Neumonía por herpes virus simple tipo 1. Entidad infrecuente de difícil diagnóstico y mal pronóstico en trasplantados pulmonares / Pneumonia due to herpes simplex virus type 1: A diffi cult to diagnose condition with a poor prognosis in lung transplants

La neumonía herpética es una rara enfermedad que afecta casi con exclusividad apersonas con un déficit de inmunidad. Con frecuencia tiene un desenlace fatal. Su aparición está descrita en los primeros 2 meses luego del trasplante pulmonar, pero en nuestra experiencia se evidenció después de los 10 meses, 1 año y medio, 8 y 19 años. Describimos los hallazgos tomográficos detectados en 4 pacientes con trasplantes pulmonares que cursaron neumonía herpética. Presentaban fiebre, tos, expectoración y disnea, con empeoramiento progresivo de su clase funcional, y todos fallecieron tras la aparición de la enfermedad. El diagnóstico histológico se realiza mediante lavado bronquioalveolar o biopsia transbronquial,con posterior tinción con hematoxilina-eosina y/o marcación inmunohistoquímica. Los hallazgos tomográficos destacados fueron: opacidades en vidrio esmerilado de distribución parcheada, consolidación del espacio aéreo, derrame pleural y bronquiectasias. Debido a su baja frecuencia y mal pronóstico, es importante conocer y tener presente esta entidad en personas trasplantadas de pulmón para no demorar el diagnóstico y actuar lo más rápidamente posible...

Peroxisome proliferator-activated receptor ligands regulate lipid content, metabolism, and composition in fetal lungs of diabetic rats.

Maternal diabetes impairs fetal lung development. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors relevant in lipid homeostasis and lung development. This study aims to evaluate the effect of in vivo activation of PPARs on lipid homeostasis in fetal lungs of diabetic rats. To this end, we studied lipid concentrations, expression of lipid metabolizing enzymes and fatty acid composition in fetal lungs of control and diabetic rats i) after injections of the fetuses with Leukotriene B4 (LTB4, PPARα ligand) or 15deoxyΔ(12,14)prostaglandin J2 (15dPGJ2, PPARγ ligand) and ii) fed during pregnancy with 6% olive oil- or 6% safflower oil-supplemented diets, enriched with PPAR ligands were studied. Maternal diabetes increased triglyceride concentrations and decreased expression of lipid-oxidizing enzymes in fetal lungs of diabetic rats, an expression further decreased by LTB4 and partially restored by 15dPGJ2 in lungs of male fetuses in the diabetic group. In lungs of female fetuses in the diabetic group, maternal diets enriched with olive oil increased triglyceride concentrations and fatty acid synthase expression, while those enriched with safflower oil increased triglyceride concentrations and fatty acid transporter expression. Both olive oil- and safflower oil-supplemented diets decreased cholesterol and cholesteryl ester concentrations and increased the expression of the reverse cholesterol transporter ATP-binding cassette A1 in fetal lungs of female fetuses of diabetic rats. In fetal lungs of control and diabetic rats, the proportion of polyunsaturated fatty acids increased with the maternal diets enriched with olive and safflower oils. Our results revealed important changes in lipid metabolism in fetal lungs of diabetic rats, and in the ability of PPAR ligands to modulate the composition of lipid species relevant in the lung during the perinatal period.

Saturated fat-rich diet increases fetal lipids and modulates LPL and leptin receptor expression in rat placentas.

Metabolic alterations in obese and overweight mothers impact the placenta and the fetus, leading to anomalies in fetal growth and lipid accretion. The primary aim of the study was to examine the effect of a saturated fat-rich diet (FD) on growth, lipid accretion, and lipases, leptin and leptin receptor (ObR) expression in the placenta and fetal liver. We also aimed to find a role for fetal leptin in the modulation of placental and fetal liver lipase and ObR expression. Six-week-old rats were fed with a standard rat chow (control) or a 25% FD for 7 weeks until mating and during pregnancy. Also, in a group of control rats, fetuses were injected with leptin on days 19, 20, and 21 of pregnancy. On day 21, we assessed lipidemia, insulinemia, and leptinemia in mothers and fetuses. In the placenta and fetal liver, lipid concentration was assessed by thin layer chromatography (TLC) and the gene expression of lipoprotein lipase (LPL), endothelial lipase, insulin receptor (Insr), leptin, and ObR by RT-PCR. The FD induced hypertriglyceridemia and hyperleptinemia (P<0.01) in mothers and fetuses, an increase in maternal (P<0.05) and fetal weight (P<0.01), overaccumulation of lipids in fetal liver (P<0.01), and enhanced leptin expression in the placenta and fetal liver (P<0.05). Placental expression of IR and LPL was increased (P<0.05), and ObR decreased (P<0.05) in the FD group. Fetal administration of leptin induced the placental and fetal liver downregulation of ObR (P<0.05) and upregulation of LPL expression (P<0.05). The FD led to increased fetal lipid levels, which may result from high maternal lipid availability and fetal leptin effects.

Folic acid and safflower oil supplementation interacts and protects embryos from maternal diabetes-induced damage.

Maternal diabetes increases the risk of embryo malformations. Folic acid and safflower oil supplementations have been shown to reduce embryo malformations in experimental models of diabetes. In this study we here tested whether folic acid and safflower oil supplementations interact to prevent embryo malformations in diabetic rats, and analyzed whether they act through the regulation of matrix metalloproteinases (MMPs), their endogenous inhibitors (TIMPs), and nitric oxide (NO) and reactive oxygen species production. Diabetes was induced by streptozotocin administration prior to mating. From Day 0.5 of pregnancy, rats did or did not receive folic acid (15 mg/kg) and/or a 6% safflower oil-supplemented diet. Embryos and decidua were explanted on Day 10.5 of gestation for further analysis of embryo resorptions and malformations, MMP-2 and MMP-9 activities, TIMP-1 and TIMP-2 levels, NO production and lipid peroxidation. Maternal diabetes induced resorptions and malformations that were prevented by folic acid and safflower oil supplementation. MMP-2 and MMP-9 activities were increased in embryos and decidua from diabetic rats and decreased with safflower oil and folic acid supplementations. In diabetic animals, the embryonic and decidual TIMPs were increased mainly with safflower oil supplementation in decidua and with folic acid in embryos. NO overproduction was decreased in decidua from diabetic rats treated with folic acid alone and in combination with safflower oil. These treatments also prevented increases in embryonic and decidual lipid peroxidation. In conclusion, folic acid and safflower oil supplementations interact and protect the embryos from diabetes-induced damage through several pathways related to a decrease in pro-inflammatory mediators.

Percutaneous radiofrequency thermal ablation for hepatocellular carcinoma.

BACKGROUND: Radiofrequency thermal ablation is the first therapeutic option in percutaneous treatment of hepatocellular carcinoma but data on its long-term efficacy and safety are not conclusive. AIM: This study reports a prospective survey on radiofrequency thermal ablation in north-east Italy. METHODS: Data were collected on 401 patients with hepatocellular carcinoma (males 301, mean age: 68 years) treated by radiofrequency thermal ablation in 13 centres. Indication to treatment was: single nodule not eligible for surgery in 77% of patients, 2-3 nodes in 18% and multiple lesions in 5%. Mean size was 3 cm (1-8 cm). Treatment response was assessed at 1 month by spiral computerized tomography and then with ultrasound examination and new spiral computerized tomography. RESULTS: Complete response was obtained in 67% of patients and in 27% response was 75-99%. Complete response raised to 77% in lesions smaller than 3 cm. The morbidity rate was 34%; the mortality was 0.5%, seeding was observed in four patients. Ten patients presented an unexpected rapid disease progression. CONCLUSION: The above data show that by radiofrequency thermal ablation, complete response can be achieved only in about two-third of the cases, clearly less than expected, and that, beyond seeding, unexpected progression can be observed.

Factors influencing post-transfusional platelet increment in pediatric patients given hematopoietic stem cell transplantation.

Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) always require platelet transfusions, but the increase in platelet count is often less than expected. Since factors responsible for poor response to platelet transfusions in this clinical setting are largely unknown, we performed a prospective study in 87 consecutive children transplanted in a single institution. The mean 16-h corrected count increment (CCI) of 598 platelet transfusions was 5.76 +/- 8.32 x 10(9)/l. Both before and after HSCT, 13.8% of patients had antibodies against HLA and/or platelet-specific antigens. Univariate analysis identified 12 factors significantly associated with a lower post-transfusion CCI, but only four reached statistical significance in the multivariate analysis. These four factors were concomitant therapy with vancomycin, alloimmunization, use of an Autopheresis cell separator for preparation of platelet concentrates and cytomegalovirus infection. We, therefore, suggest that a better response to platelet transfusions could be obtained by choosing a suitable cell separator, by avoiding the use of vancomycin and by adopting measures that reduce alloimmunization and CMV infection. Moreover, screening patients for HLA and platelet-specific antibodies before HSCT would identify the majority of subjects who will develop alloimmune refractoriness after transplantation and would allow the search for a compatible donor in advance.

Transfusion-transmitted virus infection in HIV-1-seropositive patients.

OBJECTIVES: To investigate the prevalence, persistence and genome heterogeneity of transfusion-transmitted (TTV) in HIV-1-infected patients, a group at high risk both of contracting blood-borne viruses and having viral persistence relating to immunodepression. METHODS: Plasma samples from 238 HIV-1 seropositive subjects and 226 healthy blood donors were examined for TTV-DNA both by polymerase chain reaction (PCR) using primers from the conserved regions in the N22 clone and PCR using primers deduced from the untranslated region (UTR). Direct DNA sequencing and phylogenetic analysis were used to characterize 27 TTV isolates from HIV-1 patients or healthy controls. RESULTS: Using PCR with the UTR primers, TTV DNA was detected in a very high percentage (> 80%) of samples both from HIV-1 seropositive subjects and from blood donors. Using PCR with N22 primers, shown to detect viral strains associated with hepatitis of unknown etiology, TTV DNA was found in 103 of 238 (43.3%) HIV-1-infected patients and in 22 of 226 (9.7%) blood donors. There was no difference in the prevalence of the TTV DNA in HIV seropositive subjects with regard to clinical features related to immunosuppression, markers of HCV infection or intravenous drug use; presence of TTV DNA was associated significantly only with male gender (P = 0.003). Persistent or intermittent viremia was detected in plasma samples taken up over a period of 19 months in all (15 of 15) HIV-infected patients tested. CONCLUSIONS: The persistence and high frequency of infection detected by PCR with N22 primers in HIV-1 seropositive patients suggest that further clinical investigation of immunocompromised hosts will provide information to clarify the pathogenic role of TTV.

[The effectiveness of foot reflexotherapy on chronic pain associated with a herniated disk]. / Efficacia della reflessologia plantare nel dolore cronico da ernia discale.

Foot reflexology is both a diagnostic technique and therapy. It is an alternative therapy which is considered useful in pain management. Its effectiveness as a therapy has been studied at the Mestre hospital where a clinical study has been undertaken to determine the effectiveness of reflexology in the reduction of pain. A group of 40 persons suffering almost exclusively from a lumbar-sacral disc hernia received three treatments of reflexology massage for a week. The results found that 25 persons (62.5%) reported a reduction in pain, (rating at 0.75 on a scale of 0-4). These results however did not take into consideration the relationship between the effectiveness of foot reflexology and variables such as the persons physicality (Body Mass Index), or their psychological or social status.

A system for determination of 3D vessel tree centerlines from biplane images.

With the increasing number and complexity of therapeutic coronary interventions, there is an increasing need for accurate quantitative measurements. These interventions and measurements may be facilitated by accurate and reproducible magnifications and orientations of the vessel structures, specifically by accurate 3D vascular tree centerlines. A number of methods have been proposed to calculate 3D vascular tree centerlines from biplane images. In general, the calculated magnifications and orientations are accurate to within approximately 1-3% and 2-5 degrees, respectively. Here, we present a complete system for determination of the 3D vessel centerlines from biplane angiograms without the use of a calibration object. Subsequent to indication of the vessel centerlines, the imaging geometry and 3D centerlines are calculated automatically and within approximately 2 min. The system was evaluated in terms of the intra- and inter-user variations of the various calculated quantities. The reproducibilities obtained with this system are comparable to or better than the accuracies and reproducibilities quoted for other proposed methods. Based on these results and those reported in earlier studies, we believe that this system will provide accurate and reproducible vascular tree centerlines from biplane images while the patient is still on the table, and thereby will facilitate interventions and associated quantitative analyses of the vasculature.

[Echo-guided fine-needle biopsy for the diagnosis of hepatic angioma. A report on 114 cases]. / La biopsia ecoguidata con ago sottile per la diagnosi di angioma epatico. Rapporto su 114 casi.

METHODS: Personal experience with fine-needle aspiration biopsy (FNAB) performed in 114 patients (42 males and 72 females) with hepatic angiomas, in whom imaging techniques did not allow a definite diagnosis, is reported. FNAB was made on 57.9% of the cases for atypical US pattern of the nodule, on 52.6% for a previous cancer history, with both conditions on 10.5%. The procedure was carried out by cyto-assistance for collecting material and a rapid stain diagnosis with an average of 2 biopsies per patient. Diagnostic accuracy was evaluated with following laparoscopy in 25 cases; surgery in 4 cases; angiography in 6 cases and US follow-up for 1 year at least in 78 cases (1 drop-out). RESULTS: One false-negative and 4 false-positives were detected with an overall accuracy of 96%. Two minor accidents were observed, due to a profuse bleeding of giant angiomas and resolved with medical care. CONCLUSIONS: Therefore, in case of angiomas larger than 5 cm, the use of laparoscopy after FNAB to control the bleeding and to confirm the diagnosis is suggested.

Ultrasound-guided fine needle biopsy and laparoscopy in the study of pancreatic masses: report on 136 cases.

The authors report their experience from 136 fine needle ultrasound (FN-US)-guided biopsies and laparoscopies. The pancreatic diseases considered by these methods were as follows: 9 cases of Pancreatitis, 11 cases of Pancreatic cysts, 5 cases of endocrine cancer, 109 cases of Exocrine cancer and 2 not conclusive cases. Diagnostic accuracy of FNB and laparoscopy was evaluated for each group and, in particular, for cancer patients. In the latter group, FNB helped to detect abdominal diffusion in 25 cases (33%) while laparoscopy, including laparoscopic washing, revealed a micro-diffusion in 31 cases (55%), the latter not shown previously by CT, RNM and US. The combination of these methods allows us to confirm the advanced stage of the majority of pancreatic cancers at onset. Furthermore, this seems to be a very reliable method to select resectable patients, thus avoiding useless, sometimes hazardous and expensive further investigation.

Cryopreservation of human platelets using dimethyl sulfoxide and glycerol-glucose: effects on "in vitro" platelet function.

BACKGROUND: The technique of freezing blood platelets could be very useful in the transfusion support of thrombocytopenic patients. The best method of platelet cryopreservation still remains an object of debate, though it has been suggested that dimethyl sulfoxide (DMSO) is more effective than glycerol-glucose as a cryopreservative. However, few studies have directly compared platelets cryopreserved with different methods. METHODS: We compared "in vitro" function of platelets cryopreserved with 5% dimethyl sulfoxide (DMSO) or 3% glycerol-glucose at -140 degrees C. Platelet aggregation and release reaction were studied with a Lumi aggregometer, thromboxane B2 (TxB2) production by radioimmunoassay, and Ca++ movement by the Fura 2 method. RESULTS: Cryopreservation with both of the methods dramatically reduced the ability of platelets to release ATP and to aggregate in response to single agonists. In contrast, cryopreserved platelets maintained their ability to aggregate after stimulation with paired agonists and to produce TxB2. Cytoplasmic Ca++ increase induced by thrombin was observed in the glycerol-preserved platelets, while it was nearly absent in the DMSO-preserved ones. CONCLUSIONS: We suggest that cryopreservation with glycerol-glucose or DMSO induces similar defects of platelet function. The damage is severe, but platelets are still able to respond to strong stimulation.

IgA serum levels and HLA complement markers in gastric cancer patients.

Immunoglobulin serum levels and class III HLA polymorphisms (Bf, C4A, and C4B) have been analyzed in 55 gastric cancer patients (13 having at least a first-degree relative affected by the same tumor) from the Republic of San Marino. This was done to search for possible immunoglobulin deficiencies (in particular IgA), which have been proposed to have a prognostic value in gastric cancer, and to identify possible associations between such a tumor and HLA class III determinants. All subjects had normal Ig levels with the exception of one patient (having the worst prognosis) characterized by a combined IgA, IgG, and IgM deficiency. Normal Ig levels were found in all the examined relatives of the proband. The Bf, C4A, and C4B allele frequencies we found did not differ significantly from those reported for healthy subjects in Italian samples.

Changes in composition of platelet membranes after "in vitro" incubation.

Platelet membranes were isolated by the glycerol lysis technique and incubated in Krebs-Ringer phosphate buffer, to determine their chemical modifications occurring during "in vitro" incubation. The main changes observed at the end of the incubation consist in a significant loss of protein components and in the nearly equimolar decrease of sialic acid and galactosamine. Aminoacid analysis indicate that mainly polar aminoacids are lost. SDS-polyacrylamide gel electrophoresis indicates that high molecular weight proteins disappear after incubation, while no relevant differences in the relative ratios between PAS-stained bands were evident. The reported modifications are quite similar to those described in the membranes of in vivo and in vitro aged red cells.

Colostral T lymphocytes detected by intracytoplasmic and membrane markers.

Colostral lymphocytes were studied using two established T-cell markers: intracytoplasmic alpha-naphtyl-acetate esterase (ANAE) staining and membrane receptors for sheep erythrocytes (E rosettes). ANAE staining allowed counting and identification of T-cell subsets independently of the status of membrane structures and receptors frequently altered in colostral cells. The fact that a sizeable number of colostral lymphocytes had the same phenotype as the majority of mature circulating peripheral blood lymphocytes supports the hypothesis that colostral lymphocytes may play a role in protecting neonates against infections, in transferring immune information to the newborn, or in modulating the immune response via release of soluble factors. A considerable percentage of colostral T lymphocytes are ANAE-negative. This phenotype is similar to that observed among thymocytes.