Simplified risk stratification criteria for identification of patients with MRSA bacteremia at low risk of infective endocarditis: implications for avoiding routine transesophageal echocardiography in MRSA bacteremia.

The aim of this study was to identify patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with low risk of infective endocarditis (IE) who might not require routine trans-esophageal echocardiography (TEE). We retrospectively evaluated 398 patients presenting with MRSA bacteremia for the presence of the following clinical criteria: intravenous drug abuse (IVDA), long-term catheter, prolonged bacteremia, intra-cardiac device, prosthetic valve, hemodialysis dependency, vertebral/nonvertebral osteomyelitis, cardio-structural abnormality. IE was diagnosed using the modified Duke criteria. Of 398 patients with MRSA bacteremia, 26.4 % of cases were community-acquired, 56.3 % were health-care-associated, and 17.3 % were hospital-acquired. Of the group, 44 patients had definite IE, 119 had possible IE, and 235 had a rejected diagnosis. Out of 398 patients, 231 were evaluated with transthoracic echocardiography (TTE) or TEE. All 44 patients with definite IE fulfilled at least one criterion (sensitivity 100 %). Finally, a receiver operator characteristic (ROC) curve was obtained to evaluate the total risk score of our proposed criteria as a predictor of the presence of IE, and this was compared to the ROC curve of a previously proposed criteria. The area under the ROC curve for our criteria was 0.710, while the area under the ROC curve for the criteria previously proposed was 0.537 (p < 0.001). The p-value for comparing those 2 areas was less than 0.001, indicating statistical significance. Patients with MRSA bacteremia without any of our proposed clinical criteria have very low risk of developing IE and may not require routine TEE.

Marital Status and Survival in Patients Diagnosed with Melanoma.

INTRODUCTION: Previous research suggests the presence of a spouse may considerably affect melanoma detection rates through more frequent examinations, better access to healthcare, and improved social support. Yet, the role of marital status on melanoma survival is currently unknown. The aim of this study is to assess whether marital status is associated with survival following melanoma diagnosis. METHODS: We performed secondary analysis of data from all participants of the Florida Cancer Data System (FCDS) and included adult melanoma patients diagnosed between 2001 and 2009 with follow-up information available until 2015. Marital status was categorized as single, married, divorced, or widowed. The primary outcome was survival interval after melanoma diagnosis, which was assessed according to the time from the date of diagnosis to the time of death or last contact. Cox proportional hazard models were used to assess the independent association between marital status and survival. RESULTS: We assessed data from 36,578 melanoma patients. Married patients were significantly more likely to survive than single patients (Hazard ratio (HR) = 0.65; 99% Confidence Interval (CI): 0.57-0.74; P < 0.001) after adjusting for age, sex, race, ethnicity, geographic location, insurance status, tobacco use, primary site, stage, and histology. There was no evidence of effect modification by gender (P=0.189). CONCLUSIONS: Married patients, including both men and women, had a 35% reduction in the risk of death after melanoma diagnosis compared with single patients, and mechanisms independent of earlier detection, such as social support, may play a role in survival in patients with melanoma.

[Critical study of the morphogenesis of trunco-conal malformations]. / Etude critique de la morphogenèse des malformations tronco-cônales.

Anatomical and angiocardiographic studies have made possible discussion of hypotheses of the development and differentiation of the conus and of the trunco-conal orientation of the septum. Three autopsy specimens and two angiocardiogrammes of intertwined great vessels with transposition and partial distortion of the great vessels were studied. The specimen of intertwined great vessels comprised a muscular sub-aortic infundibulum posterior to and greater than the pulmonary infundibulum. In the case of transposition the opposite situation was encountered with a muscular pulmonary infundibulum posterior to and greater than the sub-aortic infundibulum; the plane of the aortic valves was higher than that of the pulmonary valves. The specimen of partial distortion of the great vessels comprised a muscular sub-aortic infundibulum posterior to and greater than the pulmonary infundibulum with the aortic valve set higher and in fibrous continuity with the mitral valve. It is concluded that the relations of the great vessels between each other and with the ventricles depend on the orientation of the trunco-conal septum and on the process of incorporation of the cone. The presence or absence of a posterior muscular infundibulum is not related to the growth or differential reabsorption of the cone but to a process of cellular differentiation. There was no relation between the level of the valves and their spatial orientation and the length of the infundibulum. The continuity or discontinuity between the aortic and atrio-ventricular valves is not determined by the level of the aortic valves.

New contributions to the ORP & DO time profile characterization to improve biological nutrient removal.

Changes in the oxidation-reduction potential (ORP), pH and dissolved oxygen (DO), along with organic load and nutrient removal in a municipal wastewater treatment plant (WWTP) have been monitored throughout one year. The "nitrate knee" and the "nitrate break point" in ORP profiles, the "nitrate apex" and the "ammonia valley" in pH profiles and the "DO elbow" in DO profiles have been identified. Furthermore, these bending points have been correlated with the oxygen uptake rate (OUR), the temperature in the vessel and the aeration and non-aeration time profiles by using Principal Component Analysis (PCA). The data have been previously split up into wet and dry weather cycles by means of a K-means clustering algorithm. Finally, two new parameters have been defined: the "ORP Arrow", which is closely related to the inhibition of the denitrification process, and the "Oxygen Rise Average Slope" (ORAS), which shows the oxygen transfer rate.

Immunofluorescent and immunoelectron microscopic localization of protein antigens in red cells infected with the human malaria Plasmodium falciparum.

Erythrocytes infected with the human malaria Plasmodium falciparum produce elevations of the surface membrane of the red cell called knobs. Through the use of transmission electron microscopy and a post-embedding protein A-immunogold technique, it was possible to show changes in the distribution of band 3, glycophorin A and spectrin in the region of the knob. These proteins appeared to be aggregated or condensed in the area of the knob, whereas the remainder of the red cell surface showed no such dense clusters; haemoglobin and the histidine-rich protein of P. lophurae could not be localized to the knobby protuberances. It was not possible to detect any changes in protein distribution using the light microscope and indirect immunofluorescence.

[Prevention of recurrence of rheumatic cardiopathy in 564 patients]. / Profilaxis secundaria en 564 pacientes con cardiopatía reumática.

In a group of 564 patients with rheumatic heart disease seen in the period from 1971 to 1975, who were under benzatinic prophylaxis, 23% were seen in the clinic and 77% at home. The object of this revision is to analyze the latter group in order to obtain the frequency of pharyngoamigdaline infections, and of relapses. 1. During the observation, those patients who did not present pharyngeal infections had no relapses. On the other hand, all relapses were observed in those patients who presented infections. 2. Those patients who carried out the prophylaxis incorrectly and who also presented pharyngeal infections, had almost twice the percentage of relapses as those who carried out the prophylaxis correctly. 3. In the group with effective prophylaxis, including those cases with or without pharyngeal infection, 5% had recurrences. In the group with ineffective prophylaxis, 16% had relapses. 4. Those patients with subsequent attacks doubled the percentage of relapses in comparison with those with initial attacks. 5. The plurivalvular patients have a higher frequency of recurrences than the univalvular patients. 6. During the first year of post-attack prophylaxis, the incidence of relapses is only 1.7%, in comparison with the following years in which there is a higher incidence of around 10%. 7. The total number of recurrences in 564 patients was 8%.

Nitric oxide-mediated antiplasmodial activity in human and murine hepatocytes induced by gamma interferon and the parasite itself: enhancement by exogenous tetrahydrobiopterin.

Expression of inducible nitric oxide (NO) synthase has been shown to inhibit the development of several pathogens, including fungi, bacteria, parasites, and viruses. However, there is still controversy as to whether this effector mechanism can inhibit the development of human pathogens. We now report that gamma interferon (IFN-gamma) induces the elimination of Plasmodium falciparum-infected primary human hepatocytes from cultures and that the antimalarial activity is dependent on NO. Infection with the parasite alone in the absence of added IFN-gamma caused a 10-fold increase in NO formation. Both spontaneous inhibition and IFN-gamma-induced inhibition of Plasmodium yoelii-infected murine hepatocytes were increased with the addition of the NO synthase cofactor tetrahydrobiopterin, or sepiapterin, which is converted to tetrahydrobiopterin. These results indicate that under in vitro conditions the parasite itself provides a signal that triggers induction of the NO pathway in human and murine hepatocytes and that NO formation in infected hepatocytes is limited by tetrahydrobiopterin availability.

Protection against malaria by Plasmodium yoelii sporozoite surface protein 2 linear peptide induction of CD4+ T cell- and IFN-gamma-dependent elimination of infected hepatocytes.

Plasmodium falciparum sporozoite surface protein 2 (SSP2), also known as TRAP, is included in experimental human malaria vaccines because Plasmodium yoelii SSP2 is the target of protective CD8+ CTL that eliminate P. yoelii-infected hepatocytes in mice. We now report that immunization with a synthetic branched-chain peptide including four copies of a PySSP2 sequence, NPNEPS, and two tetanus toxin T helper epitopes in the adjuvant TiterMax, or with an 18 amino acid peptide (NPNEPS)3 in the adjuvant protects A/J, but not BALB/c or C57BL/6 mice. Transfer of T lymphocyte-enriched immune splenocytes protects naive mice; in vivo depletion of CD4+ T cells eliminates vaccine-induced protection; and in vivo treatment with anti-IFN-gamma reverses vaccine-induced activity against infected hepatocytes. Lymph node cells from immunized A/J, BALB/c, and C57BL/6 mice recognize the (NPNEPS)3 peptide in vitro. However, the protected A/J mice respond with a predominantly Th1 pattern of lymphocyte response, and the non-protected strains of mice respond with a Th2 pattern. There are many examples of CD4+ T cells transferring protection against infectious organisms. However, to our knowledge, this is the first formal demonstration that immunization with a linear synthetic peptide induces CD4+ T cell-dependent, IFN-gamma dependent, genetically restricted sterile protective immunity against an infectious agent.

[Response of normal children to the treadmill exercise test using the Bruce protocol]. / Respuesta de los niños sanos a la prueba de esfuerzo en banda sinfin con el protocolo de Bruce.

Fifty nine boys and 41 girls underwent exercise stress testing (ETT), utilizing the Bruce protocol. Their mean age was 10 years. They were grouped by sex, age and body surface area. Blood pressure (BP), heart rate (HR) at rest, during exercise and after were monitored as well as the duration of the test and the energy cost. The HR and-BP had a similar linear relationship in both groups during the different stages of the test. The duration of the test expressed in minutes was 11.8 +/- 1.2 in boys and 10.7 +/- 1.2 in girls (P = 0.001). The oxygen consumption (ML/kg/min) was 45.2 +/- 4.9 and 41.9 +/- 4.5 that is equivalent to 12.9 +/- 1.4 and 11.9 +/- 1.2 mets for each group respectively. The group of boys of 6 (9.8) and 14 years of age (13.6) (P = 0.002) and in the girls in the 7 (9.5) and 10 years age group (11.8) P = 0.05. We conclude that 1) The ETT can be done in children safely but was have to take in consideration their age, sex, and body surface area in evaluating the results. 2) This study gives a reference to evaluate children with an without heart disease.

[Congenital intrapericardial parietal aneurysm of the left atrium. The electrocardiogram and echocardiogram as methods of diagnostic value]. / Aneurisma congénito parietal intrapericárdico de la aurícula izquierda. El electrocardiograma y el ecocardiograma como métodos de valor diagnóstico.

A case of congenital intrapericardial aneurysm of the left atrium associated with functional mitral insufficiency is described; it was resected successfully. Clinical, radiographic, vecto-electrocardiographic, ecocardiographic and angiocardiographic findings are shown. Those are compared with those of other nine similar cases. The finding of qR or QS complexes in L-I and a VL in the electrocardiogram as a sign of left atrial enlargement and eco-fre space posterior to the left ventricular endocardium in the ecocardiogram is mentioned as useful data in the diagnosis of left atrial aneurysmal dilatation not previously reported. Considering that the surgical result is always good, it is concluded that the congenital intrapericardial aneurysm of the left atrium is a rare malformation which needs to be resected irregardless of the presence or absence of arrhythmias, embolisms or heart failure.

Plasmodium yoelii: 17-kDa hepatic and erythrocytic stage protein is the target of an inhibitory monoclonal antibody.

Infected hepatocytes are important targets for malaria vaccines. To identify Plasmodium yoelii proteins expressed in infected hepatocytes, we immunized BALB/c ByJ mice with P. yoelii liver stage schizonts and produced a panel of monoclonal antibodies (Mabs). An IgG1 Mab, navy yoelii liver stage 3 (NYLS3), had the strongest reactivity against liver stage parasites and was selected for further characterization. The Mab does not recognize P. yoelii sporozoites, but recognizes liver stage parasites within 6 hr of invasion of mouse hepatocytes and throughout the hepatic and asexual erythrocytic stages of the parasite life cycle as determined by the immunofluorescent antibody test. This Mab is species-specific, and it reacts with liver stages of P. yoelii but does not react with liver stages of other Plasmodium species. The protein recognized by this Mab is present on the parasitophorous vacuole membrane of infected hepatocytes and erythrocytes as demonstrated by immunoelectron microscopy and has a relative molecular weight of 17 kDa as demonstrated by immunoblot of an extract of infected erythrocytes. It is therefore designated P. yoelii hepatic and erythrocytic stage protein, 17 kDa or PyHEP17. When added to primary cultures of mouse hepatocytes 24 hr after inoculation with P. yoelii sporozoites, when all sporozoites have invaded hepatocytes, NYLS3 eliminates up to 98% of liver-stage parasites. Intravenous injection of NYLS3 into mice delays the onset and reduces the density of blood-stage parasitemia after sporozoite or blood-stage challenge. The P. falciparum and P. vivax homologs of PyHEP17 may therefore be important targets for vaccines designed to attack the hepatic and erythrocytic stages of the parasite life cycle.

Heterogeneity of macrophage and T cell subpopulations in peripheral nerves from HIV infected individuals: A preliminary study.

GOAL: To determine the heterogeneity of surface marker expression of macrophages in peripheral nerve of patients who died with AIDS. BACKGROUND: Peripheral neuropathy occurs in 20%-40% of AIDS patients. There is evidence that activated macrophages may be involved in the neural damage associated with HIV-1 infection. We studied the expression of macrophage surface markers CD14, CD11c, CD68, and HLA-DR and also T cell surface markers CD3, CD4, and CD8 in peripheral nerves of AIDS patients. METHODS: Three levels of peripheral nerves (sciatic, tibial, or sural) were examined from a limited number of subjects consisting of 4 HIV-seropositive and 5 HIV-seronegative individuals. Standard immunohistochemical technique utilized alkaline phosphatase conjugate and fuchsin substrate. RESULTS: Surface antigen expression was significantly (p < .0025 increased in HIV-positive tissues compared with HIV-negative controls for CD14 and CD4 in sciatic nerves, CD68 and CD4 in tibial nerves, and CD68 in sural nerves. There were trends for increased expression of HLA-DR, CD3, and CD8 in sciatic nerves, CD11c and CD14 in tibial nerves, and CD14, HLA-DR, and CD4 in sural nerves in HIV-positive tissues compared with HIV-negative controls. CONCLUSION: During the course of AIDS there may be an involvement of all three levels of peripheral nerves suggesting that HIV-related neuropathy is a multifocal process.

Two-step chromatographic purification of recombinant Plasmodium falciparum circumsporozoite protein from Escherichia coli.

The Plasmodium falciparum circumsporozoite (PfCS) protein (aa 19-405) has been cloned and expressed in E. coli. The protein was purified in a two-step process that was rapid and reproducible. E. coli cells were grown to a high density before induction for 1 h. Cells were disrupted by high pressure microfluidization and the total bacterial protein solubilized in 6 M Gu-HCl. The protein was refolded while bound to Ni-NTA agarose by exchange of 6 M Gu-HCl for 8 M urea and then slow removal of the urea. The eluted protein was further purified on Q Sepharose Fast Flow using conditions developed to remove E. coli proteins and reduce endotoxin (to 10 EU/50 microg). Yield was 20 mg of PfCS protein from 10 g of wet cell paste. The final protein product bound to HepG2 liver cells in culture and inhibited the invasion of those cells by sporozoites in an ISI assay greater than 80% over control cultures when used at 10 microg/ml.

Identification and characterization of the protective hepatocyte erythrocyte protein 17 kDa gene of Plasmodium yoelii, homolog of Plasmodium falciparum exported protein 1.

We recently reported the discovery of a 17-kDa Plasmodium yoelii protein expressed in infected hepatocytes and erythrocytes, P. yoelii hepatocyte erythrocyte protein 17 (PyHEP17), and have demonstrated that this protein is a target of protective antibodies and T cells. Here, we report the identification and characterization of the gene encoding this protein and reveal that it is composed of two exons. Immunization of mice with PyHEP17 plasmid DNA induces antibodies, cytotoxic T lymphocytes, and protective immunity directed against the infected hepatocyte. Based on extensive sequence homology, expression pattern, and antigenic cross-reactivity, the Plasmodium falciparum homolog of PyHEP17 is identified as the protein known as exported protein-1 (PfExp-1), also called antigen 5.1, circumsporozoite related antigen, or QF116. Identity between PyHEP17 and PfExp-1 is 37% at the amino acid level (60/161 residues), mapping primarily to two regions within the second exon of 73% (16/22 residues) and 71% (25/35 residues) identity. On this basis, PfExp-1 is proposed as an important component of pre-erythrocytic human malaria vaccines.

[Exercise test with cold water intake. Preliminary results]. / Prueba de esfuerzo con ingestión de agua fría. Resultados preliminares.

Thirty healthy individuals with no history of cardiovascular disease were studied to determine the electrocardiographic effects of maximal exercise immediately followed by ingestion of ice water. The subjects were subgrouped according to their training into (A) high (N = 5), (B) moderate (N = 14) and (C) low (N = 11) levels. Electrocardiograms (ECGs) were taken at rest and at rest with ingestion of ice water followed by maximal stress tests. Maximal stress tests were repeated followed by ingestion of ice water at the beginning of and at 2, 3, 6 and 9 minutes of recuperation. The stress test combining maximal effort and ice water ingestion was positive in all members of Group A, in 4 from Group B and in 1 from Group C. A stress test associating maximal effort with ice water ingestion is a useful method of detecting subjects susceptible to changes in ECG which appear to be secondary to coronary spasm. It has a low cost it is simple to perform and represents minimal risk.

[Effects of aerobic physical conditioning on the profile of plasma lipoproteins in a group of healthy volunteers]. / Efectos del acondicionamiento físico aeróbico sobre el perfil de lipoproteinas plasmáticas en un grupo de voluntarios sanos.

To evaluate the effects of aerobic physical conditioning on plasma lipoproteins, we studied 26 previously untrained, apparently healthy, non obese volunteers. All participants underwent a treadmill test performed according to the protocol of Bruce with the direct measurement of maximal oxygen consumption (VO2max). A program of aerobic exercise was prescribed for each volunteer at 70% of their corresponding VO2max. At baseline and at the end of weeks 4, 8 and 12 of the exercise program, cholesterol and triglycerides were measured by enzymatic analysis in total plasma and in the lipoprotein fractions separated by preparative ultracentrifugation and precipitation methods. At the end of week 12, the VO2max measurement was repeated. At the end of the protocol, mean VO2max increased from the value of 39.9 observed at baseline to 94.4 ml/kg/min (p less than 0.01). There were no variations in mean body weight, diet or smoking status of the participants during the exercise program. Cholesterol associated with High-density lipoproteins (C-HDL) increased from 42.5 to 46.1 mg/dl (p less than 0.05). This effect was first noticeable at week 8. We didn't observe significant changes in Total Cholesterol nor the Cholesterol fraction associated with Low-density lipoproteins (C-LDL). Total triglycerides decreased at weeks 4 and 8 but returned to near baseline values at week 12. The C-LDL/C-HDL ratio considered as an index of a high coronary risk decreased from 2.32 at baseline to 2.02 (p less than 0.05) at week 12. Thirteen of the twenty six initial volunteers completed the physical conditioning program as planned, the rest were eliminated at different stages of the protocol due to incomplete adherence to their exercise schedules.(ABSTRACT TRUNCATED AT 250 WORDS)

[A low-level stress test, in the early phase of myocardial infarction and its correlation with coronary angiography]. / Prueba de esfuerzo de bajo nivel, en la fase temprana del infarto del miocardio y su correlación con la coronariografía.

In a prospective 24-month trial at the Instituto Nacional de Cardiologia, 56 patients were studied. All patients had acute myocardial infarction (AMI), diagnosed by clinical, electrocardiographic and enzymatic means. They were studied in two groups: Group A with single localized AMI (n = 30) and Group B with AMI at two locations (n = 26); a resting electrocardiogram (EKG) was analyzed in each case and a low level stress test was performed within the 2nd and 3rd postinfarction weeks; coronary angiography was done between the 8th and 9th postinfarction weeks. In Group A the low level stress test (LLST) was positive for ischemia at a distance from the infarction site in 21, and eighteen of them had multi-vessel injuries (MVI); in 9 the LLST was negative; of these 7 had single-vessel injury; only the remaining 2 had MVI (p less than 0.001) with 90% sensitivity and 78% specificity. In Group B there was no significant relationship between LLST and coronary angiography (64% sensitivity, and 62% specificity). Relating the ischemic change at a distance in the resting EKG with coronary angiography, we found 75% sensitivity and 55% specificity in Group A. In Group B, sensitivity and specificity were even lower. We conclude that LLST in the early postinfarction phase in Group A is a safe and reliable method to suspect MVI, allowing the early identification of patients with lesions that could be treated by surgical means.

Development of two monoclonal antibodies against Plasmodium falciparum sporozoite surface protein 2 and mapping of B-cell epitopes.

The Plasmodium yoelii sporozoite surface protein 2 (PySSP2) is the target of protective cellular immunity. Cytotoxic T cells specific for the Plasmodium falciparum analog PfSSP2, also known as thrombospondin-related anonymous protein (TRAP), are induced in human volunteers immunized with irradiated sporozoites. PfSSP2 is an important candidate antigen for a multicomponent malaria vaccine. We generated and characterized three monoclonal antibodies (MAbs) specific for PfSSP2/TRAP. The MAbs PfSSP2.1 (immunoglobulin G1 [IgG1]), PfSSP2.2 (IgG2a), and PfSSP2.3 (IgM) were species specific and identified three distinct B-cell epitopes containing sequences DRYI, CHPSDGKC, and TRPHGR, respectively. PfSSP2.1 partially inhibited P. falciparum liver-stage parasite development in human hepatocyte cultures (42 and 86% in two experiments at 100 microg/ml). Mice immunized with vaccinia virus expressing full-length PfSSP2 protein produced antibodies to (DRYIPYSP)3, and humans living in malaria-endemic areas (Indonesia and Kenya), who have lifelong exposure and partial clinical immunity to malaria, had antibodies to both (DRYIPYSP)3 and (CHPSDGKCN)2. Mice immunized with multiple antigen peptides MAP4 (DRYIPYSP)3P2P30 and MAP4 (CHPSDGKCN)3P2P30 in TiterMax developed antibodies to sporozoites that partially inhibited sporozoite invasion of human hepatoma cells (39 to 71% at a serum dilution of 1:50 in three different experiments). The modest inhibitory activities of the MAbs and the polyclonal antibodies to PfSSP2/TRAP epitopes do not suggest that a single-component vaccine designed to induce antibodies against PfSSP2/TRAP will be protective. Nonetheless, the MAbs directed against PfSSP2, and the peptides recognized by these MAbs, will be essential reagents in the development of PfSSP2/TRAP as a component of a multivalent P. falciparum human malaria vaccine.