Assessing pulmonary hypertensive vascular disease in childhood. Data from the Spanish registry.

RATIONALE: There is a lack of knowledge regarding the epidemiology, clinical characterization, and survival in pediatric pulmonary hypertension. OBJECTIVES: To describe the epidemiology, outcomes, and risk factors for mortality in pediatric pulmonary hypertension in Spain. METHODS: We analyzed data from the Spanish Registry for Pediatric Pulmonary Hypertension. From January 2009 to June 2012, a total of 225 patients diagnosed with pulmonary hypertension in 1998 or after were collected from 21 referral and nonreferral centers. We included all Nice etiologies, estimated incidence and prevalence of pulmonary hypertension in the Spanish pediatric population, and analyzed risk factors for mortality (Nice etiologic group, clinical and hemodynamic variables). Patients were classified as follows: group I, pulmonary arterial hypertension (n = 142; 61%); group II, left heart disease (n = 31; 14%); group III, respiratory disease (n = 41; 18%); group IV, thromboembolic pulmonary hypertension (n = 2; 1%); or group V, mostly inherited metabolic diseases (n = 10; 4.5%). Of the patients studied, 31% had multifactorial pulmonary hypertension. MEASUREMENTS AND MAIN RESULTS: Mean age at diagnosis was 4.3 ± 4.9 years (50% < 2 yr). Survival rates at 1 and 3 years were 80 and 74% for the whole cohort, and 89 and 85% for patients with pulmonary arterial hypertension. Independent risk factors for mortality included an etiologic group other than pulmonary arterial hypertension (P < 0.001), age at diagnosis younger than 2 years old (P < 0.001), advanced functional class at diagnosis (P < 0.001), and high right atrial pressure at diagnosis (P = 0.002). CONCLUSIONS: In moderate to severe pediatric pulmonary hypertension, the prognosis is better in pulmonary arterial hypertension than in other Nice categories. In pediatric pulmonary hypertension age at diagnosis younger than 2 years is a risk factor for mortality, in addition to the previously established risk factors.

Miocarditis y síndrome coronario agudo en la infancia / Myocarditis and acute coronary syndrome in childhood

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New alternatives to the treatment of acute liver failure.

INTRODUCTION: Acute-on-chronic liver failure (ACLF) is defined as an acute deterioration of a chronic liver disease. The most effective treatment in these patients is orthotopic liver transplantation (OLT), which is highly limited by the donor shortage. The aim of this study was to increase the usefulness of hepatocyte transplantation (HT) as a bridge or alternative to OLT. METHODS: During the last 2 years, we have performed HT in 3 patients with ACLF. The diagnosis was graft cirrhosis due to hepatitis C virus in 2 of them, who were already included on waiting lists for retransplantation, and the third, unknown alcoholic cirrhosis. RESULTS: After the first HT infusion, we observed an improvement in the clinical condition in all patients, hyperammonemia, and a partial correction of the degree of encephalopathy; 1 patient was retransplanted 6 days after the first HT. DISCUSSION: The main indications for HT are inborn errors of metabolism in children. Other indications especially in adults, are acute liver failure, ACLF in patients with end-stage-liver disease who are a waiting OLT, and acute liver failure after an hepatectomy. HT may be a new treatment to improve the clinical condition in patients awaiting OLT.

[Primary cardiac tumours in infancy]. / Tumores cardíacos primarios en la infancia.

INTRODUCTION: Primary cardiac tumours are very rare in the paediatric age, their incidence varies from 0.0017 % to 0.28 %. More than 90 % are benign in nature. The most common variety is the rhabdomyoma, present in over 60 % of cases with tuberous sclerosis. MATERIAL AND METHODS: We performed a retrospective analysis of medical records with a diagnosis of primary cardiac tumor between March 1977 and March 2007, finding a total of 27 patients. RESULTS: The age of initial diagnosis is more prevalent in the neonatal period, beginning with the discovery of a heart murmur (11 cases). There was no difference in gender distribution. In 14 patients were found cardiomegaly on chest radiograph. According to the echocardiography characteristics there were diagnosed 20 rhabdomyomas, 2 fibromas, 2 pericardial teratomas and 3 non classifiable tumours. Most were located in the left ventricle. Echocardiography, cardiac catheterization was also performed in 3 cases and angioresonance in 5 cases. During their evolution, episodes of arrhythmias were observed in 11 patients, 5 patients required some sort of surgical procedure, which confirmed the histopathology diagnosis. In 3 patients the initial cause of death was cardiological. The 75 % of cases with rhabdomyomas presented or developed tuberous sclerosis. In most of the rhabdomyomas (13 cases), there was a spontaneous regression. CONCLUSIONS: Firstly, there is shown to be a low prevalence of this disorder in children. Rhabdomyoma is the most common primary cardiac tumour in our study and it was associated in 75 % of cases with tuberous sclerosis. The diagnosis is more common in the early neonatal period after auscultation of a cardiac murmur and echocardiography, the diagnostic technique of choice, other imaging techniques, such as angioMRI not being of much for diagnosis in children. The emergence of foetal echocardiography allows early detection. The course is benign in most tumours, rhabdomyomas tending to regress spontaneously. It must be monitored as the occurrence of arrhythmias during its evolution will require medical treatment. Surgery is needed in cases with severe symptoms, due to obstruction in the ventricular output tracts. One option is the surgical cardiac transplant in non-resectable life-threatening tumours.

Tumores cardíacos primarios en la infancia / Primary cardiac tumours in infancy

Introducción: Los tumores cardíacos primarios son muy poco frecuentes en la edad pediátrica, y su incidencia varía entre el 0,0017 y el 0,28 %. Más del 90 % son de naturaleza benigna. La variedad más frecuente es el rabdomioma, asociado en más del 60 % de los casos con esclerosis tuberosa. Material y métodos: Se realizó un análisis retrospectivo de historias clínicas con diagnóstico de tumor cardíaco primario entre marzo de 1977 y marzo de 2007, y se encontró a un total de 27 pacientes. Resultados: La edad de diagnóstico inicial es más frecuente en el período neonatal, a partir del hallazgo de un soplo cardíaco (11 casos). No hubo diferencias en la distribución por sexos. En 14 pacientes se encontró cardiomegalia en la radiografía de tórax. De acuerdo con las características ecocardiográficas, se diagnosticaron 20 rabdomiomas, 2 fibromas, 2 teratomas pericárdicos y 3 tumores no clasificables. La mayor parte se localizaron en el ventrículo izquierdo. Además de la ecocardiografía, se realizó cateterismo cardíaco en 3 casos y angiorresonancia en 5 casos. Durante su evolución se constataron episodios de arritmias en 11 pacientes. En 5 se requirió algún tipo de procedimiento quirúrgico, en los que se obtuvo el diagnóstico anatomopatológico. La mortalidad inicial de causa cardiológica fue de 3 pacientes. El 75 % de casos con rabdomiomas presentaba o desarrolló esclerosis tuberosa. En la mayoría de los rabdomiomas (13 casos) se produjo regresión espontánea. Conclusiones: En primer lugar, se evidencia la baja prevalencia de esta patología en la infancia. El rabdomioma es el tumor cardíaco primario más frecuente y en nuestro estudio se asoció en el 75 % de los casos a esclerosis tuberosa. El diagnóstico es más frecuente en el período neonatal precoz tras la auscultación de un soplo cardíaco y la ecocardiografía, la técnica diagnóstica de elección, mientras que no se ha encontrado utilidad de otras técnicas de imagen, como la angiorresonancia, para su diagnóstico en la población infantil. La aparición de la ecocardiografía fetal permite descubrirlos precozmente. El curso es benigno en la mayoría de los tumores, con tendencia a la regresión espontánea en los rabdomiomas. Debe vigilarse la aparición de arritmias durante su evolución, que precisará tratamiento médico. La cirugía es necesaria en los casos con síntomas graves, debidos a obstrucción en los tractos de salida ventricular. Una opción quirúrgica es el transplante cardíaco en caso de tumores irresecables con riesgo vital (AU)

Introduction: Primary cardiac tumours are very rare in the paediatric age, their incidence varies from 0.0017 % to 0.28 %. More than 90 % are benign in nature. The most common variety is the rhabdomyoma, present in over 60 % of cases with tuberous sclerosis. Material and methods: We performed a retrospective analysis of medical records with a diagnosis of primary cardiac tumor between March 1977 and March 2007, finding a total of 27 patients. Results: The age of initial diagnosis is more prevalent in the neonatal period, beginning with the discovery of a heart murmur (11 cases). There was no difference in gender distribution. In 14 patients were found cardiomegaly on chest radiograph. According to the echocardiography characteristics there were diagnosed 20 rhabdomyomas, 2 fibromas, 2 pericardial teratomas and 3 non classifiable tumours. Most were located in the left ventricle. Echocardiography, cardiac catheterization was also performed in 3 cases and angioresonance in 5 cases. During their evolution, episodes of arrhythmias were observed in 11 patients, 5 patients required some sort of surgical procedure, which confirmed the histopathology diagnosis. In 3 patients the initial cause of death was cardiological. The 75 % of cases with rhabdomyomas presented or developed tuberous sclerosis. In most of the rhabdomyomas (13 cases), there was a spontaneous regression. Conclusions: Firstly, there is shown to be a low prevalence of this disorder in children. Rhabdomyoma is the most common primary cardiac tumour in our study and it was associated in 75 % of cases with tuberous sclerosis. The diagnosis is more common in the early neonatal period after auscultation of a cardiac murmur and echocardiography, the diagnostic technique of choice, other imaging techniques, such as angioMRI not being of much for diagnosis in children. The emergence of foetal echocardiography allows early detection. The course is benign in most tumours, rhabdomyomas tending to regress spontaneously. It must be monitored as the occurrence of arrhythmias during its evolution will require medical treatment. Surgery is needed in cases with severe symptoms, due to obstruction in the ventricular output tracts. One option is the surgical cardiac transplant in non-resectable life-threatening tumours (AU)

Human mesenchymal stem cells from adipose tissue: Differentiation into hepatic lineage.

Adipose tissue represents an accessible source of mesenchymal stem cells (ADSCs), with similar characteristics to bone marrow-derived stem cells. The aim of this work was to investigate the transdifferentiation of ADSCs into hepatic lineage cells in vitro. ADSCs were obtained from human adipose tissue from lipectomy. Cells were grown in medium containing 15% AB human serum. Cultures were serum deprived for two days and exposed to a two-step protocol with two different media using growth factors and cytokines. Hepatic differentiation was assessed by RT-PCR of liver-marker genes. ADSCs exhibited a fibroblastic morphology that changed to a cuboidal shape when cells differentiated. Expression of liver genes increased when using one of the two studied media consisting of DMEM supplemented with HGF, bFGF and nicotinamide for 14 days. The results indicate that, under certain specific inducing conditions, ADSCs can be induced to differentiate into hepatic lineage in vitro. Adipose tissue may be an ideal source of high amounts of autologous stem cells.

Hyperacute unilateral gonococcal endophthalmitis in an HIV-infected man without genital infection.

PURPOSE: To demonstrate the necessity of obtaining an accurate history from patients presenting abnormal evolution of ophthalmologic diseases. METHODS: A 42-year-old patient, denying any previous ocular or systemic morbidity, presented with an unusual severe and hyperacute gonococcal endophthalmitis with corneal abscess but no concurrent genitourinary infection. Only after a further interview did the patient reveal his human immunodeficiency virus status and a previous diagnosis of acquired immunodeficiency syndrome. RESULTS: Adequate topical and intravenous antibiotic treatment and surgery led to salvage of the eye. CONCLUSIONS: An accurate history should be obtained by patients with an abnormal course of an ophthalmologic disease, focusing on immunologic deficiencies that can cause extremely serious ophthalmologic complications with ensuing risk of visual impairment or ocular loss (bulbar enucleation).

Specific intra-tissue responses to manganese in the floating lamina of Trapa natans L.

Plant tolerance to heavy metals requires morpho-physiological mechanisms that are still poorly understood, especially in hydrophytes. This study focuses on the young floating lamina of the rhyzophyte Trapa natans exposed for 10 d to 130 microM Mn. The lamina has the ability to bioaccumulate Mn (> 3000 microg g(-1)). X-ray microanalysis of Mn cellular distribution revealed accumulation in the upper epidermis, in the first palisade layer, and in the idioblasts of the spongy tissue, which were shown with electron microscopy to contain osmiophilic vacuolar deposits, also observed to a minor extent in the control leaves. On the basis of biochemical and histochemical tests, these deposits were attributed to phenolic compounds that were probably able to chelate Mn. Net photosynthesis, photosynthetic pigments, room temperature microspectrofluorimetric analyses, and ultrastructural studies of plastids were performed to evaluate the status of the photosynthetic apparatus. A greater development of thylakoid membranes was observed in plastids of the second palisade and spongy tissue, which, however, did not accumulate Mn. Only the spongy tissue experienced inadequate assembly of PS II, but this did not significantly influence the photosynthetic yield of the whole lamina. It was concluded that T. natans can optimise productivity in the presence of Mn by means of specific intra-tissue responses within the framework of the floating lamina.

[Gabexate mesilate vs gabexate mesilate combined with octreotide in the prevention of postoperative complications of pancreatic surgery: preliminary results]. / Confronto fra gabesato mesilato da solo e in associazione con octreotide nella prevenzione delle complicanze postoperatorie in chirurgia pancreatica: risultati preliminari.

To date, gabexate mesilate, a synthetic protease inhibitor, has been used in the prophylaxis and treatment of acute pancreatitis, but has yet to be tested in preventing the postoperative complications of pancreatic surgery. For this purpose we planned a pilot study based on two treatment groups, each numbering 25 patients, submitted to high-risk pancreatic resection. In the first group, all patients received a continuous infusion of gabexate mesilate 1 g/day up to postoperative day 4; the second group of patients received the same treatment plus octreotide 0.1 mg every 8 hours for 5 days after surgery. All patients were followed until discharge with clinical and instrumental investigations to detect the onset of postoperative complications. The overall incidences of an uneventful course were 40% (10/25) and 32% (8/25), respectively. We found 12 complications closely related to pancreatic surgery in the former and 8 in the latter group. In the combined treatment group therefore we observe a 33% reduction in the incidence of related abdominal complications (12 vs 8). This favourable trend, however, needs to be confirmed in a larger multicentre trial.

Successful xenografting of cryopreserved primary pancreatic cancers.

In order to assess the suitability of cryopreserved neoplastic tissues for xenografting into nude (nu/nu) mice, we compared the take rate in 28 samples of pancreatic ductal carcinoma. Eleven fresh samples were implanted in nu/nu mice, and 17 were frozen in cryopreserving solution and implanted at a later time. All samples were examined for the presence of neoplastic tissue in cryostat sections. A total of 15 tumors grew in the animals; five from the freshly implanted samples and ten from those cryopreserved. Ten xenografted tumors were characterized for alterations in p53, K-ras, and p16 genes, which were found in six, eight, and nine cases, respectively. Our results demonstrate that the take rate for xenografting is comparable between cryopreserved and fresh tissue samples. The procedure allows for the exchange of tumor material between institutions and permits the establishment of centralized facilities for the storage of an array of different primary tumor samples suitable for the production of in vivo models of cancers.

Epidemiology of endogenous uveitis in north-eastern Italy. Analysis of 655 new cases.

PURPOSE: To report the results of a retrospective analysis among endogenous uveitis patients in the north-eastern area of Italy. METHODS: The authors reviewed a series of 655 new cases treated between October 1986 and December 1993. The incidence of endogenous uveitis was calculated based on a 100,000 patient population. RESULTS: The average incidence was 11.40/100,000. The majority of patients were between the ages of 20 and 70 years (74.43%). A probable diagnosis was determined in 55.57% of cases; anterior uveitis was diagnosed in 58.01% of cases, posterior uveitis in 26.11%, panuveitis in 12.98%, and intermediate uveitis in 2.9% of cases. The authors observed recurrences in 25.49% of cases. While the first cases are almost equally distributed in the various months, the recurrences seem to be significantly more frequent in the cold (from November to February; mean air temperature <8 degrees) and transitional months (October and from March to May; mean air temperature from 8 degrees C to 18 degrees C) than in the warm months (from June to September; mean air temperature >18 degrees C). Respectively p=0.003 and p=0.029. CONCLUSION: The incidence in this series is lower than in other European and American studies. Despite the high rate of idiopathic cases in this study, the authors support that the presentation of single case experiences may allow improved multi-centric analysis and a greater understanding of the epidemiology of uveitis.

Carotenoid and ultrastructure variations in plastids of Arum italicum Miller fruit during maturation and ripening.

The changes in the pigment pattern and composition occurring in the Arum italicum berry during the various steps of maturation (ivory to deep-green stages) and ripening (yellow and red-orange stages) were studied and correlated to the ultrastructural modifications of plastids. Transmission electron microscopy showed that each stage was characterized by a specific plastidial type following the unusual sequence amyloplast-->chloroplast-->chromoplast. Plastidial transitions were accompanied by profound modifications in the pigmental composition, in particular, in the pattern of carotenoids and their precursors. The HPLC analysis of the carotenoids showed that, besides the two usual all-trans metabolic pathways leading to lutein through alpha-carotene and to auroxanthin through beta-carotene, an additional cis-isomeric biosynthetic pathway leading to cis-neoxanthin through cis-beta-carotene exists. During the pre-ripening stages, the three pathways were present even if with qualitative and quantitative variations. When complete ripening was reached, a block occurred at the cyclization level causing the accumulation of both all-trans (i.e. gamma-carotene and neurosporene) and cis-isomer (i.e. lycopene and zeta-carotene) carotene precursors. Because of the occurrence of unusual pigments and the presence of the three main plastidial types, the fruit of A. italicum may constitute a most instructive model for the study of carotenogenesis.

Cytoreductive surgery in advanced endocrine tumours of the pancreas.

Surgery still plays an important role even in advanced endocrine tumours of the pancreas, owing to their biological behaviour. Sometimes it is possible to attempt a radical approach, but more often only cytoreduction is feasible. In fact, when the malignancy is not completely resectable on account of vessel involvement or extensive liver metastases, surgical reduction of the tumour burden (debulking) can be proposed, aimed at improving the clinical conditions and survival of these patients. Forty-one patients suffering from advanced endocrine tumour of the pancreas were observed from 1985 to 1996. In 13 patients, the disease was locally advanced as far as concerns lymph node metastases and/or vessel involvement, while the other 28 patients presented liver metastases. In the former group, we performed 6 radical resections, in the latter we submitted 2 patients to radical resection and 12 patients to cytoreductive surgery, with complete removal of the pancreatic malignancy. The overall survival of the resected patients was 87% (7/8). Three patients (37.5%) are alive and free of disease, while the other 4 have subsequently developed liver metastases. One patient died with hepatic recurrence. Half the patients (6/12) undergoing cytoreductive surgery are alive, 3 with stable and 3 with progressive disease. The other 6 patients have died due to liver progression of the disease. As data in the literature concerning the role of debulking as regards the survival are conflicting, we have modified our surgical approach in patients with advanced disease. We perform cytoreductive surgery whenever complete removal of the pancreatic tumour is feasible. The rationale of this approach is to leave only a liver with residual disease, with a view to giving targeted adjuvant treatment.

Role of chemoembolization in synchronous liver metastases from pancreatic endocrine tumours.

Endocrine tumours of the pancreas, even in case of liver involvement, are generally characterized by a slower evolution and a better prognosis, if compared with ductal carcinoma. This fact gives reason to a radical surgical approach, whenever possible, and to the research of any effective adjuvant treatment. For this purpose, hepatic transarterial chemoembolization (TACE) has been proposed in recent years for the treatment of metastatic endocrine tumours. Out of 80 patients suffering from endocrine tumours of the pancreas, observed between January 1985 and December 1996, 28 (35%) presented liver metastases at the time of diagnosis. Twelve of these patients were submitted to palliative resection of pancreatic tumour and one or more cycles of TACE. Overall survival was 50% (6/12); median survival was 35.4 months (range 4-75). These results suggest that chemoembolization, combined with surgical resection of primary malignancy, appears to be able to control the disease for a certain time and to increase the survival rate.

Recovery of long-term natural protection against reactivation of CMV retinitis in AIDS patients responding to highly active antiretroviral therapy.

OBJECTIVES: To see whether in severely immunosuppressed AIDS patients (with prior Cytomegalovirus retinal disease) who have significant increases in CD4+ lymphocytes following the initiation of highly active antiretroviral therapy (HAART) anti-Cytomegalovirus (CMV) maintenance therapy can be withdrawn with no subsequent progression of CMV retinitis. METHODS: Eight patients with AIDS and one or more previous episodes of CMV retinitis interrupted anti-CMV maintenance therapy following the successful beginning of HAART. CD4 cell counts and HIV-RNA were monitored monthly while measurement of CMV antigenemia and ophthalmoscopy were carried every 2 weeks thereafter. RESULTS: The HAART recipients in whom anti-CMV maintenance therapy had been interrupted had measureable increases of CD4+ T lymphocytes, substantial control of both HIV-RNA and CMV viraemia and did not show recurrence of retinitis during a mean follow-up of 98.4 weeks (range 78-120, SD 15.2). CONCLUSIONS: Anti-CMV maintenance therapy can be interrupted with no subsequent progression of retinal damage over a long time in patients with AIDS who successfully respond to HAART with a significant increase in CD4 cell count.

Association of xerophthalmia, flecked retina, and pseudotumor cerebri caused by hypovitaminosis A.

PURPOSE: To report an unusual case of hypovitaminosis A with bilateral papilledema and flecked retina that regressed after restoration of vitamin A deficiency. METHOD: Case report. A 27-year-old woman had undergone a biliopancreatic bypass for obesity in 1990. In 1995, she presented with bilateral xerophthalmia, bilateral papilledema, and bilateral flecked retina. RESULTS: Laboratory tests demonstrated low serum levels of vitamin A (0.8 micromol/l) and vitamin E (8.54 micromol/l). Xerophthalmia, papilledema, and flecked retina disappeared after restoration of normal vitamin A blood levels. CONCLUSION: Hypovitaminosis A after biliopancreatic bypass for obesity may be associated with xerophthalmia, pseudotumor cerebri, and flecked retina.

Pancreatic cystic manifestations in von Hippel-Lindau disease.

CONCLUSION: In view of the frequent absence of symptoms related to pancreatic lesions, screening tests for VHL should always include assessment of the pancreas and, considering the frequency of polycystic manifestations, VHL should always be borne in mind in the differential diagnosis of multiple pancreatic cysts, especially when occurring in young patients and in the absence of a positive history of pancreatic disease. BACKGROUND: Von Hippel-Lindau disease (VHL) is a hereditary disease transmitted with an autosomal dominant character and characterized by hemangioblastomas of the central nervous system and retina, renal tumors and cysts, and pheochromocytoma. Pancreatic manifestations of VHL are reported in the literature with incidences ranging from 16 to 29% of cases and consist mainly in cystadenomas of the serous type and in multiple cystic lesions, often with complete replacement of the gland. METHODS AND RESULTS: We report five cases of VHL with a polycystic pancreas as the main or only manifestation, all devoid of symptoms related to involvement of the pancreas, who were referred to our Pancreatic Surgery center with diagnoses of multiple pancreatic pseudocysts of undefined origin.