Type 2 Marine-Lenhart Syndrome: An Uncommon Cause of Thyrotoxicosis.

Marine-Lenhart syndrome (MLS) is an uncommon cause of primary hyperthyroidism, which can occur in the context of diffuse goiter due to Graves disease (GD) or autonomic nodular disease (Plummer disease (PD)). The coexistence of these two conditions is the hallmark of the MLS. Patients with MLS have a lower remission rate with oral antithyroid drugs, requiring definitive management therapies with radioactive iodine or surgery. We present the case of a 48-year-old female with a history of primary autoimmune hyperthyroidism (GD) since 2016, with biochemical control of hyperthyroidism with methimazole but without the possibility of stopping treatment. The scintigraphic uptake pattern showed heterogeneous uptake of the thyroid parenchyma with three hyper-uptake nodules without inhibition of the rest of the thyroid tissue, findings of an MLS condition with the indication for definitive therapy, for which he was referred to nuclear medicine for the administration of radioactive iodine.

Macrophages and T Lymphocytes in the Ovine Placenta After Experimental Infection With Toxoplasma gondii.

Early abortion in ovine toxoplasmosis has had limited investigation. This study evaluated the immune response in the placenta of sheep orally infected with Toxoplasma gondii and euthanized between 2 and 4 weeks postinfection. Toxoplasma infection of the placenta was only found at 4 weeks after infection. Parasitic debris in foci of necrosis were immunolabeled in the maternal caruncle, whereas well-preserved intracellular parasitic vacuole-like structures were found in trophoblasts of fetal cotyledon. Early abortions had increased macrophages in caruncular septa, whereas in later abortions the placentas containing the parasite had an increase of T lymphocytes and macrophages mainly in the fetal cotyledons. This study suggests that the immune response in both the fetal and maternal compartments of the placenta may contribute to the pathogenesis of ovine toxoplasmosis and that these responses differ between early and late presentations of the disease.

Descripción de la experiencia en pacientes diagnosticados con insulinoma. Estudio multicéntrico en Medellín, Colombia / Description of the experience with patients with insulinoma diagnosis. Multicentric study in Medellín, Colombia

RESUMEN Objetivo: describir la experiencia de los pacientes con insulinoma, diagnosticados y tratados entre los años 2002 y 2017 en tres hospitales de la ciudad de Medellín, Colombia. Métodos: estudio descriptivo y retrospectivo de pacientes con criterios bioquímicos para hipoglucemia hiperinsulínica y confirmación histopatológica de insulinoma. Resultados: se estudiaron 19 casos, 10 eran mujeres (52,6 %), la edad media al diagnóstico fue 43 años (D.E 15,5). Hubo cuatro casos de insulinoma multifocal (21,1 %), tres asociados con NEM-1 (15,8 %) y dos malignos (10,6 %). Todos presentaron hipoglucemia en ayunas y 63,2 % posprandial. En la prueba de ayuno, el nadir de glucemia sucedió antes de 48 horas en todos los casos, en promedio 9 horas (D.E 8,0). El diagnóstico bioquímico fue realizado con hipoglucemia e insulina elevada en todos los casos, aunque el péptido C fue reportado en nueve pacientes (47,3 %) y las sulfonilureas en dos (11,1 %). La localización preoperatoria se hizo por imágenes en 12 individuos (68,5 %) y las pruebas invasivas fueron necesarias en seis (31,5 %). Las pruebas diagnósticas fueron positivas en un 83 % para resonancia, 50 % para ecografía endoscópica y prueba de estímulo intraarterial con calcio y 100 % para ecografía intraoperatoria. La cirugía se realizó en 18 casos (94,7 %). La mortalidad (15,8 %) fue derivada de complicaciones en el posoperatorio temprano; la curación se logró en todos los casos. Conclusiones: el insulinoma en nuestro medio tiene características demográficas y clínicas similares a otras series. Existen limitaciones locales para el acceso a los estudios bioquímicos y en el rendimiento diagnóstico de las pruebas de localización.

SUMMARY Objective: The objective of the study was to describe the characteristics of patients with insulinoma in three hospitals in Medellín, Colombia, between 2002 and 2017. Methods: A retrospective analysis of patients with hyperinsulinemic hypoglycemia and histologic confirmation of insulinoma was conducted. Results: A total of 19 cases were identified. Ten women (52.6 %) and 9 males (47.4 %). The mean age at diagnosis was 43 years (S.D: 15.5). Four cases had multifocal insulinoma (21.1%), 3 cases were secondary to multiple endocrine neoplasia type 1 (15.8 %), and 2 of them were malignant (10.6 %). All patients presented fasting hypo-glycemia, and 63.2% presented post-prandial hypoglycemia. Glucose nadir in the fasting test occurred in the first 48 hours in all cases, with a mean time to hypoglycemia of 9 hours (S.D 8.0). The biochemical diagnosis was done with increased insulin in the presence of hypoglycemia. C-peptide was done in 9 patients (47.3 %), and sulfonylureas in 2 cases (11.1 %). Preoperative localization was done by imaging in 12 cases (68.5 %), and invasive tests were required in 6 cases (31.5 %). Localization tests were positive as follows: magnetic resonance imaging in 83%, endoscopic ultrasound in 50%, selective intra-arterial calcium injection in 50 %, and intraoperative ultrasound in 100%. Eighteen patients (94. 7%) underwent surgery. Mortality (15.8 %) was secondary to early post-operative complications. Conclusions: The characteristics of patients with insulinoma in Medellín are similar to other series. However, there are important local limitations for proper biochemical testing and imaging localization. This is the largest study in our country.

Late diagnosis of pseudohypoparathyroidism in adulthood. Case series / Pseudohipoparatiroidismo diagnosticado tardíamente en la adultez, una serie de casos

Abstract Introduction: Pseudohypoparathyroidism (PHP) is a rare hereditary disease, characterized by hypocalcemia/hyperphosphatemia secondary to peripheral resistance to parathyroid hormone (PTH). PHP diagnosis is usually precluded since hypocalcemia is considered as the primary diagnosis, thus delaying further diagnostic studies and preventing an adequate management of this clinical condition. Materials and methods: Retrospective review of the databases of the Endocrinology departments of two tertiary care centers of Medellin, Colombia from January 2012 to December 2016. Patients diagnosed with PHP based on clinical presentation and confirmatory laboratory values were included. Results: Four patients met the inclusion criteria. All PHP cases were diagnosed in adulthood despite strong early clinical and laboratory evidence of the disease. Three patients were diagnosed with Fahr's syndrome and two with Albright's hereditary osteodystrophy. The mean values obtained were PTH of 376.8 pg/mL, calcium of 6.17 mg/dL and phosphorus of 6.55 mg/dL. Conclusions: PHP is a rare disorder. This paper describes four PHP cases diagnosed during adulthood. Emphasis should be placed on the judicious approach to the patient with hypocalcemia and hyperphosphatemia with increased PTH and normal renal function, since these symptoms strongly suggest a diagnosis of PHP.

Resumen Introducción. El pseudohipoparatiroidismo (PHP) es una condición rara caracterizada por hipocalcemia e hiperfosfatemia secundarias a resistencia periférica a la hormona paratiroidea (PTH). Es frecuente que la hipocalcemia sea establecida de forma equivocada como diagnóstico primario y que el diagnóstico definitivo de PHP sea tardío, difiriendo los estudios y el manejo específico que exigen estos pacientes. Materiales y métodos. Se revisaron de forma retrospectiva las bases de datos de endocrinología de dos centros terciarios de Medellín, Colombia, desde enero de 2012 a diciembre de 2016. Se incluyeron pacientes con diagnóstico de PHP por presentación clínica y valores confirmatorios de laboratorio. Resultados. Cuatro pacientes cumplieron los criterios de inclusión. Todos los casos fueron diagnosticados en la adultez a pesar de tener evidencia temprana, clínica y bioquímica de la enfermedad. Tres pacientes tenían síndrome de Fahr y dos tenían osteodistrofia hereditaria de Albright. Los valores medios registrados fueron PTH de 376.8 pg/mL, calcio de 6.17 mg/dL y fósforo de 6.55 mg/dL. Conclusiones. El PHP es un trastorno raro; se describen cuatro casos diagnosticados de forma tardía en la adultez. Se enfatiza en el enfoque juicioso del paciente con hipocalcemia, la cual, en presencia de hiperfosfatemia con PTH elevada y función renal normal, debe hacer sospechar el diagnóstico de PHP.

Immunohistochemical expression of interferon-γ in different types of granulomatous lesions associated with bovine paratuberculosis.

Animals infected with Mycobacterium avium subsp. paratuberculosis (Map) show a variety of lesions, from focal forms, seen in subclinical stages to diffuse lesions in clinical cases. The purpose of this study was to evaluate the local expression of IFN-γ by immunohistochemistry in relation with the type of lesion in naturally Map-infected cows. The number of immunolabelled cells, -the majority morphologically consistent with lymphocytes-, was higher in focal and diffuse paucibacillary forms than in diffuse multibacillary lesions, where they appeared closely related to epithelioid cells. Diffuse multibacillary lesions had the lowest numbers, but higher than controls, and positive cells were intermingled among the macrophages. The peripheral IFN-γ production was higher in all Map infected cows and a positive correlation was found with the number of immunolabelled cells in the intestine. The findings of this study show that IFN-γ would play a role in the development of the different types of lesions in paratuberculosis, and also points out the importance of adequate sampling of lymphoid tissue containing samples when studying the local immune response in which IFN-γ expression may be involved, especially in cases where focal lesions are present.

Systemic and local immune responses in sheep after Neospora caninum experimental infection at early, mid and late gestation.

Besides its importance in cattle, Neospora caninum may also pose a high risk as abortifacient for small ruminants. We have recently demonstrated that the outcome of experimental infection of pregnant sheep with 10(6) Nc-Spain7 tachyzoites is strongly dependent on the time of gestation. In the current study, we assessed peripheral and local immune response in those animals. Serological analysis revealed earlier and higher IFN-γ and IgG responses in ewes infected at early (G1) and mid (G2) gestation, when abortion occurred. IL-4 was not detected in sera from any sheep. Inflammatory infiltrates in the placenta mainly consisted of CD8+ and, to a lesser extent, CD4+ T cells and macrophages (CD163+). The infiltrate was more intense in sheep infected at mid-gestation. In the foetal mesenchyme, mostly free tachyzoites were found in animals infected at G1, while those infected in G2 displayed predominantly particulate antigen, and parasitophorous vacuoles were detected in sheep infected at G3. A similar pattern of placental cytokine mRNA expression was found in all groups, displaying a strengthened upregulation of IFN-γ and IL-4 and milder increases of TNF-α and IL-10, reminiscent of a mixed Th1 and Th2 response. IL-12 and IL-6 were only slightly upregulated in G2, and TGF-ß was downregulated in G1 and G2, suggestive of limited T regulatory (Treg) cell activity. No significant expression of TLR2 or TLR4 could be detected. In summary, this study confirms the pivotal role of systemic and local immune responses at different times of gestation during N. caninum infection in sheep.

Virulence attenuation of a Mycobacterium avium subspecies paratuberculosis S-type strain prepared from intestinal mucosa after bacterial culture. Evaluation in an experimental ovine model.

The differences in pathogenicity between an inoculum derived directly from an intestinal tissue homogenate from a paratuberculosis affected sheep and the S-type Mycobacterium avium subsp. partuberculosis (Map) strain isolated in laboratory media from the mentioned homogenate were assessed in two experiments in lambs. Specific peripheral immune responses were significantly lower in animals inoculated with the cultured organisms that showed only granulomatous lesions in the intestinal lymphoid tissue. However, in the homogenate group, more abundant granulomata also occurred in the lamina propria. Map was isolated only in lambs infected with the culture strain. Map DNA was demonstrated by nested-PCR in all the lambs but in a lower proportion (57.1% vs 100%) in those from the culture group. Under these particular experimental conditions, the results suggest that an attenuation of Map virulence has occurred in the cultured strain compared to the initial tissue homogenate, even after a low number of passages.

Experimental infection of lambs with C and S-type strains of Mycobacterium avium subspecies paratuberculosis: immunological and pathological findings.

The two main genotypes of recognized isolates of Mycobacterium avium subsp. paratuberculosis (Map) are cattle (C) and sheep (S) strains. An experimental infection was conducted to establish the effect of Map strain on the pathogenesis of ovine paratuberculosis. Twenty-four out of thirty 1.5-month-old Assaf lambs were divided into 4 groups of 6 and infected orally with three low passage field isolates, two of S- (22G and the pigmented Ovicap49) and one of C- (764) type, and the reference K-10 strain (C type). The remaining six animals were unchallenged controls. Animals were euthanized at 150 and 390 days post-infection (dpi). Throughout the experiment, the peripheral immune response was assessed and histological and molecular (PCR) studies were conducted on samples of intestine and related lymphoid tissue. Specific antibody and IFN-γ production was significantly higher in animals infected with the C strains, while no consistent IFN- γ responses were observed in the S-type strain infected groups. A positive intradermal skin test response was detected in all infected groups. Lambs infected with S-type strains had granulomatous lesions restricted to the lymphoid tissue with no differences in the lesion intensity over time. In both C-type strain groups, lesions were more severe at 150 dpi while at 390 dpi lesions, characterized by well-demarcated granulomas with fibrosis, decreased in severity. Only infected lambs were positive to PCR. These results suggest that the strain of Map has a strong influence over the immune and pathological responses developed by the host. Lesions induced by C-type strains in lambs show a regressive character and tend to decrease as the infection progresses.

Fiebre por dengue: guías de manejo / Dengue fever: management guidelines

El presente artículo refleja conceptos generales clínicos relacionados con una de las enfermedades de gran impacto epidemiológico a nivel nacional, que han llevado a la movilización de diferentes recursos para su control y manejo. Se presentan criterios de gran utilidad para abordar su manejo en los servicios de urgencia tomando como referencia la normatividad aprobada para su control.

Cardiomiopatía de Tako-tsubo: reporte de dos casos / Tako-tsubo cardiomyopathy: report of two cases

Se presentan dos casos de mujeres postmenopáusicas que consultan al servicio de urgencias presentando su primer episodio de dolor torácico desencadenado después de una situación de estrés emocional; sus EKG mostraban cambios compatibles con eventos coronarios agudos y sus niveles de Troponina T fueron francamente positivos. Al ser llevadas a coronariografía, se encontró coronarias sanas y ventriculografía con fracción de eyección disminuida. Los ecocardiogramas iniciales mostraron alteración de la contractilidad segmentaria principalmente de los segmentos apicales con confirmación de la disfunción sistólica; los de control mostraron reversión de estos hallazgos, con mejoría de la fracción de eyección; uno de los casos presentó recurrencia. El diagnóstico final de ambas pacientes fue cardiomiopatía de Tako-tsubo.