Acute Horner syndrome secondary to glandular fever due to Epstein Barr virus infection.

We present a clinical situation where a 47-year old female patient consulted with left partial ptosis and miosis that started, two weeks before, with an episode of glandular fever secondary to Epstein-Barr infection. Apraclonidine 0.5% and Phenylephrine 1% drop testing was performed with results consistent with suspected left Horner Syndrome (HS), with a probable postganglionic location. Magnetic Resonance Angiography (MRA) at the moment of the acute presentation did not show any image suggesting carotid arterial dissection but showed irregular narrowing of the left internal carotid artery on its paravertebral extracranial way, consistent to enlarged intra-carotid sheath lymphoid tissue. A week later, a Doppler ultrasound was performed, showing bilateral images compatible with internal carotid arterial dissection. When Postganglionar HS is suspected, the first aetiology to rule out is a carotid arterial dissection because of its potentially fatal outcome and for being a more described entity as postganglionic HS aetiology. However, it is also evidenced that a certain diagnose is not always possible. Furthermore, we describe the enlarged internal carotid artery sheath lymphoid tissue as a possible cause of sympathetic nerve disruption causing a Postganglionar HS, although not common.

[Comparative analysis of patients admitted to Spanish Intensive Care Units due to medical and surgical disease]. / Análisis comparativo de pacientes ingresados en Unidades de Cuidados Intensivos españolas por causa médica y quirúrgica.

OBJECTIVE: To describe the characteristics of the patients case-mix admitted to ICUs due to medical and surgical disease, and to compare both groups. DESIGN: Analysis of data covering the period 2006-2011 in the ENVIN-HELICS registry. An observational, prospective, multicenter and voluntary participation study. SETTING: A total of 188 Spanish ICUs. PATIENTS: All patients admitted for more than 24 hours. MAIN VARIABLES: Demographic data, cause of admission, severity scores, length of stay, mortality. RESULTS: A total of 138,999 patients were analyzed. Of these, 65,467 (47.1%) were admitted due to a non-coronary medical cause, 27,785 (20,0%) due to coronary-related illness, 28,044 (20,2%) after elective surgery and 17,613 (12.7%) after urgent surgery. Use of devices, nosocomial infections and isolation of multirresistant organisms were more prevalent in urgent surgery patients. Longer length of stay (median 5 days; interquartile range 2-11) as well as higher severity scale values (APACHE II and SAPS II) corresponded to this same group of patients. Mortality was higher in non-coronay medical patients. On categorizing the patients according to the APACHE II score, mortality was seen to be higher in urgent surgery cases than in elective surgery patients in all groups. The largest difference was observed in the APACHE II score 6-10 group (3% vs. 0.9%) (OR: 2.14, 95% CI 1.825-2.513; p<0.001). CONCLUSIONS: The mortality rate is higher in non-coronary medical patients, though resource use per patient is greater in the urgent surgery cases. The APACHE II scale underestimates mortality in emergency surgery patients.

Modelling survival kinetics of Staphylococcus aureus and Escherichia coli O157:H7 on stainless steel surfaces soiled with different substrates under static conditions of temperature and relative humidity.

The survival of Escherichia coli O157:H7 and Staphylococcus aureus on stainless steel surfaces with Saline Solution (SS), Tryptone Soy Broth (TSB) and meat purge was studied, and based on results, mathematical models describing survival of pathogens as a function of time were proposed. Results indicated that S. aureus was able to survive longer than E. coli O157:H7 in all substrates. The type of substrate had a greater impact on the survival of E. coli O157:H7. This microorganism only remained viable for 8 and 50 h (hours) on surfaces with SS and TSB, respectively while on meat purge, the microorganism could be recovered after 200 h. For S. aureus, SS and TSB led to similar survival times (250 h) whereas on meat purge, survival capacity increased to 800 h. Survival data for S. aureus could be well described by a log-linear model or a Weibull model depending on the type of substrate (R(2) > 0.85). E. coli O157:H7 displayed an evident tail zone which made the Weibull model more appropriate (R(2) > 0.94). These survival models may be used in quantitative risk assessment to produce more accurate risk estimates. Finally, the results highlight the importance of performing effective cleaning procedures to prevent cross contamination.

Modeling the growth of Listeria monocytogenes in pasteurized white asparagus.

Growth of Listeria monocytogenes in pasteurized white asparagus was monitored at different storage temperatures (4, 10, 20, and 30 degrees C). Among the main microbial kinetic parameters, growth rate (mu) per hour was calculated at each temperature using the Baranyi-Roberts model. L. monocytogenes was able to grow at all temperatures, although at 4 degrees C only a slight increment of the microbial population was observed (approximately 1 log CFU/g) after 300 h of storage. Subsequently, two different secondary modeling approaches were proposed to study the relationship between mu and storage temperature: the Arrhenius and Ratkowsky models. Although both models properly described the data observed, smaller values of root mean square error (RMSE) and standard error of prediction (SEP) were obtained with the Ratkowsky model, providing a better goodness of fit (Ratkowsky model: RMSE = 0.010, SEP = 21.23%; Arrhenius model: RMSE = 0.026, SEP = 54.37%). The maximum population density (MPD) was calculated at each temperature studied. A clear dependence between MPD and temperature was found; lower temperatures produced lower values of MPD. This finding confirmed the Jameson effect, indicating that multiple hurdles in the food-processing chain plus lower temperatures reduced L. monocytogenes growth. Predicting the growth of L. monocytogenes along the food chain will help to reduce microbial risks associated with consumption of pasteurized white asparagus.

[Pulmonary capillary hemangiomatosis: a rare cause of pulmonary hypertension]. / Hemangiomatosis capilar pulmonar: una causa poco frecuente de hipertensión pulmonar.

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary hypertension characterized by capillary proliferation infiltrating the structures of the pulmonary parenchyma. Although veins are particularly involved, proliferation also affects bronchiolar, interstitial and other structures. We report a case of PCH in a 70-year-old man. Pulmonary artery hypertension was demonstrated by echocardiogram and angiography. Severe emphysema could be seen in a computed tomographic scan of the thorax, even though spirometric values indicated that airflow obstruction was mild. Dyspnea and respiratory insufficiency progressed with marked shunting until death. Tissue inspection at the autopsy revealed capillary proliferation in the alveolar walls with occasional oviform protrusions into air spaces or around small vessels and bronchioles. Endothelial cells in newly formed vessels were not atypical and mitosis was scarce; p53 expression was negative and Ki67 proliferation slight, indicating that PCH is not a neoplastic process as has sometimes been suggested.

Distinct requirements for IFNs and STAT1 in NK cell function.

NK cell functions were examined in mice with a targeted mutation of the STAT1 gene, an essential mediator of IFN signaling. Mice deficient in STAT1 displayed impaired basal NK cytolytic activity in vitro and were unable to reject transplanted tumors in vivo, despite the presence of normal numbers of NK cells. IL-12 enhanced NK-mediated cytolysis, but poly(I:C) did not, and a similar phenotype occurred in mice lacking IFNalpha receptors. Molecules involved in activation and lytic function of NK cells (granzyme A, granzyme B, perforin, DAP10, and DAP12) were expressed at comparable levels in both wild-type and STAT1(-/-) mice, and serine esterase activity necessary for CTL function was normal, showing that the lytic machinery was intact. NK cells with normal cytolytic activity could be derived from STAT1(-/-) bone marrow progenitors in response to IL-15 in vitro, and enhanced NK lytic activity and normal levels of IFN-gamma were produced in response to IL-12 treatment in vivo. Despite these normal responses to cytokines, STAT1(-/-) mice could not reject the NK-sensitive tumor RMA-S, even following IL-12 treatment in vivo. Whereas in vitro NK cytolysis was also reduced in mice lacking both type I and type II IFN receptors, these mice resisted tumor challenge. These results demonstrate that both IFN-alpha and IFN-gamma are required to maintain NK cell function and define a STAT1-dependent but partially IFN-independent pathway required for NK-mediated antitumor activity.

STAT1 affects lymphocyte survival and proliferation partially independent of its role downstream of IFN-gamma.

Lymphocytes derived from mice deficient in STAT1 showed reduced apoptosis and enhanced proliferation in vitro. To understand the involvement of STAT1 in the observed reduction in apoptosis, we examined the levels of caspase and bcl-2 family genes that are involved in cell survival and/or apoptosis. The levels of caspase 1 and 11, two enzymes involved in both cytokine protein processing and induction of apoptosis, were reduced in STAT1-/- cells compared with wild-type. However, the levels of bcl-2 genes were comparable in both mice. STAT1-/- cells also displayed an enhanced proliferation following TCR stimulation. This hyperproliferation could not be ascribed completely to the loss of IFN-gamma-mediated antiproliferation. First, similar phenotypes were also observed in fibroblasts and pre-B cells derived from STAT1-/- mice, which do not produce IFN-gamma. Second, comparisons with cells lacking the gene for IFN-gamma or with cells treated with neutralizing Abs to IFN-gamma only partially mimicked the STAT1-/- phenotype. Interestingly, the kinetics of degradation of p27kip1, a CDK inhibitor, following TCR ligation were faster, and, concomitantly, the up-regulation of CDK2 kinase activity and protein levels were increased in stimulated T cells of STAT1-/- mice relative to those of wild-type mice. Furthermore, STAT1-/- animals were more susceptible to carcinogen-induced thymic tumors, a possible consequence of altered T cell growth and/or survival. These results demonstrate an essential role for STAT1 for lymphocyte survival and proliferation that is only partially dependent on IFN-gamma signaling.

Differential regulation of constitutive major histocompatibility complex class I expression in T and B lymphocytes.

Major histocompatibility complex (MHC) class I antigens are constitutively expressed yet highly induced by interferon (IFN) during inflammation. We found that not only IFN-induced but also normal basal expression of MHC I required IFN receptors and signal transducer and activator of transcription (STAT)1, providing genetic evidence for continuous IFN signaling. Surprisingly, an IFN-independent requirement for STAT1 was also found, specifically in T lymphocytes, where MHC class I expression was not fully accounted for by IFN signaling. This IFN-independent pathway maintained tyrosine phosphorylation of STAT1 in T but not B lymphocytes even in the absence of IFN receptors. Interestingly, interleukin (IL)-7 selectively activated STAT1 and induced MHC class I in mature T but not B cells. These loss of function studies demonstrate an essential role of endogenous IFN and activated STAT1 for constitutive MHC class I expression in normal mice and define IL-7-dependent but IFN-independent regulation of STAT1 restricted to T lymphocytes.

LST1 is a SEC24 homologue used for selective export of the plasma membrane ATPase from the endoplasmic reticulum.

In Saccharomyces cerevisiae, vesicles that carry proteins from the ER to the Golgi compartment are encapsulated by COPII coat proteins. We identified mutations in ten genes, designated LST (lethal with sec-thirteen), that were lethal in combination with the COPII mutation sec13-1. LST1 showed synthetic-lethal interactions with the complete set of COPII genes, indicating that LST1 encodes a new COPII function. LST1 codes for a protein similar in sequence to the COPII subunit Sec24p. Like Sec24p, Lst1p is a peripheral ER membrane protein that binds to the COPII subunit Sec23p. Chromosomal deletion of LST1 is not lethal, but inhibits transport of the plasma membrane proton-ATPase (Pma1p) to the cell surface, causing poor growth on media of low pH. Localization by both immunofluorescence microscopy and cell fractionation shows that the export of Pma1p from the ER is impaired in lst1Delta mutants. Transport of other proteins from the ER was not affected by lst1Delta, nor was Pma1p transport found to be particularly sensitive to other COPII defects. Together, these findings suggest that a specialized form of the COPII coat subunit, with Lst1p in place of Sec24p, is used for the efficient packaging of Pma1p into vesicles derived from the ER.

Signal transducer and activator of transcription 1 in human muscle: implications in inflammatory myopathies.

Polymyositis (PM) and dermatomyositis (DM) are two major and distinct inflammatory myopathies. Cytokines, implicated in the immune process, have been recognized in the muscle tissue from PM and DM patients, but their functional in situ role has not been identified. We analyzed the expression of the signal transducer and activator of transcription 1 (STAT1), a molecule whose up-regulation indicates the interaction of cytokines, or growth factors, with their target receptors in muscle fibers and inflammatory infiltrates in PM and DM. An immunohistochemical analysis was performed using monoclonal antibodies to STAT1 in 57 muscle biopsies from 10 patients with DM, 10 with PM, and 37 controls. The profile of STAT1 up-regulation was also investigated in cultured muscle stimulated by interferon-gamma, epidermal growth factor, platelet-derived growth factor, and interleukin-2, using semiquantitative polymerase chain reaction and Western blot. High STAT1 expression was observed in many perifascicular atrophic muscle fibers from DM patients in 10/10 biopsies. In contrast, only a few muscle fibers undergoing necrosis were STAT1 positive in 2/10 patients with PM and in 2/37 controls. STAT1 reactivity was noted in most cells of the infiltrates in DM, PM, and controls. In vitro, STAT1 was stimulated by interferon-gamma but not by the other molecules studied. These results suggest that in DM, but not in PM, there is distinctive functional local cytokine activity able to increase STAT1 expression in muscle fibers. As interferon-gamma specifically activates STAT1 in vitro, this cytokine in conjunction with ischemia is probably involved in perifascicular muscle fiber pathology in DM.

The two isoforms of the 90-kDalton nucleolus organizer region autoantigen (upstream binding factor) bind with different avidity to DNA modified by the antitumor drug cisplatin.

It has been previously described that some proteins containing HMG boxes are able to bind more strongly to DNA modified with cis-diamminedichloroplatinum (II) (cisplatin) than to unmodified DNA. In the present study, we analyzed the interaction of cisplatin-modified DNA with the human autoantigen NOR-90 (UBF), a transcription factor that contains several HMG boxes. Using autoantibodies against NOR-90 to perform ELISA and immunoprecipitation, it was confirmed that NOR-90 (UBF) was able to bind cisplatin-modified DNA more avidly than unmodified DNA or trans-diamminedichloroplatinum(II) (transplatin) modified DNA. Moreover, by Southwestern, we observed that the 97 kDalton isoform of NOR-90 (UBF1) was able to bind cisplatin-modified DNA more strongly than the 94 kDalton isoform (UBF2); binding of unmodified DNA or transplatin-modified DNA was not detected with either isoform. Sera containing autoantibodies against NOR-90 did not inhibit, but increased the binding of NOR-90 to cisplatin-modified DNA.

Influence of vegetative cycle of asparagus (Asparagus officinalis L.) on copper, iron, zinc and manganese content.

The essential elements copper (Cu), iron (Fe), zinc (Zn) and manganese (Mn) were analyzed in fresh asparagus to determine the effects of the vegetative cycle of the plant on the micronutrient content. Asparagus samples were classified in two groups by diameter (< 11 mm and > 14 mm). Asparagus from a sample group with the same diameter were divided into two portions (apical and basal) according to distance from the tip. The concentrations of copper, iron, zinc and manganese increased during the vegetative cycle of the asparagus, mainly in the apical portion which showed significantly greater concentrations with respect to the basal portion. The > 14 mm diameter asparagus presented higher levels of copper, zinc and manganese, whereas the concentration of iron was greater in the < 11 mm diameter asparagus. The mean element levels were (mg/kg dry weight): Cu, 18.9 +/- 3.9; Fe, 91.7 +/- 33.7; Zn, 69.5 +/- 24.6 and Mn, 20.9 +/- 5.0).

[Adenosine deaminase activity in the pleural effusion. A study of 64 cases]. / Actividad de adenosindesaminasa en líquido pleural. Estudio realizado en 64 casos.

Clinical and analytic data of 64 patients with firm etiologic diagnosis of pleural effusion with adenosine deaminase (ADA) present, were analyzed retrospectively. The patients had entered our hospital over a 40-month period. ADA activity in pleural fluid was analyzed by the Blake and Berman kinetic method. Mean ADA activity of the total sample was 32 U/l (SD:23.9). In patients with tuberculous pleural effusion ADA activity was higher than in the remaining patients (47.7, SD:21.4, versus 15.5 SD: 13.2; p < 0.0001). In the group of patients with tuberculous pleuritis diagnosed by pleural biopsy (22 cases) the presence of necrotizing granulomas was associated with slightly higher ADA activity although the difference was not statistically significant (49.2 SD 10.1 versus 41.3 SD 8.9; p = 0.07). Among only patients with tuberculous pleuritis or neoplasia with lymphocytic exudate, a cut off point greater than 23 U for ADA predicted a diagnosis of tuberculous pleuritis with a sensitivity of 0.96, specificity of 1, positive predictive value of 1, negative predictive value of 0.94, and a confidence limit of 0.97. In conclusion, ADA activity greater than 23 U determined by the kinetic method in pleural fluid with signs of lymphocytic exudate is strongly suggestive of pleural tuberculosis based on our sample of patients with pleural effusion.

[Pulmonary lymphangioleiomyomatosis. Presentation of a new case]. / Linfangioleiomiomatosis pulmonar. Presentación de un nuevo caso.

A 48-year-old woman hospitalized because of spontaneous pneumothorax. She suffered dyspnea since three years before. Diffuse reticulonodular interstitial pattern was observed in the radiography. The transbronchial biopsy suggested lymphangioleiomyomatosis, the diagnosis being supported by open pulmonary biopsy. Usefulness of transbronchial biopsy is discussed and several treatment modalities are described.

Long-term behavior of bovine collagen membrane used as vascular substitute. Experimental study in rats.

The aim of the present study was to evaluate the sequence of the immediate and the mid/long-term organization of the blood interface of a collagenous membrane used as vascular substitute in rats. The implants were prepared from calf skin type I insoluble collagen, obtained after acidic dispersion, in absence of chemical or tanning treatment. They were used to patch an aortic defect by means of microsurgical techniques. The animals were sequentially sacrificed for immediate hemocompatibility studies at 10 s, 30 s, 10 min, 3 h, and 6 h, for long-term analyses of the organization of the blood material interface at the 7th, 15th, 45th, 60th, 90th day following the surgery and each month until 14 months after aortic replacement. The superficial immediate events at the blood patch interface demonstrated erythrocytes heavily engulfed in a thin but dense fibrin mesh both at the patch and at the adjacent aortic wall surfaces. Neither adherent platelet nor platelet aggregate were detectable on the collagen patch surface. This fibrinoerythrocytic membrane covered the patch completely at 60 s and at 3 h the deposit was limited to 5-6 erythrocyte layers as confirmed by histology. It did not further develop on the 7th day. At the blood-collagen interface there progressively developed a tissue composed of active myofibroblasts, collagen bundles, and elastic fibers. After 4 months, nests of fibroendothelial cells were present, and between 6 and 14 months surface cell differentiation, although complete on the adjacent aorta was still incomplete on the bovine collagen patch, amorphous fibers, and fibroendothelial cells coexisting. Heterologous patch debris were still present 14 months after implantation and were associated with macroscopic and ultrastructural calcification, which need further investigations concerning the exact nature and mechanism of mineralization of vascular substitutes of biological nature.