HLA-B*57 and IFNL4-related polymorphisms are associated with protection against HIV-1 disease progression in controllers.

Background: HIV-1-controllers maintain HIV-1 viremia at low levels (normally <2000 HIV-RNA copies/mL) without antiretroviral treatment. However, some HIV-1-controllers have evidence of immunologic progression with marked CD4+T-cell decline. We investigated host genetic factors associated with protection against CD4+T-cell loss in HIV-1-controllers. Methods: We analysed the association of interferon lambda 4 (IFNL4)-related polymorphisms and HLA-B haplotypes within Long Term Non-Progressor HIV-1-controllers ((LTNP-C), defined by maintaining CD4+T-cells counts >500 cells/mm3 for more than 7 years after HIV-1 diagnosis) versus non-LTNP-C, who developed CD4+T-cells counts <500 cells/mm3 Both a Spanish study cohort (n=140) and an international validation cohort (n=914) were examined. Additionally, in a subgroup of individuals HIV-1-specific T-cell responses and soluble cytokines were analysed RESULTS: HLA-B*57 was independently associated with the LTNP-C phenotype (OR=3.056 (1.029-9.069) p=0.044 and OR=1.924 (1.252-2.957) p=0.003) while IFNL4 genotypes represented independent factors for becoming non-LTNP-C (TT/TT, ss469415590, OR=0.401 (0.171-0.942) p=0.036 or A/A, rs12980275, OR=0.637 (0.434-0.934) p=0.021) in the Spanish and validation cohort, respectively, after adjusting for sex, age at HIV-1 diagnosis, IFNL4-related polymorphisms and different HLA-B haplotypes. LTNP-C showed lower plasma IP-10 (p=0.019) and higher IFN-γ (p=0.02) levels than the HIV-1-controllers with diminished CD4+T-cell numbers. Moreover, LTNP-C exhibited higher quantities of IL2+CD57- and IFN-γ+CD57- HIV-1-specific CD8+T-cells (p=0.002 and 0.041, respectively) than non-LTNP-C. Conclusions: We have defined genetic markers able to segregate stable HIV-1-controllers from those who experience CD4+T-cell decline. These findings allow for identification of HIV-1-controllers at risk for immunologic progression, and provide avenues for personalized therapeutic interventions and precision medicine for optimizing clinical care of these individuals.

[Decreasing susceptibility to vancomycin in isogenic Staphylococcus aureus strains isolated from a single patient]. / Sensibilidad disminuida a vancomicina en cepas isogénicas de Staphylococcus aureus aisladas del mismo paciente.

BACKGROUND: We aimed at evaluating the microbiological characteristics and clinical implication of 7 isogenic strains of Staphylococcus aureus with decreased susceptibility to vancomycin. SUBJECT AND METHOD: A patient with nosocomial trival vularendocarditis due to methicillin-resistant S. aureus had positive blood cultures for 8 weeks despite antimicrobial therapy with vancomycin (normal serum levels) and rifampicin. The patient rejected surgical treatment but the process cured with antimicrobial therapy. The epidemiological relationship of strains was evaluated by pulsed field gel electrophoresis. The susceptibility to vancomycin was evaluated by microdilution and E-test using two different in ocula. The activity of oxacillin, ampicillin and cephalotin was evaluated in Mueller Hinton (MH) agar containing different concentrations of vancomycin (0.06 to 4 mg/l). Heteroresistant subpopulations were determined in both MH and brain heart infussion agar containing vancomycin (0.5 to 512 mg/l). All seven strains belonged to the same clone. Vancomycin MIC ranged from 1 mg/l (isolates 1 to 5) to 4 mg/l (isolates 6 and 7). Isolates 6 and 7 displayed differences in pigmentation and slower growth rates. The susceptibility of these isolates to betalactams inMH containing different concentrations of vancomycin was greater than that in controls. Subpopulations heteroresistant to vancomycin were not detected. CONCLUSION: The decreased susceptibility of the isogenic S. aureus strains evaluated in this study was not due to heteroresistance and did not cause therapeutic failure.

Actividad comparada de diversos macrólidossobre cepas de Haemophilus influenzae / Comparison of the activity of different macrolideson strains of Haemophilus influenzae

Presentamos los resultados de un estudio multicéntrico de sensibilidad de Haemophilus influenzae realizado con cepas aisladas durante 1998 en ocho ciudades españolas. De las 174 cepas estudiadas, el 29 por ciento eran productoras de betalactamasas. Entre los antibióticos macrólidos estudiados, azitromicina es el que mejor actividad ha presentado sobre este patógeno, con CMI90 de 4 mg/l, sin encontrar ninguna cepa resistente. La resistencia a la ampicilina fue del 29 por ciento. Encontramos una cepa con resistencia intrínseca a los betalactámicos (0,65 por ciento del total de cepas estudiadas) y dos cepas productoras de betalactamasas y resistentes a amoxicilina-ácido clavulánico (1,2 por ciento). La presencia de este tipo de cepas, aunque escasas actualmente, nos obliga a determinar de forma habitual la actividad de los antimicrobianos sobre H. influenzae (AU)

Appendiceal CT in 140 cases. Diagnostic criteria for acute and necrotizing appendicitis.

Computed tomography (CT) was performed in 140 patients with suspected acute appendicitis. Thin collimation (5 mm), intravenous contrast enhancement, 1-second scan times, and supplementary cecal air insufflation were emphasized. CT accuracy was 98% overall (137/140), and 99% in the 124 cases with early surgery. Necrotizing appendicitis was diagnosed by CT with 86% accuracy and 90% positive predictive value.

Distal lower extremity arteries: evaluation with two-dimensional MR digital subtraction angiography.

PURPOSE: To test the hypothesis that magnetic resonance (MR) digital subtraction angiography is superior to two-dimensional time-of-flight (TOF) MR angiography for demonstration of patent arteries in the distal lower extremity. MATERIALS AND METHODS: Thirty-seven lower extremities in 23 consecutive patients were imaged with two-dimensional TOF MR angiography and two-dimensional MR digital subtraction angiography. Images were interpreted in a randomized and blinded manner. Each lower extremity was subdivided into seven potential arterial segments. The number of digital arteries visualized was also determined. Overall image quality of MR digital subtraction and TOF angiograms was compared. The relative ability of MR digital subtraction angiography and TOF MR angiography to demonstrate patent arterial segments was assessed. RESULTS: MR digital subtraction angiography was significantly superior to TOF MR angiography for demonstration of patent arterial segments and digital arteries (P < .001). MR digital subtraction angiographic images were qualitatively superior to TOF images (P < .001). CONCLUSION: Two-dimensional MR digital subtraction angiography is superior to two-dimensional TOF MR angiography for help in identifying patent segments in the distal lower extremity.

CT and US of the pancreas.

The diagnostic capabilities of pancreatic imaging continue to improve with technological advancements in computed tomography (CT), ultrasound (US), and magnetic resonance imaging (MRI). To update the practicing radiologist, this article summarizes the current literature on pancreatic imaging, with particular emphasis on CT and US. Pertinent clinical considerations of the disease entities are included, along with illustrative material from the authors' experience.

Adenosine-sensitive ventricular tachycardia: right ventricular abnormalities delineated by magnetic resonance imaging.

BACKGROUND: Adenosine-sensitive ventricular tachycardia (VT) is thought to be due to cAMP-mediated triggered activity. It typically originates from the RVOT and occurs in patients with apparently normal hearts. Using magnetic resonance imaging (MRI), we tested the hypothesis that adenosine-sensitive VT occurs in patients without structural heart disease. METHODS AND RESULTS: Fourteen patients (9 women; age, 47+/-19 years) presented with sustained VT (n=3), repetitive monomorphic VT (n=7), or both (n=4). VT terminated with adenosine in each patient and was sensitive to vagal maneuvers in 9 of 11 and verapamil in 10 of 12. VT originated from the right ventricular outflow tract in 10 patients, the right ventricular apex in 1, and the left ventricular septum in 3. Conventional studies included normal signal-averaged ECGs in 9 of 9, normal right ventricular echocardiography in 10 of 10, and normal left ventriculography and coronary angiography in 6 of 7. In contrast, MRI scans were abnormal in 10 of 14 patients. These abnormalities included focal thinning (6), fatty infiltration (4), and wall motion abnormalities (4) of the right ventricle. The most common site of MRI abnormalities was the right ventricular free wall, but there was a poor correlation between the site of MRI abnormalities and the origin of VT. Among 18 control patients without clinical heart disease, thinning of the right ventricular wall was noted in only 1 patient (patients versus control subjects, P=.0001). CONCLUSIONS: Patients with idiopathic adenosine-sensitive VT comprise a heterogeneous group as assessed by MRI, with 70% demonstrating mild structural abnormalities. However, it is unlikely that these findings are causally related to tachycardia, and the functional significance of these anatomic abnormalities is uncertain.

[Antimicrobial activity in Staphylococcus epidermidis biofilms on polyvinyl chloride catheters]. / Actividad de antimicrobianos en biocapas de Staphylococcus epidermidis sobre catéteres de cloruro de polivinilo.

OBJECTIVES: We have evaluated the effect of polyvinylchloride (PVC) catheters on the activity of eight antimicrobials. Secondly the activity of these antimicrobials against Staphylococcus epidermidis biofilms on PVC catheters was also studied. METHOD: The MIC and MBC values of amikacine, clindamycine, cloxacilline, ciprofloxacine, vancomycine, teicoplanine, daptomycine and rifampicine was evaluated by a microdilution assay in the presence of 0.5 cm length segments of PVC catheters. Catheter segments with bacteria attached for different periods of time were used as inocula for the studies of antimicrobial activity against bacterial biofilms. Both slime producing and non-producing strains were evaluated. RESULTS: The presence of PVC did not affect the activity of the antimicrobials evaluated against S. epidermidis. For the non-slime producing strains MBC values against sessile bacteria were significantly higher than those against planktonic bacteria. For the slime-producing strain MBCs of ciprofloxacine, amikacine and teicoplanine against both bacterial populations were similar. At high concentrations (16 x MBC), clindamycine was the only antimicrobial that sterilized non-slime producing S. epidermidis biofilms on PVC. Against the slime producing strains ciprofloxacine yielded the highest reduction on bacterial viability (99.9%). CONCLUSIONS: S. epidermidis biofilms on PVC were more resistant to antimicrobials than planktonic bacteria. Slime production is not the only factor involved in this phenomenon.

Activity of sparfloxacin on Staphylococcus epidermidis attached to plastic catheters.

The activity of sparfloxacin on Staphylococcus epidermidis biofilms on different plastic catheters was evaluated. Sparfloxacin showed high bactericidal activity against S. epidermidis biofilms on Vialon and polyvinylchloride catheters. The combination of sparfloxacin with amikacin or rifampicin significantly increased its activity against bacterial biofilms on polyurethane and Teflon catheters.

Sonographic diagnosis of cisternal subarachnoid hemorrhage in the premature infant.

PURPOSE: To evaluate sonographic criteria for the diagnosis of subarachnoid, and particularly cisternal, hemorrhage in the preterm infant. METHODS: The subarachnoid cisterns were studied on cadaveric anatomic sections and on postmortem ultrasonograms, as well as on in vivo ultrasonograms of healthy neonates. Based on the normal ultrasound appearances of these cisterns, criteria were developed for the recognition of abnormal cisternal fluid collections, which strongly suggest the presence of subarachnoid hemorrhage in the premature infant. These criteria were evaluated prospectively in a group of 63 preterm infants who underwent subsequent autopsy. RESULTS: In the 63 infants with neuropathologic verification, increased echogenicity and/or increased echo-free content of the subarachnoid cisterns correctly predicted subarachnoid hemorrhage with an accuracy of 75%, sensitivity of 69%, and specificity of 93%. The positive and negative predictive values were 97% and 46%, respectively. In 47% of the cases, ultrasound correctly detected cisternal subarachnoid hemorrhage before intraventricular hemorrhage could be diagnosed. CONCLUSION: A highly specific, although somewhat insensitive, sonographic diagnosis of subarachnoid hemorrhage can be made from the appearance of the subarachnoid cisterns. The diagnosis of subarachnoid hemorrhage may predate the ultrasound diagnosis of intraventricular hemorrhage and may alert the neonatologist to the need for follow-up sonograms in the absence of ultrasound evidence of intraventricular hemorrhage.

Activity of glycopeptides in combination with amikacin or rifampin against Staphylococcus epidermidis biofilms on plastic catheters.

The in vitro activity of vancomycin and teicoplanin (fourfold the MBC), alone and in combination with amikacin (16 mg/l) or rifampin (1 mg/l), against Staphylococcus epidermidis (slime-producing and non slime-producing strains) biofilms on different plastic catheters was evaluated. The addition of amikacin or rifampin significantly increased the activity of glycopeptides against sessile bacteria. With the slime-producing strain, these combinations were able to sterilize the surface of Vialon and polyvinylchloride catheters. It is concluded that the in vitro activity of glycopeptides against Staphylococcus epidermidis biofilms on plastic catheters can be increased by the addition of amikacin or rifampin.

Activity of eight antibacterial agents on Staphylococcus epidermidis attached to Teflon catheters.

The presence of a Teflon catheter had no effect on the in-vitro activity of a range of antibacterial agents against slime producing and non-producing Staphylococcus epidermidis strains as determined by a microdilution assay. The susceptibility of S. epidermidis attached to Teflon catheters for 6, 24 and 48 h was also evaluated. MICs for planktonic and attached bacteria were similar. When bacteria attached to Teflon for 6 h were used as inocula, MBC values increased 32-8192-fold for the antibacterial agents tested. Similar results were observed when bacteria attached for 24 and 48 h were used as inocula. The activity of a high concentration (16 x MBC) of these antimicrobial agents against S. epidermidis biofilms in Teflon catheters was evaluated; for five slime non-producing strains, the highest reduction (around 99%) in bacterial viability was produced by cloxacillin and teicoplanin; for the slime producers, the highest effect (99.5% reduction) was shown by amikacin, clindamycin cloxacillin and ciprofloxacin but all cases still showed bacterial counts higher than 10(3) cfu/catheter segment. It is concluded that adherence of S. epidermidis to Teflon catheters decreases the bactericidal activity of the antibacterial agents tested in vitro.

Susceptibility to antimicrobial agents of Pseudomonas aeruginosa attached to siliconized latex urinary catheters.

The effect of siliconized latex urinary catheters on the in vitro activity of amikacin, ceftazidime, ciprofloxacin, norfloxacin and meropenem against Pseudomonas aeruginosa was determined by a microdilution assay. MICs of amikacin and meropenem increased at least 4-fold and 16-fold respectively in the presence of catheter material. The effect of catheter material on meropenem activity was not strain dependent and was similar for different brands of catheters. The susceptibility to antimicrobial agents of Pseudomonas aeruginosa attached to catheters for 6 and 24 hours was also evaluated. When bacteria attached for 6 hours were used as inoculum, MBCs increased at least 8-fold for amikacin, 64-fold for ceftazidime, 64-fold for ciprofloxacin, 32-fold for norfloxacin and 2048-fold for meropenem. Similar results were observed when bacteria attached to catheters for 24 hours were used as inoculum. It is concluded that catheter material itself affected the in vitro activity of meropenem, and that the bactericidal activity of all antimicrobial agents against Pseudomonas aeruginosa present in biofilms on the surface of siliconized latex urinary catheters decreased dramatically, this effect being more pronounced with meropenem.

Effect of polyurethane catheters and bacterial biofilms on the in-vitro activity of antimicrobials against Staphylococcus epidermidis.

The effect of two polyurethane ['Cavafix Certo' (CAV); 'Viacath' (VIA)] catheters on the in-vitro activity of amikacin (AN), clindamycin (CM), cloxacillin (CX), ciprofloxacin (CIP), vancomycin (VA), teicoplanin (TEI) and daptomycin (DAP) against slime producing and non-producing Staphylococcus epidermidis strains was determined using a microdilution assay. None of the antimicrobial agents was significantly affected in the presence of the catheters. The susceptibility of S. epidermidis attached to CAV and VIA catheters was also evaluated. Minimum inhibitory concentration (MIC) values were similar when planktonic and attached bacteria were compared. Minimum bactericidal concentrations (MBCs) markedly increased in the presence of 6 and 48 h bacterial biofilms. These increases in MBC values occurred when either slime producing or non-producing strains were used, and in most cases were higher for CAV catheters than for VIA catheters. This phenomenon was shown not to be due to differences in bacterial adherence. It is concluded that the in-vitro bactericidal activity of certain antimicrobials markedly decreased when bacteria adhered to plastic catheters, but this effect could have been dependent partially on the nature of the catheters.

Prostate visualization studies in males homozygous and heterozygous for 5 alpha-reductase deficiency.

Male pseudohermaphrodites with 5 alpha-reductase deficiency have ambiguous genitalia and nonpalpable prostates on rectal examination, suggesting the dihydrotestosterone dependency of these structures. To clearly delineate the status of the prostate, male pseudohermaphrodites with 5 alpha-reductase deficiency had transrectal sonography of the prostate performed, and the results were compared to that of age-matched male controls. In six male pseudohermaphrodites, magnetic resonance imaging studies of the prostate were also performed. Heterozygote fathers also had transrectal sonography of the prostate performed and the results compared to age-matched controls. The prostates of the male pseudohermaphrodites appeared as platelike soft tissue structures posterior to the urethra on both prostatic ultrasound and magnetic resonance imaging. Prostatic volume, as determined on prostatic ultrasound by two different methods, was significantly smaller (approximately one-tenth) than the volume of age-matched controls. Transurethral ultrasound guided biopsy of the prostate in two affected subjects revealed stromal tissue. These results correlate with undetectable prostate-specific antigen in affected subjects, suggesting atrophic epithelium or lack of epithelial differentiation. This study demonstrates the dihydrotestosterone dependence of the prostate for normal differentiation and growth. The presence of some prostatic tissue in the male pseudohermaphrodites may be due to the fact that there is a decrease and not an absence of 5 alpha-reductase activity, and/or that the increased level of testosterone in subjects with this condition partially compensates for the decreased level of dihydrotestosterone. There was no difference, however, in prostate size between heterozygous fathers and age-matched control males. The heterozygote fathers had dihydrotestosterone production sufficient for normal prostate growth and development.

[Evaluation of 5 methods for the diagnosis of infections by respiratory syncytial virus]. / Evaluación de 5 métodos para el diagnóstico de las infecciones por virus respiratorio sincitial.

BACKGROUND: To compare and evaluate four different rapid methods of respiratory syncytial virus antigen detection with the isolation of the virus in cell culture. METHOD: Ninety-eight nasopharyngeal swabs were studied, for respiratory syncytial virus isolation in Hep-2 cell line and for RSV antigen detection using direct immunofluorescence and three ELISA methods: Abbot RSV EIA (ELISA-1), RSV Antigen Detection System (ELISA-2) and Directigen RSV (Directigen). RESULTS: Of all 98 samples studied using the five mentioned methods, 42 (43%) were positive for respiratory syncytial virus. The most sensitive methods were ELISA-1 (82%) and immunofluorescence (82%). The most specific ones were direct immunofluorescence (86%) and Directigen (84%). The higher percentage of concordant positive results with respiratory syncytial virus culture were direct immunofluorescence (84%) and Directigen (82%). CONCLUSIONS: Rapid diagnostic methods for respiratory syncytial virus infection can not substitute the isolation method using cell line culture. We believe that respiratory syncytial virus isolation in cell culture combined direct with direct immunofluorescence or Directigen methods are the first choice diagnostic techniques for achieve a higher number of positive results in respiratory syncytial virus infected patients.