitativas y cambios cualitativos en la evaluación diagnóstica. A nivel sanguíneo el péptido natriurético tipo B (BNP), ha mostrado ser útil en el seguimiento; en cuanto a imágenes, la tomografía computarizada se utiliza en casos severos. En cuanto a las terapias, se han propuesto el óxido nítrico inhalado como vasodilatador pulmonar, los inhibidores de la fosfodies-terasas -sildenafil-, los antagonistas de la endotelina -bosentán- y los análogos de prostaciclinas -iloprost-. Aún no se cuenta con evidencia de alta calidad para su uso, dosis y duración del trata miento, pero hay variadas experiencias clínicas. Además, es relevante el cuidado interdisciplinario, destacando optimizar la nutrición. El desafío es lograr una prevención efectiva de la DBP y de sus complicaciones. Un protocolo de tamizaje de HP debe asociarse a una estratificación de riesgo y directrices de tratamiento.

Abstract 50 years ago, Northway described Broncopulmonary Dysplasia (BPD) in preterm infants exposed to mechanical ventilation. Since then, their survival has increased, nevertheless a "new BPD" has appeared and its incidence has not diminished. One of the characteristics of this pathology is the the abnormal vascular remodeling, which in its most severe expression is known as Pulmonary Hyper tension (PH); with an incidence of 17% in patients with BPD, which is proportional to the severity of the disease (33% in severe BPD), and as mortality factor (up to 48% 2-year mortality in PH-BPD). Thereby, it is important to know the diagnostic methods and therapeutic alternatives, topics discus sed in this review. Considering the high mortality in BPD associated PH, screening strategies in at risk population become important. The gold standard is cardiac catheterization; however, transtho-rathic echocardiography is a useful tool for the screening and diagnosis of PH in displasic patients, using cuantitive measures and cualitative changes in the evaluation. Seric type-B natriuretic peptide has shown to be useful for follow-up; regarding images, CT scan is used in severe cases. In terms of therapy; inhaled Nitric Oxide as a pulmonary vasodilator, phosphodiesterase inhibitors -sildenafil-, endotelin antagonists -bosentan-, and prostacyclin analogues -iloprost-, have been proposed. Their use, dosis and treatment lenght still lack support of high quality evidence, but diverse clinical expe riences have been described. Interdisciplinary care is also important, highlighting to optimize nu trition. Therefore, the challenge is to effectively prevent BPD and its complications. A PH screening protocol should be associated with risk stratification and treatment guidelines.

[The role of pulmonary hypertension on bronchopulmonary dysplasia]. / El rol de la hipertensión pulmonar en la displasia broncopulmonar.

50 years ago, Northway described Broncopulmonary Dysplasia (BPD) in preterm infants exposed to mechanical ventilation. Since then, their survival has increased, nevertheless a "new BPD" has appeared and its incidence has not diminished. One of the characteristics of this pathology is the the abnormal vascular remodeling, which in its most severe expression is known as Pulmonary Hyper tension (PH); with an incidence of 17% in patients with BPD, which is proportional to the severity of the disease (33% in severe BPD), and as mortality factor (up to 48% 2-year mortality in PH-BPD). Thereby, it is important to know the diagnostic methods and therapeutic alternatives, topics discus sed in this review. Considering the high mortality in BPD associated PH, screening strategies in at risk population become important. The gold standard is cardiac catheterization; however, transtho-rathic echocardiography is a useful tool for the screening and diagnosis of PH in displasic patients, using cuantitive measures and cualitative changes in the evaluation. Seric type-B natriuretic peptide has shown to be useful for follow-up; regarding images, CT scan is used in severe cases. In terms of therapy; inhaled Nitric Oxide as a pulmonary vasodilator, phosphodiesterase inhibitors -sildenafil-, endotelin antagonists -bosentan-, and prostacyclin analogues -iloprost-, have been proposed. Their use, dosis and treatment lenght still lack support of high quality evidence, but diverse clinical expe riences have been described. Interdisciplinary care is also important, highlighting to optimize nu trition. Therefore, the challenge is to effectively prevent BPD and its complications. A PH screening protocol should be associated with risk stratification and treatment guidelines.

EphA2 promotes infiltrative invasion of glioma stem cells in vivo through cross-talk with Akt and regulates stem cell properties.

Diffuse infiltrative invasion is a major cause for the dismal prognosis of glioblastoma multiforme (GBM), but the underlying mechanisms remain incompletely understood. Using human glioma stem cells (GSCs) that recapitulate the invasive propensity of primary GBM, we find that EphA2 critically regulates GBM invasion in vivo. EphA2 was expressed in all seven GSC lines examined, and overexpression of EphA2 enhanced intracranial invasion. The effects required Akt-mediated phosphorylation of EphA2 on serine 897. In vitro the Akt-EphA2 signaling axis is maintained in the absence of ephrin-A ligands and is disrupted upon ligand stimulation. To test whether ephrin-As in tumor microenvironment can regulate GSC invasion, the newly established Efna1;Efna3;Efna4 triple knockout mice (TKO) were used in an ex vivo brain slice invasion assay. We observed significantly increased GSC invasion through the brain slices of TKO mice relative to wild-type (WT) littermates. Mechanistically EphA2 knockdown suppressed stem cell properties of GSCs, causing diminished self-renewal, reduced stem marker expression and decreased tumorigenicity. In a subset of GSCs, the reduced stem cell properties were associated with lower Sox2 expression. Overexpression of EphA2 promoted stem cell properties in a kinase-independent manner and increased Sox2 expression. Disruption of Akt-EphA2 cross-talk attenuated stem cell marker expression and neurosphere formation while having minimal effects on tumorigenesis. Taken together, the results show that EphA2 endows invasiveness of GSCs in vivo in cooperation with Akt and regulates glioma stem cell properties.

Expression of BMP-7 and USAG-1 (a BMP antagonist) in kidney development and injury.

Once developed, end-stage renal disease cannot be reversed by any current therapy. Bone morphogenetic protein-7 (BMP-7), however, is a possible treatment for reversing end-stage renal disease. Previously, we showed that the BMP antagonist uterine sensitization-associated gene-1 (USAG-1, also known as ectodin and sclerostin domain-containing 1) negatively regulates the renoprotective action of BMP-7. Here, we show that the ratio between USAG-1 and BMP-7 expression increased dramatically in the later stage of kidney development, with USAG-1 expression overlapping BMP-7 only in differentiated distal tubules. Examination of USAG-1 expression in developing kidney indicated that a mosaic of proximal and distal tubule marker-positive cells reside side by side in the immature nephron. This suggests that each cell controls its own fate for becoming a proximal or distal tubule cell. In kidney injury models, the ratio of USAG-1 to BMP-7 expression decreased with kidney damage but increased after subsequent kidney regeneration. Our study suggests that USAG-1 expression in a kidney biopsy could be useful in predicting outcome.

Análisis crítico de un artículo: Cáncer de próstata inicial ¿operar o esperar? / Early prostate cancer: Radical prostatectomy or watchful waiting?

Background In 2002, we reported the initial results of a trial comparing radical prostatectomy with watchful waiting in the management of early prostate cancer. After three more years of follow-up, we report estimated 10-year results. Methods: From October 1989 through February 1999, 695 men with early prostate cancer (mean age, 64.7 years) were randomly assigned to radical prostatectomy (347 men) or watchful waiting (348 men). The follow-up was complete through 2003, with blinded evaluation of the causes of death. The primary end point was death due to prostate cancer; thesecondary end points were death from any cause, metastasis, and local progression. Results: During a median of 8.2 years of follow-up, 83 men in the surgery group and 106 men in the watchful-waiting group died (P=0.04). In 30 of the 347 men assigned to surgery (8.6 percent) and 50 of the 348 men assigned to watchful waiting (14.4 percent), death was due to prostate cancer. The difference in the cumulative incidence of death due to prostate cancer increased from 2.0 percentage points after 5 years to 5.3 percentage points after 10 years, for a relative risk of 0.56 (95 percent confidence interval, 0.36 to 0.88; P=0.01 by Gray's test). For distant metastasis, the corresponding increase was from 1.7 to 10.2 percentage points, for a relative risk in the surgery group of 0.60 (95 percent confidence interval, 0.42 to 0.86; P=0.004 by Gray's test), and for local progression, the increase was from 19.1 to 25.1 percentage points, for a relative risk of 0.33 (95 percent confidence interval, 0.25 to 0.44; P<0.001 by Gray's test). Conclusions: Radical prostatectomy reduces disease-specific mortality, overall mortality, and the risks of metastasis and local progression. The absolute reduction in the risk of death after 10 years is small, but the reductions in the risks of metastasis and local tumor progression are substantial.

Experiencia en traumatismo torácico: Hospital Valparaíso / Experience in thoracic traumatism: Valparaiso Hospital

Las lesiones del tórax son el resultado de trauma cerrado o abierto, que generalmente ocurren como consecuencia de lesiones por arma de fuego, arma blanca, accidentes de tránsito o compresiones torácicas por aplastamientos, entre otros. Se revisaron 163 fichas clínicas del Servicio de Cirugía Torácica del Hospital de Valparaíso entre enero de 1998 y junio de 2001. Se confeccionó un protocolo con datos a obtener de la ficha. Se analizaron los datos en valores absolutos y porcentajes. Posteriormente se efectuó una comparación de algunas variables entre el grupo de trauma abierto y el de cerrado. El 94,5 por ciento (154 pactes) correspondió a hombres y 5,5 por ciento (9 pactes) a mujeres. El promedio de edad fue de 30,9 años (rango 16-86). El mecanismo de trauma más frecuente fueron lesiones por armas blancas, (125 casos), seguido de caídas de altura (19 casos), accidentes de tránsito (9 casos), y armas de fuego (6 casos). Ciento veintiséis pacientes presentaron traumatismo abierto y 37 cerrado. Las lesiones más frecuentes fueron: neumotórax, 116 casos; hemotórax, 92 casos; y fracturas costales, 28 casos. El 87,1 por ciento de los traumatismos se manejó con tubo pleural (142 pactes). Sólo 11 pacientes necesitaron toracotomía de urgencia.

Evaluación de la comunicación entre el equipo médico y los familiares de los pacientes hospitalizados en UCI / Evaluation of communication between medical equipment and intensive care unit patient families

Introducción: Una labor importante del médico intensivista es su capacidad para comunicarse con la familia del paciente crítico en forma clara, directa y empática, a fin de lograr mejor calidad en la atención. No existen estudios a nivel nacional que evalúen la calidad de la comunicación médico-familia en UCI. Objetivo: Diagnóstico de situación sobre la calidad de la comunicación entre la familia del paciente hospitalizado en UCI y el equipo médico de salud. Método: Estudio descriptivo, prospectivo, doble ciego. Aplicación de encuesta de opinión validada internacionalmente a familiares del paciente hospitalizado en la UCI General por un período de 72 horas o más entre los meses de marzo a mayo del 2002. Los datos fueron expresados en porcentajes. Se utilizó test de Anova para determinar diferencia de medias y obtener grado de significancia estadística. Resultados: Se aplicó la encuesta a 51 personas visitantes de un total de 20 pacientes en UCI. De los encuestados, 60,7 por ciento eran mujeres y 39,2 por ciento hombres; 74,6 por ciento familiares directos y 25,4 por ciento otros visitantes; 37,2 profesionales y 62,8 por ciento no profesionales. Un 98 por ciento piensa que la información siempre o la mayor parte del tiempo es dada en términos que se pueda entender, honesta y suficiente. Un 60 por ciento de los familiares reconoce al equipo de salud siempre o la mayor parte del tiempo y cerca del 100 por ciento considera que siempre o la mayor parte del tiempo se le está dando la mejor atención a su familiar y que el equipo de salud se preocupa por él. Entre 74 y 80 por ciento de los entrevistados considera que el médico siempre es cortés y tiene disponibilidad para recibirlo. El grupo de profesionales se encuentra menos satisfecho en este aspecto que el grupo de no profesionales (p<0,01). El grupo de otros visitantes del paciente se siente en un 100 por ciento cómodo al visitar al paciente en la UCI, a diferencia de los familiares directos que en 15 por ciento se sentían cómodos sólo algunas veces o nunca (p< 0,01). Conclusiones: En nuestro estudio la familia evalúa la comunicación con el equipo médico, su disponibilidad y cortesía en la atención de mejor forma que lo expresado en la literatura. El grupo de los profesionales se encuentra menos satisfecho en cuanto a la disponibilidad o cortesía por parte del médico.

La obesidad como trastorno de la alimentación / Obesity seen as an eating disorder

El siguente artículo es una revisión de la obesidad vista desde la perspectiva de la psiquiatría. Se puede considerar que el transtorno alimentario más prevalente en el mundo actual es la obesidad, a pesar de que está no se encuentre dentro de una clasificación psiquiátrica establecida. Se considara aquí la obesidad como una enfermedad crónica de origen multifactorial caractrizada por un aumento anormal del tejido graso secundario a un aumento de la energía absorbida con respecto a la gastada, que conlleva riesgos para la salud. Se revisa en este artículo desde la epidemiología, etiología, clasificación y diagnóstico de la obesidad hasta sus aspectos psicopatológicos y sociales que permiten considerar a esta enfermedad como un transtorno alimentario. Por último se incluye una reseña del tratamiento multidisciplinario de la obesidad con énfasis en el papel del psiquiatra

Identification of ubiquitin ligases required for skeletal muscle atrophy.

Skeletal muscle adapts to decreases in activity and load by undergoing atrophy. To identify candidate molecular mediators of muscle atrophy, we performed transcript profiling. Although many genes were up-regulated in a single rat model of atrophy, only a small subset was universal in all atrophy models. Two of these genes encode ubiquitin ligases: Muscle RING Finger 1 (MuRF1), and a gene we designate Muscle Atrophy F-box (MAFbx), the latter being a member of the SCF family of E3 ubiquitin ligases. Overexpression of MAFbx in myotubes produced atrophy, whereas mice deficient in either MAFbx or MuRF1 were found to be resistant to atrophy. These proteins are potential drug targets for the treatment of muscle atrophy.

Ror2, encoding a receptor-like tyrosine kinase, is required for cartilage and growth plate development.

Receptor tyrosine kinases often have critical roles in particular cell lineages by initiating signalling cascades in those lineages. Examples include the neural-specific TRK receptors, the VEGF and angiopoietin endothelial-specific receptors, and the muscle-specific MUSK receptor. Many lineage-restricted receptor tyrosine kinases were initially identified as 'orphans' homologous to known receptors, and only subsequently used to identify their unknown growth factors. Some receptor-tyrosine-kinase-like orphans still lack identified ligands as well as biological roles. Here we characterize one such orphan, encoded by Ror2 (ref. 12). We report that disruption of mouse Ror2 leads to profound skeletal abnormalities, with essentially all endochondrally derived bones foreshortened or misshapen, albeit to differing degrees. Further, we find that Ror2 is selectively expressed in the chondrocytes of all developing cartilage anlagen, where it essential during initial growth and patterning, as well as subsequently in the proliferating chondrocytes of mature growth plates, where it is required for normal expansion. Thus, Ror2 encodes a receptor-like tyrosine kinase that is selectively expressed in, and particularly important for, the chondrocyte lineage.

Dominant mutations in ROR2, encoding an orphan receptor tyrosine kinase, cause brachydactyly type B.

Inherited limb malformations provide a valuable resource for the identification of genes involved in limb development. Brachydactyly type B (BDB), an autosomal dominant disorder, is the most severe of the brachydactylies and characterized by terminal deficiency of the fingers and toes. In the typical form of BDB, the thumbs and big toes are spared, sometimes with broadening or partial duplication. The BDB1 locus was previously mapped to chromosome 9q22 within an interval of 7.5 cM (refs 9,10). Here we describe mutations in ROR2, which encodes the orphan receptor tyrosine kinase ROR2 (ref. 11), in three unrelated families with BDB1. We identified distinct heterozygous mutations (2 nonsense, 1 frameshift) within a 7-amino-acid segment of the 943-amino-acid protein, all of which predict truncation of the intracellular portion of the protein immediately after the tyrosine kinase domain. The localized nature of these mutations suggests that they confer a specific gain of function. We obtained further evidence for this by demonstrating that two patients heterozygous for 9q22 deletions including ROR2 do not exhibit BDB. Expression of the mouse mouse orthologue, Ror2, early in limb development indicates that BDB arises as a primary defect of skeletal patterning.

Mange epizootic in white-nosed coatis in western Mexico.

From November of 1994 to June of 1996 an epizootic of mange, probably caused by the mite Notoedres cati, occurred in white-nosed coatis (Nasua narica) in the tropical dry forests of the Chamela-Cuixmala Biosphere Reserve in western Mexico. A monitoring scheme to determine the extent and severity of the epizootic within coatis was implemented. Trapping periods and transects were conducted for 2 yr. To control the spread of the disease, all captured infected coatis were either euthanized or treated with acaricides such as Butox and Ivomec-F, depending on the severity of their infection. Four other species of wild mammals and feral cats had skin conditions resembling mange. A more severe problem with the disease was predicted and later confirmed in the less isolated areas of the reserve, with a higher density of coatis. Our results indicate that epizootics may be more prone to occur in areas with greater fragmentation and less isolation from anthropogenic influence. Interestingly, although there was an apparently severe impact of the mange epizootic in the coati population, the long-term impact of the disease is unknown but appears to be negligible. So in order to understand the role of diseases in wildlife populations, long-term experimental studies are required.