Patología apendicular: de lo frecuente a lo infrecuente / Appendicular pathology: from frequent to infrequent

La apendicitis aguda es la patología más común en el apéndice y la causa principal del abdomen quirúrgico. Aproximadamente 300,000 personas se someten a apendicectomía cada año en los Estados Unidos. El riesgo estimado de presentar un cuadro de apendicitis aguda en algún momento de la vida está estimado en un 7%. El uno por ciento de las apendicectomías corresponde a tumores apendiculares. Los tumores malignos se confirman por análisis patológico en 0,9 al 1.4% de todas las apendicetomías realizadas.Objetivos. Evaluar incidencia de patología apendicular benigna, analizar la incidencia de tumores apendiculares, determinar sobrevida y mortalidad de tumores apendiculares a 5 años. (AU)

The acute appendicitis is the most common pathology in the appendix and the main cause of the surgical abdomen. Approximately 300,000 people undergo appendectomy each year in the United States. The life-time risk of acute appendicitis is around 7%. One percent of the appendicectomies correspond to appendicular tumors. Malignant tumors are confirmed by pathological analysis in 0.9­1.4% of all appendectomies performed. Objectives To evaluate the incidence of benign appendicular pathology, to analyze the incidence of appendicular tumors, to determine survival and mortality of appendicular tumors at 5 years. (AU)

Placental programmed cell death: insights into the role of aquaporins.

STUDY HYPOTHESIS: Are the placental aquaporins (AQPs) involved in the apoptosis of human trophoblast? STUDY FINDING: The general blocking of placental AQPs with HgCl2 and, in particular, the blocking of AQP3 activity with CuSO4 abrogated the apoptotic events of human trophoblast cells. WHAT IS KNOWN ALREADY: Although apoptosis of trophoblast cells is a natural event involved in the normal development of the placenta, it is exacerbated in pathological processes, such as pre-eclampsia, where an abnormal expression and functionality of placental AQPs occur without alterations in the feto-maternal water flux. Furthermore, fluctuations in O2 tension are proposed to be a potent inducer of placental apoptotic changes and, in explants exposed to hypoxia/reoxygenation (H/R), transcellular water transport mediated by AQPs was undetectable. This suggests that AQPs might be involved in processes other than water transport, such as apoptosis. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Explants from normal term placentas were maintained in culture under conditions of normoxia, hypoxia and H/R. Cell viability was determined by assessing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide incorporation. For the general or specific inhibition of AQPs, 0.3 mM HgCl2, 5 mM CuSO4, 0.3 mM tetraethylammonium chloride (TEA) or 0.5 mM phloretin were added to the culture medium before explants were exposed to each treatment. Oxidative stress parameters and apoptotic indexes were evaluated in the presence or absence of AQPs blockers. AQP3 expression was confirmed by western blot and immunohistochemistry. MAIN RESULTS AND THE ROLE OF CHANCE: First, we observed that in H/R treatments cell viability decreased by 20.16 ± 5.73% compared with those explants cultured in normoxia (P = 0.009; n = 7). Hypoxia did not modify cell viability significantly. Both hypoxia and H/R conditions induced oxidative stress. Spontaneous chemiluminescence and thiobarbituric acid reactive substance levels were significantly increased in explants exposed to hypoxia (n = 6 per group, P = 0.0316 and P = 0.0009, respectively) and H/R conditions (n = 6 per group, P = 0.0281 and P = 0.0001, respectively) compared with those cultured in normoxia. Regarding apoptosis, H/R was a more potent inducer of trophoblast apoptosis than hypoxia alone. Bax expression and the number of apoptotic nuclei were significantly higher in explants cultured in H/R compared with normoxia and hypoxia conditions (n = 12, P = 0.0135 and P = 0.001, respectively). DNA fragmentation was only observed in H/R and, compared with normoxia and hypoxia, the activity of caspase-3 was highest in explants cultured in H/R (n = 12, P = 0.0001). In explants exposed to H/R, steric blocking of AQP activity with HgCl2 showed that DNA degradation was undetectable (n = 12, P = 0.001). Bax expression and caspase-3 activity were drastically reduced (n = 12, P = 0.0146 and P = 0.0001, respectively) compared with explants cultured in H/R but not treated with HgCl2. Similar results were observed in explants exposed to H/R when we blocked AQP3 activity with CuSO4. DNA degradation was undetectable and the number of apoptotic nuclei and caspase-3 activity were significantly decreased compared with explants cultured in H/R but not treated with CuSO4 (n = 12, P = 0.001 and P = 0.0001, respectively). However, TEA and phloretin treatments, to block AQP1/4 or AQP9, respectively, failed in abrogate apoptosis. In addition, we confirmed the expression and localization of AQP3 in explants exposed to H/R. LIMITATIONS, REASONS FOR CAUTION: Our studies are limited by the number of experimental conditions tested, which do not fully capture the variability in oxygen levels, duration of exposure and alternating patterns of oxygen seen in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that any alteration in placental AQP expression might disturb the equilibrium of the normal apoptotic events and may be an underlying cause in the pathophysiology of placental gestational disorders such as pre-eclampsia. Furthermore, the dysregulation of placental AQPs may be one of the crucial factors in triggering the clinical manifestations of pre-eclampsia. LARGE SCALE DATA: n/a. STUDY FUNDING AND COMPETING INTERESTS: This study was supported by UBACyT 20020090200025 and 20020110200207 grants and PIP-CONICET 11220110100561 grant, and the authors have no conflict of interest to declare.

Oxygen tension modulates AQP9 expression in human placenta.

UNLABELLED: Placental hypoxia has been implicated in pregnancy pathologies such as preeclampsia. We have previously reported that AQP9 is highly expressed in syncytiotrophoblast from normal placentas and shows an overexpression in preeclamptic placentas, with a lack of functionality for water transport. Up to now, the response of AQP9 to changes in the oxygen tension in trophoblast cells is still unknown. OBJECTIVE: Our aim was to establish whether alterations in oxygen levels may modulate AQP9 expression in human placenta. METHODS: A theoretical analysis of the human AQP9 gene to find conserved DNA regions that could serve as putative HIF-1 binding sites. Then, explants from normal placentas were cultured at different concentrations of oxygen or with 250 µM CoCl2. AQP9 molecular expression and water uptake was determined. RESULTS: Fourteen consensus HIF-1 binding sites were found in the human AQP9 gene, but none of them in the promoter region. However, placental AQP9 decreased abruptly when HIF-1α is expressed by deprivation of oxygen or CoCl2 stabilization. In contrast, after reoxygenation, HIF-1α was undetectable while AQP9 increased significantly and changed its cellular distribution, showing the same pattern as that previously described in preeclamptic placentas. Accordingly with the decrease in AQP9 expression, water uptake decreased in explants exposed to hypoxia or treated with CoCl2. Conversely as we expected, after reoxygenation, water uptake decreased dramatically compared to the control and was not sensitive to HgCl2. CONCLUSION: Our findings suggest that oxygen tension may modulate AQP9 expression in human placenta. However, the role of AQP9 still remains uncertain.

Evidence for insulin-mediated control of AQP9 expression in human placenta.

UNLABELLED: The AQP9 gene contains a negative insulin response element, suggesting that it may be modulated by insulin. Previously, we reported AQP9 overexpression in preeclamptic placentas but a lack of functionality of AQP9 in water and mannitol transport. We also observed high serum levels of insulin and TNF-α in preeclamptic women. OBJECTIVE: To evaluate whether AQP9 expression is regulated by insulin in the human placenta, and whether the dysregulation of AQP9 observed in preeclamptic placentas may be related to the inability to respond to insulin stimuli. METHODS: Explants from normal and preeclamptic placentas were cultured at different concentrations of insulin. Treatment with TNF-α was used to induce phosphorylation of insulin receptor substrate (IRS), which may desensitize insulin action. AQP9 molecular expression and water uptake was determined. RESULTS: Insulin decreased the molecular expression of AQP9 exclusively in explants from normal placentas in a concentration-dependent manner. Treatment with TNF-α previous to insulin addition prevented these changes. Moreover, insulin treatment did not modify water uptake neither its sensitivity to HgCl(2.) CONCLUSION: AQP9 water permeability seems to be independent of its molecular expression, strongly suggesting that AQP9 might not have a key role in water transport in human placenta. We also propose another mechanism of down-regulation of AQP9 molecular expression mediated by insulin in a concentration-dependent manner in human placenta and provide new evidence that in preeclamptic placentas the mechanisms of insulin signaling may be altered, producing an overexpression of AQP9 that does not correlate with an increase in its functionality.

CFTR may modulate AQP9 functionality in preeclamptic placentas.

UNLABELLED: Preeclampsia (PE) is a hypertensive disorder unique to human pregnancy. Although its causes remain unclear, it is known that altered placental villous angiogenesis and a poorly developed fetoplacental vasculature can affect the transport functions of the syncytiotrophoblast (hST). We have previously observed that in preeclamptic placentas there is an increase in AQP9 protein expression, with a lack of functionality. Up to now, the mechanisms for AQP9 regulation and the role of AQP9 in the human placenta remain unknown. However, there is strong evidence that the cystic fibrosis transmembrane conductance regulator (CFTR) regulates AQP9 functionality. OBJECTIVE: Here, we studied CFTR expression and localization in hST from preeclamptic placentas in order to investigate if alterations in CFTR may be associated with the lack of activity of AQP9 observed in PE. METHODS: The expression of CFTR in normal and preeclamptic placentas was determined by Western Blot and immunohistochemistry, and CFTR-AQP9 co-localization was determined by immunoflurescence. Water uptake experiments were performed using explants from human normal term and preeclamptic placentas treated with CFTR inhibitors. RESULTS: We found that CFTR expression significantly decreased in preeclamptic placentas, and that the hST apical labeling almost disappeared, losing its co-localization with AQP9. Functional experiments demonstrated that water uptake diminished in normal term explants incubated with CFTR inhibitors. CONCLUSIONS: These results suggest that CFTR expression decreases in preeclampsia and may thus be implicated in the regulation of AQP9 activity.

The role of imaging techniques in the study of renal osteodystrophy.

Secondary hyperparathyroidism is the most common form of this condition found in renal osteodystrophy. Enlarged parathyroid glands are the rule in severe secondary hyperparathyroidism because of a marked parathyroid cell hyperplasia. For several years, ultrasonography, computed tomography, and scintigraphy with thallium201-technetium99 have been useful techniques to identify enlarged parathyroid glands. More recently, ultrasonography with color Doppler and parathyroid scintigraphy with 99mTc-sestamibi have proved to be useful as well. Computed tomography and magnetic resonance imaging can be used, but their sensitivity is similar to ultrasonography and they cost more. Ultrasonography with color Doppler signals has made it possible to evaluate tissue blood supply, an aid in differentiating thyroid nodules. The degree of blood supply may be an indirect index of cell proliferation when there is neither necrosis nor calcification, because an enriched blood supply suggests vigorous cell growth and nodule formation. Scintigraphy with 99mTc-sestamibi allows identification of ectopic glands, including those located in the mediastinum, and also provides functional information. Sestamibi uptake is closely related to both parathyroid hormone levels and to the histological type of parathyroid proliferation. In our experience, when hyperparathyroidism is not too severe, 2 weeks after 2 g of calcitriol is administered intravenously, these scintigraphic images can disappear (inhibition test). This suggests a possibility for a medical treatment. By contrast, when parathyroid hormone levels are higher, parathyroid sestamibi uptake remained unchanged. In such patients, parathyroidectomy or ethanol injection should be the best treatment. These glands would correspond to the most actively functioning glands; they would have a lesser expression of vitamin D receptors, rendering them refractory to medical treatment with calcitriol.

Evaluacioón de dos protocolos de quimioterapia (EBV-1 y EBV-2) más radioterapia en niños con enfermedad de hodgkin / Evaluation of two chemoterapy of protocolic (EBV-1 And EBV-2) more children in radioterapy with hodgkin desease

Se presentan los resultados obtenidos en 46 niños tratados en la unidad de linfomas del Hospital Universitario de Caracas con el esquema EBV más Rt a bajas dosis. Veinticuatro se trataron entre enero 1988-diciembre de 1990 con el EBV-1 (epirubicina 30 mg/m² yviblastina 6 mg/m² los días 1 y 15, cada 4 semanas) yveintidós se trataron entre enero 1991-diciembre 1994 con el EBV-2, cuya diferencia con el anterior fue el incremento de las dosis de epirubicina a 6o mg/m²Las características clínicas e histológicas de los grupos fueron similares. Se consideraron factores pronósticos (FP): los estadios clínicos III Y IV, la masa medistinal mayor del 30 por ciento del diámetro torácico, los síntomas B y el volumen tumoral mayor de 5 cm. Los pacientes con 0 ó 1 FP se ubicaron en el grupo favorable y recibieron 4 ciclos de Qt, combinados en ambos grupos con Rt: 20-25 C y a zonas afectas. Se obtuvo remisión completa en el 76 por ciento de los pacientes y sobrevidas libre de enfermedad, libre de eventos y total de 84 por ciento, 68 por ciento y 78 por ciento respectivamente a los 5 años de seguimiento. No se observaron diferencais significativas en los resultados obtenidos con el EBV-1 y el EBV-2, pero fueron superiores en el grupo favorable. La Qt fue bien tolerada y pudo administrarse ambulatoriamente. Los efectos tóxicos tardíos fueron hipotiroidismo subclínico en 5/14 pacientes (36 por ciento), carcinoma de tiroides en 1/46 (2 por ciento) y cardiomiopatía dilatada en 1/46 (2 por ciento) tratado con EBV-2. Concluimos que 4 ciclos de EBV-1 combinados con Rt. a bajas dosis es una alternativa efectiva en el tratamiento de los niños con E.H grupo favorable y que el incremento de la dosis de epirubicina a 60 mg/m² no mejora los resultados

Gastric ulcer and cancer ulcer. Retrospective evaluation of the current endoscopic diagnosis.

Aim of this experience has been to evaluate the current diagnostic potentiality of the endoscopy in the framework of the gastric ulcerous pathology. On the total of the gastric ulcers 17.9% have resulted to be neoplastic with the hystologic examination. The diagnostic accurracy of the endoscopy has resulted to be of the 87% compared to hystology. From our data it is evidenced how the endoscopy examination has a relevant diagnostic accuracy in defining the nature of the gastric ulcer which however has to be confirmed by the histology which seems to be diriment.