SHH pathway inhibition is protumourigenic in adamantinomatous craniopharyngioma.

Pharmacological inhibition of the sonic hedgehog (SHH) pathway can be beneficial against certain cancers but detrimental in others. Adamantinomatous craniopharyngioma (ACP) is a relevant pituitary tumour, affecting children and adults, that is associated with high morbidity and increased mortality in long-term follow-up. We have previously demonstrated overactivation of the SHH pathway in both human and mouse ACP. Here, we show that this activation is ligand dependent and induced by the expression of SHH protein in a small proportion of tumour cells. We investigate the functional relevance of SHH signalling in ACP through MRI-guided preclinical studies using an ACP mouse model. Treatment with vismodegib, a clinically approved SHH pathway inhibitor, results in a significant reduction in median survival due to premature development of highly proliferative and vascularised undifferentiated tumours. Reinforcing the mouse data, SHH pathway inhibition in human ACP leads to a significant increase in tumour cell proliferation both ex vivo, in explant cultures, and in vivo, in a patient-derived xenograft model. Together, our results demonstrate a protumourigenic effect of vismodegib-mediated SHH pathway inhibition in ACP.

The role of the sonic hedgehog signalling pathway in patients with midline defects and congenital hypopituitarism.

INTRODUCTION: The Gli family of zinc finger (GLI) transcription factors mediates the sonic hedgehog signalling pathway (HH) essential for CNS, early pituitary and ventral forebrain development in mice. Human mutations in this pathway have been described in patients with holoprosencephaly (HPE), isolated congenital hypopituitarism (CH) and cranial/midline facial abnormalities. Mutations in Sonic hedgehog (SHH) have been associated with HPE but not CH, despite murine studies indicating involvement in pituitary development. OBJECTIVES/METHODS: We aimed to establish the role of the HH pathway in the aetiology of hypothalamo-pituitary disorders by screening our cohort of patients with midline defects and/or CH for mutations in SHH, GLI2, Shh brain enhancer 2 (SBE2) and growth-arrest specific 1 (GAS1). RESULTS: Two variants and a deletion of GLI2 were identified in three patients. A novel variant at a highly conserved residue in the zinc finger DNA-binding domain, c.1552G > A [pE518K], was identified in a patient with growth hormone deficiency and low normal free T4. A nonsynonymous variant, c.2159G > A [p.R720H], was identified in a patient with a short neck, cleft palate and hypogonadotrophic hypogonadism. A 26·6 Mb deletion, 2q12·3-q21·3, encompassing GLI2 and 77 other genes, was identified in a patient with short stature and impaired growth. Human embryonic expression studies and molecular characterisation of the GLI2 mutant p.E518K support the potential pathogenicity of GLI2 mutations. No mutations were identified in GAS1 or SBE2. A novel SHH variant, c.1295T>A [p.I432N], was identified in two siblings with variable midline defects but normal pituitary function. CONCLUSIONS: Our data suggest that mutations in SHH, GAS1 and SBE2 are not associated with hypopituitarism, although GLI2 is an important candidate for CH.

Laparoscopic repair of Bochdalek's hernia with gastric volvulus.

Bochdalek's hernia is the most common congenital diaphragmatic hernia in newborns, but it is an uncommon clinical feature in adults. In most cases, there are no symptoms or only minor gastrointestinal problems. Rarely, it may manifest as an acute abdomen due to viscus strangulation, requiring emergency surgery. We report the case of a 52-year-old man with herniation of the colon and a volvulated stomach through a Bochdalek's hernia. The patient was operated on via a laparoscopic approach and had an uneventful recovery. We recommend the laparoscopic approach as an alternative to open surgery in cases of noncomplicated Bochdalek's hernia.

Single and multiple pyogenic liver abscesses: etiology, clinical course, and outcome.

BACKGROUND: Pyogenic liver abscesses are uncommon but they still carry a high mortality rate when encountered. This study was undertaken to evaluate the differences in the clinical behaviour of patients with single and multiple abscesses. METHODS: From January 1985 to December 1997, 133 patients with this disease were treated in the surgical departments of five hospitals, 97 had a single abscess and 36 had multiple abscesses. Clinical features, methods of treatment, and outcome were assessed and compared in both types of abscesses. RESULTS: A biliary origin from ascending cholangitis was most frequently found in multiple abscesses (p = 0.007). Mean age and duration of symptoms were higher in multiple lesions (p = 0.03 and p = 0.001). High levels of alkaline phosphatase were more frequently seen in multiple abscesses than in solitary ones (p = 0.02). They were both most frequently located on the right side. Antibiotic therapy alone was most frequently used in multiple abscesses (p = 0.01). Mortality rate was also higher in this type of patients (p = 0.01). The abscess-related morbidity rate was higher in multiple lesions as well but the statistical difference was not significant. CONCLUSIONS: These results suggest that multiple liver abscesses comprise a disease of biliary origin, higher age, longer symptomatic periods, and also higher mortality rate than in single abscess.

Formulación de una mezcla vitamínica intravenosa para nutrición parenteral total pediátrica / Intravenous multivitamin formulation for use in pediatric total parenteral nutrition

Background: No intravenous multivitamin formulation is available at the Chilean market that fulfills the requirements of pediatric patients on total parenteral nutrition. Therefore, adult formulations must be used. Aim: To prepare a parenteral aqueous multivitamin solution, to be used in pediatric patients. Material and methods: The solution was prepared, mixing vitamins according to their stability and compatibility, in a horizontal laminar flow hood. The quality control for this formulation at times zero and 30 days consisted of an organoleptic analysis, microbiologic and pyrogen controls and vitamin quantification. In addition, the effect of vitamin solution incorporation on the stability of total parenteral nutrition formulae was evaluated. The approximated production cost was calculated. Results: The ampoules did not show changes on the organoleptic characteristics. No bacterial contamination or pyrogens were detected. Total parenteral nutrition solutions were not modified after the incorporation of the vitamins. The vitamin solution was stable for one month at 4ºC. Conclusions: The manufacture of this formulation results in significant savings, because it has a low manufacturing cost and fulfills pediatric requirements

Clinical course, treatment, and multivariate analysis of risk factors for pyogenic liver abscess.

BACKGROUND: Pyogenic liver abscess is a threatening condition. The purpose of this study was to audit the clinical behavior and to analyze the risk factors. METHODS: One hundred and thirty-three patients treated in five hospitals during the years 1985 to 1997 were studied. By univariate and multivariate analysis we tried to identify any risk factor associated with complicated clinical course and complicated-related clinical course, and with hospital mortality. RESULTS: Sixty-three patients (47%) were subjected to a percutaneous drainage, 45 (34%) were treated by open surgical drainage, and the remaining 25 cases (19%) received antibiotic therapy alone. Prognostic variables for a complicated clinical course were the presence of shock, low hemoglobin level, elevated prothrombin time, and polymicrobial infection. Shock, distress, low hemoglobin level, increased creatinine, and positive blood culture were significant predictors of a complicated-related clinical course. Concerning mortality, a biliary origin, shock, multiple abscesses, low hemoglobin level, and high concentration of blood urea nitrogen were independent predictors. CONCLUSIONS: Treatment of pyogenic liver abscesses should be tailored to each patient, however, the majority of them can be successfully treated with antibiotics and percutaneous methods. Those with signs of organ failure or septicemia should preferably be managed in the intensive care unit.

Efectividad del secnidazol en el tratamiento de escolares asintomáticos parasitados por giardia lamblia y/o entamoeba histolytica / Effectiveness of secnidazol in the treatment of asymptomatic schoolchildren parasited by giardia lamblia and/or entamoeba histolytica

El propósito de la investigación es conocer la eficacia del Secnidazol en el tratamiento de escolares asintomáticos portadores de Giardia lamblia y/o Entamoeba histolytica, así como el evaluar su tolerancia. Se escogieron 50 niños parasitados (totalizando 53 casos con Entamoeba histolytica y/o Giardia lamblia), con edades comprendidas entre 5 y 14 años, de uno u otro sexo, a quienes se les administró el medicamento y tres días después se realizaron exámenes coproparasitológicos controles. La tolerancia del medicamento se evaluó mediante encuesta. De 53 casos parasitados, la relación de protozoarios fue: Giardia lamblia (66,03 por ciento) seguidos de Entamoeba hitolytica (33,97 por ciento). La efectividad parasitológica del Secnidazol contra Giardia lamblia fue del 100 por ciento y de Entamoeba histolytica de 95,45 por ciento. Se obtuvo un solo caso portador que no respondió al tratamiento (4,55 por ciento). El medicamento fue bien tolerado en el 50 por ciento de los casos. Los síntomas más frecuentes fueron: hiporexia, cefalea, dolor abdominal, mareos, náuseas, vómitos, diarrea, fatiga, alteración del gusto y prurito. La eficacia y la relativamente buena tolerancia del Secnidazol fue demostrada en el presente estudio. Se obtuvo cura parasitológica al tercer día de administrado el medicamento

Prevalencia de enteroparasitosis en una escuela urbana en el Municipio San Francisco, Estado Zulia, Venezuela / Prevalence of enteric parasitosis in an urban area school in San Francisco Municipality, Zulia State, Venezuela

El propósito de la investigación es conocer la prevalencia de las enteroparasitosis en una escuela urbana de la parroquia San Francisco. Del total de la población escolar, se escogieron 114 niños, de edades comprendidas entre 5 y 15 años de ambos sexos, donde se les realizó exámenes coproparasitológicos y de recolección de información a través de encuestas epidemiológicas. De los niños seleccionados, 74,56 por ciento reportaron positividad para uno o más enteroparásitos. 40,35 por ciento fueron masculinos y 34,21 por ciento femeninos. Las edades más parasitadas fueron comprendidas entre 8 y 12 años (34,24 por ciento) segudas de 5 a 8 años 30,69 por ciento. Los helmintos más frecuentes fueron: Enterobius vermicularis (45,55 por ciento), Trichus trichuria (27,80 por ciento). Ascaris lumbricoides (23,35 por ciento) e Hymenolepis nana (3,30 por ciento) y los protozoos fueron: Blastocystis hominis (37,28 por ciento), Giardia lamblia (17,79 por ciento). Endolimax nana (16,95 por ciento), Entamoeba coli (15,26 por ciento). El poliparasitismo predominó sobre el monoparasitismo. Las helmintiasis observadas presentaron en su mayoría una infestación leve. Se evidencia acentuados malos hábitos higiénicos en los niños así como en la escuela. Se obtuvo elevada prevalencia parasitaria en la población estudiada. La Enterobiasis fue la helmintiasis más común

Estudio de patologia de alto riesgo obstetrico en poblacion rural. Hospital de Llay-Llay. / Pathology of high obstetrical risk in a rural population. Hospital de Llay-Llay

Se analizan las fichas clinicas de embarazadas de alto riesgo obstetrico y perinatal controladas en el Hospital de LlayLlay en los meses comprendidos entre noviembre de 1981 y junio de 1982. Se consideran en este estudio las patologias mas frecuentes, indices de estratificacion social, ruralismo, estado civil, forma de resolucion del embarazo, indices Apgar y peso de los RN, y la relacion entre ellos

Central nervous system alterations as sequelae of Venezuelan equine encephalitis virus infection in the rat.

Alterations of the Central Nervous System (CNS) in rats surviving acute infection with a virulent strain of Venezuelan Equine Encephalitis (VEE) virus were studied by light and electron microscopy. Cavitary necrosis of the cerebral cortex, macrophage activity and degenerative axonal changes were considered to be sequelae of the lesions induced during the acute phase of the infection. Mononuclear cell infiltrates of the neuropil, 3 mth after inoculation, were related to the immune response of the host. Focal lesions and mononuclear cell activity in the brain are thought to be the equivalent of the lesions induced in the CNS of humans during VEE virus infection. The findings are discussed in the light of recent reports of cerebral dysfunction occurring as a sequel of VEE virus infection in children.