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.

[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.

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).

Brain receptor binding and lipophilic character of benzodiazepines.

A series of measurements of the potency of 26 benzodiazepines (BDZs) to inhibit the binding of [3H]diazepam to rat brain synaptosomal membranes has been undertaken. All compounds studied are NO2 or Cl 7-substituted, a class of BDZs known to have the highest biological activities and binding affinities (expressed as Ki). The results show that: (a) 2'-unsubstituted BDZs display a parabolic dependence of -log Ki values on lipophilic character of the molecule (expressed by means of the chromatographic Rm value); (b) 2'-halogen substituted BDZs show quite high binding affinities (ki values in the range 2-5 nM) giving rise to another class of BDZs whose dependence on the lipophilic character remains to be studied; and (c) BDZs lacking the carbonyl oxygen at position 2 (see Table 1), and having an oxygen at position 4, show low or very low binding affinities (Ki values in the range 600-7000 nM). Moreover for the compounds under examination, statistically significant correlations have been obtained between -log Ki values and psychopharmacological activity data.

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.

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.

PROTOANEMONIN-INDUCED CYTOTOXIC EFFECTS IN EUGLENA GRACILIS

The changes that protoanemonin, an antimicrobial agent of natural origin, brought about in the alga Euglena gracilis were studied with light and electron microscopy and with flow cytometry. The compound proved lethal for the alga at a dose of 5x10(-5)m. At the sublethal dose of 3.5x10(-5)m it caused: marked inhibition of growth; increase in the average cell volume; inhibition of cytokinesis and induction of coenocytic organisms; loss of the flagellum and stigma. Most nuclei were arrested in the G2/M phase of the cellular cycle. The chloroplasts were still well organized, but there was a conspicuous decrease in carotenoids and chlorophylls a and bwith a corresponding increase in pheophytins. The multifarious alterations seen in Euglena are discussed on the basis of a possible interaction between this lactone and several enzymatic systems.Copyright 1997 Academic Press Limited Copyright 1997Academic Press Limited

The role of surgery in the major early complications of severe acute pancreatitis.

The early complications of severe acute pancreatitis may constitute a dramatic clinical dilemma in the first 2 weeks of the disease, when the surgical approach is made even more difficult by failure to define the precise extent of the necrotic component of the disease. Moreover, the surgical indication itself is not always based on clear guidelines to which the clinician can refer, and this is due to factors of two types: (i) the intrinsic complexity of the pancreatitis syndrome in its early toxic stages and (ii) the difficulty in understanding the relevant information reported in the literature in this connection, which is often incomplete and based on confused terminology. While the surgical indication is universally accepted in the case of infection of the necrotic tissue (an event, however, which is by no means frequent in the early stages of severe pancreatitis), the development of multi-organ failure despite adequate intensive care is a potential indication which not all specialists go along with, at least not as regards the ideal timing of the intervention. Other surgical indications which have emerged are evidence of complete rupture of the main pancreatic duct and the presence of very extensive sterile necrosis. As things stand at present, however, we are witnessing a general tendency to postpone surgery, since delayed surgery is associated with a lower incidence of complications than is the case with early surgery. If, as is known, the role of surgery is aimed mainly at the treatment of superinfections and severe multi-organ failures, targeted antibiotic prophylaxis and earlier, more complete anti-enzymatic therapy may, as suggested by a number of pilot studies, offer a promising alternative to invasive procedures which are sometimes risky, though indispensable, in an attempt to save patients who would otherwise have no chance of survival.

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.

High-pressure liquid chromatographic feprazone determination in pharmaceutical formulations.

A high-pressure liquid chromatographic method was developed for the quantitative determination of feprazone, a nonsteroidal anti-inflammatory agent, in different pharmaceutical formulations. The results agree with those obtained with GLC and UV spectrophotometric assays.

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.

[Closed surgical treatment in acute severe pancreatitis]. / Il trattamento chirurgico chiuso della pancreatite acuta severa.

Between 1976 and 1994, 318 patients underwent surgical closed retro-endoperitoneal drainage and post-operative lavage for acute necrotizing severe pancreatitis. The main indication was sepsis (66.4%). The ratio between operated on and the overall number of observed patients has been progressively shifting towards medical treatment. Furthermore in the operated group the timing of surgery has been delayed step by step. The Authors discuss improvements in the understanding of the etiological and therapeutical aspects of the disease which has had a better outcome in recent years, survival rate of 91.4%. The personal option for the closed surgical approach is based on the progressive improvement of the technique and on the good results obtained both in terms of mortality and associated morbidity; as regards the latter problem the open techniques seems to be related to a higher complication rate than the closed one.

[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.

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.

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

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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.

Separation and quantitative determination of imipramine and desipramine from rat biological samples by high pressure liquid chromatography.

Imipramine and its metabolite, desipramine, have been determined in several rat biological samples by high pressure liquid chromatography. The method allows one to detect 15 ng in column of both drugs with a lower sensitivity limit of 20 microgram1-(1).

Separation and quantitation of protoanemonin in ranunculaceae by normal- and reversed-phase HPLC.

A method is described for the extraction and high-performance liquid chromatographic separation and quantitation of the lactone protoanemonin in leaves of Ranunculaceae. For samples with a protoanemonin concentration over 10 microg/g W. W., a reversed-phase technique using a Lichrosorb RP 18 column and a binary solvent system was developed. Alternatively, for samples with a lower lactone concentration, a normal-phase technique with a Lichrosorb Si 60 and quaternary elution system was elaborated. Protoanemonin was detected at 258 nm; its calibration curves were established, and its response factor was calculated using, as standard, the pure compound extracted from HELLEBORUS NIGER. A survey of ten different taxa of Ranunculaceae was performed and it showed the suitability of the method for routine work with high sensitivity limit.