Aggressive Papillary Thyroid Carcinoma Presenting with Metastasis to the Pancreas.

Papillary thyroid cancer is the most common type of thyroid cancer. Aggressive forms tend to metastasize to the lungs and bones, but the abdomen is a rare site of metastasis. We present a 46-year-old male patient who presented with a neck mass associated with shortness of breath and hemoptysis. He was found to have a large thyroid mass on imaging. He underwent a total thyroidectomy with bilateral neck dissection, with pathology showing a multifocal tall cell variant of papillary thyroid carcinoma with lymphovascular invasion in both thyroid lobes. Due to recurrent findings of residual thyroid tissue on whole-body scan imaging, the patient underwent radioactive iodine ablation therapy twice, with poor response to therapy, suggested by persistently elevated thyroglobulin levels. However, the residual tissue responded to external beam radiation. After the initial response to radiation, thyroglobulin was noted to have increased again, prompting a PET-CT after administration of recombinant TSH. PET showed a focal area of increased uptake in the head of the pancreas. The patient underwent the Whipple procedure for resection of the metastasis. Pathology showed papillary thyroid carcinoma with strong and diffuse staining for TTF-1 and thyroglobulin. The patient was started on lenvatinib in the postoperative period and is currently tolerating treatment well with evidence of decreasing thyroglobulin levels. Intra-abdominal metastasis from a thyroid malignancy source is quite rare and can be challenging as far as diagnosis and treatment. Surgical resection can be curative and can be followed by radioactive iodine ablation therapy if cancer cells show avidity. Tyrosine kinase inhibitors can be used in refractory disease. New research is being conducted on new agents that can reverse the resistance to radioactive iodine therapy.

Pathophysiology and Clinical Features of Neuropsychiatric Manifestations of Thyroid Disease.

Thyroid hormones (TH) have a cardinal role in the development of the central nervous system during embryogenesis and early infancy. However, the TH-responsive genes in the developing brain cease to respond to TH in adulthood. Nevertheless, thyroid dysfunction in adults is commonly associated with a host of cognitive and psychiatric problems. Cognitive decline, dysphoria, and depression are common manifestations of overt hypothyroidism while hyperthyroidism can cause agitation, acute psychosis, and apathy, especially in older people. Whereas levothyroxine treatment can reverse dementia in the setting of hypothyroidism, the effect of levothyroxine on depressive symptoms in subjects with subclinical hypothyroidism is controversial. The use of supraphysiologic doses of TH to treat depression refractory to antidepressant remains a viable therapeutic tool with the caveat that excessive doses of thyroid hormone to treat depression may have potentially damaging effects on other organ systems. The present communication describes the pathophysiology of neuropsychiatric manifestations of thyroid disease, including changes in neurotransmission, alterations in neuronal or glial cell gene expression, blood-brain barrier dysfunction, increased risk of cerebrovascular disease, and occasionally cerebral inflammatory disease in the context of autoimmune thyroid disease. Elucidating the molecular mechanisms of TH effect on cerebral tissue will help identify novel therapeutic targets for managing people with neuropsychiatric disorders.

Inhibition of Pro-Inflammatory Cytokine Secretion by Select Antioxidants in Human Coronary Artery Endothelial Cells.

Inflammatory and oxidative stress in endothelial cells are implicated in the pathogenesis of premature atherosclerosis in diabetes. To determine whether high-dextrose concentrations induce the expression of pro-inflammatory cytokines, human coronary artery endothelial cells (HCAEC) were exposed to either 5.5 or 27.5 mM dextrose for 24-hours and interleukin-1ß (IL-1ß), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF α) levels were measured by enzyme immunoassays. To determine the effect of antioxidants on inflammatory cytokine secretion, cells were also treated with α-tocopherol, ascorbic acid, and the glutathione peroxidase mimetic ebselen. Only the concentration of IL-1ß in culture media from cells exposed to 27.5 mM dextrose increased relative to cells maintained in 5.5 mM dextrose. Treatment with α-tocopherol (10, 100, and 1,000 µM) and ascorbic acid (15, 150, and 1,500 µM) at the same time that the dextrose was added reduced IL-1ß, IL-6, and IL-8 levels in culture media from cells maintained at 5.5 mM dextrose but had no effect on IL-1ß, IL-6, and IL-8 levels in cells exposed to 27.5 mM dextrose. However, ebselen treatment reduced IL-1ß, IL-6, and IL-8 levels in cells maintained in either 5.5 or 27.5 mM dextrose. IL-2 and TNF α concentrations in culture media were below the limit of detection under all experimental conditions studied suggesting that these cells may not synthesize detectable quantities of these cytokines. These results suggest that dextrose at certain concentrations may increase IL-1ß levels and that antioxidants have differential effects on suppressing the secretion of pro-inflammatory cytokines in HCAEC.

The Effects of Known Cardioprotective Drugs on Proinflammatory Cytokine Secretion From Human Coronary Artery Endothelial Cells.

BACKGROUND: Endothelial cell dysfunction in diabetes is involved in the pathogenesis and progression of premature atherosclerosis. High-dextrose has been shown to induce both oxidative stress and endoplasmic reticulum stress in cultured human coronary artery endothelial cells (HCAEC). STUDY QUESTION: To determine whether or not several classes of cardioprotective drugs inhibit proinflammatory cytokine expression by HCAEC. MEASURES AND OUTCOMES: To determine the effects of high dextrose on expression of proinflammatory cytokines by HCAEC, cells were treated with either 5.5 mM or 27.5 mM dextrose for 24 hours and interleukin-1ß (IL-1ß), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α were measured by enzyme immunoassay in the presence or absence of known cardioprotective drugs, including select ß-blockers, statins, and renin-angiotensin system inhibitors. RESULTS: IL-1ß levels increased significantly in cells treated with high dextrose; however, IL-6 and IL-8 levels did not change. Treatment of cells with carvedilol, atenolol, and propranolol decreased levels of all 3 cytokines in cells exposed to either 5.5 or 27.5 mM dextrose. Similar effects on IL-1ß, IL-6, and IL-8 levels were observed when cells were treated with simvastatin, pravastatin, and the renin-angiotensin system inhibitors spironolactone, captopril, lisinopril, candesartan, and losartan. No Il-2 or tumor necrosis factor α expression was observed in any of the experiments indicating that HCAEC do not express these cytokines. CONCLUSIONS: We conclude that each of the classes of drugs tested possess pleiotropic anti-inflammatory activities and are effective in both low- and high-dextrose-treated cells.

Regulation of apolipoprotein A-I gene expression by the histamine H1 receptor: Requirement for NF-κB.

AIMS: Earlier it had been found by us that apolipoprotein A-I (apo A-I) is suppressed by histamine in HepG2 cells. Histamine has been shown to regulate NF-κB activity, though not in hepatocytes. Therefore we examined the role of the histamine receptors and NF-κB in histamine-mediated apo A-I gene expression in HepG2 liver cells. MAIN METHODS: The effect of histamine on histamine H1 receptor expression, and NF-κB p65 and p50 subunits was examined by Western blot. Histamine H1 receptor involvement was examined by loss-of-function (via siRNA) and gain-of-function studies overexpressing the histamine H1 receptor. The requirement for the p65 subunit of NF-κB for histamines effect was elucidated by loss-of-function studies (siRNA). Finally, the effect of histamine on NF-κB binding to the apo A-I gene promoter was examined by chromatin immunoprecipitation. KEY FINDINGS: Treatment of HepG2 cells with histamine had no effect on histamine H1 receptor expression. However, treatment with histamine increased NF-κB p65 and p50 subunit expression significantly. At low levels, the exogenous histamine H1 receptor plasmid suppressed apo A-I gene promoter activity while addition of higher levels of plasmid DNA actually increased apo A-I gene promoter activity. Inhibition of NF-κB activity with SN50 prevented histamine from repressing apo A-I promoter activity as did silencing p65 expression via siRNA. Finally, treatment with histamine increased binding of the p65 subunit of NF-κB to the apo A-I gene promoter. SIGNIFICANCE: Histamine suppresses apo A-I gene expression in hepatocytes via the histamine H1 receptor by elevating NF-κB expression and binding to the apo A-I promoter.

[Gollop-Wolfgang complex and cloacal exstrophy, a strange association]. / Complejo de Gollop-Wolfgang y extrofia cloacal, una rara asociación.

Cloacal exstrophy and Gollop-Wolfgang complex are very rare pathologies and their association has been reported in only one patient. We present a case of a newborn of indeterminate sex with anomalies of the lower limbs, and an anterior abdominal wall defect. External genitalia were not observed, ectrodactyly of lower limbs, omphalocele, lipomeningocele and imperforate anus were detected. During the diagnostic and therapeutic surgery other anomalies were found, such as vesical exstrophy, cecal fistula, uterine duplication, vaginal agenesis, urethral agenesis, ectopic ureters, stenosis of the left ureter, biphid clitoris and patent urachus. The abdominal ecography showed ectopic right lower quadrant localization of right kidney. Radiographic images of lower limbs showed bifurcation of left femur and absent tibia in both limbs. Due to the findings a diagnosis of cloacal exstrophy and Gollop- Wolfgang complex was made. The patient developed sepsis, liver failure, metabolic acidosis and hyponatremia, she died at seven weeks of age.

Complejo de Gollop-Wolfgang y extrofia cloacal, una rara asociación / Gollop-Wolfgang complex and cloacal exstrophy, a strange association

La extrofia cloacal y el complejo de Gollop-Wolfgang son patologías muy raras y su asociación ha sido comunicada en un solo paciente. Presentamos el caso de un neonato, de sexo indeterminado, con anormalidades de miembros inferiores y defecto en la pared abdominopélvica anterior. No se observan genitales, presenta ectrodactilia en miembros inferiores, onfalocele, lipomeningocele y ano imperforado. Se realiza cirugía diagnóstica y terapéutica que revela extrofia vesical, fístula cecal, útero doble, agenesia de vagina, agenesia de uretra, uréteres mal implantados, estenosis de uréter izquierdo, clítoris bífido y uraco persistente. La ecografía abdominal mostró riñón derecho ectópico en fosa ilíaca derecha. Radiografías de los miembros inferiores mostraron bifurcación del fémur izquierdo y ausencia de tibia en ambos miembros. Debido a los hallazgos se llega al diagnóstico de extrofia cloacal y complejo de Gollop-Wolfgang. La paciente presentó sepsis, insuficiencia hepática, acidosis metabólica e hiponatremia; falleció a las siete semanas de edad.

Complejo de Gollop-Wolfgang y extrofia cloacal, una rara asociación / Gollop-Wolfgang complex and cloacal exstrophy, a strange association

La extrofia cloacal y el complejo de Gollop-Wolfgang son patologías muy raras y su asociación ha sido comunicada en un solo paciente. Presentamos el caso de un neonato, de sexo indeterminado, con anormalidades de miembros inferiores y defecto en la pared abdominopélvica anterior. No se observan genitales, presenta ectrodactilia en miembros inferiores, onfalocele, lipomeningocele y ano imperforado. Se realiza cirugía diagnóstica y terapéutica que revela extrofia vesical, fístula cecal, útero doble, agenesia de vagina, agenesia de uretra, uréteres mal implantados, estenosis de uréter izquierdo, clítoris bífido y uraco persistente. La ecografía abdominal mostró riñón derecho ectópico en fosa ilíaca derecha. Radiografías de los miembros inferiores mostraron bifurcación del fémur izquierdo y ausencia de tibia en ambos miembros. Debido a los hallazgos se llega al diagnóstico de extrofia cloacal y complejo de Gollop-Wolfgang. La paciente presentó sepsis, insuficiencia hepática, acidosis metabólica e hiponatremia; falleció a las siete semanas de edad.(AU)

Gripe aviar h5n1: h1n1: ¿la nueva pandemia del siglo? / Avian influenza h5n1: h1n1: the new pandemy of the century?

Las pandemias de gripe se han caracterizado hasta ahora por la adaptación en humanos de un virus que contiene determinantes antigénicos derivados de cepas de virus propios de aves para los cuales no existe inmunidad en humanos. La ausencia de vacunas y de fármacos eficaces contra una posible epidemia provoca una gran expectativa en cuanto a la repercusión que una pandemia de tales magnitudes tendrá sobre la humanidad no sólo en el aspecto económico sino sobre la tasa de mortalidad tan elevada que podría producirse. Este artículo va dirigido al personal de salud, tanto profesionales como estudiantes, con el fin de informarlos y prevenirlos frente a una nueva pandemia de influenza.

The influenza pandemies are characterized by the adaptation in humans of viruses that only affect the avian population. This is because there is not immunity by humans in front of these new serotypes of influenza. The absence of vaccines and efficient drugs against a possible pandemy, provoke huge expectations according to the repercussion of this kind of pandemy in the humanity, not only in the economical aspect but in a possible mortality rate that could be produced. This article is aimed at the professional and students of the health area. Its objective is to inform and prevent them in the case they need to face a new pandemy of influenza.