Aplicabilidad de la escala de riesgo Finnvasc en pacientes con isquemia crítica tratados mediante revascularización infrainguinal / Usefulness of the Finnvasc risk score in patients with critical ischemia subjected to infrainguinal revascularization

OBJETIVOS: Múltiples estudios demuestran que la escala de riesgo Finnvasc tiene alto valor predictivo de mortalidad y amputación mayor precoces en pacientes con revascularización de miembros inferiores por isquemia crítica (IC). Se estudió la aplicabilidad de Finnvasc en nuestro centro. MATERIAL Y MÉTODOS: Se estudió a 190 pacientes tratados mediante revascularización infrainguinal por IC desde enero de 2012 hasta diciembre de 2013. Se estratificaron grupos según la puntuación Finnvasc y se midieron los eventos adversos postoperatorios. Mediante un análisis de la varianza (ANOVA) se estudió la asociación entre la puntuación obtenida y la ocurrencia de eventos adversos. Se utilizó la curva ROC para estimar el valor predictivo de la escala de riesgo. RESULTADOS: En los primeros 30 días postoperatorios, 6 pacientes (3,2%) fallecieron y 14 (7,4%) fueron amputados. Para los grupos con puntuación de 0, 1, 2 y ≥3, la incidencia de amputación fue de 0; 3,3; 10 y 15%. La mortalidad fue 0; 5; 1,3 y 7,7% y la mortalidad/amputación combinada fue de 0; 8; 11 y 23% respectivamente. El ANOVA para estas diferencias no obtuvo significación estadística (p = 0,08; p = 0,2; p = 0,057 respectivamente). Las curvas ROC muestran que el valor de la escala fue regular para predecir amputación mayor precoz (AUC = 0,694; 0,570-0,818) y malo para mortalidad precoz (AUC = 0,563; 0,316-0,811). La curva ROC para mortalidad/amputación combinada fue similar (AUC = 0,664; 0,543-0,785). CONCLUSIONES: La escala Finnvasc en la población de nuestro estudio no ha demostrado un valor predictivo aceptable para la mortalidad y la amputación. Además, no se objetivó una relación estadísticamente significativa para estas variables aisladas o combinadas

OBJECTIVES: Many studies show that the Finnvasc risk score predicts early mortality and major amputation in patients with critical lower limb ischemia (CI) after revascularization. A study is made on the applicability of the score in our center. MATERIAL AND METHODS: A total of 190 patients underwent infrainguinal revascularization for CI from January 2012 to December 2013. The patients were stratified into 4 groups according to the Finnvasc score. The incidence of postoperative adverse events was measured. Analysis of variance (ANOVA) was used to determine the association between the score and adverse events. The ROC curve was used to estimate the predictive value of the risk score. RESULTS: In the first 30 postoperative days, 6 patients (3.2%) died and 14 (7.4%) underwent major amputation. For groups with scores of 0, 1, 2 and ≥3, the incidence of amputation was 0, 3.3, 10 and 15%; the mortality rate was 0, 5, 1.3 and 7.7%, and the mortality/amputation combined was 0, 8, 11 and 23%, respectively. The ANOVA for these results did not achieve statistical significance (P=.08; P=.2; P=.057, respectively). The ROC curves showed that the score was average for predicting early major amputation (AUC=.694; 0.570-0.818) and poor for predicting mortality (AUC=.563; 0.316-0.811). The ROC curve for mortality/amputation combined was similar (AUC=.664; 0.543-0.785). CONCLUSIONS: The Finnvasc score in the studied population did not demonstrate an acceptable predictive value for early mortality and major amputation

Level of maternal antibody required to protect neonates against early-onset disease caused by group B Streptococcus type Ia: a multicenter, seroepidemiology study.

Because of the difficulty of conducting efficacy trials of vaccines against group B streptococcus (GBS), the licensure of these vaccines may have to rely on studies that measure vaccine-induced antibody levels that correlate with protection. This study estimates the level of maternal antibody required to protect neonates against early-onset disease (EOD) caused by GBS type Ia. Levels of maternal serum IgG GBS Ia antibodies, measured by ELISAs in 45 case patients (neonates with EOD caused by GBS Ia) and in 319 control subjects (neonates colonized by GBS Ia but without EOD) born at > or =34 weeks gestation were compared. The probability of developing EOD declined with increasing maternal levels of IgG GBS Ia antibody (P = .03). Neonates whose mothers had levels of IgG GBS Ia antibody > or =5 microg/mL had an 88% lower risk (95% confidence interval, 7%-98%) of developing type-specific EOD, compared with those whose mothers had levels < 0.5 microg/mL. A vaccine that induces IgG GBS Ia antibody levels > or =5 microg/mL in mothers can be predicted to confer a high degree of type-specific immunity to EOD to their infants.

Induction of group 17 specific antibodies by pneumococcal type 17F and 17A polysaccharide vaccines.

Pneumococcal capsular polysaccharide group 17 contains two distinct serotypes, 17F and 17A. Pneumococcal group 17 is present in the licensed 23 valent polysaccharide vaccines. One such vaccine contains type 17A, while the other vaccine contains type 17F. The purpose of these studies was to determine the extent of cross-protection that could be expected, as both type 17F and 17A cause disease. The antibody responses of one group of adults to a vaccine containing type 17F was compared to that of another group that received a type 17A containing vaccine. By ELISA the 17A vaccine induced more cross-reactive antibodies. Opsonophagocytic antibodies are a good predictor of protection and both vaccines induced antibodies opsonic for both 17F and 17A. We conclude that either 17F or 17A will provide similar protection against group 17 disease.

Pneumococcal type 22f polysaccharide absorption improves the specificity of a pneumococcal-polysaccharide enzyme-linked immunosorbent assay.

The specificity of the immune response to the 23-valent pneumococcal-polysaccharide (PS) vaccine in healthy adults and to a pneumococcal conjugate vaccine in infants was examined by measuring immunoglobulin G (IgG) antibody titers by enzyme-linked immunosorbent assay (ELISA) and the opsonophagocytosis assay. ELISA measures total antipneumococcal IgG titers including the titers of functional and nonfunctional antibodies, while the opsonophagocytosis assay measures only functional-antibody titers. Twenty-four pairs of pre- and post-pneumococcal vaccination sera from adults were evaluated (ELISA) for levels of IgG antibodies against serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. Twelve of the pairs were also examined (opsonophagocytosis assay) for their functional activities. The correlation coefficients between assay results for most types ranged from 0.75 to 0.90, but the correlation coefficient was only about 0.6 for serotypes 4 and 19F. The specificities of these antibodies were further examined by the use of competitive ELISA inhibition. A number of heterologous polysaccharides (types 11A, 12F, 15B, 22F, and 33A) were used as inhibitors. Most of the sera tested showed cross-reacting antibodies, in addition to those removed by pneumococcal C PS absorption. Our data suggest the presence of a common epitope that is found on most pneumococcal PS but that is not absorbed by purified C PS. Use of a heterologous pneumococcal PS (22F) to adsorb the antibodies to the common epitope increased the correlation between the IgG ELISA results and the opsonophagocytosis assay results. The correlation coefficient improve from 0.66 to 0.92 for type 4 and from 0.63 to 0.80 for type 19F. These common-epitope antibodies were largely absent in infants at 7 months of age, suggesting the carbohydrate nature of the epitope.

Genetic and immunologic characterization of a novel serotype 4, 15 strain of Neisseria meningitidis.

The porin proteins of Neisseria meningitidis are important components of outer membrane protein (OMP) vaccines. The class 3 porin gene, porB, of a novel serogroup B, serotype 4, 15 isolate from Chile (Ch501) was found to be VR1-4, VR2-15, VR3-15 and VR4-15 by porB variable region (VR) typing. Rabbit immunization studies using outer membrane vesicles revealed immunodominance of individual PorB (class 3) VR epitopes. The predominant anti-Ch501 PorB response was directed to the VR1 epitope. Anti-PorB VR1 mediated killing was suggested by the bactericidal activity of Ch501 anti-sera against a type 4 strain not expressing PorA or class 5 OMPs. Studies that examine the molecular epidemiology of individual porB VRs, and the immune responses to PorB epitopes, may contribute to the development of broadly protective group B meningococcal vaccines.

Efficacy and tolerability of olanzapine in elderly patients with psychotic disorders: a prospective study.

Olanzapine is a novel antipsychotic effective in reducing positive and negative symptoms of schizophrenia and with a safe side-effect profile. Premarketing trials, however, included only a few elderly patients. Further data are needed regarding the effects of olanzapine in the elderly and those with comorbid medical illness. In this pilot study, 11 hospitalized patients (age range 60-85 years) who manifested symptoms of psychosis related to schizophrenia and schizoaffective disorders were treated with olanzapine (dose range, 5-20 mg/day). Efficacy and safety were assessed by the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale (CGI), Extrapyramidal Symptom Rating Scale (ESRS), Mini-Mental State Examination (MMSE), Calgary Depression Scale For Schizophrenia (CDSS), EKG, physical examination, and various laboratory tests. Seven patients responded to treatment and all of them showed improvement in both positive and negative symptoms, with greater reduction in positive symptoms. Treatment was discontinued in 2 patients whose symptoms showed no improvement or worsened. The CGI showed significant improvement in 9 patients, remained the same in 1, and worsened in 1 patient. ESRS showed significant reduction from baseline to final visit. Of the 10 patients who cooperated for MMSE, 9 had improved scores. The CDSS showed significant reduction in scores from baseline to final visit. No significant changes were noted in laboratory tests, prolactin levels, EKG, and physical examination. Concomitant administration of lorazepam, carbamazepine, divalproex sodium, and lithium carbonate caused no adverse consequences. The reduction of positive and negative symptoms, lack of significant extrapyramidal symptoms and other side effects, and lack of any significant drug interaction suggest that olanzapine may be a safe and effective antipsychotic medication in the elderly.

Specificity of human antibodies reactive with pneumococcal C polysaccharide.

Antibodies reactive with C polysaccharide (PS) were found in healthy adults, pneumococcal patients, and vaccinees. These antibodies were not directed to the phosphocholine determinant of the C PS, as they appear to be in mice, since the human antibodies were inhibitable only with C PS. We found another population of phosphocholine-specific antibodies inhibitable only by phosphocholine and related compounds.

Pneumococcal capsular polysaccharide preparations may contain non-C-polysaccharide contaminants that are immunogenic.

We measured the capacity to opsonize Streptococcus pneumoniae serotype 6B and estimated the concentration of immunoglobulin G anti-6B capsular polysaccharide (PS) antibodies in 25 pre- and postimmune sera from adults immunized with a pneumococcal PS vaccine. We first studied two postvaccination serum samples displaying less opsonophagocytic capacity than expected. The majority of anti-6B antibodies in the two samples reacted with the capsular PSs of several unrelated serotypes (2, 4, 9V, 19F, and 23F) and with the lysate of noncapsulated S. pneumoniae bacteria but not with C-PS. The non-type-specific antibodies accounted for at least one-half of anti-6B antibodies in 40% of prevaccination sera and 10% of postvaccination sera from adults. The non-type-specific antibodies could be demonstrated in the enzyme-linked immunosorbent assays (ELISAs) for pneumococcal antibodies to other serotypes (4, 9V, 18C, 19F, and 23F). The nonspecific antibodies appear to bind a contaminant(s) in the current preparations of capsular PS. ELISA for antibodies to pneumococcal capsules may not be serotype specific for some samples.

Purification of CMP-N-acetylneuraminic acid synthetase from bovine anterior pituitary glands.

CMP-beta-N-acetylneuraminic acid (CMP-neuNAc) is the substrate for the sialylation of glycoconjugates by sialyltransferases in microbes and higher eukaryotes. CMP-neuNAc synthetase catalyzes the formation of this substrate, CMP-neuNAc, from CTP and neuNAc. In this report we describe the purification of CMP-neuNAc synthetase from bovine anterior pituitary glands. The enzyme was purified by ion exchange, gel filtration, and affinity chromatography. The protein was homogeneous on SDS-PAGE with a molecular weight of 52 kDa, a subunit size similar to that of the E.coli K1 (48.6 kDa). The identity of the 52 kDa protein band was confirmed by native gel electrophoresis in that the position of the enzyme activity in gel slices coincided with the position of major bands in the stained gel. Photoaffinity labeling with 125I-ASA-CDP ethanolamine resulted in the modification of a 52 kDa polypeptide that was partially protected against modification by the substrate CTP. Enzyme activity in crude fractions could be adsorbed onto an immunoadsorbent prepared from antibody against the purified 52 kDa protein. Taken together these data suggest that the 52 kDa polypeptide purified by this procedure described in this report is indeed CMP-neuNAc synthetase. The active enzyme chromatographed on a gel filtration column at 158 kDa suggesting it exists in its native form as an oligomer.

Evaluation of previously assigned antibody concentrations in pneumococcal polysaccharide reference serum 89SF by the method of cross-standardization.

An enzyme-linked immunosorbent assay (ELISA) and the antibody concentrations assigned to different pneumococcal capsular polysaccharide types were used to estimate concentrations of antibody to additional pneumococcal types in reference serum 89SF and to confirm assigned antibody values. This was possible because the slopes of curves of antibody binding to all polysaccharide types evaluated (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F) were similar. The point estimates for total anti-pneumococcal antibody and immunoglobulin G (IgG) antibody determined by cross-standardization by an ELISA based on use of methylated human serum albumin (mHSA) to improve the efficiency of polysaccharide binding to the ELISA plate differed by less than 40% from those reported by Quataert et al. (Clin. Diagn. Lab. Immunol. 2:590-597, 1995) for types 1, 4, 6B, 7F, 9V, 14, 18C, and 23F. However, large differences were found between the assigned values and those obtained by our mHSA ELISA for types 3 and 19F. The mHSA ELISA and the direct polysaccharide coat ELISA may not measure antibodies to the same epitopes on polysaccharides of types 3 and 19F. The functional importance of these different antibody specificities is being investigated. We have thus confirmed the assigned IgG antibody values for most types by a different method and have extended antibody assignments to several additional types.

Relation between maternal age and serum concentration of IgG antibody to type III group B streptococci.

Coded serum samples collected from healthy obstetric patients at delivery were examined by ELISA for IgG antibody to the purified type III polysaccharide of group B streptococci. When 217 patients were divided into 4 groups according to age (group I =16-20 years, n = 56; group II = 21-25, n = 53; group III = 26-30, n = 54; group IV = 31-35, n = 54), antibody concentrations were significantly lower in group I than in older patients. Fewer subjects in group I had measurable antibody levels (> or = 0.05 microgram/mL) than in groups II-IV (41% vs. 76%, P < .001). The geometric mean in group I (0.09 microgram/mL) was significantly lower (P < .001) than in the older groups (0.23, 0.19, and 0.20 microgram/mL, respectively) with little or no overlap of the 95% confidence limits (1.96 SE) about the means. These findings may be relevant to the observation of a significantly greater risk of both early- and late-onset group B streptococcal disease in infants of teenage mothers.

Solid-phase antigen density and avidity of antibodies detected in anti-group B streptococcal type III IgG enzyme immunoassays.

Two enzyme immunoassays which measure anti-group B streptococcal type III capsular carbohydrate IgG antibodies were compared. One utilised poly-L-lysine conjugated coating antigen while the other used tyraminated coating antigen. Both carbohydrate antigens appeared to be antigenically identical but the poly-L-lysine based assay gave significantly lower values for some sera. Sera were identified which had low and high avidity anti-group B streptococcal type III IgG antibodies by the thiocyanate elution method. These antibodies gave results on a dilution range of coating concentrations consistent with their relative avidity. Comparison of dilution ranges of the two conjugates used for coating suggests that the poly-L-lysine conjugate coats with a ten-fold lower efficiency than the tyramine conjugate and therefore detects only higher avidity antibodies. Four fractions containing different relative avidities of affinity-purified IgG were produced from a single serum. These fractions behaved in the same manner as sera containing antibodies of different avidities. The results of this study suggest that the method of polysaccharide conjugation in enzyme immunoassays may affect the antigen concentration on the solid phase and thence the detection of antibodies of various avidities.

Opsonic effect of jacalin and human immunoglobulin A on type II group B streptococci.

This study examined the effect of immunoglobulin A (IgA) and the IgA-binding lectin jacalin on the phagocytosis of type II group B streptococci (GBS). Strains possessing the trypsin-sensitive and trypsin-resistant components of the c protein (II/c) and type II GBS lacking the c protein (II) were examined by radiolabeled bacterial uptake, bactericidal assays, and electron microscopy. Type II/c GBS resisted phagocytosis by monocytes (4.9% +/- 0.8% uptake, mean +/- SE, n = 25) compared with type II GBS (8.5% +/- 1.4% uptake, n = 14, P = 0.03). Phagocytic killing by polymorphonuclear leukocytes was also less for the type II/c strain 78-471 than for the type II strain 79-176 (68% +/- 5% versus 86% +/- 4% reduction in CFU at 45 min, P = 0.03). IgA binding did not explain the resistance of type II/c GBS to phagocytosis. The uptake of type II/c GBS was not significantly different after opsonization in cord sera lacking endogenous IgA (5.93% +/- 1.4%) than in the same cord sera after addition of exogenous IgA (5.48% +/- 1.4%, P = 0.69, n = 9). Attempts to remove serum IgA with the IgA-binding lectin jacalin resulted in the binding of IgA-jacalin complexes to II/c GBS. This combination of nonspecific IgA and jacalin increased uptake of II/c GBS from 4.9% +/- 0.8% to 11.8% +/- 1.9% (P = 0.002). Jacalin also combined with specific, immune, monoclonal IgA bound to the surface of Haemophilus influenzae and promoted the uptake of these bacteria. Jacalin and IgA mediated phagocytosis of II/c GBS via receptors that were not dependent on divalent cations and that were not modulated by plating monocytes on antigen-antibody complexes.

Nonimmune binding of human immunoglobulin A to type II group B streptococci.

The binding of 125I-labeled human myeloma immunoglobulin A (IgA) to four type II strains and one nontypable strain of group B streptococci was measured after streptococcal chains were broken by brief sonication. Some IgA binding was observed with all strains, but specific binding (binding that was inhibited by excess unlabeled IgA, was dose dependent, and was saturable) occurred only with those strains possessing the trypsin-sensitive beta component of the c protein. Similar amounts of binding were observed with myeloma IgA and IgA1 purified from normal serum. Specific binding was more rapid at 25 degrees C than at 0 or 37 degrees C and reached a plateau in 6 to 8 h. Binding was drastically reduced (85 to 90%) when streptococci had been heated (90 degrees C for 1 h). Most radioactivity bound to group B streptococci could be displaced (greater than 60% in 3 days) by the addition of excess unlabeled IgA. The binding capacity of one strain (10(8) streptococci in 1 ml of buffer) was saturated by approximately 24 micrograms of IgA. When transformed for Scatchard analysis, these data indicated that there was a specific binding capacity of 16,000 molecules of monomeric serum IgA per single streptococcal cell. The dissociation constant for IgA binding was 19.3 nM. Since enzyme-linked immunosorbent assay studies showed that the myeloma IgA used for the studies described above was IgA1, our quantitative data apply only to the binding of this subclass to group B streptococci. However, an enzyme-linked immunosorbent-filtration assay showed that both IgA1 and IgA2 bound to a type II group B streptococcus bearing the c protein.

Opsonic activity of human IgG and IgM antibody for type III group B streptococci.

We separated IgG and IgM from 10 adult sera containing measurable (greater than or equal to 0.05 micrograms/mL) antibody of both isotypes to the type III polysaccharide of group B streptococci. Ig preparations were used to preopsonize 3H-labeled type III group B streptococci which were added to adherent monolayers of human, monocyte-derived macrophages. Reproducibly significant phagocytosis, measurable by accumulation of radioactivity and confirmed by electron microscopy, required both antibody (from adult serum or Ig preparation) and complement (from cord serum deficient in specific antibody). All adult IgG and IgM preparations were opsonic in the presence of complement. When a cord serum containing IgG but no IgM antibody was separated by the same procedure, the IgG fraction was opsonic but the fraction that would contain IgM was not. The opsonic activity of IgM in adult sera persisted after the removal of contaminating IgG4. These observations indicate that both IgG and IgM antibody in adult sera are opsonic for type III GBS and support the hypothesis that IgM deficiency in newborns may be a contributing factor to certain bacterial infections.

Demonstration of opsonic and protective activity of human cord sera against type III group B streptococcus that are independent of type-specific antibody.

In an effort to further understand the host defense against group B streptococcus (GBS), we examined 71 human cord sera for their content of type III GBS IgG antibody by enzyme-linked immunosorbent assay and correlated the results with opsonic and protective activity against type III GBS. Most cord sera (67%) containing greater than 0.1 microgram/ml of type III GBS IgG antibody promoted phagocytosis and killing in vitro and protection against type III GBS in neonatal rats. However, 26% of cord sera containing less than 0.1 microgram/ml of type III IgG antibody exhibited similar activity in vitro and in vivo against type III GBS. This opsonic and protective activity was retained in IgG fraction of whole serum, and was not directly associated with complement activity or with fibronectin. Further studies are needed to understand the mechanisms responsible for the opsonic and protective activity of some cord sera against type III GBS that may be independent of antibody to the type-specific polysaccharide antigen.

Quantitative morphometry measurements of transitional cell bladder cancer nuclei as indicator of tumor aggression.

Superficial transitional cell carcinomas of the urinary bladder in 30 patients were studied by quantitative morphometry of the initial and subsequent tumor occurrences. Nuclear histograms were constructed and demonstrated narrow base and single modal peak in 9 of 10 patients not exhibiting tumor recurrence or invasion. In contrast, broad-based multimodal nuclear histograms were present in 15 of 20 patients in whom tumor invasion of carcinoma in situ subsequently developed. Nuclear histograms may provide an accurate means of determining invasive/recurrence potential of transitional cell carcinoma.

Relative functional activity of purified human immunoglobulin G against a type III group B streptococcal strain.

Human immunoglobulin G (IgG) separated from whole serum by a quaternary aminoethyl-Sephadex A-50 ion exchanger was evaluated for its activity against a type III group B streptococcal strain in the newborn rat model. Separated IgG yielded approximately 70 to 80% of whole serum IgG and did not contain detectable IgM or IgA. This IgG preparation also contained similar ratios of specific type III group B streptococcal antibody to total IgG in comparison with whole serum. In vivo, 50% protection from death was achieved by 3.9 ng of type III-specific antibody per 10 g of rat body weight. This value was considerably lower than 50% protective doses obtained in our previous studies with different human IgG preparations. Further studies are needed to understand the mechanisms responsible for these differences in the functional activity of IgG antibody.